1. Jun 2024
    1. Reviewer #3 (Public Review):

      Summary:

      Buck et al., set out to characterize small DNA tumor viruses through the generation and analysis of ~100,000 public sequencing datasets from the SRA and other databases. Using a variety of powerful bioinformatic methods including alignment-based searches, statistical modelling, and structure-aware detection, the authors successfully classify novel protein sequences which support the occurrence of evolutionary gene transfer between DNA virus families. The authors propose a naming scheme to better capture viral diversity and uncover novel chimeric viruses, those containing genes from multiple established virus families. Additional analysis using the generated dataset was performed to search for DNA and RNA viruses of interest, demonstrating the utility of generated datasets for exploratory screens. The assembled sequencing datasets are publicly available, providing invaluable resources for current and future investigations within this subfield.

      Strengths:

      The scope of data analysis (100,000+ SRA records and additional libraries) is substantial, and the authors have contributed to further insight into the modularity of previously uncharacterized viral genomes, through computationally demanding advanced bioinformatics analyses in addition to extensive manual inspection.

      The publicly available resources generated as a result of these analyses provide useful data for further experiments to inspect viral diversity and modularity. Other scanning experiments and further investigation of biologically relevant viruses using these contigs may uncover, for example, animal reservoirs or novel recombinant viruses of significance.

      Novel instances of genomic modularity provide excellent starting points for understanding virus evolutionary pathways and gene transfer events.

      Weaknesses:

      Overall, the methods section of this paper requires more detail.

      The inclusion criteria for which "SRA" datasets were or were not utilized within this study are poorly defined. This means the comprehensiveness of the study for a given search space of the SRA is not defined, and the results are ultimately not reproducible, or expandable. For example, are all vertebrate RNA-seq samples processed? Or just aquatic vertebrate RNA-seq? Were samples randomly sampled from a more comprehensive data set? What is the make-up of the search space and how much was DNA-seq or RNA-seq? This section should be expanded and explicit accounting provided for how dataset selection was performed. This would provide additional confidence in the results and conclusions, as well as allow for future analysis to be conducted.

      Hallmark virus genes require further clarification, as it is unclear what genes are utilized as bait, or in the initial search process. The reported "Hallmark gene sets" are not described in a systematic way. What is the sensitivity and specificity of these gene sets? Was there a validation of the performance characteristics (ROC) for this gene set with different tools? How is this expected to be utilized? Which kinds of viruses are excluded/missed? Are viroids included?

      For the Tailtomavirus, additional information is needed for sufficient confidence. Was this "chimeric" genomic arrangement detected in a single library? This raises a greater issue of how technical artifacts, which may appear as chimeric assemblies, are ruled out in the workflow. If two viral genomes share a k-mer of length greater than the assembly k, the graph may become merged. Are there read pairs that span all regions of the genome? Is there evidence for multiple homologous viruses with synteny between them that supports the combination of these genes as an evolving genome, or is this an anomalous observation? Read alignments should be included and Bandage graph visualization for all cases of chimeric assemblies and active steps to disprove the baseline hypotheses that these are technical artifacts of genome assembly.

      Justification for exclusion of endogenized sequences is not included and must be described, as small DNA tumor viruses may endogenize into the host genome as part of their life cycle. How is such an integration resolved from an evolutionary "endogenization"? What's the biological justification for this step?

      Additional supporting information, clear presentation, and context are needed to strengthen results and conclusions.

      Basic reporting of global statistics, such as the total number of viruses found per family, should be included in the main text to better support the scope of the results. How many viruses (per family) were previously known, and therefore what is the magnitude of the expansion performed here?

      Additional parameters and information should be included in bioinformatic tool outputs to provide greater clarity and interpretation of results. For example, reporting the "BLASTp E-val", as for the PolB homology (BLASTp 6E-12) is not informative, and does not tell the reader this is (we assume) an expectancy value. For each such case please report, the top database hit accession, percent identity, query coverage, and E-value. Otherwise, a judgment cannot be adequately made regarding the quality of evidence for homology. Similarly, for HHpred what does the number represent - confidence, identity, or coverage?

      Some findings described in the Results section may require revision. Several of the Nidoviruses (Nidovirus takifugu, Nidovirus hypomesus, Nidovirus ambystoma, etc...) have been previously described by three groups, first by Edgar et al., (https://www.nature.com/articles/s41586-021-04332-2), then Miller et al., (https://academic.oup.com/ve/article/7/2/veab050/6290018) and then Lauber et al., (https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1012163). This is now the 4th description of the same set of viruses. These sequences are in GenBank (https://www.ncbi.nlm.nih.gov/nuccore/OV442424.1), although it is unclear why they're not returned as BLAST hits. Miller also described the Togavirus co-segment previously.

      It is also uncertain what is being described with HelPol/maldviruses which was not previously described in distantly similar relatives. How many were described in the previous literature and how many are described by this work?

      Co-phylogenies should be used to convey gene transfer and flow clearly to support the conclusions made in the text.

      Statements such as, "The group encompasses a surprising degree of genomic diversity...", should be supported by additional information to strengthen conclusions (e.g., what the expected diversity is). What is the measurement for genomic diversity here, and why is this surprising? There is overall a lack of quantification to support the conclusions made throughout the paper.

    1. eLife assessment

      This study investigates the role of queuosine (Q) tRNA modification in aminoglycoside tolerance in Vibrio cholerae and presents convincing evidence to conclude that Q is essential for the efficient translation of TAT codons, although this depends on the context. The absence of Q reduces aminoglycoside tolerance potentially by reprogramming the translation of an oxidative stress response gene, rxsA. Overall, the findings point to an important mechanism whereby changes in Q modification levels control the decoding of mRNAs enriched in TAT codons under antibiotic stress.

    2. Reviewer #1 (Public Review):

      Summary of the work: In this work, Fruchard et. al. study the enzyme Tgt and how it modifies guanine in tRNAs to queuosine (Q), essential for Vibrio cholerae's growth under aminoglycoside stress. Q's role in codon decoding efficiency and its proteomic effects during antibiotic exposure is examined, revealing Q modification impacts tyrosine codon decoding and influences RsxA translation, affecting the SoxR oxidative stress response. The research proposes Q modification's regulation under environmental cues reprograms the translation of genes with tyrosine codon bias, including DNA repair factors, crucial for bacterial antibiotic response.

      The experiments are well-designed and conducted and the conclusions, for the most part, are well supported by the data. However, a few clarifications will significantly strengthen the manuscript.

      Major:<br /> Figure S4 A-D. These growth curves are important data and should be presented in the main figures. Moreover, given that it is not possible to make a rsxA mutant, I wonder if it would be possible to connect rsx and tgt using the following experiment: expression of tgt results in resistance to TOB (in B), while expression of only rsx lower resistance to TOB (in D). Then simultaneous overexpression of both tgt/rsx in the WT strain should have either no effect on TOB resistance or increased resistance, relative to the WT. Perhaps the authors have done this, and if so, the data should be included as it will significantly strengthen their model.

      Figure S4 - Is there a rationale for why it is possible to make rsx mutants in E. coli, but not in V. cholerae? For example, does E. coli have a second gene/protein that is redundant in function to rsxA, while V. cholerae does not? I think your data hint at this, since in the right panel growth data, your double mutant does not fully rescue back to rsx single mutant levels, suggesting another factor in tgt mutant also acts to lower resistance to TOB. If so, perhaps a line or two in text will be helpful for readers.

      -For growth curves in Figure 2 and relative comparisons like in Figure 5D and Figure S4 (and others in the paper), statistics and error bars, along with replicate information should be provided.

      -Figure 6A - Is the transcript fold change in linear or log? If linear, then tgt expression should not be classified as being upregulated in TOB. It is barely up by ~2-fold with TOB- 0.6....which is a mild phenotype, at best.

      -Line 779- 780: "This indicates that sub-MIC TOB possibly induces tgt expression through the stringent response activation." To me, the data presented in this figure, do not support this statement. The experiment is indirect.

      -Figure 3B and D. - These samples only have tobramycin, correct? The legend says both carbenicillin and tobramycin.

      -Figure 5. The color schemes in bars do not match up with the color scheme in cartoons below panels B and C. That makes it confusing to read. Please fix.

      -A lot of abbreviations have been used. This makes reading a bit cumbersome. Ideally, less abbreviations will be used.

    3. Reviewer #2 (Public Review):

      Fruchard et al. investigate the role of the queuosine (Q) modification of the tRNA (Q-tRNA) in the human pathogen Vibrio cholerae. First, the authors state that the absence of Q-modified tRNAs (tgt mutant) increases the translation of TAT codons and proteins with a high TAT codon bias. Second, the absence of Q increases rsxA translation, because rsxA gene has a high TAT codon bias. Third, increased RsxA in the absence of Q inhibits SoxR response, reducing resistance towards the antibiotic tobramycin (TOB). Authors also predict in silico which genes harbor a higher TAT bias and found that among them are some involved in DNA repair, experimentally observing that a tgt mutant is more resistant to UV than the wt strain. It is worth noting that authors employ a wide variety of techniques, both experimental and bioinformatic. However, some aspects of the work need to be clarified or reevaluated.

      (1) The statement that the absence of Q increases the translation of TAT codons and proteins encoded by TAT-enriched genes presents the following problems that should be addressed:

      (1.1) The increase in TAT codon translation in the absence of Q is not supported by proteomics, since there was no detected statistical difference for TAT codon usage in proteins differentially expressed. Furthermore, there are some problems regarding the statistics of proteomics. Some proteins shown in Table S1 have adjusted p-values higher than their p-values, which makes no sense. Maybe there is a mistake in the adjusted p-value calculation. In addition, it is not common to assume that proteins that are quantitatively present in one condition and absent in another are differentially abundant proteins. Proteomics data software typically addresses this issue and applies some corrections. It would be advisable to review that.

      (1.2) Problems with the interpretation of Ribo-seq data (Figure 4D). On the one hand, the Ribo-seq data should be corrected (normalized) with the RNA-seq data in each of the conditions to obtain ribosome profiling data, since some genes could have more transcription in some of the conditions studied. In other articles in which this technique is used (such as in Tuorto et al., EMBO J. 2018; doi: 10.15252/embj.201899777), it is interpreted that those positions in which the ribosome moves most slowly and therefore less efficiently translated), are the most abundant. Assuming this interpretation, according to the hypothesis proposed in this work, the fragments enriched in TAT codons should have been less abundant in the absence of Q-tRNA (tgt mutant) in the Rib-seq experiment. However, what is observed is that TAT-enriched fragments are more abundant in the tgt mutant, and yet the Ribo-seq results are interpreted as RNA-seq, stating that this is because the genes corresponding to those sequences have greater expression in the absence of Q. On the other hand, it would be interesting to calculate the mean of the protein levels encoded by the transcripts with high and low ribosome profiling data.

      (1.3) This statement is contrary to most previously reported studies on this topic in eukaryotes and bacteria, in which ribosome profiling experiments, among others, indicate that translation of TAT codons is slower (or unaffected) than translation of the TAC codons, and the same phenomenon is observed for the rest of the NAC/T codons. This is completely opposed to the results showed in Figure 4. However, the results of these studies are either not mentioned or not discussed in this work. Some examples of articles that should be discussed in this work:<br /> - "Queuosine-modified tRNAs confer nutritional control of protein translation" (Tuorto et al., 2018; 10.15252/embj.201899777)<br /> - "Preferential import of queuosine-modified tRNAs into Trypanosoma brucei mitochondrion is critical for organellar protein synthesis" (Kulkarni et al., 2021; doi:10.1093/nar/gkab567.<br /> - "Queuosine-tRNA promotes sex-dependent learning and memory formation by maintaining codon-biased translation elongation speed" (Cirzi et al., 2023; 10.15252/embj.2022112507)<br /> - "Glycosylated queuosines in tRNAs optimize translational rate and post-embryonic growth" (Zhao et al., 2023; 10.1016/j.cell.2023.10.026)<br /> - "tRNA queuosine modification is involved in biofilm formation and virulence in bacteria" (Diaz-Rullo and Gonzalez-Pastor, 2023; doi: 10.1093/nar/gkad667). In this work, the authors indicate that Q-tRNA increases NAT codon translation in most bacterial species. Could the regulation of TAT codon-enriched proteins by Q-tRNAs in V. cholerae an exception? In addition, authors use a bioinformatic method to identify genes enriched in NAT codons similar to the one used in this work, and to find in which biological process are involved the genes whose expression is affected by Q-tRNAs (as discussed for the phenotype of UV resistance). It will be worth discussing all of this.

      (1.4) It is proposed that the stress produced by the TOB antibiotic causes greater translation of genes enriched in TAT codons. On the one hand, it is shown that the GFP-TAT version (gene enriched in TAT codons) and the RsxA-TAT-GFP protein (native gene naturally enriched in TAT) are expressed more, compared to their versions enriched in TAC in a tgt mutant than in a wt, in the presence of TBO (Fig. 5C). However, in the absence of TOB, and in a wt context, although the two versions of GFP have a similar expression level (Fig. 3SD), the same does not occur with RsxA, whose RsxA-TAT form (the native one) is expressed significantly more than the RsxA-TAC version (Fig. 3SA). How can it be explained that in a wt context, in which there are also tRNA Q-modification, a gene naturally enriched in TAT is translated better than the same gene enriched in TAC? It would be expected that in the presence of Q-tRNAs the two versions would be translated equally (as happens with GFP) or even the TAT version would be less translated. On the other hand, in the presence of TOB the fluorescence of WT GFP(TAT) is higher than the fluorescence of WT GFP(TAC) (Figure S3E) (mean fluorescence data for RsxA-GFP version in the presence of TOB is not shown). These results may indicate that the apparent better translation of TAT versions could be due to indirect effects rather from TAT codon translation.

