This article goes into why people can easily be cancelled over their joking tweets, and why people continue to tweet. Context collapse take tweets outside of their intended circle, so they are easily misread. However, people continue to tweet because of that hope for connection.

This article is a satirical piece that emphazies the obsession with celebrity culture. Creating a ficitional group called, Citizens for Renewed Celebrity Consumption. It claims that Lindsay Lohan and Britney Spears are overexposed and no longer satisfying. It also talks about about emotionally unstable stars, nude photos of Megan Fox, and new teenage singing sensations. The article, as a joke, exaggerates society's insatiable appetite for celebrity scandals and the exploitation of fame.

Seth Meyers' article questions the impact of Jimmy Kimmel's Halloween Candy Prank on children, suggesting it could harm their trust and emotional health. This raises ethical concerns about using children for entertainment and its potential long-term effects on their psychological well-being.

Apartheid separated communities and limited the rights of the majority black population. This system ended in the early 1990s through negotiations that led to democratic elections and a new government.

"Shame is a part of healthy human development however the experience of it within the context of trauma and abuse is very different." The article talked about how shame is part of human development and is actually good for you. In the context of trauma however is different. I thought the starting sentence to be powerful because everyone has trauma one way or another, and learn differently through their truama.

In these societies, social control is primarily maintained through the internalized feeling of guilt for violating personal or societal standards. Individuals are motivated by a sense of right and wrong and the anticipation of punishment or moral repercussions. Guilt cultures emphasize law, punishment, and individual conscience​.

The source mentions Confucianism, where people, even if not punished, will feel ashamed because of their self-consciousness. When people do something wrong, they may experience such a strong sense of shame that they even consider extreme actions like suicide and can never forgive themselves.

The concept of the "guilt–shame–fear spectrum of cultures" as detailed in the Wikipedia article highlights how different cultures prioritize and experience these emotions, shaping their social norms and individual behaviors. The spectrum classifies cultures based on which emotion predominantly governs social control and conformity.

This has kind of made me rethink how I joke around with children. Generally, as most people do I think pranking children is usually harmless but I didn't consider the impact on a child's sense of trust and betrayal.

test annotation

What strikes me about this story is that there is so much built up around it. If this joke was said aloud in a group of friends, the correction would be over instantly (assuming they pushed back on it). The joke is mean-spirited to be sure, but I'm not sure it required this level of deep public reflection and apology (and certainly not the harassment it probably received).

I think there definitely are situations where reconciliation is not possible, depending on the severity of the harm endured and the genuineness of the repentance. The biggest example I can think of is the Holocaust. The scale and severity of the atrocities committed there mean that no form of reconciliation can adequately address the harm done. Although some people have apologized, the severity of the harm still has a lasting impact on all the descendants whose family members suffered due to the Holocaust.

简化的全局照明模型：

ambientStrength * lightColor * objectColor

，即环境光照。

.

eLife assessment

This valuable work describes a new protein factor that is required for filamentous phage assembly. Convincing evidence is provided for the binding of PSB15 to the packaging signal of the single-stranded DNA, Trx, and cardiolipin, and a mechanism for how the phage DNA is targeted to the assembly site in the bacterial inner membrane is presented. The work will be of interest to microbiologists.

Reviewer #1 (Public Review):

Summary:

This work describes a new protein factor required for filamentous phage assembly. The protein PSB15 binds to the packaging signal of the ssDNA, Trx and cardiolipin. A mechanism how the phage DNA is targeted to the assembly site in the bacterial inner membrane is discussed.

Strengths:

The work describes a clever way to detect factors required for phage propagation by looking at the plaque size of pseudorevertants that arise after infection of a phage with a directed mutation in the packaging signal. This led to the detection of a phage protein expressed from ORF9, the PSB15.

The authors convincingly show that PSB15 is expressed in infected cells and can complement a phage with a mutated orf9.

Weaknesses:

Given the fact that the phage LF-UK is not well explored, many open questions should be mentioned in the introduction. For the study, it is important to know if the phageLF-UK has a mimick or homolog of gV and gXI, and if not, whether PSB15 could take their role.

I am not convinced of the proposition of their term "checkpoint". The truth is that the authors do not know the real purpose of PSB15. I do not see an advantage for a checkpoint that only adds an additional step to enter the phage assembly site. There must be a biochemical reason for the action of PSB15. Looking at Figure 7, the step from "Release" to "Loading" is just adding many unknowns, e.g. how to transfer the DNA, how to dispose of PSB15 and Trx? Also, in the previous step are three question marks that do not add any solid information.

The in vivo study of subcellular localization is very questionable. Why is there a single fluorescent dot if there are thousands of PSB15 molecules expressed in the cell? I have my doubts that the conclusions the authors make here are correct and meaningful. The movies do not add anything significant.

Reviewer #2 (Public Review):

Secretion of the prototypical F-associated filamentous phage (Ff) of E. coli depends on the selective binding of a hairpin (the packaging signal, PS) by two phage encoded protein, pVII and pIX. PVII and pIX target the PS to IM channels formed by pI and pIV. However, integrative filamentous phages lack a homologue of pIX and pIV, and many of them also lack a homologue of pVII, raising questions on the assembly and secretion of new phages. In the manuscript, Yueh et al. present the identification of a phage-encoded protein, PSB15, which binds to the PS signal of a Xanthomonas integrative filamentous phage, ΦLf-UK. They showed that PSB15 is required for viral assembly and is conserved in several other integrative filamentous phages. They further analyzed how PSB15 binds to PS and demonstrated that it associates to the IM, which targets phage DNA to it. Finally, they show that thioredoxin, the only host protein that was found to be essential for Ff secretion, interacts with PSB15 and releases the PSB15-PS complex from the IM. These results are important because they elucidate a major step in the secretion of integrative filamentous phage, and the role of thioredoxin on filamentous phage secretion in general.

I found the data and interpretation convincing. However, the presentation and description are confusing in places because the reader has to juggle between figures. A scheme depicting what is known and unknown in the integration of Ff phages and interactive filamentous phages in the introduction would be useful to the general reader.

This view on how parents should address bad or dangerous behavior in their children resonates deeply with me. Growing up, I recall moments where my parents would firmly stop me from doing something wrong but then take the time to explain why the action was inappropriate and reassure me of their love and acceptance. This approach helped me understand that my actions were separate from my identity. It’s a powerful method that not only corrects behavior but also strengthens the parent-child bond.

when I felt guilt, especially when I knew I had hurt someone, I was more inclined to apologize and make amends. This distinction resonates with my experiences and highlights how important it is for parents and educators to understand these emotions and guide children accordingly. Understanding that shame can lead to withdrawal and isolation suggests that it might be more constructive to address children's actions and encourage reparative behaviors rather than inducing feelings of shame.

I think this passage highlights the delicate balance that a good parent must strike in correcting their child's behavior. It emphasizes the importance of distinguishing between the act of rejecting the child rather than rejecting the child itself. By comforting the child afterwards, parents reinforce the idea that the value of the child does not diminish because of their mistakes. Over time, this approach can help children learn guilt, which is healthier than shame, and encourage them to repair hurt instead of hiding from it. This approach fosters positive parent-child relationships and promotes emotional growth.

I remember the time I felt ashamed four years ago when I lost a hockey speed competition. I sprained my ankle during the race, so I did not run as fast as I could. Even now, I can still recall it vividly.

It is important to recognize the difference the difference between shame and guilt as it can produce different outcomes of how one handles a situation. Even myself as a 21 year old sometimes can't differentiate between the two in certain situation because of my adolescence years.

The distinction between shame and guilt in childhood development, as discussed in the chapter, highlights a crucial aspect of emotional growth and socialization. My personal opinion is that understanding this distinction is fundamental not only for parents and educators but also for society at large. Shame, which internalizes a sense of being inherently bad, can be detrimental to a child's self-esteem and overall psychological health. It often leads to avoidance behaviors and a desire to hide, which can hinder social integration and personal development.

I think a major issue for a lot of more sensitive people is that they did not develop this idea that you are not your worst moment.

Main points - PA is positively associated with classroom behaviour and learning. - Hamer et al 2017 study found that environmental intervention increased light PA and decreased sedentary behaviour in younger children - In this study the intervention included specific furniture designed to accomodate children's natural urges to fidget and discourage frequently phases of static sitting - this is why the sedentary behaviour was reduced, as the intervention created a classroom design that provided dynamic furniture and ample space for different activities.

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Reply to the reviewers

Manuscript number: RC- 2023-02122

Corresponding author(s): Andrew Graham Cox and Juan Manuel González-Rosa

1. General Statements

We thank the reviewers for taking the time to assess our work and for their considered and constructive comments. We are glad that they appreciate the value of the methodology we have developed. In addressing the points raised by the reviewers, we have significantly strengthened the conclusions reached in our study. Below is a point-by-point response (in regular type, blue) to the specific reviewer comments (in italics, black).

1. Point-by-point description of the revisions

Experiment 1: Perform lineage tracing of hepatocytes following cryoinjury.