      (2) Another problem is related to the already known role of Q in prevention of stop codon readthrough, which is not discuss at all in the work. In the absence of Q, stop codon readthrough is increased. In addition, it is known that aminoglycosides (such as tobramycin) also increase stop codon readthrough ("Stop codon context influences genome-wide stimulation of termination codon readthrough by aminoglycosides"; Wanger and Green, 2023; 10.7554/eLife.52611). Absence of Q and presence of aminoglycosides can be synergic, producing devastating increases in stop codon readthrough and a large alteration of global gene expression. All of these needs to be discussed in the work. Moreover, it is known that stop codon readthrough can alter gene expression and mRNA sequence context all influence the likelihood of stop codon readthrough. Thus, this process could also affect to the expression of recoded GFP and RsxA versions.

      (3) The statement about that the TOB resistance depends on RsxA translation, which is related to the presence of Q, also presents some problems:

      (3.1) It is observed that the absence of tgt produces a growth defect in V. cholerae when exposed to TOB (Figure 1A), and it is stated that this is mediated by an increase in the translation of RsxA, because its gene is TAT enriched. However, in Figure S4F, it is shown that the same phenotype is observed in E. coli, but its rsxA gene is not enriched in TAT codons. Therefore, the growth defect observed in the tgt mutant in the presence of TOB may not be due to the increase in the translation of TAT codons of the rsxA gene in the absence of Q. This phenotype is very interesting, but it may be related to another molecular process regulated by Q. Maybe the role of Q in preventing stop codon readthrough is important in this process, reducing cellular stress in the presence of TOB and growing better.

      (3.2) All experiments related to the effect of Q on the translation of TAT codons have been performed with the tgt mutant strain. Considering that the authors have a pSEVA-tgt plasmid to overexpress this gene, they would have to show whether tgt overexpression in a wt strain produces a decrease in the translation of proteins encoded by TAT-enriched genes such as RsxA. This experiment would allow them to conclude that Q reduces RsxA levels, increasing resistance to TOB.

      (3.3) On the other hand, Fig. 1B shows that when the wt and tgt strains compete, both overexpressing tgt, the tgt mutant strain grows better in the presence of TOB. This result is not very well understood, since according to the hypothesis proposed, the absence of modification by Q of the tRNA would increase the translation of genes enriched in TAT, therefore, a strain with a higher proportion of Q-modified tRNAs as in the case of the wt strain overexpressing tgt would express the rsxA gene less than the tgt strain overexpressing tgt and would therefore grow better in the presence of TOB. For all these reasons, it would be necessary to evaluate the effect of tgt overexpression on the translation of RsxA.

      (3.4) According to Figure 1I, the overexpression of tRNA-Tyr(GUA) caused a better growth of tgt mutant in comparison to WT. If the growth defect observed in tgt mutant in the presence of TOB is due to a better translation of the TAT codons of rsxA gene, the overexpression of tRNA-Tyr(GUA) in the tgt mutant should have resulted in even better RsxA translation a worse growth, but not the opposite result.

      (4) It cannot be stated that DNA repair is more efficient in the tgt mutant of V. cholerae, as indicated in the text of the article and in Fig 7. The authors only observe that the tgt mutant is more resistant to UV radiation and it is suggested that the reason may be TAT bias of DNA repair genes. To validate the hypothesis that UV resistance is increased because DNA repair genes are TAT biased, it would be necessary to check if DNA repair is affected by Q. UV not only produces DNA damage, but also oxidative stress. Therefore, maybe this phenotype is due to the increase in proteins related to oxidative stress controlled by RsxA, such as the superoxide dismutase encoded by sodA. It is also stated that these repair genes were found up for the tgt mutant in the Ribo-seq data, with unchanged transcription levels. Again, it is necessary to clarify this interpretation of the Ribo-seq data, since the fact that they are more represented in a tgt mutant perhaps means that translation is slower in those transcripts. Has it been observed in proteomics (wt vs tgt in the absence of TOB) whether these proteins involved in repair are more expressed in a tgt mutant?

      (5) The authors demonstrate that in E. coli the tgt mutant does not show greater resistance to UV radiation (Fig. 7D), unlike what happens in V. cholerae. It should be discussed that in previous works it has been observed that overexpression in E. coli of the tgt gene or the queF gene (Q biosynthesis) is involved in greater resistance to UV radiation (Morgante et al., Environ Microbiol, 2015 doi: 10.1111/1462-2920.12505; and Díaz-Rullo et al., Front Microbiol. 2021 doi: 10.3389/fmicb.2021.723874). As an explanation, it was proposed (Diaz-Rullo and Gonzalez-Pastor, NAR 2023 doi: 10.1093/nar/gkad667) that the observed increase in the capacity to form biofilms in strains that overexpress genes related to Q modification of tRNA would be related to this greater resistance to UV radiation.

    4. Reviewer #3 (Public Review):

      Summary:

      In this manuscript the authors begin with the interesting phenotype of sub-inhibitory concentrations of the aminoglycoside tobramycin proving toxic to a knockout of the tRNA-guanine transglycosylase (Tgt) of the important human pathogen, Vibrio cholerae. Tgt is important for incorporating queuosine (Q) in place of guanosine at the wobble position of GUN codons. The authors go on to define a mechanism of action where environmental stressors control expression of tgt to control translational decoding of particularly tyrosine codons, skewing the balance from TAC towards TAT decoding in the absence of the enzyme. The authors use advanced proteomics and ribosome profiling to reveal that the loss of tgt results in increased translation of proteins like RsxA and a cohort of DNA repair factors, whose genes harbor an excess of TAT codons in many cases. These findings are bolstered by a series of molecular reporters, mass spectrometry, and tRNA overexpression strains to provide support for a model where Tgt serves as a molecular pivot point to reprogram translational output in response to stress.

      Strengths:

      The manuscript has many strengths. The authors use a variety of strains, assays, and advanced techniques to discover a mechanism of action for Tgt in mediating tolerance to sub-inhibitory concentrations of tobramycin. They observe a clear phenotype for a tRNA modification in facilitating reprogramming of the translational response, and the manuscript certainly has value in defining how microbes tolerate antibiotics.

      Weaknesses:

      The conclusions of the manuscript are mostly very well-supported by the data, but in some places control experiments or peripheral findings cloud precise conclusions. Some additional clarification, discussion, or even experimental extension could be useful in strengthening these areas.

      (1) The authors have created and used a variety of relevant molecular tools. In some cases, using these tools in additional assays as controls would be helpful. For example, testing for compensation of the observed phenotypes by overexpression of the Tyrosine tRNA(GUA) in Figure 2A with the 6xTAT strain, Figure 5C with the rxsA-GFP fusion, and/or Figure 7B with UV stress would provide additional information of the ability of tRNA overexpression to compensate for the defect in these situations.<br /> (2) The authors present a clear story with a reprogramming towards TAT codons in the knockout strain, particularly regarding tobramycin treatment. The control experiments often hint at other codons also contributing to the observed phenotypes (e.g., His or Asp), yet these effects are mostly ignored in the discussion. It would be helpful to discuss these findings at a minimum in the discussion section, or possibly experimentally address the role of His or Asp by overexpression of these tRNAs together with Tyrosine tRNA(GUA) in an experiment like that of Figure 1I to see if a more "wild type" phenotype would present. In fact, the synergy of Tyr, His, and/or Asp codons likely helps to explain the effects observed with the DNA repair genes in later experiments.<br /> (3) Regarding Figure 6D, the APB northern blot feels like an afterthought. It was loaded with different amounts of RNA as input and some samples are repeated three times, but Δcrp only once. Collectively, it makes this experiment very difficult to assess.

      Minor Points:<br /> (4) Fig S2B, do the authors have a hypothesis why the Asp and Phe tRNAs lead to a growth decrease in the untreated samples? It appears like Phe(GAA) partially compensates for the defect.<br /> (5) Lines 655 to 660 seem more appropriate as speculation in the discussion rather than as a conclusion in the results, where no direct experiments are performed. The authors might take advantage of the "Ideas and Speculation" section that eLife allows.

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    1. eLife assessment

      This study provides valuable new insights into insect cognition and problem-solving in bumblebees. The authors present convincing evidence that bumblebees lack causal understanding in a string-pulling task, although evidence that bumblebees instead use image-matching for this task, which would benefit from further experiments, is currently incomplete.

    2. Reviewer #1 (Public Review):

      Summary:

      In this paper, the researchers aimed to address whether bees causally understand string-pulling through a series of experiments. I first briefly summarize what they did:

      - In experiment 1, the researchers trained bees without string and then presented them with flowers in the test phase that either had connected or disconnected strings, to determine what their preference was without any training. Bees did not show any preference.

      - In experiment 2, bees were trained to have experience with string and then tested on their choice between connected vs. disconnected string.

      - experiment 3 was similar except that instead of having one option which was an attached string broken in the middle, the string was completely disconnected from the flower.

      - In experiment 4, bees were trained on green strings and tested on white strings to determine if they generalize across color.

      - In experiment 5, bees were trained on blue strings and tested on white strings.

      - In experiment 6, bees were trained where black tape covered the area between the string and the flower (i.e. so they would not be able to see/ learn whether it was connected or disconnected).

      - In experiments 2-6, bees chose the connected string in the test phase.

      - In experiment 7, bees were trained as in experiment 3 and then tested where the string was either disconnected or coiled i.e. still being 'functional' but appearing different.

      - In experiment 8, bees were trained as before and then tested on a string that was in a different coiled orientation, either connected or disconnected.

      - In experiments 7 and 8 the bees showed no preference.

      Strengths:

      I appreciate the amount of work that has gone into this study and think it contains a nice, thorough set of experiments. I enjoyed reading the paper and felt that overall it was well-written and clear. I think experiment 1 shows that bees do not have an untrained understanding of the function of the string in this context. The rest of the experiments indicate that with training, bees have a preference for unbroken over broken string and likely use visual cues learned during training to make this choice. They also show that as in other contexts, bees readily generalize across different colors.

      Weaknesses:

      (1) I think there are 2 key pieces of information that can be taken from the test phase - the bees' first choice and then their behavior across the whole test. I think the first choice is critical in terms of what the bee has learned from the training phase - then their behavior from this point is informed by the feedback they obtain during the test phase. I think both pieces of information are worth considering, but their behavior across the entire test phase is giving different information than their first choice, and this distinction could be made more explicit.

      In addition, while the bees' first choice is reported, no statistics are presented for their preferences.

      (2) It seemed to me that the bees might not only be using visual feedback but also motor feedback. This would not explain their behavior in the first test choice, but could explain some of their subsequent behavior. For example, bees might learn during training that there is some friction/weight associated with pulling the string, but in cases where the string is separated from the flower, this would presumably feel different to the bee in terms of the physical feedback it is receiving. I'd be interested to see some of these test videos (perhaps these could be shared as supplementary material, in addition to the training videos already uploaded), to see what the bees' behavior looks like after they attempt to pull a disconnected string.

      (3) I think the statistics section needs to be made clearer (more in private comments).

      (4) I think the paper would be made stronger by considering the natural context in which the bee performs this behavior. Bees manipulate flowers in all kinds of contexts and scrabble with their legs to achieve nectar rewards. Rather than thinking that it is pulling a string, my guess would be that the bee learns that a particular motor pattern within their usual foraging repertoire (scrabbling with legs), leads to a reward. I don't think this makes the behavior any less interesting - in fact, I think considering the behavior through an ecological lens can help make better sense of it.

    3. Reviewer #2 (Public Review):

      Summary:

      The authors wanted to see if bumblebees could succeed in the string-pulling paradigm with broken strings. They found that bumblebees can learn to pull strings and that they have a preference to pull on intact strings vs broken ones. The authors conclude that bumblebees use image matching to complete the string-pulling task.

      Strengths:

      The study has an excellent experimental design and contributes to our understanding of what information bumblebees use to solve a string-pulling task.

      Weaknesses:

      Overall, I think the manuscript is good, but it is missing some context. Why do bumblebees rely on image matching rather than causal reasoning? Could it have something to do with their ecology? And how is the task relevant for bumblebees in the wild? Does the test translate to any real-life situations? Is pulling a natural behaviour that bees do? Does image matching have adaptive significance?

    4. Reviewer #3 (Public Review):

      Summary:

      This paper presents bees with varying levels of experience with a choice task where bees have to choose to pull either a connected or unconnected string, each attached to a yellow flower containing sugar water. Bees without experience of string pulling did not choose the connected string above chance (experiment 1), but with experience of horizontal string pulling (as in the right-hand panel of Figure 4) bees did choose the connected string above chance (experiments 2-3), even when the string colour changed between training and test (experiments 4-5). Bees that were not provided with perceptual-motor feedback (i.e they could not observe that each pull of the string moved the flower) during training still learned to string pull and then chose the connected string option above chance (experiment 6). Bees with normal experience of string pulling then failed to discriminate between connected and unconnected strings when the strings were coiled or looped, rather than presented straight (experiments 7-8).

      Weaknesses:

      The authors have only provided video of some of the conditions where the bees succeeded. In general, I think a video explaining each condition and then showing a clip of a typical performance would make it much easier to follow the study designs for scholars. Videos of the conditions bees failed at would be highly useful in order to compare different hypotheses for how the bees are solving this problem. I also think it is highly important to code the videos for switching behaviours. When solving the connected vs unconnected string tasks, when bees were observed pulling the unconnected string, did they quickly switch to the other string? Or did they continue to pull the wrong string? This would help discriminate the use of perceptual-motor feedback from other hypotheses.

      The experiments are also not described well, for my below comments I have assumed that different groups of bees were tested for experiments 1-8, and that experiment 6 was run as described in line 331, where bees were given string-pulling training without perceptual feedback rather than how it is described in Figure 4B, which describes bees as receiving string pulling training with feedback.

      The authors suggest the bees' performance is best explained by what they term 'image matching'. However, experiment 6 does not seem to support this without assuming retroactive image matching after the problem is solved. The logic of experiment 6 is described as "This was to ensure that the bees could not see the familiar "lollipop shape" while pulling strings....If the bees prefer to pull the connected strings, this would indicate that bees memorize the arrangement of strings-connected flowers in this task." I disagree with this second sentence, removing perceptual feedback during training would prevent bees memorising the lollipop shape, because, while solving the task, they don't actually see a string connected to a yellow flower, due to the black barrier. At the end of the task, the string is now behind the bee, so unless the bee is turning around and encoding this object retrospectively as the image to match, it seems hard to imagine how the bee learns the lollipop shape.

      Despite this, the authors go on to describe image matching as one of their main findings. For this claim, I would suggest the authors run another experiment, identical to experiment 6 but with a black panel behind the bee, such that the string the bee pulls behind itself disappears from view. There is now no image to match at any point from the bee's perspective so it should now fail the connectivity task.

      Strengths:

      Despite these issues, this is a fascinating dataset. Experiments 1 and 2 show that the bees are not learning to discriminate between connected and unconnected stimuli rapidly in the first trials of the test. Instead, it is clear that experience in string pulling is needed to discriminate between connected and unconnected strings. What aspect of this experience is important? Experiment 6 suggests it is not image matching (when no image is provided during problem-solving, but only afterward, bees still attend to string connectivity) and casts doubt on perceptual-motor feedback (unless from the bee's perspective, they do actually get feedback that pulling the string moves the flower, video is needed here). Experiments 7 and 8 rule out means-end understanding because if the bees are capable of imagining the effect of their actions on the string and then planning out their actions (as hypotheses such as insight, means-end understanding and string connectivity suggest), they should solve these tasks.

      If the authors can compare the bees' performance in a more detailed way to other species, and run the experiment suggested, this will be a highly exciting paper

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      Sanitäranlagen

      Umsetzung Analysen Optimieren in Stand-Stellung Service und Pikettdienste

      Wir installieren Sanitäranlagen im Industriebereich, Einkaufcenter und Gewerbe. Analysieren und optimieren von Sanitäranlagen macht uns Freude und liegt in unser Fachkompetenz. Bei Instand-Stellen von Sanitäranlagen legen wir Wert auf Betriebssicherheit und Nachhaltigkeit. Den Service- und Pikettdienst stellen wir mit Partnerfirmen sicher.

    2. Kältetechnik

      Lüftungs- und Klimaanlagen

      Konzeptentwicklung Planung Beratung Umsetzung Lüftungsanlagen Umsetzung Klimaanlagen Umsetzung Absaugungsanlagen Analysen Optimieren in Stand-Stellung Service und Pikettdienste

      Unser vorwiegendes Segmente sind Lüftungs- und Klimaanlagen im Bereich der Industrie, Einkaufcenter, und Gewebe Wir bieten das ganze Spektrum von der Beratung bis hin zur Umsetzung und Nachbetreuung der Anlagen. Ein Service- und Pikettdienst ist im Aufbau.

      Ob Neubau oder Sanierungen und Anlageerweiterungen, wir können auf Grund unser langjährigen Erfahrung und durch permanente Schulung unser Mitarbeiter stehts die optimale Lösung anbieten.

    3. Heizungstechnik

      Heizung- und Kältesystem

      Konzeptentwicklung Planung Beratung Umsetzung Heizungsbau Umsetzung Kältesysteme Fernwärme-Leitungsbau Analysen Optimieren in Stand-Stellung Service und Pikettdienste

      Unser vorwiegendes Segmente sind Heizungs- und Kältezentralen und Industrieanlagen sowie die Verteilung. Der Fernwärme -Leitungsbau gehört zu unser Haupt-Kompetenz. Wir bieten das ganze Spektrum von der Beratung bis hin zur Umsetzung und Nachbetreuung der Anlagen. Ein Service- und Pikettdienst ist im Aufbau.

      Ob Neubau oder Sanierungen und Anlageerweiterungen sind wir mit Konzeptentwicklung, Beratung und Umsetzung für Sie da. Wir bearbeiten Rohrsystem bis zu einem Durchmesser DN 600 mm. Durch die Vorfabrikation in unser Werkstatt können auf der Baustelle die Montagetermine kurz gehalten werden.

    4. Aktuelle Stellenangebote:

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    5. Links für Social Media entfernen

    6. Unsere Erfolgsgeschichten

      Erfolgsgeschichten in Projekte umwandeln und für den Moment ausblenden

    7. Unsere Partner/Kunden

      Partner würde ich aktuell komplett entfernen

    8. William Anderson

      Federica Blumer Admin/HR Mobile: 078 266 66 07 E-Mail: f.blumer@bay-teec.ch

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      Mehmet Bayar Partner Mobile: 078 928 40 91 E-Mail:

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      Rolf Poltéra Geschäftsführer Mobile: 076 680 30 28 E-Mail: r.poltéra@bay-tec.ch

    11. Phone: +1 5589 55488 55 Email: info@example.com

      Telefon: 044 544 26 16 E-Mail: info@bay-tec.ch

    12. Email info@example.comcontact@example.com

      E-Mail info@bay-tec.ch

    13. Friedenstrasse 5C 8304 Wallisellen

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    14. Ihr Partner für umweltbewusste und innovative Lösungen in Heizungs-, Kälte- und Sanitärtechnik.

      Ihr Partner für umweltbewusste und innovative Lösungen in Heizungs-, Kälte-, Lüftungs- und Sanitärtechnik.

    15. Addresse A108 Adam Street,New York, NY 535022

      Adresse

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    16. Telefon +1 5589 55488 55+1 6678 254445 41

      044 544 26 16

    17. Öffnungszeiten Montag - Freitag8:00 - 17:00

      Büroöffnungszeiten

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    1. eLife assessment

      In this study, the authors found that a species of aphid that is a known agricultural pest salivated longer and produced more honeydew when feeding at night. The authors identified aphid genes with diurnal expression patterns, including potential saliva-related genes. Silencing these genes reduced aphid performance only on real plants, suggesting a specific role in plant feeding. While this study is valuable for understanding plant-insect interactions in agriculture, it is currently incomplete, as further research is needed to elucidate the function of the identified genes.

    2. Reviewer #1 (Public Review):

      Summary :

      This study presents valuable data on diurnal patterns in aphid (Rhopalosiphum padi) feeding behavior and transcriptome profiles. The authors measured honeydew production by the aphids on plants and artificial diet during the day and night and conducted a comprehensive feeding behavior study using EPG with many biological replicates at 6 time-points in 24 hours. They also conducted transcriptome analyses of three samples of each 30 aphids at these time points. Differentially expressed transcripts were grouped into four clusters with distinct expression patterns. The expression of two genes found to be diurnally rhythmic was knocked down with RNAi and these aphids did less well, especially at night. They also analyzed the differential expression of candidate effector genes and found rhythmic ones to be enriched for more expression in aphid heads versus bodies - this pattern is expected given that effectors are most likely expressed in the salivary glands. Knockdown of a known effector (C002) that is diurnally rhythmic, and a novel effector gene, was found to alter aphid feeding dynamics and performance.

      Strengths:

      The manuscript was highly accessible, with clear writing, and the figures provided were both comprehensive and of good quality. The datasets generated from this research are valuable to the research field, especially the findings for honeydew secretion, EPG analysis, and transcriptome experiments.

      The datasets generated in this study will be useful to scientists working on aphids and aphid-plant interactions and will inform similar studies on other insect species.

      Weaknesses:

      The weaknesses mainly relate to the (depth of) analyses and interpretation of the data. Also, some methods require more explanation, as follows:

      In Figure 1, data show that aphids produce more honeydew at night than during the day. This suggests that the aphids ingest more phloem (E2 phase). However, in Figure 1d the duration of the E2 phase does not show obvious differences among the time points in the 24 hours. The authors contribute the explanation that the aphids may osmoregulate more during the night, leading to more honeydew secretion at night. This may be the case, but there could be other explanations. For example, the physiology, including regulation of water transport, of plants is known to change during night/day. The authors may focus this section more on the differences in the E1 phase, as this involves the delivery of aphid saliva and effectors into the plant phloem.

      Transcriptome data shown in Figure 2 (and the experimental procedure of Figure 5b) appears to be based on three biological replicates. However, these replicates appear to have been harvested at the same time in the experiment, and this makes them technical replicates, not biological replicates. The inclusion of true biological replicates that include samples from time series experiments done on different days should be considered.

      The authors conducted knockdown experiments targeting aquaporin 1 and gut sucrase 1 in aphids, resulting in reduced nymph production and decreased honeydew secretion. It is concluded that these results indicate significant roles of aquaporin 1 and gut sucrase 1 in diurnal regulation. However, it is essential to consider that these genes likely play crucial roles in aphid physiology beyond diurnal rhythms. Consequently, reduced expression would naturally impair aphid performance. The dsAQP1 and dsSUC1 aphids consistently produced less honeydew, regardless of the time of day, indicating a broader impact of gene knockdown. The observed increase of the phenotype at night may not be attributable to the specific roles of these genes in diurnal regulation but rather due to heightened aphid activity during that time (as evidenced by increased honeydew secretion) that could magnify the impact of the knockdown effect, making it easier to observe. Therefore, the knockdown of aquaporin 1 and gut sucrase 1 may exert a general negative influence on aphid fitness, independently of diurnal factors.

      To analyze the roles of genes in diurnal regulation, additional controls should be incorporated. This could involve the knockdown of genes with essential functions that are not influenced by diurnal rhythms, providing a baseline comparison. Furthermore, consider including genes known to be involved in diurnal regulation in other insects, as documented in the existing literature, in the experimental design.

      The same arguments as for aquaporin 1 and gut sucrase 1 above may be made for knockdown of effector genes (Figure 4). It has already been shown that knockdown of C002 impacts aphid performance, and the data herein may be explained by a general lower performance of aphids rather than a specific function of these effectors in diurnal regulation. It is also expected that knockdown of the effectors has less impact on aphids feeding from artificial diets. This does not necessarily indicate the role of the effectors in diurnal regulation.

      In the abstract and elsewhere, the authors assert priority by stating, "...the first evidence of...". However, it's important to note that priority claims are often challenging to verify across many fields. Instead of relying solely on claims of precedence, the evidence presented in the research could stand on its own merit.

      Conclusion:

      The study presents intriguing new findings, particularly in the realms of honeydew analysis, EPG, and transcriptome analysis. However, the interpretation of subsequent studies employing gene knockdowns needs further consideration.

    3. Reviewer #2 (Public Review):

      Summary:

      The authors conducted a time-course of whole-body transcriptional analysis of a pest aphid, Rhopalosiphum padi, and identified four major clusters of the genes that show diurnal rhythmicity in transcription. In addition, they conducted the analysis of aphid feeding behaviour and showed that aphids salivate longer from the end of the day toward the beginning of the night while their phloem feeding time does not change throughout the day. The genes up-regulated at night time were enriched with the genes involved in metabolic activities, collaborating with the results showing a higher number of honeydew excretion at night. The authors identified the list of candidate salivary genes that show diurnal rhythmicity in the transcription and silenced a salivary gene C002 and the candidate salivary gene E8696. Silencing of these genes reduced aphid fecundity and survival rate on the host plant but not on the artificial diet.

      Strengths:

      The time-course transcription study and its analysis will be of interest to researchers studying diurnal rhythms in insect biology. Also, the analysis of aphid feeding behaviour at different times of day is interesting. This study provides variable resources for those who study insect biology.

      Weaknesses:

      It is not clear to me which data was used to define the putative salivary effectors for R. padi, but the candidate salivary gene list made by Thorpe et al consists of the aphid genes encoding secreted proteins that are up-regulated in the head samples compared to the body samples. Although some proteins were confirmed to be secreted into the aphid saliva, many genes in the list are not confirmed to be expressed in the aphid salivary glands, and their products are not confirmed to be secreted into the saliva and the plant. Is E8696 expressed in the aphid salivary glands and secreted into its host plant? Without the data confirming the expression of the gene in the salivary glands and its secretion into the saliva and into the host plant, we cannot call the protein a salivary protein. Furthermore, without the observation that E8696 has some effect on plant biology, we cannot call it an aphid effector. Therefore, I cannot agree with the parts of the manuscript that refer to E8686 as an aphid salivary effector.