Reviewer #1 would like us to have a better understanding of the origin of the regenerative hepatocytes following cryoinjury. There are two potential sources of regenerating hepatocytes. In many cases, hepatocytes proliferate giving rise to regenerative hepatocytes. However, during severe injury, the liver can undergo a ductular reaction in which biliary epithelial cells (BECs) can expand and transdifferentiate to give rise to regenerating hepatocytes.

● To address this query we have now used a new transgenic line created in laboratory that can indelibly label hepatocytes for lineage tracing Tg(fabp10a:Tet-ON-Cre). We have crossed this line to floxed reporters (Ubb:Switch) and collect livers at 7 dpci. The healthy parenchyma surrounding the injured area was predominantly labelled in the tracing experiment suggesting that pre-existing hepatocytes are driving the regenerative response.

Experiment 2: Examine BEC and EC proliferation in the ventral and contralateral lobes following cryoinjury.

Reviewers #1 and #2 would like us to better characterise the temporal dynamics of proliferation in BECs and ECs following cryoinjury. Specifically, the reviewers would like to know whether then compensatory hyperplasia in the contralateral lobe also leads to increased BEC and EC proliferation. Moreover, the reviewers would like us to better quantify the extent of EC and BEC proliferation at different stages of regeneration after cryoinjury.

● We have now performed extensive BrdU pulse-chase cryoinjury experiments using Tg(fli1a:nEGFP) zebrafish to visualise ECs. We have also conducted multiplexed immunostaining of the regenerating livers with the BEC marker (Anxa4) in conjunction with immunodetection of proliferation (BrdU and PCNA). These studies outline the kinetics of the regenerative response and provide evidence to support epimorphic regeneration around the site of injury as well as a compensatory hyperplasia on the contralateral lobe.

Experiment 3: Quantification of the temporal dynamics of fibrosis upon cryoinjury.

Reviewer #1 suggested we better characterise the extent of fibrosis in our model.

● We have now performed extensive studies quantifying the extent of collagen deposition at the regenerative margin over the time course (SHAM, 1, 3, 5, and 7 dpci) using immunohistochemical detection.

Experiment 4: Examine the role of Macrophage depletion in liver regeneration.

Reviewer #1 suggested we examine regeneration following cryoinjury in immunodeficient zebrafish in order to understand the role of macrophages in the model.

● To address this question, we have now performed studies involving macrophage depletion, using the well established IP injection of clodronate liposomes. We have now performed cryoinjury comparing untreated and chlodronate-treated Tg(fabp10a:NLSmCherry) or Tg(fabp10a: GreenLantern-H2B) zebrafish and examined the extent of regeneration at 3 and 7 dpci.

Experiment 5: Examine the impact of age and gender on liver regeneration following cryoinjury.

Reviewer #3 wanted to know if the regenerative response to cryoinjury was different depending on age and gender.

● To address this query, we have now performed cryoinjuries on young (4 month) and aged (9 month) males and females in a Tg(fabp10a:NLS-mCherry) or Tg(fabp10a: GreenLantern-H2B) background and examined regeneration at 7 dpci.

Experiment 6: Characterization of the dynamics of Hepatoblasts, Hepatic Stellate Cells, Macrophages and Neutrophils following cryoinjury.

Reviewer #3 suggested that it would be good to have a better cellular characterization of regeneration in the cryoinjury model.

● To address this question, we have now examined distinct cell types over the cryoinjury timecourse including SHAM, 1, 3, 5, and 7 dpci livers to provide a temporal landscape of the cellular response. In addition to BECs and ECs as discussed above, we have also performed immunofluorescence to detect macrophages (mfap4) neutrophils (mpx) during liver regeneration.

Specific Reviewer comments

Reviewer #1

Major points:

Full Revision

1) In this cryoinjury model, the authors found cell proliferation in hepatocytes, BECs, and other cell types near the injury site. The proliferating hepatocytes exclusively provide hepatocytes, and BECs provide BECs, or some transdifferentiation is involved? Like other extreme ablation models, BECs can contribute to some hepatocytes in this model.

We thank the Reviewer #1 for the interesting suggestion. We have addressed this by performing lineage tracing analysis as explained in Experiment 1 (above). For this approach, we have used Tg(fabp10a:Tet-ON-Cre; Ubb:Switch) to indelibly label and trace hepatocytes. These experiments reveal that the new regenerated tissue is derived from pre-existing hepatocytes (see Supplementary Figure 2 Q, R, S, T).

2) In this model, the authors observed the long-range effect of the cryoinjury as they identified increased cell proliferation in the contralateral liver lobes. Is this long-range effect specific to hepatocytes? BECs or endothelial cells also undergo increased cell proliferation in the contralateral lobes?

We thank the Reviewer #1 for this question. We have addressed this query by performing Experiment 2 (above). Briefly, cryoinjuries were performed and markers of proliferating HCs and BECs (PCNA or BrdU stained) were quantified in the ventral and contralateral lobes (see Supplementary Figure 6). The data clearly demonstrates that proliferation is higher at the site of injury, however lower rates of compensatory hyperplasia are still evident on the contralateral lobe. A strong epimorphic hyperplasia and weaker compensatory growth response, has been previously observed in the cardiac cryoinjury model (Pauline Sallin et al. Developmental Biology 2015).

3) This model is a unique liver regeneration model as it induces transient focal fibrosis. Is the fibrosis beneficial for liver regeneration? What happens if you reduce fibrosis pharmacologically? Will it interfere with the rate of regeneration?

We thank the Reviewer #1 for the comments. Although pharmacological interventions of fibrosis are beyond the scope of the current manuscript, we have better quantified the extent of fibrosis in the first week following cryoinjury in Experiment 3 (above; Figure 3I).

4) Do Lcp1+ leucocytes contribute to liver regeneration in this model? In immunodeficiency models such as irf8 mutant, liver regeneration after cryoinjury changed?

We thank the Reviewer #1 for the suggestion of using an immunodeficiency model. We addressed this question by performing Experiment 4 (above). Briefly, we have IP injected clodronate liposomes, which are a well-established method for macrophage depletion, and examined the effect on liver regeneration (Supplementary Figure 5). These extensive experiments showed that macrophage depletion had no significant effect on liver regeneration at 3 and 7 dpci.

5) The CUBIC-clearing procedure is beneficial in the field. The quantitative benefit of the CUBICbased method should be added. Supplement figures 1C and D need scale bars, especially for X Z and Z-Y planes. Can you quantify the Z-plane depth that you can scan with or without CUBIC treatment?

We thank the Reviewer #1 for the input and apologise if we did not present the current data clearly. We have now included the scale bars on the reviewed manuscript in Supplementary Figure 1C, 1D, and 1G. We have quantified the Z-plane depth on our current acquisitions and modified our current panels to make clear the difference in depth (z-stack) that CUBIC-imaging enables during liver acquisitions in Supplementary Figure 1D-I.

6) In the manuscript, the authors measured the injured area after the cryoinjury. But how about the depth of the injury? Does the procedure induce a relatively constant injury depth, or can it not be controlled? The total volume of injured tissue would be more important than the surface injured area.

We thank the Reviewer #1 for the comments. The hepatic cryoinjury approach was developed to injure the liver and avoid deeper tissue lesions to the gastrointestinal tract. Our existing CUBIC data suggests that injury depth remains constant.

Minor points:

7) The sham procedure means exposing the liver by removing the scale and cutting the skin, right? What is the survival rate of the sham procedure? Is the survival rate of sham group significantly lower than cryoinjury-induced group?

The Reviewer #1 is correct about the cryoinjury procedure in SHAM samples. SHAM survival is 95% while the injured animal survival is 92.97% (Figure below; n= 444). This analysis shows no significant difference between the groups (unpaired Student's t-test; p-value: 0.5843)

8) The original RNA-seq data, including FASTQ files, should be deposited to NCBI (Gene Expression Omnibus) or other public databases.

We apologize for not submitting our Bulk RNA-seq data to NCBI GEO during the initial submission. The Bulk RNA-seq data can be found under the accession number GSE245878.

Full Revision

Reviewer #2

Major points:

1) While the authors assayed changes in major cell types during liver regeneration in this model, the selection of varying timepoints for analysis and incomplete quantification for all timepoints precludes detailed comparisons that may lead to mechanistic insights. For example, closure of injury area is assayed at 1,3,7,14 dpci but hepatocyte proliferation is measured at 1,3,5,7, 18, 30 dpi. Fibrosis was only assayed at 5 dpi (assume dpi is the same as dpci). Cholangiocytes and endothelial cells are imaged at 1, 3, 7, 30 dpci but no quantification was provided only a single image. Since most changes are occurring at 1-7 dpci, the authors should at least measure the same timepoints from 1-7 dpci for the different cell types so comparisons can be made and conclusions can be drawn. For example, does hepatocyte proliferation, which seem to peak at 5 dpci, happen before endothelial proliferation, which is measured at 3 and 5 dpci but not measured at 5 dpci?

We thank the Reviewer #2 for the comments regarding temporal dynamics of regeneration. In response we have performed Experiment 2 (above). Briefly, this included examination of BECs and ECs at different time points during regeneration (SHAM, 1, 3, 5, and 7 dpci; Figure 6, Supplementary Figure 6L-P).