      It is interesting to know that some candidate salivary gene expression showed a diurnal rhythm. However, without the knowledge of the functions of the salivary effectors, especially their targets, it is not possible to conclude that the rhythmical expression is important for the aphid performance. In addition, I wonder whether the increase in gene expression is directly correlated with the increase of protein secretion into the saliva and the plant.

      Finally, the authors examined aphid survival, fecundity, and feeding behaviour. Those are important for overall aphid performance, but they do not "shape" aphid colonization. Aphid colonisation is shaped by the mechanisms by which aphids find and select their host plant and start to feed on it. Therefore, I do not agree with the title of this manuscript and some parts of the discussion.

      I would like the authors to develop how the knowledge of the diurnal rhythm of aphid feeding can contribute to optimise pest management. I see that there are some differences in aphid metabolism and feeding behaviour between day and night, but I would like to hear how such knowledge can optimise pest management strategies.

    1. (2:03) "The average man can't prove of most of the things that he chooses to speak of. And still won't research and find the root of the truth that you seek of."

      So true this quote. Dunning-Krueger. Ignorance. Stupidity.

      Men should listen to Charlie Munger's advice: "I never allow myself to have [express] an opinion about anything that I don't know the opponent side's argument better than they do."

    2. One of the greatest songs ever.

      Much meaning. Depth.

      Patience.

    1. keine

      kein

    2. Friedenstrasse 5C 8304 Wallisellen

      Industriestrasse 22 8604 Volketswil

    3. Friedenstrasse 5C 8304 Wallisellen

      Industriestrasse 22 8604 Volketswil

    1. the learner’s experience that inmany learning activities, the online mode and the use of digitaldevices are absolutely helpful and expand learning

      This inferred assumption seems the most accurate framing of the concept, lacking an explicit definition.

    2. Every human activity is embedded in theconcrete interests, needs, and motives of the individual subject,and so every learning activity has an intentional dimension.
    3. digital distraction

      What does that even mean? Ok, I can imagine some specific things that are both "distraction" and inherently "digital", but how are those significant compared to specific non-digital distractions, like drugs and whatever type of music not in your particular taste?

    4. Promethean devide

      seemingly more often labelled as Promethean gap

    5. As soon as learners pick up a digital device, they are placed ina specific situation and confronted with an individualization oftheir learning activity

      Any digital device, according to the text, inherently individualizes learning.

      I disagree, and instead blame subjectivity here: Our imposing expectatons of digitalizations being more efficient amplifies the development and use of such efficiency-oriented tools.

    6. the learning method and the performative,operational, and organizational aspects of the act of learning areexamined. As already indicated, this is exactly where the strengthsof digital technologies for expanding the learning activity oflearners lie

      If not pretty close to a definition, then what is the purpose of "exactly" here?

    7. Based on the analysis of digital technology inthe last chapter, the potential of digital technology lies mainly inthe operative dimension of the learning action.

      Wait, what? Where in previous chapter was that concluded, rather than than just superficially mentioned?

    8. Research into the digitalization of educational practice, however,has so far widely reproduced the logic of bisected learning. Whenlearning is articulated as an activity of the learners, the focusis only on the how of learning and on questions regarding theperformative, operational, and organizational dimensions of theact of learning.

      These are some concrete assumptions that could be interesting to challenge, e.g. in DigiPro.

    9. dimension

      A dimension is quantifiable, which seems not the relevant feature here.

      Perhaps better use aspect or group?

    10. address the learning content as a fact to be determined bythe teacher

      looks close to a definition

    11. the content dimension of the learning action,such as identifying learning problems, exploring them, andforming independent ways of gaining knowledge, recedes into thebackground precisely because in bisected learning learners haveno reason to address these aspects since they have no influence onthem
    12. As Hartmut Rosa points out, digital world reachextension paradoxically leads to progressive forms of world lossand therefore requires a countermovement and the developmentof a reflective practice of temporary

      Hartmut Rosa talks about digital communication and digital media, and a problem of those being always available.

      That is not digitalization in general, but the subset of never sleeping systems, commonly referred to as "online" systems.

    1. we all know that's crazy talk

      crazy talk

    2. your API magically becomes usable from a browser if it just uses HTML as its format

      API usable from the browser if it uses HTML as its format

    3. UI is a nice side effect

      for using HTML as a data exchange format

    1. mitigate cross-origin cache fingerprinting
    2. With ESM and cross-origin caching

      cross origin caching

      that happens if resources are loaded from ipfs

    3. third-party libraries can be loaded, cached, and shared across sites

      loaded cached accross site

    4. No more single-line changes blowing out your applications entire cached bundle.

      no more single change blow up

    5. No more bundling dependencies with source code

      no more bundling

    1. eLife assessment

      This study provides a single-cell atlas for syngnathid fishes (seahorses, pipefishes, and seadragons), a valuable new resource to investigate the molecular basis of the many unique characters that define the pipefish embryo. The findings are generally supported by solid arguments, but whereas the single-cell RNA-sequencing analysis appears to be of good quality, the spatiotemporal expression data only incompletely support the authors' arguments. Additional computational analyses on cell identity and developmental trajectories would allow a deeper examination of the current data from these unconventional model organisms, to provide new insights into understanding the extraordinary adaptations of the Syngnathidae family. If appropriately improved, the work could be of broad interest for evolutionary developmental biology, particularly for fishes.

    2. Reviewer #1 (Public Review):

      Syngnathid fishes (seahorses, pipefishes, and seadragons) present very particular and elaborated features among teleosts and a major challenge is to understand the cellular and molecular mechanisms that permitted such innovations and adaptations. The study provides a valuable new resource to investigate the morphogenetic basis of four main traits characterizing syngnathids, including the elongated snout, toothlessness, dermal armor, and male pregnancy. More particularly, the authors have focused on a late stage of pipefish organogenesis to perform single-cell RNA-sequencing (scRNA-seq) completed by in situ hybridization analyses to identify molecular pathways implicated in the formation of the different specific traits.

      The first set of data explores the scRNA-seq atlas composed of 35,785 cells from two samples of gulf pipefish embryos that authors have been able to classify into major cell types characterizing vertebrate organogenesis, including epithelial, connective, neural, and muscle progenitors. To affirm identities and discover potential properties of clusters, authors primarily use KEGG analysis that reveals enriched genetic pathways in each cell types. While the analysis is informative and could be useful for the community, some interpretations appear superficial and data must be completed to confirm identities and properties. Notably, supplementary information should be provided to show quality control data corresponding to the final cell atlas including the UMAP showing the sample source of the cells, violin plots of gene count, UMI count, and mitochondrial fraction for the overall dataset and by cluster, and expression profiles on UMAP of selected markers characterizing cluster identities.

      The second set of data aims to correlate the scRNA-seq analysis with in situ hybridizations (ISH) in two different pipefish (gulf and bay) species to identify and characterize markers spatially, and validate cell types and signaling pathways active in them. While the approach is rational, the authors must complete the data and optimize labeling protocols to support their statements. One major concern is the quality of ISH stainings and images; embryos show a high degree of pigmentation that could hide part of the expression profile, and only subparts and hardly detectable tissues/stainings are presented. The authors should provide clear and good-quality images of ISH labeling on whole-mount specimens, highlighting the magnification regions and all other organs/structures (positive controls) expressing the marker of interest along the axis. Moreover, ISH probes have been designed and produced on gulf pipefish genome and cDNA respectively, while ISH labeling has been performed indifferently on bay or gulf pipefish embryos and larvae. The authors should specify stages and species on figure panels and should ensure sequence alignment of the probe-targeted sequences in the two species to validate ISH stainings in the bay pipefish. Moreover, spatiotemporal gene expression being a very dynamic process during embryogenesis, interpretations based on undefined embryonic and larval stages of pipefish development and compared to 3dpf zebrafish are insufficient to hypothesize on developmental specificities of pipefish features, such as on the absence of tooth primordia that could represent a very discrete and transient cell population. The ISH analyses would require a clean and precise spatiotemporal expression comparison of markers at the level of the entire pipefish and zebrafish specimens at well-defined stages, otherwise, the arguments proposed on teleost innovations and adaptations turn out to be very speculative.

      To conclude, whereas the scRNA-seq dataset in this unconventional model organism will be useful for the community, the spatiotemporal and comparative expression analyses have to be thoroughly pushed forward to support the claims. Addressing these points is absolutely necessary to validate the data and to give new insights to understand the extraordinary evolution of the Syngnathidae family.

    3. Reviewer #2 (Public Review):

      Summary:

      The authors present the first single-cell atlas for syngathid fishes, providing a resource for future evolution & development studies in this group.

      Strengths:

      The concept here is simple and I find the manuscript to be well written. I like the in situ hybridization of marker genes - this is really nice. I also appreciate the gene co-expression analysis to identify modules of expression. There are no explicit hypotheses tested in the manuscript, but the discovery of these cell types should have value in this organism and in the determination of morphological novelties in seahorses and their relatives.

      Weaknesses:

      I think there are a few computational analyses that might improve the generality of the results.

      (1) The cell types: The authors use marker gene analysis and KEGG pathways to identify cell types. I'd suggest a tool like SAMap (https://elifesciences.org/articles/66747) which compares single-cell data sets from distinct organisms to identify 'homologous' cell types -- I imagine the zebrafish developmental atlases could serve as a reasonable comparative reference.

      (2) Trajectory analyses: The authors suggest that their analyses might identify progenitor cell states and perhaps related differentiated states. They might explore cytoTRACE and/or pseudotime-based trajectory analyses to more fully delineate these ideas.

      (3) Cell-cell communication: I think it's very difficult to identify 'tooth primordium' cell types, because cell types won't be defined by an organ in this way. For instance, dental glia will cluster with other glia, and dental mesenchyme will likely cluster with other mesenchymal cell types. So the histology and ISH is most convincing in this regard. Having said this, given the known signaling interactions in the developing tooth (and in development generally) the authors might explore cell-cell communication analysis (e.g., CellChat) to identify cell types that may be interacting.

    4. Reviewer #3 (Public Review):

      Summary:

      This study established a single-cell RNA sequencing atlas of pipefish embryos. The results obtained identified unique gene expression patterns for pipefish-specific characteristics, such as fgf22 in the tip of the palatoquadrate and Meckel's cartilage, broadly informing the genetic mechanisms underlying morphological novelty in teleost fishes. The data obtained are unique and novel, potentially important in understanding fish diversity. Thus, I would enthusiastically support this manuscript if the authors improve it to generate stronger and more convincing conclusions than the current forms.

      Weaknesses:

      Regarding the expression of sfrp1a and bmp4 dorsal to the elongating ethmoid plate and surrounding the ceratohyal: are their expression patterns spatially extended or broader compared to the pipefish ancestor? Is there a much closer species available to compare gene expression patterns with pipefish? Did the authors consider using other species closely related to pipefish for ISH? Sfrp1a and bmp4 may be expressed in the same regions of much more closely related species without face elongation. I understand that embryos of such species are not always accessible, but it is also hard to argue responsible genes for a specific phenotype by only comparing gene expression patterns between distantly related species (e.g., pipefish vs. zebrafish). Due to the same reason, I would not directly compare/argue gene expression patterns between pipefish and mice, although I should admit that mice gene expression patterns are sometimes helpful to make a hypothesis of fish evolution. Alternatively, can the authors conduct ISH in other species of pipefish? If the expression patterns of sfrp1a and bmp4 are common among fishes with face elongation, the conclusion would become more solid. If these embryos are not available, is it possible to reduce the amount of Wnt and BMP signal using Crispr/Cas, MO, or chemical inhibitor? I do think that there are several ways to test the Wnt and/or BMP hypothesis in face elongation.

    1. אוניברסיטת בן גוריוןhttps://orenlab.sise.bgu.ac.il › RobustFingerprintin...אוניברסיטת בן גוריוןhttps://orenlab.sise.bgu.ac.il › RobustFingerprintin...PDFby A Shusterman · Cited by 154 — A well-studied mitigation approach from the domain of network-based cache fingerprinting involves creating spurious network activity to mask the
    1. eLife assessment

      This valuable study proposes that protein secreted by colon cancer cells induces cells with Paneth-like properties that favor colon cancer metastasis. The evidence supporting the conclusions is incomplete and would benefit from more direct experiments to test the functional role of Paneth-like cells and to monitor metastasis from colon tumors. The work will be of interest to researchers studying colon cancer metastasis.

    2. Reviewer #2 (Public Review):

      Summary:

      The authors propose that DKK2 is necessary for the metastasis of colon cancer organoids. They then claim that DKK2 mediates this effect by permitting the generation of lysozyme-positive Paneth-like cells within the tumor microenvironmental niche. They argue that these lysozyme-positive cells have Paneth-like properties in both mouse and human contexts. They then implicate HNF4A as the causal factor responsive to DKK2 to generate lysozyme-positive cells through Sox9.

      Strengths:

      The use of a genetically defined organoid line is state-of-the-art. The data in Figure 1 and the dependence of DKK2 for splenic injection and liver engraftment, as well as the long-term effect on animal survival, are interesting and convincing. The rescue using DKK2 administration for some of their phenotype in vitro is good. The inclusion and analysis of human data sets help explore the role of DKK2 in human cancer and help ground the overall work in a clinical context.