2) Fibrosis level seems to be highly variable at 5 dpci, which is the only time point measured. If this level of variability is found across all timepoints then this might not be a good model to study the intersection of fibrosis and regeneration. Since the authors have collected animals at all timepoints, it should be fairly straight forward to carry out collagen staining and quantification across different timepoints without the need of additional fish experiments.

We thank the Reviewer #2 for the comments regarding the fibrotic response. In response we have undertaken Experiment 3 (above). This experiment involves quantifying collagen deposition at the different timepoints (SHAM, 1, 3, 5, and 7 dpci; Figure 3I).

3) The lack of quantification of cholangiocytes and endothelial cells makes it difficult to gauge the reproducibility of this model across different animals and experiments.

We thank the Reviewer #2 for the comments regarding the need to quantify ECs and BECs during regeneration. In response we will undertake Experiment 2 (above). Briefly, this included examination of BECs and ECs at different time points during regeneration (SHAM, 1, 3, and 7 dpci; Figure 6 and Supplementary Figure 7).

4) Transcriptomic data analysis/presentation in Figure 7 can be improved. Cannot read any of the gene labels in Figure 7B. Figure 7H should use at least a few different gene markers from each cell type to approximate cell abundance.

We apologise for the inconvenience and have addressed the issue of legibility. We have increased font size on the volcano plots in Figure 7 and incorporate a new analysis with more markers for each cell type in Figure 7H. In addition, we have included the comparison between Bulk RNA-seq ventral samples and contralateral lobe samples, together with further GOenrichment of the samples in Supplementary Figure 8.

Full Revision

Minor:

5) Is "dpi" the same as "dpci"? Please use the same nomenclature throughout manuscript.

We apologise. Dpi means days post-injury and dpci means days post-cryoinjury. Nomenclature has been corrected in revised version of the manuscript.

6) In the mouse PHx model, hepatocytes reach max proliferation (as measured with Ki67/PCNA staining) at 40-48hrs across different labs and experiments, not at 24rs.

We thank the Reviewer #2, we have changed this reference.

7) Zebrafish references are used when the author is talking about mouse PHx model on page 12.

We thank the Reviewer #2, we have changed this reference 7 and 8 to reference the right papers.

Reviewer #3

Major points:

1) It is not clear whether both male and female fish were used in the analyses and whether there is any gender difference in regeneration responses at cellular and molecular levels. The method mentioned that 4-9 month old fish were used in the study. Was there any difference between young and old fish?

We thank the Reviewer #3 for the comments regarding the need to consider age and gender in regeneration studies. Our experiments have been performed on adult male zebrafish. To examine the impact of age and gender on regeneration we have performed Experiment 5 (above). In brief, we have undertaken cryoinjuries in 4 month or 9 month old females and males in the Tg(fabp10a:NLS-mCherry) or Tg(fabp10a: GreenLantern-H2B) background and examine regeneration at 7 dpci (Supplementary Figure 2 J-N and P. We could not detect a significant difference among any of these comparisons. However, we observed a subtle trend with female adult zebrafish showing smaller insult area compared to adult male zebrafish, both at 3 and 7 dpci (Supplementary Figure 2P).

2) The authors detected increased hepatocyte proliferation following cryoinjury. It will be interesting to investigate if activation of stem cells and transdifferentiation of cholangiocytes also contribute to regeneration in this particular model.

We thank the Reviewer #3 for the comments regarding the need to examine the potential involvement of hepatoblasts and transdifferentiating BECs in regeneration following cryoinjury. We have addressed these aspects with Experiment 6 (above). Briefly, we have performed cryoinjuries in adult zebrafish and utilised Anxa4 staining for detection of BECs at SHAM, 1, 3, 5, and 7 dpci (Figure 6A-F). This analysis showed that the were no detectable signs of transdifferentiation between hepatocytes and cholangiocytes (ie: there were no double positive cells (Anxa+/fabp10a:H2B-GreenLantern+ or fabp10a:H2B-mCherry+). Moreover, we performed lineage tracing experiments and found evidence that pre-existing hepatocytes give rise to the regenerating tissue (Supplementary Figure 2 Q-T). Together, these experiments indicate that hepatocytes are responsible for the regeneration of the liver upon cryoinjury without the necessity of BEC transdifferentiation.

3) It will be important to characterize hepatic stellate cells, macrophages, and neutrophils in this model, given their critical and complex roles in liver regeneration. Transgenic reporter lines marking these cell types are available.

We thank the Reviewer #3 for the comments regarding the need to examine hepatic stellate cells (HSCs), macrophages and neutrophils in regeneration following cryoinjury. We have addressed these aspects with Experiment 6 (above). Briefly, we have studied the temporal dynamics of neutrophils upon cryoinjury by immunofluorescent detection of myeloperoxidase (mpx) (Supplementary Figure 4). We have also explored the role of macrophage depletion in response to cryoinjury by performing clodronate injections. We found no significant changes in liver regeneration following clodronate injections (Supplementary Figure 5). To examine the temporal dynamics of HSCs we attempted to use two approaches, namely imaging transgenic lines labelling HSCs (Tg(BAC-pdgfrb:EGFP) and HCR for HSCs (pdgfrb), but unfortunately we were not able to detect HSCs with these approaches.

4) It is not appropriate to call Fli1a + cells liver sinusoidal cells. As far as I know, there is no specific marker for LSEC in zebrafish. Fli1a transgene labels all vascular cells.

We acknowledge this mistaken nomenclature and have made the necessary amendment to use the term endothelial cells (ECs).

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Referee #3

Evidence, reproducibility and clarity

In this manuscript, Sande-Melon et al described a new model for studying liver regeneration in zebrafish that is induced by cryoinjury. They showed that this model induced hepatocyte proliferation, transient fibrosis and inflammation, and regeneration of the biliary and vascular network. Compared to the other established models, such as partial hepatectomy, drug-induced liver injury, the cryoinjury model is easy to perform, consistent, and involves shorter recovery time. Overall, it is a useful tool that complements existing liver regeneration models. The tissue clearing methodology is highly effective.

Main critiques:

1. It is not clear whether both male and female fish were used in the analyses and whether there is any gender difference in regeneration responses at cellular and molecular levels. The method mentioned that 4-9 month old fish were used in the study. Was there any difference between young and old fish?
2. The authors detected increased hepatocyte proliferation following cryoinjury. It will be interesting to investigate if activation of stem cells and transdifferentiation of cholangiocytes also contribute to regeneration in this particular model.
3. It will be important to characterize hepatic stellate cells, macrophages, and neutrophils in this model, given their critical and complex roles in liver regeneration. Transgenic reporter lines marking these cells types are available.
4. It is not appropriate to call Fli1a + cells liver sinusoidal cells. As far as I know, there is no specific marker for LSEC in zebrafish. Fli1a transgene labels all vascular cells.

Significance

In this manuscript, Sande-Melon et al described a new model for studying liver regeneration in zebrafish that is induced by cryoinjury. They showed that this model induced hepatocyte proliferation, transient fibrosis and inflammation, and regeneration of the biliary and vascular network. Compared to the other established models, such as partial hepatectomy, drug-induced liver injury, the cryoinjury model is easy to perform, consistent, and involves shorter recovery time. Overall, it is a useful tool that complements existing liver regeneration models. The tissue clearing methodology is highly effective.

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Referee #2

Evidence, reproducibility and clarity

In this manuscript titled "Development of a hepatic cryoinjury model to study liver regeneration" by Sande-Melon et al., the authors developed a novel model to study liver regeneration, namely a cryoinjury model in adult zebrafish. The authors described the methodology in detail and extensively characterized the kinetics of liver regeneration in this model, including hepatocyte necrosis/apoptosis, the proliferation of hepatocytes, cholangiocytes, endothelial cells, and infiltration of leukocytes. Most of the characterization were performed by immunostaining for various cell markers, which the authors corroborated with transcriptomic analysis by bulk RNAseq.

Major comments:

• While the authors assayed changes in major cell types during liver regeneration in this model, the selection of varying timepoints for analysis and incomplete quantification for all timepoints precludes detailed comparisons that may lead to mechanistic insights. For example, closure of injury area is assayed at 1,3,7,14 dpci but hepatocyte proliferation is measured at 1,3,5,7, 18, 30 dpi. Fibrosis was only assayed at 5 dpi (assume dpi is the same as dpci). Cholangiocytes and endothelial cells are imaged at 1, 3, 7, 30 dpci but no quantification was provided only a single image. Since most changes are occurring at 1-7 dpci, the authors should at least measure the same timepoints from 1-7 dpci for the different cell types so comparisons can be made and conclusions can be drawn. For example, does hepatocyte proliferation, which seem to peak at 5 dpci, happen before endothelial proliferation, which is measured at 3 and 5 dpci but not measured at 5 dpci?
• Fibrosis level seems to be highly variable at 5dpci, which is the only time point measured. If this level of variability is found across all timepoints then this might not be a good model to study the intersection of fibrosis and regeneration. Since the authors have collected animals at all timepoints, it should be fairly straight forward to carry out collagen staining and quantification across different timepoints without the need of additional fish experiments.
• The lack of quantification of cholangiocytes and endothelial cells makes it difficult to gauge the reproducibility of this model across different animals and experiments.
• Transcriptomic data analysis/presentation in Figure 7 can be improved. Cannot read any of the gene labels in Figure 7B. Figure 7H should use at least a few different gene markers from each cell type to approximate cell abundance.
• OPTIONAL: Sheets of DAPI staining are observed in Figure 6G'. Is this DNA from necrotic cells? Could they make up a neutrophil extracellular trap (NET)-scaffold like structure that covers/protects the injury site from infection? This is purely speculative but might represent an interesting area of study.
• OPTIONAL: To demonstrate this a useful model that complements existing models of liver regeneration, the authors can try to capitalize on the proposed strength of the model to provide some novel insights into liver regeneration. A notable feature of this model that is missing from the PHx and APAP rodent models is the development of robust fibrosis that rapidly resolves within a short time frame, providing an unique opportunity to investigate the potential crosstalk between fibrosis and regeneration that often co-occur in chronic liver disease patients.