      Weaknesses:

      In this work by Shin et al., the authors expand upon prior work regarding the role of Dickkopf-2 in colorectal cancer (CRC) progression and the necessity of a Paneth-like population in driving CRC metastasis. The general topic of metastatic requirements for colon cancer is of general interest. However, much of the work focuses on characterizing cell populations in a mouse model of hepatic outgrowth via splenic transplantation. In particular, the concept of Paneth-like cells is primarily based on transcriptional programs seen in single-cell RNA sequencing data and needs more validation. Although including human samples is important for potential generality, the strength could be improved by doing immunohistochemistry in primary and metastatic lesions for Lyz+ cancer cells. Experiments that further bolster the causal role of Paneth-like CRC cells in metastasis are needed.

    1. refinement to this approach, which reduces the amount ofinformation exchanged and the size of the tables, is to have the DBMPsexchange only the oldest of the entries in the first table (oftimestamps of last modifications received from other DBMPs).

      Resembles delta-based state CRDTs optimization technique, where only latest vals are broadcast.

    2. (T1,D1)>(T2,D2) <=> (T1>T2) or (T1=T2 and D1>D2)

      Resembles tie-breaking based on origin ID, seen in systems that use other T (e.g., Lamport Clock).

    1. it did so by taking some short cuts. Android itself was an acquisition in 2005 (for $50 million, with a keyboard interface) and, in response to the iPhone, a new touch user interface was developed

      I totally forgot that android was an acquisition

    1. In [2], Berners-Lee and Connolly proposed Delta, an ap-proach in which the RDF-Graphs differences are calculatedon their serialized forms

      This resembles the way Git works, we have snapshots and deltas are calculated out of them.

      Ironically, that made Git use deltas more, not less.

    1. Highlights Highlights can be created by clicking the button. Try it on this sentence.

      I think that I shall never see

    1. I've been following a similar WASM-first language, Moonbit (https://www.moonbitlang.com/), which was created by the creator of Rescript.

      Well that's compelling! Would love to see such a promising effort work to cross the chasm from interesting esoteric language to something participating in the broader Webassembly Interface Types world, but not holding my breath on this. Still, one to look at!

    1. the real issues are Insidious they're 00:22:00 underground they're down in our our Baseline premises of understanding what life is and what it means

      for - key insight - the unconscious - fundamental assumptions are the root problem - Nora Bateson

      key insight, quote - the unconscious - fundamental assumptions are the root problem - Nora Bateson - (see below) - Even though we can point with - language and - statistics and - all sorts of measurements - to all the aspects of what we might call - the meta crisis or - the poly crisis - the real issues are: - insidious - they're underground - they're down in our our baseline premises of understanding - what life is and - what it means - To ask - what's in it for me - what's the point of this - where is this going - what am I going to get out of this - These type of questions that have to do with in some way embellishing our individual takeback - are deeply and totally unecological responses - so they're disrupting our possibility for perception

    2. we can't solve this problem

      for - epiphany - we can't solve this problem

      epiphany - we can't solve this problem - We need another name to replace the dualistic framework of - problem - solving - I've felt this for awhile but only this morning in listening here to Nora that the implicit surfaced to explicit articulation - From the etymology, the word "problem" comes from "to put forward" - This is like noticing something salient from an entire complex phenomenological perspective and field of view and salience landscape - We choose one from many - From the etymology of the word "solution", it means - from Latin solutionem (nominative solutio) "a loosening or unfastening," - A holistic replacement for the problem/solution framework which has led to progress traps is absolutely necessary to create new imaginations of alternatives

      to - problem etymology - means to put forward - https://hyp.is/8qr_miFlEe-Lx6ubSiCR6w/www.etymonline.com/word/problem - solution etymology - means to loosen, unfasten - https://hyp.is/yIcQciFmEe-LzBs-xcXIag/www.etymonline.com/search?q=solution

    3. if we just had a big enough spreadsheet we could get the data in and then we could get you know something like AI or some you know some other computational 00:12:32 process in to help us deal with all this complexity because our little brains can't handle it and my feeling about this is that 00:12:44 actually no

      for - adjacency - AI - Nora Bateson - solving wicked problems - no - Human Intelligence - HI - yes - @gyuri

    4. you can take a lot more than you are and have a lot more information

      for - adjacency - open source - Stop Reset Go complexity mapping - objective - Nora Bateson comment on more information - diversity - Indyweb/Indranet - progress trap mitigation

      adjacency - between - Nora Bateson comment - Stop Reset Go complexity mapping<br /> - open source - progress trap mitigation - Indyweb/Indranet

      • adjacency relationship
        • When Nora talks about the
          • oversimplified,
          • reductionist
        • problem-solving approach that most of modernity employs to tackle wicked problems,
        • it boils down to oversimplification.
        • There are usually far more causes and conditions to a problem than are known to construct the solution
        • In Deep Humanity praxis, this is how we get into progress traps, the shadow side of progress
        • The Stop Reset Go complexity mapping system is designed to reveal greater information by
          • creating a space for diverse perspectives to systematically engage in addressing the same wicked problem
        • This system must be open source in order to create the space for maximum diversity
        • The Stop Reset Go process is specifically designed as a workspace for diversity for the purpose of
          • mitigating progress traps and
          • helping find more effective ways to address wicked problems
        • This is done by using Trailmark Markin notation within the Indyweb/Indranet people-centered, interpersonal software ecosystem
    5. that causality is not singular and so if you address a problem 00:11:06 that's created by a multiple causal process with a singular response you don't actually do anything but make it worse

      for - quote, key insight - progress trap - Nora Bateson

      quote - progress trap - Nora Bateson - Nora hits the head of the nail with this observation - There are always multiple causes to one result - and by addressing only one cause, we cannot solve the problem, but in fact - allow it to continue and often make it worse - This is essentially another way of stating the teachings of millenia of Eastern philosophy, - that the universe is - infinitely interconnected - and its inherent nature of continuous transformation - Therefore, any state, which might be recognized as a problem state - is the result of many different causes and conditions coalescing

    6. that first order 00:10:10 response does not take into account the next and the next and the next order of consequences

      for - progress trap - Nora Bateson

    7. I think important in this moment of trying to get out of orientation to these structures and habits 00:07:14 semantics um and and and epistemological patterns that that lock us into the kind of thinking that is the source of the 00:07:27 colonial violence and the industrial violence that we're living within

      for - quote - unconscious patterns locking us into colonial and industrial violence - Nora Bateson

      quote - unconscious patterns locking us into colonial and industrial violence - Nora Bateson - (see below) - It's actually I think important in this moment of trying to get out of orientation to these - structures and - habits, - semantics and - epistemological patterns - that that lock us into the kind of thinking - that is the source of - the colonial violence and - the industrial violence - that we're living within

    8. you don't meet something head-on you meet it around you meet it within you meet it 00:04:24 totally in ecological systems nothing is happening one thing at a time there's not a solution to a problem

      for - key insight - problem solving paradox - emptiness

      key insight- problem solving paradox - emptiness - Due to the complex nature of reality - in which everything we perceive is connected to so many other things beyond our wildest imagination - a - *problem" doesn't have - a "solution" - Why not? - because a problem is human attention devoted to one aspect in our entire field of view (nature) - It's like looking at one stitch in the entire fabric of a weave - That one stitch could be so critical that tearing it off - can cause the entire fabric to fall apart - This massive connectedness and innumerable relationships is also described by the Eastern philosophical terms - emptiness - interdependent origination - references already provided in earlier annotations of this video.

    9. there are many um and that that pulls us into 00:00:26 reaction mode that has been long steeped in industrial responsiveness which is to the first order

      for - quote - progress trap - Nora Bateson

      quote - progress trap - Nora Bateson - (see below) - it's really easy to get distracted by the alarms that are ringing - and like you said, there are many that pulls us into reaction mode - that has been long steeped in industrial responsiveness - which is to the first order - that is, if something is happening we want to stop that thing from happening - whatever it is, whether it's - a refugee crisis or - a nuclear war threat or a this or a that - and that first order response does not take into account - the next and the next and the next order of consequences - so it's a kind of thinking that is very much appropriate for - engineering, - for building machines - but it's not appropriate for complex living systems

      adjacency - between - Nora Bateson comment on first order industrial responsiveness - progress trap - Stop Reset Go complexity mapping - Deep Humanity - progress trap - emptiness/shunyata - adjacency relationship - What Nora is saying is articulated within the Deep Humanity praxis using the language of progress traps - Dan O'Leary - https://jonudell.info/h/facet/?max=100&expanded=true&user=stopresetgo&exactTagSearch=true&any=dan+o%27leary - Ronald Wright - https://jonudell.info/h/facet/?max=100&expanded=true&user=stopresetgo&exactTagSearch=true&any=ronald+wright - which are the unintended consequences of progress - Deep Humanity praxis relates progress traps to the intertwingled Eastern philosophical ideas of - emptiness (shunyata) - https://jonudell.info/h/facet/?max=100&expanded=true&user=stopresetgo&exactTagSearch=true&any=emptiness - dependent arising and - https://jonudell.info/h/facet/?max=100&expanded=true&user=stopresetgo&exactTagSearch=true&any=dependent+arising - interdependent origination - https://jonudell.info/h/facet/?max=100&expanded=true&user=stopresetgo&exactTagSearch=true&any=interdependent+origination - In the context of the Stop Reset Go complexity mapping process, - to be integrated into the Indyweb / Indranet web 3 software ecosystem, - is designed to map multiple perspectives of how to solve a problem - so that we can see the many different solutions and avoid simply adopting a first order response solution - in so doing, it integrates complexity into our problem solving process and helps to mitigate - future progress traps in our solutions - The Indyweb / Indranet is a technology ecosystem designed to reflect the two pillars of emptiness: - (evolutionary) change and - interdependent origination / intertwingularity, - reflecting a universe that is fractally connected in all - dimensions and - scales - Stop Reset Go will be integrated into the Indyweb/Indranet as a specific Markin notation.

    10. we're getting nowhere because the thinking that we're using to address the uh the problems is the same thinking that's creating them

      for - quote - Einstein

      quote - Einstein - Nora opens with the quote often attributed to Einstein but who's likely source is Ram Dass misquoting Einstein

      to - page discussing Einstein's misquote and attributing to Ram Dass - https://hyp.is/GffY3iFNEe-4Lft-dGCoPA/hsm.stackexchange.com/questions/7751/did-einstein-say-we-cannot-solve-our-problems-with-the-same-thinking-we-used-to

    11. for - book - Combining - Nora Bateson - podcast - Entangled World - Navigating the greatest challenges of our time - interview - A New World Combining - Nora Bateson

      summary - Nora discusses her book, Combining

    1. What does Microsoft Word look like with a Photoshop-like palette on the side?

      This is today's tech. It's not in product form yet, but some startups are trying to build writer tools based on this.

      A startup called me to talk about a potential "consult" regarding this, sucked a lot of ideas and hard-earned experience, and they never got back to me or paid up. So fuck them!

      That sounded bitter, and I really am. Can you blame me? I want to support founders, and I take these calls in good faith and end up with this "brain rape". I can't wait to dance on their grave.

    2. Text is becoming something new,

      text is not becoming new, but everything around text is.

      The middlemen of text production, consumption, and distribution are either getting eliminated or replaced with AI models.

      The economic implication of this is obvious and yet profound.

      A larger truth is text has descended from the realm of the sacred to that of the profane. Now, try to map what that means to everything we do with text :)

    3. So the camera doesn’t just observe and record, it changes us.

      all measurements change the thing being measured when examined deeply

    4. Could you dynamically change the register or tone of text depending on audience, or the reading age, or dial up the formality or subjective examples or mentions of wildlife, depending on the psychological fingerprint of the reader or listener?

      as I mentioned earlier, these don't need to be rhetorical questions.

    5. to take a chapter of a book and edit it, not by changing words, but by scrubbing it with the semantic equivalent of the burn and dodge tools in Photoshop.

      We can now do style-conditioned generation, style transfer, and style editing for text. I did this for a DARPA project. To make it cool, we can do it even on short texts like tweets and personalized in your writing style. One day, I will explain how we can fight state-sponsored propaganda using that.

    6. But this is super early technology. vec2text will improve.

      This part is hope.

    7. Again I don’t know what that means, to have associations and contextualisations always present with a text, a structuralist’s dream, but… it’s different.

      whatever brain wiring I am suffering with, I have this going all the time. I cannot read anything without associations and contexts popping up in my head all the time. Many times I wish I can turn them off and just read the damn words :)

    8. All text will be auto-glossed

      gloss over (v.): "try to conceal or disguise something unfavorable by treating it briefly or representing it misleadingly."

      this is my big worry. For convenience we build tools that gloss and hence gloss over.

    9. nce, for me, is that two thresholds have been crossed: speed and automation.

      true .. this means more self-service tools. See the shovel cartoon I sent earlier.

    10. Sean Graves at the Autonomy Institute has developed a tool called GERM. We used GERM to build a dataset of risks mentioned by the 266,989 UK companies who filed their accounts throughout March 2024. – Sean Graves (Autonomy Data Unit), GERM (Geopolitical & Environmental Risk Monitor) (2024)

      this looks cool.

    11. What if the difference between statements that are simply speculative and statement that mislead are as obvious as, I don’t know, the difference between a photo and a hand-drawn sketch?

      Instead of answering a rhetorical question, I will let you imagine how people read memes. They know it is a meme, yet they will believe it and engage with it instead of looking up the real stuff behind the meme. The real question here is whether people will ignore the difference (my hypothesis is yes) and whether knowing the difference matters (my bet is no).