Minor comments:

• Is "dpi" the same as "dpci"? Please use the same nomenclature throughout manuscript
• In the mouse PHx model, hepatocytes reach max proliferation (as measured with Ki67/PCNA staining) at 40-48hrs across different labs and experiments, not at 24rs
• Zebrafish references are used when the author is talking about mouse PHx model on page 12

Significance

Mouse 2/3 partial hepatectomy surgery (PHx) is the most frequently used model to study liver regeneration and much has been learnt from this model. However, mouse PHx involving tying off certain lobes of the liver and the inducing a sterile injury, where hepatocyte proliferation and liver regeneration occurs in the absence of significant inflammation and fibrosis. To understand the full complexity of the liver regeneration response, especially against the backdrop of a necroinflammatory environment that characterize chronic liver disease in patients, alternative models to study liver regeneration have been used such as the rodent APAP model of chemically induced injury. Here, Sande-Melon et al. aims to establish such a liver regeneration model in adult zebrafish that would harness the power of the zebrafish model, such as availability of various transgenic lines that label different cell populations, ease of accessibility to imaging techniques, large N number, and the convenience of working with lower complexity model organisms. While such a zebrafish liver regeneration model will be welcomed by the greater research community interested in studying liver regeneration, this paper in its current forms falls short of demonstrating the robustness and reproducibility of this model that would make it a useful research tool.

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Referee #1

Evidence, reproducibility and clarity

Summary:

In this study, the authors presented a novel cryoinjury model of liver damage and regeneration that reflects essential features of liver disease, including local fibrosis. Because of its rapid and consistent method, this model will be helpful and provide opportunities to delve into the molecular basis of liver regeneration. This manuscript also contains a high technique of visualization of the regenerating liver. The manuscript is well-written, and the points are clear. However, this form of manuscript might be overly descriptive, and adding functional, mechanical, or lineage tracing-based fate decision insights would make this manuscript significantly better.

Major points:

1. In this cryoinjury model, the authors found cell proliferation in hepatocytes, BECs, and other cell types near the injury site. The proliferating hepatocytes exclusively provide hepatocytes, and BECs provide BECs, or some transdifferentiation is involved? Like other extreme ablation models, BECs can contribute to some hepatocytes in this model.
2. In this model, the authors observed the long-range effect of the cryoinjury as they identified increased cell proliferation in the contralateral liver lobes. Is this long-range effect specific to hepatocytes? BECs or endothelial cells also undergo increased cell proliferation in the contralateral lobes?
3. This model is a unique liver regeneration model as it induces transient focal fibrosis. Is the fibrosis beneficial for liver regeneration? What happens if you reduce fibrosis pharmacologically? Will it interfere with the rate of regeneration?
4. Do Lcp1+ leucocytes contribute to liver regeneration in this mode? In immunodeficiency models such as irf8 mutant, liver regeneration after cryoinjury changed?
5. The CUBIC-clearing procedure is beneficial in the field. The quantitative benefit of the CUBIC-based method should be added. Supplement figures 1C and D need scale bars, especially for X-Z and Z-Y planes. Can you quantify the Z-plane depth that you can scan with or without CUBIC treatment?
6. In the manuscript, the authors measured the injured area after the cryoinjury. But how about the depth of the injury? Does the procedure induce a relatively constant injury depth, or can it not be controlled? The total volume of injured tissue would be more important than the surface injured area.

Minor points:

1. The sham procedure means exposing the liver by removing the scale and cutting the skin, right? What is the survival rate of the sham procedure? Is the survival rate of sham group significantly lower than cryoinjury-induced group?
2. The original RNA-seq data, including FASTQ files, should be deposited to NCBI (Gene Expression Omnibus) or other public databases.

Significance

The strength of this manuscript is that the authors established the new cryoinjury liver regeneration model. Compared to other models, this model introduced local fibrosis and relatively quick resolution of the fibrosis, which is unique to this model. Fibrosis is like a double-edged sword, as it can be a severe problem, but it may also enhance healing and regeneration. This useful model would advance our understanding of the role of fibrosis in liver regeneration. Also, this manuscript contains important new technologies, such as CUBIC-clearing, and will be helpful for the research field.

eLife assessment

This study presents important data describing cell states of olfactory ensheathing cells, and how these cell states may relate to repair after spinal cord injury. While the overall framework used for characterizing these cells is solid, the quantification and contextualization of results are incomplete, given that measurements, significance statistics, and discussion of both previous work and experimental methods that would be necessary to support several claims are not provided. With more thorough quantification and discussion, this work will be of interest to stem cell biologists and spinal cord injury researchers.

Joint Public Review:

Summary

This manuscript explores the transcriptomic identities of olfactory ensheathing cells (OECs), glial cells that support life-long axonal growth in olfactory neurons, as they relate to spinal cord injury repair. The authors show that transplantation of cultured, immunopurified rodent OECs at a spinal cord injury site can promote injury-bridging axonal regrowth. They then characterize these OECs using single-cell RNA sequencing, identifying five subtypes and proposing functional roles that include regeneration, wound healing, and cell-cell communication. They identify one progenitor OEC subpopulation and also report several other functionally relevant findings, notably, that OEC marker genes contain mixtures of other glial cell type markers (such as for Schwann cells and astrocytes), and that these cultured OECs produce and secrete Reelin, a regrowth-promoting protein that has been disputed as a gene product of OECs.

This manuscript offers an extensive, cell-level characterization of OECs, supporting their potential therapeutic value for spinal cord injury and suggesting potential underlying repair mechanisms. The authors use various approaches to validate their findings, providing interesting images that show the overlap between sprouting axons and transplanted OECs, and showing that OEC marker genes identified using single-cell RNA sequencing are present in vivo, in both olfactory bulb tissue and spinal cord after OEC transplantation.

Despite the breadth of information presented, however, further quantification of results and explanation of experimental approaches would be needed to support some of the authors' claims. Additionally, a more thorough discussion is needed to contextualize their findings relative to previous work.

(1) Important quantification is lacking for the data presented. For example, multiple figures include immunohistochemistry or immunocytochemistry data (Figures 1, 5, 6), but they are presented without accompanying measures like fractions of cells labeled or comparisons against controls. As a result, for axons projecting via OEC bridges in Figure 1, it is unclear how common these bridges are in the presence or absence of OECs. For Figure 6., it is unclear whether cells having an alternative OEC morphology coincide with progenitor OEC subtype marker genes to a statistically significant degree. Similar quantification is missing in other types of data such as Western blot images (Fig. 9) and OEC marker gene data (for which p-values are not reported; Table S2).

The addition of quantitative measures and, where appropriate, statistical comparisons with p-values or other significance measures, would be important for supporting the authors' claims and more rigorously conveying the results.

(2) Some aspects of the experimental design that are relevant to the interpretation of the results are not explained. For example, OECs appear to be collected from only female rats, but the potential implications of this factor are not discussed.

Additionally, it is unclear from the manuscript to what degree immunopurified cells are OECs as opposed to other cell types. The antibody used to retain OECs, nerve growth factor receptor p75 (Ngfr-p75), can also be expressed by non-OEC olfactory bulb cell types including astrocytes [1-3]. The possible inclusion of Ngfr-p75-positive but non-OEC cell types in the OEC culture is not sufficiently addressed. Such non-OEC cell types are also not distinguished in the analysis of single-cell RNA sequencing data (only microglia, fibroblasts, and OECs are identified; Figure 2). Thus, it is currently unclear whether results related to the OEC subtype may have been impacted by these experimental factors.

(3) The introduction, while well written, does not discuss studies showing no significant effect of OEC implantation after spinal cord injury. The discussion also fails to sufficiently acknowledge this variability in the efficacy of OEC implantation. This omission amplifies bias in the text, suggesting that OECs have significant effects that are not fully reflected in the literature. The introduction would need to be expanded to properly address the nuance suggested by the literature regarding the benefits of OECs after spinal cord injury. Additionally, in the discussion, relating the current study to previous work would help clarify how varying observations may relate to experimental or biological factors.

(a) Cragnolini, A.B. et al., Glia, (2009), doi: 10.1002/glia.20857.<br /> (b) Vickland H. et al., Brain Res., (1991), doi: 10.1016/0006-8993(91)91659-O.<br /> (c) Ung K. et al., Nat Commun., (2021), doi: 10.1038/s41467-021-25444-3.

eLife assessment

This study presents valuable research comparing three different species of extant cartilaginous fishes and describes new data on ratfish. The methods are convincing although the reviewers noted that standardized methods are essential when comparing numerical datasets. This study would be of interest to skeletal biologists working on the evolution of chondrichthyan skeletons.

Reviewer #1 (Public Review):

Summary:

It seems as if the main point of the paper is about the new data related to rat fish although your title is describing it as extant cartilaginous fishes and you bounce around between the little skate and ratfish. So here's an opportunity for you to adjust the title to emphasize ratfish is given the fact that leader you describe how this is your significant new data contribution. Either way, the organization of the paper can be adjusted so that the reader can follow along the same order for all sections so that it's very clear for comparative purposes of new data and what they mean. My opinion is that I want to read, for each subheading in the results, about the the ratfish first because this is your most interesting novel data. Then I want to know any confirmation about morphology in little skate. And then I want to know about any gaps you fill with the cat shark. (It is ok if you keep the order of "skate, ratfish, then shark, but I think it undersells the new data).

Strengths:

The imagery and new data availability for ratfish are valuable and may help to determine new phylogenetically informative characters for understanding the evolution of cartilaginous fishes. You also allude to the fossil record.

Opportunities:

I am concerned about the statement of ratfish paedomorphism because stage 32 and 33 were not statistically significantly different from one another (figure and prior sentences). So, these ratfish TMDs overlap the range of both 32 and 33. I think you need more specimens and stages to state this definitely based on TMD. What else leads you to think these are paedomorphic? Right now they are different, but it's unclear why. You need more outgroups.

Your headings for the results subsection and figures are nice snapshots of your interpretations of the results and I think they would be better repurposed in your abstract, which needs more depth.

Historical literature is more abundant than what you've listed. Your first sentence describes a long fascination and only goes back to 1990. But there are authors that have had this fascination for centuries and so I think you'll benefit from looking back. Especially because several of them have looked into histology and development of these fishes.

I agree that in the past 15 years or so a lot more work has been done because it can be done using newer technologies and I don't think your list is exhaustive. You need to expand this list and history which will help with your ultimate comparative analysis without you needed to sample too many new data yourself.

I'd like to see modifications to figure 7 so that you can add more continuity between the characters, illustrated in figure 7 and the body of the text. Generally Holocephalans are the outgroup to elasmobranchs - right now they are presented as sister taxa with no ability to indicate derivation. Why isn't the catshark included in this diagram?

In the last paragraph of the introduction, you say that "the data argue" and I admit, I am confused. Whose data? Is this a prediction or results or summary of other people's work? Either way, could be clarified to emphasize the contribution you are about to present.

Reviewer #2 (Public Review):

General comment:

This is a very valuable and unique comparative study. An excellent combination of scanning and histological data from three different species is presented. Obtaining the material for such a comparative study is never trivial. The study presents new data and thus provides the basis for an in-depth discussion about chondrichthyan mineralised skeletal tissues. I have, however, some comments. Some information is lacking and should be added to the manuscript text. I also suggest changes in the result and the discussion section of the manuscript.

Introduction:

The reader gets the impression almost no research on chondrichthyan skeletal tissues was done before the 2010 ("last 15 years", L45). I suggest to correct that and to cite also previous studies on chondrichthyan skeletal tissues, this includes studies from before 1900.

Material and Methods:

Please complete L473-492: Three different Micro-CT scanners were used for three different species? ScyScan 117 for the skate samples. Catshark different scanner, please provide full details. Chimera Scncrotron Scan? Please provide full details for all scanning protocols.

TMD is established in the same way in all three scanners? Actually not possible. Or, all specimens were scanned with the same scanner to establish TMD? If so please provide the protocol.

Please complete L494 ff: Tissue embedding medium and embedding protocol is missing. Specimens have been decalcified, if yes how? Have specimens been sectioned non-decalcified or decalcified?

Please complete L506 ff: Tissue embedding medium and embedding protocol is missing. Description of controls are missing.

Results:

L147: It is valuable and interesting to compare the degree of mineralisation in individuals from the three different species. It appears, however, not possible to provide numerical data for Tissue Mineral Density (TMD). First requirement, all specimens must be scanned with the same scanner and the same calibration values. This in not stated in the M&M section. But even if this was the case, all specimens derive from different sample locations and have, been preserved differently. Type of fixation, extension of fixation time in formalin, frozen, unfrozen, conditions of sample storage, age of the samples, and many more parameters, all influence TMD values. Likewise the relative age of the animals (adult is not the same as adult) influences TMD. One must assume different sampling and storage conditions and different types of progression into adulthood. Thus, the observation of different degrees of mineralisation is very interesting but I suggest not to link this observation to numerical values.

Parts of the results are mixed with discussion. Sometimes, a result chapter also needs a few references but this result chapter is full of references.

Based on different protocols, the staining characteristics of the tissue are analysed. This is very good and provides valuable additional data. The authors should inform the not only about the staining (positive of negative) abut also about the histochemical characters of the staining. L218: "fast green positive" means what? L234: "marked by Trichrome acid fuchsin" means what? And so on, see also L237, L289, L291<br /> Discussion

Please completely remove figure 7, please adjust and severely downsize the discussion related to figure 7. It is very interesting and valuable to compare three species from three different groups of elasmobranchs. Results of this comparison also validate an interesting discussion about possible phylogenetic aspects. This is, however, not the basis for claims about the skeletal tissue organisation of all extinct and extant members of the groups to which the three species belong. The discussion refers to "selected representatives" (L364), but how representative are the selected species? Can there be a extant species that represents the entire large group, all sharks, rays or chimeras? Are the three selected species basal representatives with a generalist life style?

Please completely remove the discussion about paedomorphosis in chimeras (already in the result section). This discussion is based on a wrong idea about the definition of paedomorphosis. Paedomorphosis can occur in members of the same group. Humans have paedormorphic characters within the primates, Ambystoma mexicanum is paedormorphic within the urodeals. Paedomorphosis does not extend to members of different vertebrate branches. That elasmobranchs have a developmental stage that resembles chimera vertebra mineralisation does not define chimera vertebra centra as paedomorphic. Teleost have a herocercal caudal fin anlage during development, that does not mean the heterocercal fins in sturgeons or elasmobranchs are paedomorphic characters.

L432-435: In times of Gadow & Abott (1895) science had completely wrong ideas bout the phylogenic position of chondrichthyans within the gnathostomes. It is curious that Gadow & Abott (1895) are being cited in support of the paedomorphosis claim.

The SCPP part of the discussion is unrelated to the data obtained by this study. Kawaki & WEISS (2003) describe a gene family (called SCPP) that control Ca-binding extracellular phosphoproteins in enamel, in bone and dentine, in saliva and in milk. It evolved by gene duplication and differentiation. They date it back to a first enamel matrix protein in conodonts (Reif 2006). Conodonts, a group of enigmatic invertebrates have mineralised structures but these structure are neither bone nor mineralised cartilage. Cat fish (6 % of all vertebrate species) on the other hand, have bone but do not have SCPP genes (Lui et al. 206). Other calcium binding proteins, such as osteocalcin, were initially believed to be required for mineralisation. It turned out that osteocalcin is rather a mineralisation inhibitor, at best it regulates the arrangement collagen fiber bundles. The osteocalcin -/- mouse has fully mineralised bone. As the function of the SCPP gene product for bone formation is unknown, there is no need to discuss SCPP genes. It would perhaps be better to finish the manuscript with summery that focuses on the subject and the methodology of this nice study.

Main points - Inclusivity, not all children have access to nature as part of their lives - Forest school can contribute to children's health as a space to be active. - Outdoor play can integrate cognitive, emotional and social behaviours (Kahn and Kellert 2002) - Constructivist approach, involved more experimentation and problem solving. Kahn (1999) children - Results of the analysis were, increase of self esteem and confidence, imprved scial skills, dev of lang and communication skills. Motor skills concentration. - Theme of social skills, l

其实我感觉这句话贯穿整个光照理论。颜色的浓淡深浅 + 人眼的视错觉 = 模拟的光照效果

一个及其简单但在本章中很重要的公式：lightColor * toyColor 计算物体的颜色。

这一段从物理的角度解释了现实中物体为何会呈现颜色。物体本没有颜色，是光照到了物体上吸收一部分和反射一部分才有了颜色。（=... =）地上本没有路，走的人多了才有路。

eLife assessment

This useful study reports that epididymal proteins are required for embryogenesis after fertilization. The data presented are generally convincing, but the study is incomplete because it does not investigate in detail how those proteins cause DNA fragmentation and compromised embryonic development. This work will be of interest to reproductive biologists and andrologists.

Reviewer #1 (Public Review):

Summary:

The main observation that the sperm from CRISP proteins 1 and 3 KO lines are post-fertilization less developmentally competent is convincing. However, the molecular characterization of the mechanism that leads to these defects and the temporal appearance of the defects requires additional studies.