      Further, you will have people questioning your photo/sketch classifier.

    12. What would it mean to listen to a politician speak on TV, and in real-time see a rhetorical manoeuvre that masks a persuasive bait and switch?

      This can be done in real time today. We tried versions of real-time fact-checking back in the day, and I am convinced people will believe what they want to believe.

    13. hermeneutics

      BTW, did you read Eliade?

    14. For example, here’s a sequence of episode titles that transitions smoothly from geology to history: Vulcanology 1816, the Year Without a Summer Climate Change Meterology Voyages of James Cook Astronomy and Empire Longitude …and so on.

      the smooth transition is not a property of the method but the careful transitions of the episode topics that BBC content creators managed. I would also bet that if you scroll past the list

      again this "trick" has been around for a few decades, but we now have tooling for everyone to play with it, which is fun!

      note: both t-sne and pca are dimension reduction techniques, but with different objectives.

    15. So I tried it, and yes you can.

      haha .. you can, but should you, and does that make sense?

    16. There is something there! New information to be interpreted!

      I am doubtful, but hey, I am also not smart :)

    17. , I feel like I’m peering into the world’s first microscope and spying bacteria, or through a blurry, early telescope, and spotting invisible dots that turn out to be the previously unknown moons of Jupiter…

      okay .. nice analogy

    18. can individual authors be fingerprinted by how they construct text?

      I even wrote a paper about it, which does a lot more than fingerprinting :)

    19. embeddings also change our relationship with text, and what we can do with text

      don't forget "what we cannot do with text"

    20. January on the PartyKit blog: Using Vectorize to build an unreasonably good search engine in 160 lines of code (2024). (That post has diagrams and source code.) But what I want to emphasise is how little code there is.

      This is a booby trap. Why? It's the sort of thing that makes people on HN post, "I can build this in a weekend". But when you build an actual search engine, you realize how messy everything is and especially so when you build something for more than one person.

    21. Search for main roman god – this is also Jupiter, but a different one: this Jupiter is the king of the gods in the Roman pantheon. The top result is an episode about Rome and European civilisation, not the episode about the planet Jupiter, showing that embeddings can distinguish concepts even when similarly named.

      I feel that when non-technical folks are empowered enough to experience building with tech (because it is simple to do now), they marvel at things traditional devs/researchers have taken for granted. That's what's happening here.

    22. Search for the biggest planet – again, the episode about the planet Jupiter is at the top. There is no synonyms database here, which is how a traditional search engine would work. The phrase the biggest planet has been translated into its “coordinates” and the search engine has looked for “nearby” coordinates representing episodes.

      hmm .. not a new capability .. this existed prior to modern DL, and I am not sure what changes it can bring that devs / data scientists haven't already tried.

    1. "Get ready to be challenged. And even vulnerable"

      I feel like the final quote should speak to the incredible result and how happy he is with his offer. You could even add a section where you check in with him 3 months down the track to see how the job is serving him today. If it's still a great fit, and he's loving it, add it in as an quote.

    2. The company put forward a strong offer. Juraj was pumped, but he was hoping for more on the base. We pulled market data and leveraged the numbers from his previous salaries, as well as other roles he’d pursued in the search, to help him negotiate a 14% increase on the original base salary.

      Can you include here where that offer compares to the market data you pulled? Of course, only if it's above market average...

    3. Ultimately there was one clear fit for Juraj, and once he saw it was possible to land that job, he went all-in. He shared extra materials. He prepped testimonials and references from past employers. And together we worked through stories and experiences to address all the potential flags they might have about him head-on

      I feel like you could go into even more detail here, because it's such an important part of the process. I feel like I want to join Juraj behind the scenes as he lands this job. The questions I have here are: Which stories did he share? What were those extra materials? And, most importantly, what did he have to say when he received the YES, you're it?

    4. Strategic Moves:

      Potentially rename this section so it works with the renamed section above: 'The strategic moves that got us there'

    5. Juraj could do it all. But rather than position Juraj as a “Partnerships Generalist” because he could own integrations, business development, and partner marketing, we honed in on his specialization: Product Juraj is an incredibly talented and experienced partnerships leader who blends business development acumen with a strong product sense to build the next generation of SaaS software. He’d held both Partnerships and Product titles, and he’d led integrations with some of the biggest players in the industry (Google, Zoom, Microsoft, Slack, etc.) The Challenges:That meant he truly had to make the most of every opportunity he pursued. The fact is, there just weren’t a lot of Partnerships roles, especially not at the leadership level Juraj had previously operated as VP in his previous company. And the roles he did see were not necessarily perfect fits. Some had VP titles but no teams. Other focused primarily on Channel Partnerships (which he could do, but that was not his strongest skillset.) Once we leaned into this, he had a story to tell.

      could you rename this section somewhat and make it all about Juraj's Inevitable Edge? Possibly 'Juraj's Inevitable Edge'.

      You go into great details when it comes to identifying it in the section below, so why not make this a to-the-point snapshot of his 'point of difference'.

    6. The fact is, there just weren’t a lot of Partnerships roles, especially not at the leadership level Juraj had previously operated as VP in his previous company. And the roles he did see were not necessarily perfect fits. Some had VP titles but no teams. Other focused primarily on Channel Partnerships (which he could do, but that was not his strongest skillset.)

      This is where I would explore the trigger moment(s) that saw him seek support from you. What made this time around different to all the other job applications? What were some of the mindset struggles he was coming up against? What were some of the application hurdles he hadn't experienced previously?

    7. Juraj had been doing fractional and advisor work for the past year and a half. When he reached out to us, he’d recently landed at a very early-stage startup that turned out to be a bad culture fit. This time around? He knew he needed to leverage a more focused effort and intentional strategy to land his next full-time role.

      Can you go into a little more detail around Juraj's background? I'd love to learn more about him.... include a little more about his career background here rather than in the challenges section. If you can showcase that he had a solid career behind him when approaching you, that takes the stigma out of seeking help for others.

    8. Title

      His expertise

    9. CLIENT NAME

      The client

    10. How he secured a 14% increase on an original offer

      I'd totally reword this so it sounds like you were a team:

      How we helped Juraj secure a 14% increase on an original offer

    11. Partnerships Leader

      I'm tempted to get rid of this section because it distracts from the attention-grabbing opener right underneath...

    1. Essentially it analyzes the process of an illusion crystallizing out of emptiness and being taken for reality.

      for - key insight - the real is the illusory - interdependent origination - emptiness

      key insight - the real is the illusory - There is profundity in this single statement that takes huge effort to truly understand - because we've been heaped with so much social conditioning - For example, a lot of psychological science research distinguishes between - what is real and - what is an illusion - However, the investigations that these teachings are referring to reveal that what both - conventional science and - the ordinary, mundane view of reality - take for real are both illusory when we deeply understand interdependent origination - The illusion is extraordinarily real and - it is a huge leap to know, feel and experience that ALL of reality, including both your - inner private world and the - outer shared world are illusory - That is, that while appearing, everything that appears is only due to other causes and conditions - Another way to say this is that nouns (things/objects) are temporary designations - underneath them is always verbs (processes)

    2. The four noble truths

      for - adjacency - Buddhist teachings - Four Noble Truths - life and death - mortality salience - terror management technique

      adjacency - between - Buddhist teachings - Four Noble Truths - life and death - mortality salience - terror management technique - adjacency relationship - The Four Noble Truths are: - the recognition of inherent suffering - the cause of suffering - understanding the cause of suffering - the cessation of suffering - and are really - a way to deal with mortality salience and therefore - a terror management technique

    3. three marks of existence

      for - Buddhist teachings - 3 marks of existence - birth and death

      Buddhist teachings - 3 marks of existence - The 3 marks of existence - there is no unchanging self - it is characterized by impermanence and suffering - whatever comes into being must pass away - also describe that we ourselves as human INTERbeCOMings, are aspects of reality - that come into being - and must pass away

    4. The late Dilgo Khyentse Rinpoche said that the whole range of teachings, from the shravakayana to dzogchen, has only the meaning of interdependent origination.

      for - adjacency - primacy of interdependent origination - Dilgo Khyentse Rinpoche

    5. According to this law, nothing has independent, permanent, or absolute existence. Everything is part of a limitless web of interconnections and undergoes a continual process of transformation.

      for - definition - emptiness - interdependent origination - dependent arising - definition - interdependent origination - Francesca Fremantle

      definition - interdependent origination - According to this law (of interdependent origination), - nothing has - independent, - permanent, or - absolute - existence. - Everything is - part of a limitless web of interconnections and - undergoes a continual process of transformation. - Every appearance arises from - complex causes and - conditions, - and in turn combines with others to produce countless effects. - By interrupting the causal chain at certain key points, - the course of existence can be altered and - effects prevented by eliminating their causes.

      comment - This definition of interdependent origination is very closely related to that of - emptiness (shunyata) and - https://hyp.is/nyBf5CFTEe-wpwveR5kjtg/www.dalailama.com/news/2014/teaching-about-emptiness-and-dependent-arising-at-likir-ladakh - dependent arising - relationship between - dependent arising and - emptiness - from his Holiness, the Dalai Lama - https://hyp.is/nyBf5CFTEe-wpwveR5kjtg/www.dalailama.com/news/2014/teaching-about-emptiness-and-dependent-arising-at-likir-ladakh

      adjacency - between - emptiness - dependent arising - interdependent origination - Indyweb/Indranet - adjacency relationship - The Indyweb/Indranet is epistemologically designed to reflect this trilogy of intertwingled Buddhist ideas: - emptiness - interdependent origination - dependent arising - within the sphere of human thinking - The Indyweb/Indranet is designed as people-centered, - which means that individual human beings are the locus which their entire world of ideation - evolving moment by moment - can be captured to detect the evolutionary flow of ideation - The Deep Humanity praxis employs the term - "human INTERbeCOMing" to shift the frame of a person - from a noun / object - to a verb / evolutionary process - Ideas are intrinsically dependently arising - from other causes and conditions - which are the source ideas that inspired the new ones - The Indyweb/Indranet's people-centered provenance feature assures that - any idea generated by a person is ASSOCIATED to that person - and tracks the exact time of the occurrence of that idea - The other half of the Indyweb/Indranet is that it is INTERPERSONAL - allowing all people, - with their people-centered nexus of evolutionary ideas to - SHARE them with OTHER people - Hence, from looking at a record of our evolutionary history of ideas - we can see that we are psychologically fundamentally following interdependent origination - Ideas are in constant flux, giving rise to new ideas - in a continuous process of transformation

    1. Resourcefulness and using recycled materials - Ryan utilized many recycled and repurposed items to build his tiny home affordably, such as wood from pallets, parts from his grandparents' old camper trailer, and discounted windows and doors from the restore. This shows the value of being resourceful.

      Learning by doing - Ryan had never built a tiny home before but wanted to do it himself so he would gain the skills to fix things if needed. He learned as he went, which gave him more respect for and knowledge of his home. This demonstrates the power of hands-on learning.

      Keeping things open and simple - In the home's design, Ryan tried to maximize open space and keep things simple. He used a lot of windows for natural light, kept storage up and off the floor, and was thoughtful about only keeping what he truly needed. This minimalist and open approach makes the small space feel larger.

      Living with less - Ryan found that living tiny made him realize how little he actually needs to live a good life. It curbed unnecessary shopping and accumulation of stuff. His key advice is to "change your lifestyle, not your income" and learn to happily live with less.

      Following your own pace - His advice is to not get ahead of yourself or your own energy when taking on a project like this - go with the flow based on your needs rather than wants. This measured approach can make the process more manageable.

    1. “Buzz! Check out this active conversation”, “Connect with someone new”

      How were these suggestions/prompts developed? From my experience, I might check the conversation to see if I catch some keywords that interest me, but I may not just follow the Canvas instruction that "don't miss this conversation that happened on the discussion board." Some keywords about the conversation extracted by NLP might make LA-driven suggestions more authentic and related to learners.

    2. For instance, instructors may routinely mandate students to annotate and reply for a certain number of times during a week.

      I am Shiyao Wei, a second-year PhD student from Florida State University. I used hypothesis.io in my class when teaching an undergraduate course, Introduction to Educational Technology. We have an assignment asking students to use hypothesis.io to read an article together to familiarize themselves with this technology. However, as Xiran noted, students just finished it and ran. I observed from their practice that nobody ever engaged in meaningful knowledge construction/building. At AERA, I listened to Xinran's poster and really liked the way the authors made knowledge synthesis meaningfully related to students. I am here to learn more about solutions to students' engagement with such tools.

    1. It can do data analysis you can give it data and it will do analysis for you it can be used as a privacy detector it's medical and law knowledge is amazing and here I would like to do to make a plug for a book that was written at Microsoft research and I helped with that by Peter Lee as a lead author Kerry Goldberg who is in in the in the room and zako any from Harvard you know on using gpt4 for healthcare the book is titled the AI revolution in medicine.

    2. GPT-4 provides an opportunity to rethink the definition of intelligence, as it represents a new process that has led to intelligent-like behavior.

      Maybe it's an opportunity to rethink what intelligence is because you know in a way even though we have Decades of psychology studying you know intelligence we had only one example of intelligence which is you know the intelligence that Natural Evolution brought us you know the natural intelligence of the natural world but here we kind of have a new process that led to some and the varies which looks intelligent.