Strengths:

The generation of these double mutant mice is valuable for the field. Moreover, the fact that the double mutant line of Crisp 1 and 3 is phenotypically different from the Crisp 1 and 4 line suggests different functions of these epididymis proteins. The methods used to demonstrate that developmental defects are largely due to post-fertilization defects are also a considerable strength. The initial characterization of these sperm has altered intracellular Ca2+ levels, and increased rates of DNA fragmentation are valuable.

Weaknesses:

The study is mechanistically incomplete because there is no direct demonstration that the absence of these proteins alters the epididymal environment and fluid, wherein during the passage through the epididymis the sperm become affected. Also, a direct demonstration of how the proteins in question cause or lead to DNA damage and increased Ca2+ requires further characterization.

Reviewer #2 (Public Review):

The authors showed that CRISP1 and CRISP3, secreted proteins in the epididymis, are required for early embryogenesis after fertilization through DNA integrity in cauda epididymal sperm. This paper is the first report showing that the epididymal proteins are required for embryogenesis after fertilization. However, some data in this paper (Table 1 and Figure 2A) are overlapped in a published paper (Curci et al., FASEB J, 34,15718-15733, 2020; PMID: 33037689). Furthermore, the authors did not address why the disruption of CRISP1/3 leads to these phenomena (the increased level of the intracellular Ca2+ level and impaired DNA integrity in sperm) with direct evidence. Therefore, if the authors can address the following comments to improve the paper's novelty and clarification, this paper may be worthwhile to readers.

Who would have thought even on water they be having time for reading or writing down their voyage.

Christopher Columbus is really admiring the other people and how well toned they look.

This word sounds like they are saying canneries.

Long name even back then, they would use middle names with their last names.

Who is the admiral? Who named him that and why?

It's amazing how many people fit in a canoe that the indigenous built from trunks. These people were very smart.

That's so fascinating knowing that these people made canoes too to get from destination to destination.

I get it that they are poor but why not grab something and make it into a dress to cover up.

Why are all the people uninformed like same color makeup.

eww can't believe they would be head they're enemies head and feed it to the poor doggies

I wonder how they're ships looked like back then

Why is he trying to buy people? He's not even wanting friendship from them.

Main points - Play episodes last longer on naturally structured playgrounds in comparison to traditional playgrounds. Children on trad playgrounds rarely play longer than 15 minutes but children on the nature-oriented play space might last up to 30minutes. Why? Link to biophilic nature of chilren. - Less affordances in the trad playground as equipment put there was t be child appropriate, monofunctionality of this, difficult to convert this equipment that is already appropriate, and they know what it's for. There is no sense of wonder. -Nature-oriented playgrounds put their focus on the experience of nature rather than appropriateness. - Children in the trad playgrounds tend to spend more time waiting for their turn on the equipment present. - Most complex forms of play happen in antural play areas, confirms the need to re-evaluate approaches to outdoor play.

Principle #8: The Lost Principle of CARE

Mark Passio breaks down the Hermetically sealed, Natural Law Generative Principle of Care. https://via.hypothes.is/https://www.youtube.com/watch?v=VvIdopW-rjw

Principle #8: The Lost Principle of CARE

Mark Passio breaks down the Hermetically sealed, Natural Law Generative Principle of Care. https://via.hypothes.is/https://www.youtube.com/watch?v=VvIdopW-rjw https://hypothes.is/a/bfj17BZuEe-3nO9SDzyJMw

Principle #8: The Lost Principle of CARE

Mark Passio breaks down the Hermetically sealed, Natural Law Generative Principle of Care. https://hypothes.is/a/bfj17BZuEe-3nO9SDzyJMw

"(AMPHIBIAN CHYTRID FUNGUS DISEASE) Chytridiomycosis is an infectious disease that affects amphibians worldwide. It is caused by the chytrid fungus (Batrachochytrium dendrobatidis), a fungus capable of causing sporadic deaths in some amphibian populations and 100 per cent mortality in others." (https://www.dcceew.gov.au/sites/default/files/documents/c-disease_1.pdf)

"Biotics describe living or once living components of a community; for example organisms, such as animals and plants. Biotic may refer to: Life, the condition of living organisms." (Wikipedia).

I need to keep track of my ideas. Fortunately I generate a lot of them, making up for late start.

This demo seems borken. iwwa is not able to pick up any object. Is it because some package is out-of-date?

I think the diversity and broad impact of "cancel culture" is thought-provoking, especially when it ranges from minor offenses to serious crimes. Criticizing and shaming someone without fully understanding the facts is unfair.

Allusion to Diomedes and Glaucus

Public shaming is harmful when the punishment is too harsh, based on wrong information. It can cause severe mental health issues and long-lasting damage to a person's reputation.

Main points - Free play is complex by nature (Hewes 2014) - Classifications of play - Dyment and O'Connell (2013) study recorded the dominant types of play - Research to show that children learn best in diverse environments that are functional enough to interact with their interests (Hirsh-Pasek et al 2003) - In this study, the results how that children spent more time in functional play outdoors, more time in constructive and symbolic play indoors. Architecture affects the type of play children engage in, affects their affordances - the amount of play was not too different indoors vs outdoors but the type of play was different - why is engaging in different types of play important? - All types of play are related to children's well-being, the observations were only conducted during the times available for free play. A variety of play affords children to gain essential experiences.

test

At my school it has been a struggle to find general education teachers who are reliable and willing to come to the IEP meeting. Even though I have made it very clear it is a legal obligation, many of them are hesitant to want to commit to coming to the meeting, especially if it is outside of contract time. Many times, I have had to end up filling out an excusal form due to the general education teacher not being able to come to the meeting. It has been frustrating and I am working with my LEA to come up with better solutions and approaches to the meaning of the general education teacher's role in the IEP process.

With my specific population of students, we celebrate the tiniest success and progress. I have had to spend a lot of time working to find the balance of writing goals to challenge the student in each subject and in keeping the goals realistic. I really value the parental input to help brainstorm small steps or strategies we can use to help scaffold the student's learning and progress.

I am constantly looking for more efficient ways to progress monitor my student's IEP goals. Right now in my class we work on the goals daily and I have a folder for each student with different sheets for each goal. We do up to 10 trials for each goal depending on what it is and will mark with three different symbols depending on if the student can do it independently, does not do, or if they need staff support.

Most of these procedural, substantive, and implementation issues concerning IEPs are, at least at my school, the responsibility of the Special Education file holder. Our current admin do not know enough about the IEP process to make a difference in any of these areas. We had a previous admin that was a former SpEd teacher, and he really supported us through at least the first two, not so much implementation. Do admins have the training to know their roles in the IEP process if they haven't taught Special Education? Curious as to how this works in other districts?

Schools and districts must adhere to these requirements to help ensure the implementation of technically sound and educationally meaningful IEPs and to provide FAPE.

Failure to assemble an appropriate IEP team:

地方

I am struggling with administrative push back right now. This next year we're going to have more severe students and need to make sure we have a continuum of placement and there literally isn't space in my building. I brought up a portable and my director was not happy about it. I don't know what she expects me to do...

DOI: 10.1016/j.celrep.2021.108887

Resource: (Proteintech Cat# 20770-1-AP, RRID:AB_10696319)

Curator: @Naa003

SciCrunch record: RRID:AB_10696319

What is this?

DOI: 10.1016/j.celrep.2021.108887

Resource: (Santa Cruz Biotechnology Cat# sc-515, RRID:AB_630975)

Curator: @Naa003

SciCrunch record: RRID:AB_630975

What is this?

Language 3: A personal aside that ties back to the title and subject of love that was prevalent in the first few sections of the narrative.

Style: This is a common sentence pattern used throughout the narrative. It consists of Subject-Verb, Subject-Verb.

The diction throughout is well chosen, and lacks any particularly large, distracting words. There are no words I feel a high school student would not know.

The tone remains neutral in the beginning, despite talking about sentimental moments in the author's life. It briefly dips into mournful territory with the paragraph under A Walk Down a Different History Lane, and changes to remorseful with the third paragraph of Last Call to Flight Number 2356 Leaving to the States. Finally, the tone returns neutral, but with a slight tinge of optimism when looking towards the future in the final paragraph.

Main point of the narrative and the moral the author has been building towards throughout the text.

Content: Part B The author admits her character flaws, and ultimately mends her shortcomings as mentioned on the following page. Pivotal moment in her life as she took advantage of the power she held to further warp the view of the Middle East which the Americans held. It was here she realized that fighting a false single story with another single story with aspects of the truth omitted continues to obfuscate the truth.

Content: Part A. To be referenced in annotation Content: Part B.

Details: describes the American embassy. Directed Reading: the American embassy is described through the actions of Jordan civilians passing by, rather than a simple description of the building. This in turns creates a sense of respect and fear the people had for the embassy, as well as implies a coming tension between the author and the Americans.

Language 2: use of 1st person pronouns to make it as though we are in the moment with her.

Context 2: Another goal of hers and another purpose identified as honoring those that were killed.

Organization: Contrasts the teacher with the idealized teacher from literacy narratives. Then, shows how the teacher was in fact a superhero in disguise despite her unassuming presentation.

Design: Uses imagery to first describe the teacher's role in society, then her physical appearance, next her demeanor, and finally her teachings that were influential on shaping the author.