  2. www.tripleeframework.com www.tripleeframework.com
    1. Does the technology tool aid students in developing or demonstrating a more sophisticated understanding of the content? (creates opportunities for creation/production over consumption)Does the technology create scaffolds to make it easier to understand concepts or ideas?Does the technology create paths for students to demonstrate their understanding of the learning goals in a way that they could not do with traditional tools?

      The three questions for measuring the enhancement of learning through technology help to define the actual usefulness of the tools in the classroom. I feel that these three questions are good gauges for the classroom, but at the same time give a guideline that an educator can help to change appropriately for their classroom. Being able to utilize these as a set of guidelines obviously helps to set a certain level of classroom expectations for each educator.

    1. he read Buddhapalita’s commentary and came to a full realisation of emptiness

      for - quote - emptiness - Je Tsongkhapa's realization

      quote - (see below) - Je Tsongkhapa was dissatisfied with explanations he had - received - sought out and - read - all the extant texts on emptiness and their commentaries and - analysed what he read to reach the correct view. - In retreat he had a vision of Manjushri, after which - he read Buddhapalita’s commentary and - came to a full realisation of emptiness. - He understood that - because things are dependent on other factors - they are empty of inherent existence; - but they are not non-existent. - Neither - non-existent nor - inherently existent, - they exist as functional phenomena, - but only by way of designation.

    2. Je Tsongkhapa’s text, ‘In Praise of Dependent Arising’ which emphasises the importance of both emptiness and dependent arising

      for - adjacency - emptiness - dependent arising - Je Tsongkhapa

      adjacency - between - emptiness - dependent arising - Je Tsongkhapa - adjacency relationship - (quote - see below) - His Holiness then announced his intention to give a transmission of Je Tsongkhapa’s text, - ‘In Praise of Dependent Arising’ - which emphasizes the importance of both - emptiness and - dependent arising. - He suggested that it would be good to recite the Heart Sutra followed by this text daily. - He said that - emptiness and - dependent arising - are complementary. - If - dependent arising makes you think of emptiness and - emptiness makes you think of dependent arising - at the same time, - you have a proper understanding of emptiness.

    3. Perfection of Wisdom literature, among which the Heart Sutra is one of the shortest.

      for - emptiness - Heart Sutra - Perfection of Wisdom - HH Dalai Lama

      adjacency - between - Heart Sutra - Perfection of Wisdom - attainment of enlightenment - emptiness - adjacency relationship, - (quote - see below) - His Holiness mentioned that the Heart Sutra is revered and recited across the Northern Buddhist World of - China, - Korea, - Japan, - Vietnam, - Tibet, - Mongolia and - the Himalayan Region. - On the basis of what it says, - whatever practice we do - must be qualified by - an understanding of emptiness, - otherwise we will not reach enlightenment.

    4. it’s important to know that it is the perfection of wisdom rather than the perfection of meditation that is stressed as the key to attaining enlightenment.

      for - quote - HH Dalai Lama - attaining enlightenment through wisdom, not just meditation

      quote - HH Dalai Lama - attaining enlightenment through wisdom, not just meditation - (see below) - Even today I meet Buddhists in Japan for example - who tell me that Buddhahood can be attained through non-conceptual meditation, - but there seems little room for wisdom. - I feel it’s important to know that - it is the perfection of wisdom rather than - the perfection of meditation - that is stressed as the key to attaining enlightenment

    5. Emptiness implies dependent arising.

      for - adjacency - emptiness - dependent arising

    6. for - emptiness - teachings - Dalai Lama

  3. accessmedicine-mhmedical-com.ezproxy.lib.utexas.edu accessmedicine-mhmedical-com.ezproxy.lib.utexas.edu
    1. standards of growth, development, and maturation provide a frame of reference against which every pathologic process in early life must be viewed

      standard human development provides a reference point to compare disease to

    1. The interpretation of Jesus Christ as a symbol of various historical and theological figures emphasizes the continuity of divine guidance throughout human history. This perspective suggests that the essence of divine intervention is to steer humanity towards unity, peace, and prosperity, transcending historical and cultural boundaries.

      hi

    1. Résumé de la vidéo [00:00:02][^1^][1] - [00:28:50][^2^][2] : Cette vidéo présente une conférence de Jean Michel Azorin sur la phénoménologie des troubles de l'humeur. Il explore les relations entre la phénoménologie philosophique et la psychiatrie, la constitution des troubles de l'humeur à travers les travaux de Binswanger, et la phénoménologie génétique avec Tellenbach et Kraus. Azorin discute des niveaux d'expérience humaine, de la réduction phénoménologique et de l'importance du temps dans la structure de l'expérience humaine.

      Points forts : + [00:00:02][^3^][3] Introduction et structure de la conférence * Présentation des trois parties de la conférence * Relations entre phénoménologie et psychiatrie * Phénoménologie des troubles de l'humeur + [00:03:21][^4^][4] Niveaux d'expérience humaine selon Binswanger * Expérience empirique et sujet empirique * Expérience transcendantale et sujet transcendantal * Niveau constitutif et sujet constituant + [00:10:00][^5^][5] L'humeur comme accord des expériences * L'humeur est ce qui accorde les niveaux d'expérience * Les troubles de l'humeur proviennent de l'ego pur * L'importance de l'accord dans l'expérience naturelle + [00:15:11][^6^][6] Le rôle du temps dans la constitution de l'expérience * Le temps comme élément fondamental de la structure de l'expérience * La perception du temps chez les patients mélancoliques * Altérations temporelles et troubles de l'humeur + [00:20:00][^7^][7] Constitution de l'espace et de l'expérience * L'espace humain centré autour du corps vivant * Constitution de l'espace à travers le temps * Altérations de l'espace vécu dans la mélancolie Résumé de la vidéo [00:28:53][^1^][1] - [00:55:50][^2^][2]:

      La vidéo présente une discussion approfondie sur la phénoménologie des troubles de l'humeur, en se concentrant sur la mélancolie et la manie. Elle explore comment ces états affectent la perception du temps et de l'espace, la relation avec autrui et la constitution de l'expérience subjective. Les exemples de patients illustrent les altérations vécues, telles que la perte de la réalité charnelle et la difficulté à établir des liens entre le passé, le présent et le futur.

      Points saillants: + [00:28:53][^3^][3] La mélancolie et la perception de l'espace-temps * Perte de la perspectivité et de la réalité vécue * Difficulté à relier les faits historiques * Sentiment de vide et d'absence d'objet concret + [00:32:32][^4^][4] La manie et la constitution d'autrui * Perturbation de la constitution d'autrui à travers les rôles sociaux * Exemples de patients illustrant la désarticulation des rôles * Passage d'un espace à l'autre sans motivation temporelle + [00:39:02][^5^][5] Le suicide altruiste dans la mélancolie * Confusion entre le soi et l'autre * Sacrifice de niveaux d'expérience pour rester en vie * Importance des rôles sociaux dans la constitution de l'expérience + [00:44:01][^6^][6] La dissociation dans la phénoménologie * La dissociation comme révélateur de désaccords entre niveaux d'expérience * La schizophrénie et la perte de l'évidence naturelle * La nécessité de reconstruire constamment le transcendantal Résumé de la vidéo [00:55:53][^1^][1] - [01:23:52][^2^][2]:

      La vidéo présente une analyse phénoménologique des troubles de l'humeur, en se concentrant sur la transition de l'expérience normale à la psychotique. Elle explore le concept de "typus mélancolicus" et son lien avec la vulnérabilité à la mélancolie, ainsi que la distinction entre les identités unipolaires et bipolaires.

      Points forts: + [00:55:53][^3^][3] Phénoménologie génétique * Examine la transition vers l'expérience psychotique * Introduit le concept d'"endon" et la métaphore de l'habitation du monde * Discute de la constitution du monde et de soi + [01:01:04][^4^][4] Typus mélancolicus * Décrit comme une prédisposition à la mélancolie * Caractérisé par un attachement excessif à l'ordre et aux valeurs sociales * Manque de liberté et difficulté à s'adapter au changement + [01:07:06][^5^][5] Mutation mélancolique * Interprétée comme une perte d'identité et une inversion des valeurs * La mélancolie clinique reflète une stagnation du temps vécu * Les symptômes mélancoliques continuent l'organisation du temps et de l'identité + [01:15:32][^6^][6] Différenciation des identités unipolaires et bipolaires * Les bipolaires montrent des traits d'instabilité et de rébellion contre les normes * Les unipolaires s'identifient fortement à leurs rôles sociaux et professionnels * La crise mélancolique est vue comme une perte d'identité et de capacité d'action Résumé de la vidéo [01:23:55][^1^][1] - [01:50:05][^2^][2]:

      Cette vidéo présente une conférence de Jean Michel Azorin sur la phénoménologie des troubles de l'humeur. Il explore la notion d'identité de jeu et son impact sur les expériences subjectives, en particulier dans le contexte de la mélancolie et de la manie. Azorin discute également de l'importance des événements inattendus dans la reconstitution de l'identité de jeu et de la façon dont les interventions thérapeutiques doivent être abordées avec prudence.

      Points saillants: + [01:26:00][^3^][3] La notion d'ego pur * L'ego pur est mal compris comme un sujet personnel * Il s'agit plutôt de la vie sollicitée par l'entourage pour se construire * Le temps transcendantal est formateur d'un sujet anonyme + [01:27:08][^4^][4] Les difficultés de dépasser les expériences de vie * Certains individus ne parviennent pas à aller au-delà de ce que la vie leur offre * Ils trouvent sécurité dans la répétition et l'adhésion aux normes communes * La liberté émerge lorsque les niveaux d'expérience se désaccordent légèrement + [01:30:10][^5^][5] Le rôle de la psychothérapie dans la mélancolie * Il est difficile de faire émerger une identité de jeu chez les patients mélancoliques * Une tentative peut conduire au suicide si elle n'est pas abordée avec prudence * La santé est un équilibre dialectique entre des tendances contraires + [01:34:40][^6^][6] L'impact des événements inattendus sur la mélancolie * Les événements inattendus peuvent aider à reconstituer l'identité de jeu * Des exemples littéraires illustrent la relation entre la mélancolie et la constitution du monde * La rencontre avec des éléments extérieurs peut parfois retisser la trame de la vie

    1. Résumé de la vidéo [00:00:01][^1^][1] - [00:27:00][^2^][2]:

      Cette vidéo présente une conférence de Roland Gori intitulée « Nos nouvelles servitudes, comment s’en émanciper ? ». Gori discute de la manière dont les nouvelles technologies, bien qu'initialement libératrices, sont devenues des outils de contrôle social et de normalisation culturelle. Il explore l'idée que nous sommes devenus esclaves de ces technologies et comment elles ont conduit à une prolétarisation des professionnels dans divers domaines.

      Points saillants: + [00:00:01][^3^][3] Introduction de la conférence * Présentation de Roland Gori * Thème de la conférence sur l'émancipation des nouvelles servitudes + [00:01:00][^4^][4] Les nouvelles technologies comme outils de contrôle * Discussion sur la transformation des technologies en vecteurs de contrôle * Citation de La Boétie sur les dangers de l'habitude + [00:06:00][^5^][5] La prolétarisation des professionnels * Impact des nouvelles normes d'évaluation sur divers métiers * Perte de sens et de responsabilité dans les professions + [00:10:00][^6^][6] Stratégies pour échapper aux nouvelles servitudes * Propositions pour revendiquer une dimension ouvrière des actes professionnels * Importance de l'habitude et de la structure mentale dans la production sociale + [00:15:00][^7^][7] La logique entrepreneuriale dans le secteur public * Critique de l'application des normes entrepreneuriales dans la recherche et la santé * Exemples de l'impact négatif de ces normes sur la qualité des services + [00:20:00][^8^][8] Conclusion sur la nécessité de lutter contre la rationalité pratique formelle * Appel à résister à la colonisation des esprits par le rationalisme financier * Importance de distinguer entre la valeur des activités et leur numérisation Résumé de la vidéo [00:27:02][^1^][1] - [00:52:53][^2^][2] : Cette vidéo présente une conférence de Roland Gori, intitulée « Nos nouvelles servitudes, comment s’en émanciper ? ». Gori explore les thèmes de l'autonomie, de la liberté individuelle et des dangers du totalitarisme néolibéral. Il critique l'évaluation quantitative comme moyen de contrôle social et plaide pour une réappropriation du pouvoir de décision par les professionnels. Gori souligne l'importance de la parole et de la créativité dans la résistance aux structures oppressives et appelle à une réhumanisation face à la déshumanisation technologique.

      Points forts : + [00:27:02][^3^][3] Autonomie et liberté * Questionnement sur la capacité d'être autonome dans un système de travail oppressif * Discussion sur les limites de l'autonomie face aux exigences normatives + [00:28:01][^4^][4] Critique du totalitarisme néolibéral * Analyse de la digitalisation et de son impact sur l'humanité * Mise en garde contre l'utilisation des chiffres pour contrôler les individus + [00:32:02][^5^][5] Éducation et technocratie * Examen des modèles éducatifs actuels et leur tendance à déshumaniser les élèves * Appel à la réhabilitation de l'éducation centrée sur l'humain et la créativité + [00:35:14][^6^][6] Résistance par la parole et la création * Importance de la parole dans la démocratie et la résistance sociale * Lien entre l'acte de création et les luttes sociales + [00:41:48][^7^][7] Réhumanisation et créativité * Nécessité de réhumaniser les individus par la créativité et la parole * Opposition à la réduction des êtres humains à des données et des algorithmes + [00:47:51][^8^][8] L'avenir de la démocratie et du vivant * Réflexion sur le rôle du sensible dans la démocratie * Plaidoyer pour la biodiversité des savoirs et la valorisation de toutes les disciplines Résumé de la vidéo [00:52:55][^1^][1] - [01:02:09][^2^][2] :

      Cette partie de la vidéo aborde les nouvelles formes de servitude dans le monde professionnel et comment s'en émanciper. Roland Gori discute de l'aliénation des travailleurs, non seulement dans le prolétariat mais dans toutes les professions, sous l'influence d'une poignée d'oligarques dans un monde globalisé.

      Points forts : + [00:52:55][^3^][3] L'aliénation moderne * L'aliénation s'étend au-delà du prolétariat * Toutes les professions sont affectées * Influence d'une élite oligarchique + [00:54:18][^4^][4] Influence des travaux de Lukács * Importance de la conscience de classe * L'aliénation crée un monde fantomatique * Nécessité de repenser le prolétariat + [00:56:02][^5^][5] La généralisation de l'aliénation * L'aliénation touche tous ceux qui travaillent * La colonisation totale par la normativité * La liberté est perdue dans un filet normatif + [00:59:00][^6^][6] Difficultés de lutte dans les établissements * Lutte contre l'asservissement et le benchmarking * Réappropriation du métier est complexe * Importance de la parole et des alliances professionnelles

    1. Since it is well known that the Web is a huge garbage-bin, this information can be well unreliable, perhaps even invented.

      for - quote - web is a huge garbage-bin - adjacency - Indyweb / Indranet provenance - web is a huge garbage bin

      quote - web is a huge garbage-bin - (see below) - Since it is well known that the Web is a huge garbage-bin, this infomration can be well unreliable, perhaps even invented.

      adjacency - between - Indyweb / Indranet provenance - quote - web is a huge garbage-bin - adjacency relationship - Indyweb / Indranet feature of provenance, - the permanent, immutable association with information with the original information source person(s) - can eliminate the problem of misquoting information sources through its inherent people-centered design philosophy - which associates all information created with the information creator - Information that is created within the Indyweb is naturally and permanently associated to the creator in a provable, immutable way

      from - Nora Bateson discussion of her new book Combining opening with a phrase that sounds much like the misattributed Einstein quote - Nora does not attribute the quote to Einstein, but I am just noting how it is often attributed to him - https://hyp.is/i1BRviFNEe-vdOMVw3775g/docdrop.org/video/kb-hsIv9zoE/

    1. celebrate advancements made in the oil and gas industry as well as Canada’s prosperity

      They are clearly trying to make a link between canadian patriotism (an inherently emotional, ie. not logic-heavy, topic) and the oil industry, so that any initiative against the oil industry can later be labelled as unpatriotic.

    2. Ethical Oil

      Greenwashing, thinking up and solving a fictive problem (oil 'ethics') to sidestep solving the actual problem.

    1. Résumé de la vidéo [00:00:03][^1^][1] - [00:26:10][^2^][2]:

      Cette vidéo présente une conférence sur la révolution de l'éducation avec l'intelligence artificielle, donnée par Sal Khan. Il explore les implications de l'IA dans l'apprentissage et la manière dont elle peut transformer l'éducation en offrant une expérience personnalisée et adaptative pour chaque apprenant.

      Points forts: + [00:00:03][^3^][3] Introduction de la conférence * Présentation des Rencontres Michel Foucault * Annonce des modifications de programme * Information sur les enregistrements et les dédicaces + [00:02:40][^4^][4] Présentation de Roland Gori * Introduction de Roland Gori par Isabelle Lamotte * Évocation de ses contributions à la psychanalyse et à la société * Mention de ses publications et de son engagement social + [00:07:00][^5^][5] La folie de la norme dans les sociétés de contrôle * Analyse de la normalisation et de son impact sur la société * Discussion sur les technologies de pouvoir et la surveillance * Réflexion sur la psychiatrie comme pratique sociale + [00:13:18][^6^][6] Évolution de la psychiatrie et médicalisation de l'existence * Examen de la psychiatrie comme fait de civilisation * Commentaire sur la médecine et son rôle dans la société * Critique de la médicalisation généralisée et de l'hygiène sociale + [00:20:25][^7^][7] Les mécanismes de contrôle et d'assujettissement * Discussion sur les nouvelles formes de contrôle social * Impact sur les professions telles que la psychiatrie et l'éducation * Évolution vers des sociétés de contrôle et de gestion des risques + [00:25:02][^8^][8] Des territorialisation et impact sur les institutions * Observation de la des territorialisation des institutions traditionnelles * Conséquences pour des domaines comme la santé, l'éducation et le travail * Réflexions finales sur les changements sociétaux et le rôle de l'individu Résumé de la vidéo [00:26:12][^1^][1] - [00:50:37][^2^][2] : La vidéo présente une discussion approfondie sur l'impact de la technologie et de la langue sur la société et l'éducation. Elle aborde la manière dont les normes et les pratiques évoluent avec l'introduction de nouvelles technologies, affectant les institutions et les individus.

      Points forts : + [00:26:12][^3^][3] Changement des normes et pratiques * L'impact des technologies sur les institutions et les savoirs * La transition des récits narratifs aux données non narratives * L'influence des chiffres et des protocoles sur les pratiques médicales et éducatives + [00:33:01][^4^][4] La langue comme outil de domination * L'importance de la langue dans la colonisation et le contrôle des peuples * L'exemple historique de la standardisation de la langue espagnole * La relation entre la langue et le pouvoir dans la société moderne + [00:45:28][^5^][5] Résistance à l'uniformisation de la langue * Les conséquences de l'imposition d'une langue unique sur la diversité culturelle * L'importance de préserver les langues vernaculaires et les dialectes locaux * La lutte contre l'homogénéisation de la langue et la pensée Résumé de la vidéo [00:50:40][^1^][1] - [01:16:34][^2^][2]:

      Cette partie de la vidéo aborde la révolution de l'éducation avec l'IA, en se concentrant sur la différenciation entre le savoir et la science, l'importance de la langue et des pratiques sociales dans la compréhension du monde, et l'impact de la technologie sur la société.

      Points forts: + [00:50:40][^3^][3] L'IA en éducation * L'IA atteint une précision de 85 à 90% dans des domaines comme la radiologie * La distinction entre savoir pathologique et normal grâce aux données + [00:52:01][^4^][4] Savoir vs Science * Michel Foucault enseigne la différence entre savoir et science * Le savoir est lié à la langue et aux pratiques sociales d'une époque + [00:54:08][^5^][5] Influence de l'époque sur la science * Les découvertes scientifiques peuvent être influencées par l'esprit de l'époque * Exemple de la physiologie sanguine et son lien avec l'époque baroque + [00:56:01][^6^][6] La science dans la culture * La manière dont la science est intégrée dans la culture dépend des filtres sociaux * La science obéit à des méthodologies, mais sa communication est filtrée par la société + [01:01:13][^7^][7] L'espoir dans l'éducation * L'espoir de retrouver une psychiatrie artisanale et ouvrière * La redécouverte de traditions perdues et la réinvention de la culture Résumé de la vidéo [01:16:37][^1^][1] - [01:23:12][^2^][2]:

      La partie 4 de la vidéo aborde la révolution de l'éducation avec l'IA, discutée par Sal Khan. Il explore les défis de l'éducation moderne et comment l'IA peut personnaliser l'apprentissage pour répondre aux besoins individuels des élèves.

      Points forts: + [01:17:01][^3^][3] Défis de l'éducation moderne * La nécessité de sortir de l'ontologie naturaliste * L'importance de redonner du sens aux mots dans l'éducation * La critique de la réduction des élèves à des ensembles de compétences + [01:18:37][^4^][4] Rôle des professionnels de l'éducation * Restituer aux professionnels la responsabilité morale et méthodologique * Encourager les enseignants à répondre de leurs actes * L'importance de la responsabilité dans l'éducation + [01:19:54][^5^][5] Liberté et émancipation dans l'éducation * Redonner aux élèves le désir d'apprendre * L'impact des méthodes pédagogiques comme celles de Freinet * La nécessité de réinventer la démocratie dans l'éducation + [01:21:36][^6^][6] La démocratie et le travail * La démocratie comme dimension existentielle dans nos métiers * La cité du travail comme lieu de réinvention de la démocratie * Le gouvernement par la parole et les débats contradictoires

    1. The Eyes around - had wrung them dry -

      She uses metaphors to describe the emotions and experiences of the speaker facing death.She compares the mourners' eyes to vessels that have run out of tears, showing their deep sadness.

    2. The Eyes around - had wrung them dry - And Breaths were gathering firm For that last Onset - when the King Be witnessed - in the Room -

      I believe that these lines was her expressing that she was close to her death and can feel everyone in the room giving their goodbye.

    1. Addgene plasmid 22453

      DOI: 10.1242/dev.202525

      Resource: RRID:Addgene_22453

      Curator: @olekpark

      SciCrunch record: RRID:Addgene_22453


      What is this?

    2. Addgene vector 64022

      DOI: 10.1242/dev.202525

      Resource: RRID:Addgene_64022

      Curator: @olekpark

      SciCrunch record: RRID:Addgene_64022


      What is this?

    3. Addgene vector 26029

      DOI: 10.1242/dev.202525

      Resource: RRID:Addgene_26029

      Curator: @olekpark

      SciCrunch record: RRID:Addgene_26029


      What is this?

    1. 12260

      DOI: 10.1038/s41467-024-48800-5

      Resource: RRID:Addgene_12260

      Curator: @olekpark

      SciCrunch record: RRID:Addgene_12260


      What is this?

    2. 12259

      DOI: 10.1038/s41467-024-48800-5

      Resource: RRID:Addgene_12259

      Curator: @olekpark

      SciCrunch record: RRID:Addgene_12259


      What is this?

    3. 22903

      DOI: 10.1038/s41467-024-48800-5

      Resource: RRID:Addgene_22903

      Curator: @olekpark

      SciCrunch record: RRID:Addgene_22903


      What is this?

    4. 22902

      DOI: 10.1038/s41467-024-48800-5

      Resource: RRID:Addgene_22902

      Curator: @olekpark

      SciCrunch record: RRID:Addgene_22902


      What is this?

    5. 22900

      DOI: 10.1038/s41467-024-48800-5

      Resource: RRID:Addgene_22900

      Curator: @olekpark

      SciCrunch record: RRID:Addgene_22900


      What is this?

    6. 17606

      DOI: 10.1038/s41467-024-48800-5

      Resource: RRID:Addgene_17606

      Curator: @olekpark

      SciCrunch record: RRID:Addgene_17606


      What is this?

    7. 17605

      DOI: 10.1038/s41467-024-48800-5

      Resource: RRID:Addgene_17605

      Curator: @olekpark

      SciCrunch record: RRID:Addgene_17605


      What is this?

    8. 17603

      DOI: 10.1038/s41467-024-48800-5

      Resource: RRID:Addgene_17603

      Curator: @olekpark

      SciCrunch record: RRID:Addgene_17603


      What is this?

    9. 17608

      DOI: 10.1038/s41467-024-48800-5

      Resource: RRID:Addgene_17608

      Curator: @olekpark

      SciCrunch record: RRID:Addgene_17608


      What is this?

    1. 12259

      DOI: 10.1016/j.isci.2024.109921

      Resource: RRID:Addgene_12259

      Curator: @olekpark

      SciCrunch record: RRID:Addgene_12259


      What is this?

    2. 12260

      DOI: 10.1016/j.isci.2024.109921

      Resource: RRID:Addgene_12260

      Curator: @olekpark

      SciCrunch record: RRID:Addgene_12260


      What is this?

    3. 52962

      DOI: 10.1016/j.isci.2024.109921

      Resource: RRID:Addgene_52962

      Curator: @olekpark

      SciCrunch record: RRID:Addgene_52962


      What is this?

    4. 76192

      DOI: 10.1016/j.isci.2024.109921

      Resource: RRID:Addgene_76192

      Curator: @olekpark

      SciCrunch record: RRID:Addgene_76192


      What is this?

    5. 76191

      DOI: 10.1016/j.isci.2024.109921

      Resource: RRID:Addgene_76191

      Curator: @olekpark

      SciCrunch record: RRID:Addgene_76191


      What is this?

    6. 77415

      DOI: 10.1016/j.isci.2024.109921

      Resource: Addgene_77415

      Curator: @olekpark

      SciCrunch record: RRID:Addgene_77415


      What is this?

    7. 9019

      DOI: 10.1016/j.isci.2024.109921

      Resource: RRID:Addgene_9019

      Curator: @olekpark

      SciCrunch record: RRID:Addgene_9019


      What is this?

    8. 9018

      DOI: 10.1016/j.isci.2024.109921

      Resource: RRID:Addgene_9018

      Curator: @olekpark

      SciCrunch record: RRID:Addgene_9018


      What is this?

    9. 15266

      DOI: 10.1016/j.isci.2024.109921

      Resource: Addgene_15266

      Curator: @olekpark

      SciCrunch record: RRID:Addgene_15266


      What is this?