Directed Reading: With the idealized teacher paradigm established, the contrast with her own teacher builds tension. The tension hooks the reader, and this tension is released when we learn that Miss Sandy was in fact a positive influence on the author despite the boring presentation.

Language: The "Usually" followed by a generalization is an acknowledgement of shared knowledge or experience.

Directed Reading: Sets up the paradigm of which the author will contrast her own teacher with.

Content: showing how the origin of one of her literacies comes from influences outside of what is traditionally thought of.

Details: The author writes extensively about her father throughout the narrative, even including nearly a whole paragraph about his influence on her life. It is clear that her father played a significant role in her life whether it was teaching basketball, his teachings about love, or his story about growing up in Palestine under Zionist occupation.

Absent from the narrative is a discussion of her mother that extends beyond the mention of her heritage and two quotes of love she attributes to her mother.

Author: The author, Natali Barakat, is the narrator of the story. She grew up in Jordan surrounded by Middle Eastern culture. The only non-Arabic item in her family home was a poster of her parents with the words "Love Ain't a Thing, Love Is a Verb", which became her personal philosophy.

Context: the purpose is to tell a story of how they became the writer they now are.

Audience: Produced as part of an university assignment in Fall 2018, and published in Spring 2019 as indicated by the header on even numbered pages. The intended audience is college educated people or those currently in college that are unfamiliar with the author's life or work.

Design: The large, script font for the title, along with the horizontal lines and author name underneath, gives me the impression that this is supposed to read like an article rather than a formal essay. There are headers used throughout to block the text and provide brief context of the paragraph contained. The large rectangles of interjected sentences on pages 3 and 4 feel like meaningful thoughts that popped into the author's mind while writing, but would have been difficult to work into the overall narrative.

I wonder how the Huitzilopochtli dressed back then versus the other people.

Who is Itzcohuatzin? Is he like a servant to Montezuma?

Who did Montezuma give necklaces too?

Is Cortes like another Christopher Columbus?

test

It seems this demo is broken. The iiwa's gripper is not following the planned trajectory. Maybe the connection to differetnialIK is not up-to-date?

Begs the question how do we work together and promote small web and each other?

Comment sections are an existing solution to leverage. We’re not doing it enough.

Lefebvre outlines some planning styles below: - Planning by writers and architects, for the human scale, yet trends towards a formalism or aestheticism that is muddied by nostalgia. - Planning by the administrative public sector, one whcih sees itself as scientific. - Planning by developers who do so for and by the interests of the market.

Coherence is the cure to ordering this chaotic, paradoxical reality. Now, what is coherence and how to establish it?

Three periods of industrialized urbanization.

Now, that is curious!

One of the most abominable and frudtrating realities of industrial economy.

Suburbia had always been paradoxical, eh?

Crucial difference between the early industrial economy and our present industrial and urban reality.

A curious definition of inhabiting to bring up here. An awaiting... while we conduct lives in preservation and use...

Lefebvre proposes here that the modern bourgeoise class has not destroyed the city as ouevres, but replaced it with and as a product.

What has changed since this book was written? How differently would we hold this notion?

Brilliant articulation of a city's function.

Though the causes may be similar, the impacts of urban core explosions are myriad different yet altogether impactful on the urban fabric.

Interesting articulation of how urban and industrial reality relates. Conflictually.

Those factors are connected and concentrated in cities. Many are built from one of those factors of emergent industries.

The paradox of the cities of antiquity contrasted with industrialized cities can be explained with this thesis.

Now, what does "refugees of use value" mean here? How has the industrial paradigm of exchange value subordinate the city and urban reality?

The pre-industrial city termed as "ouevres" yet considers the industrial-induced city as not reveals what Lefebvre thinks of how industrialism changed the city.

This book was certainly written a while ago.

Industrialism is the inducer of the "urban problematic".

The "induced" include problems with growth and planning, development of urban reality, and leisure's place in the culture and city.

This here seems to be Lefebvre's goal in the book. Not a critique, but a sort of political agitation for urbanism as ideology to enter public consciousness and achieve political importance.

Provocative opening statement. Acknowledges possible divisiveness among reader base. But why? Anticipating such offense implies the work here will interact with "systems" or values the readers find sensitive. In what sense are they sensitive, and how will the author "offend" productively?

What is "The System" here? What assumed system of formalism is Lefebvre attempting to open up in this book?

Track down source? Unfamiliar with quote. Not deeply familiar with Nietzsche...

Bold

What is a risk management standard?

Not only is growth hacking soulless, it’s not sustainable over the long term.

Starting to see a lot of these techniques in newsletters lately. Ugh.

music programs must be a big deal if presidents are commenting about their efficacy

Résumé de la vidéo [00:00:00][^1^][1] - [00:04:38][^2^][2]:

Cette vidéo présente Bruno Humbeeck expliquant le concept de co-éducation, qui consiste à éduquer ensemble parents et enseignants tout en respectant les identités et rôles de chacun. Il souligne l'importance de l'harmonisation autour du développement de l'enfant et de la création de communautés éducatives pour former des citoyens actifs.

Points forts: + [00:00:04][^3^][3] Définition de la co-éducation * Éduquer ensemble est complexe * Nécessite une construction et le respect des identités * Importance de ne pas interchanger les rôles + [00:01:55][^4^][4] La cité de l'éducation * Émergence naturelle de la cité de l'éducation * Contribution de chacun au développement de l'enfant * Importance des communautés éducatives + [00:03:01][^5^][5] Rôle des structures locales * Liaison essentielle entre l'école et la famille * Soutien aux familles en difficulté * Communication et réduction de la violence à l'école

Это можно приписать вообще к большей части из всего "левого" движа.

И сейчас меня закидают камнями, но этому способствуют и некоторые предпосылки, заложенные в хомо сапиенс. Мещанское нетерпение "здесь и сейчас", что бы можно было лично воспользоваться.

Да и многие "лозунги" на это давят. "Политический коммунизм" у них в стиле: "что бы классовое сознание проснулось нужны лишения". А классовое ли сознание "проснётся" у мещанина, или это просто удобный лозунг которым можно прикрывать свои "вульгарные" действия для удовлетворения "надо же что-то делать"?

Втаптывать в грязь, вешать ярлыки и т.п. думаю стоит хотя бы после того как читатель полностью и нейтрально введён в курс дела. А то так получается что логика "дела" строится на эмоциях (негативных в частности).

Проблема в том, что данным недочётом можно половину текста многих статей пометить. 😢 Эта заметка в единичном виде бессмысленна, толко если не размечены вся статья, и многие книги. Поэтому более продвунтуой системой будут не заметки (hypothes.is в частности), а полная манипуляция с векторизированным текстом, когда можно будет манипулировать текстом "по осям смыслов" (скрыть "навешивание ярлыков", поменять порядок повествования, убрать "уточнения", увидеть "цитирование в других статьях").

Формулировка само по себе бессмысленна, в отрыве от контекста, от смысла который хотел ею передать автор. Даже если прикрываться "общественными определениями", всё равно, они не точны (могут постоянно уточнятся) и не всегда кто-либо постояно может придерживаться общим определением.

Формула повестования "Не секрет что непонятно что непонятно кем провозглашается". Блеск манипулятивного повествования. 🥸

Если тема была сказана выше, то начиналось бы так "Как писалось выше ..." Если явно указывалось на кого-то, то так "Как некто писал ..." со ссылкой на цитату/ы.

А так как будто сами приписали и сами же обвинили.

Дело не в "хотели ли явно этого", а втом "как это в итоге смотрится, со стороны".

progress trap - illegal drug manufacture - nitazene - fentanyl - pharmacological research becomes a source for new illicit drug production

for - synthetic opiod - nitazene - history

from - youtube - VICE - The new fentanyl killing drug users in Europe - https://hyp.is/IVWJThYeEe-Szku3PU8_8g/docdrop.org/video/JqqfI-bIvnI/

for - new synthetic opiod - nitazene produced by Chinese labs

to - The Conversation - Nitazenes are a powerful class of street drugs emerging across the US - https://hyp.is/aeMEIBYeEe-VK49zALV-KA/theconversation.com/nitazenes-are-a-powerful-class-of-street-drugs-emerging-across-the-us-222244

for - question - how EU avoided synthetic opiod crisis until now?

question - how did EU avoid synthetic opiod crisis until now? - answer - authentic Afghan Heroin - but with the crackdown on poppy in Afghanistan, EU drug users are primed to start using synthetic opiods

for - wicked problems - synthentic opiods coming to EU faster due to successful Taliban war on poppy industry

summary - the new synthetic opiod "Nitazene" is being manufactured in China and replaces the banned fentanyl. It is 300x stronger than heroin. - Due to the Taliban's successful war on drugs that has stamped out 95% of the poppy production, EU drug addicts are turning to the far more deadly nitazine

from - youtube - BBC - Inside the Taliban's war on Drugs - https://hyp.is/hKPiKBYbEe-2ZCPwUTz0Lg/docdrop.org/video/W-gMRFEZOGY/

.

for - question - how will the Taliban's successful destruction of the poppy industry affect drug supplies in Europe?

to - youtube - Vice - The new fentanyl killing drug users in Europe - https://hyp.is/MDez0BYcEe-rq0sJ-I6FRg/docdrop.org/video/JqqfI-bIvnI/

for - complexity - wicked problem - polycrisis - afghanistan Taliban drug war

wicked problem - Taliban drug war - Afghanistan produced 80% of the world's opium for heroin and now it has lauched an aggressive and successful campaign to eradicate opium production - The farmers grow opium because it is a lucrative crop and they can feed their family - It is now illegal to grow opium and the Taliban enforce by monitoring and destroying poppy fields - This is one of the ironies that poor families grow poppy to try to survive, yet are disconnected from the chaos their product causes in other parts of the world

Why does a user interface font need personality?

An anonymous default encourages other apps to use the font also - to avoid any form of conflict.

for - adjacency - scientific revolution in action - paradigm shift - ignored by scientific community - critique of gene centricity

adjacency - between - scientific revolution - paradigm shift - critique of gene centricity - ignored by scientific community - adjacency relationship - Ray and Denis Noble's work advocating for an alternative to gene centricity demonstrates scientific revolution in realtime. - They are at the stage of being ignored by the peers for scientifically invalid reasons. That's a good indicator of the early stages of a paradigm shift. - As they point out, this refusal to openly debate has realworld consequences. - The entire medical community is oriented towards the wrong direction, looking for medical interventions in gene therapies which aren't going to happen because the science does not allow it.

for - follow up - book - The Music of Life - Biology Beyond Genes

to - book - The Music of Life - Biology Beyond Genes - https://hyp.is/OI8RVBYIEe-t-rObPCPKoQ/www.univ.ox.ac.uk/book/the-music-of-life-biology-beyond-genes/

for - health advice - aging well - Denis Noble

health advice - aging well - ll if you want to age well do something! - It can be - dancing - music - swimming - whatever but do something - That's the first bit of advice to those who want to make sure that they stay on top

for - follow up - 2001 human genome Nature paper - proteins synthesized by higher level processes, not just genes - 2001 Nature paper on human genome project

to - 2001 human genome project Nature paper - https://hyp.is/KMjUJBYFEe-U9JdKN9-cVw/www.nature.com/articles/35057062

for - critique - of Watson & Cricks DNA - agency of organisms

critique - of Watson & Cricks DNA - agency of organisms - Watson & Cricks advocated the now disproven idea that causality is only one direction - from genes to - proteins to - functionality of living organisms - when in fact, it goes the other way, giving the high level living organism agency

for - book - Understanding living systems - challenging selfishness - critique - of Richard Dawkins' Selfish Gene

• Ray Noble points out a contradiction in Richard Dawkin's use of the word selfish in his "Selfish gene".
  • Unless there is purposefulness, choice and agency, there cannot be any concept of selfishness

for - paradigms - science - gene centrism - critique - reductionism - behaviorists

paradigms - science - gene centrism - critique - reductionism - behaviorists - One of the problems of the behaviorists back in the 1960s and so on was that - to some extent they unrooted organisms from their environment and - put them into boxes and tested how they behaved under these extraordinary artificial circumstances - You you cannot understand intelligence by doing that because - intelligence is how we respond to the niche that we're involved in - People are increasingly aware of just how extraordinarily intelligent in the moment organisms are the decision making process even of the tiniest organisms

comment - see Michael Levin and problem solving spaces of organisms at different scales

for - key insight - reproduction is for adaptability, not to reproduce the gene pool

key insight - reproduction is for adaptability, not to reproduce the gene pool - for example, trees reproduce so they can move themselves - They are rooted so they cannot get up and walk - so they produce seeds that are transported by over living organisms and by the wind

for - question - impact of climate change on male and female population distribution of the biosphere

question - impact of climate change on male and female population distribution of the biosphere - How will climate change affect the proportion of males and females of the many species that are and will be impacted by dramatic temperature changes?

for - key insight - evolution - not producing the same, but different, more adaptive

key insight - evolution - not producing the same, but different, more adaptive - The goal of evolution is not to replicate the same individual, but to create a different one that is BETTER ADAPTED to its environment - and towards this end, physiology is evolution, evolution is physiology (via epigenetics)

for - individual / collective gestalt - gene centrism - paradigm shift - adjacency - mistake of 20th century biology - reductionism - separating organism from environment - individual / collective gestalt, individual / environment gestalt - quote - mistake of 20th century biology - Ray Noble - key insight - mistake of 20th century biology- Ray Noble

quote - mistake of 20th century biology - Ray Noble - (see below)

• I think one of the other mistakes that have been made in biology of the 20th century
  • was to treat organisms as if they existed within an environment that was sort of like some nebulous box as it were
  • and you could study the organism by taking it out
  • and you study it in isolation
• It's the beginning of reductionism in a sense because
  • you taken it away from the environment but the organism has an intimate relationship with the environment
• It's feeding both
  • to the environment and
  • from the environment
• What is that environment?
  • That environment in large part is
    • other organisms of the same species but
    • other organisms of different species
• and it's in a continuous bubble of change
• It's like a cauldron of change
• So the big question for life is
  • how do you maintain yourself in this cauldron of change?
• You cannot do it by standing still
• You have to respond to it
  • so it's not surprising therefore that you find that you know organisms have mechanisms for responding to those changes

adjacency - mistake of 20th century biology - between - reductionism - separating organism from environment - individual / collective gestalt, - individual / environment gestalt - adjacency relationship - The mistake that 20th century biology has made is in - ascribing too much power to the gene, and - minimizing the role of epigenetics - Focusing the majority of attention and resources on the genes of the organism, and - defocusing attention on the organisms (epigenetic) interactions with the environment, including both - biotic elements and - abiotic elements - It's not the case that the genes are the major determinant factor and the epigenetics play a minor role - It IS the case that epigenetics play an equally important role in transmitting and assimilating features into the genome - The individual organism is intertwingled with its environment and with other living organisms - The individual / collective gestalt and the individual / environment gestalt is the appropriate unit of study

for - paradigm shift - evolutionary biology - epigenetic's critical role in inheritance - experimental proof - C. Elegan - Oded Rechavi

for - follow up - Oded Rechavi - Israeli neurobiologist

to - Oded Rechavi - Israeli neurobiologist - https://hyp.is/qAmEVhXqEe-1e1OUyXnC2A/english.tau.ac.il/profile/odedrech_66

for - explanation - lay - natural selection happens by epigenetic change first

explanation - lay - natural selection happens by epigenetic change first - The change in narrative has enormous ramifications. - It means that you can change the course of history for your offspring based on: - your exercise - your diet - your drinking habits - and many other behavioral and lifestyle choices and environmental explosure you exist in

for - key insight - natural selection happens by epigenetic change followed by genetic change

key insight - natural selection happens by epigenetic change followed by genetic change - It's an advantage for epigenetic changes to be temporary because - if the environment is only a temporary change you can forget about it - if the environment is long lasting it can get assimilation in the genome and you've got speciation - That's the extraordinary thing - natural selection is not the origin of speciation, - it's epigenetics - followed by the genetic changes - The epigenetic leads - therefore, the environment leads

for - progress trap - genetic engineering - Denis Noble

for - explanation - evolutionary biology - neo-darwinian mistake - view of epigenetic inheritance

explanation - evolutionary biology - neo-darwinian mistake - view of epigenetic inheritance - Neo-darwinians believe that epigenetic inheritance is only short lived. - However, the Noble brothers contend that if the changes in the environment last for many generations, - the epigenetic change can exceed a threshold and become permanently assimilated into the genome - Such a threshold is plausible because without it, a permanent change encoded into the genome would be maladaptive if the environmental change reverted back to the previous state

for - adjacency - magic wand -;gene therapy - personalized medicine

3.2

2.2

carbon: 2.6

Some values are not correct.

Which column? None seems to be right.

Really?

for - critique of - Gene Centricity - Denis Noble

from - youtube -Evolution 2 Podcast Interview - Denis Noble - Book - Understanding Living Systems - https://hyp.is/-EuWvBYHEe-t9xtn9h1dhA/docdrop.org/video/oHZI1zZ_BhY/

for - recombination of proteins in higher level proteins - from - youtube - Evolution 2 podcast interview - book - Understanding Living Systems - Denis Noble - Ray Noble

from - youtube - Evolution 2 podcast interview - book - Understanding Living Systems - Denis Noble - Ray Noble - https://hyp.is/OttWABYFEe--gLNFyeNyTw/docdrop.org/video/oHZI1zZ_BhY/

It's crucial to explore alternative energy sources. New energy vehicles serve as a prime example for tackling the issue of carbon dioxide emissions.

Reducing the population is undeniably one of the most effective methods to lower carbon dioxide emissions. The global climate warming, which is a result of human activities, wouldn't have led to such a catastrophe without human intervention.

I was unaware that appliances consume more energy when they are switched off than when they are on. I'll be mindful of this in the future.

As trees are important plants that absorb carbon dioxide, we should cut down less and plant more trees.

Increasing the amount of greenery can help decrease the amount of carbon dioxide produced. Consuming more plant-based food can lead to more land being used for planting, which in turn reduces the impact of global warming.

With the improvement in today's living standards, there is a tendency for people to waste more resources. It is crucial for us to be mindful of resource wastage and strive to use them more efficiently.

Going shopping in a greener way is also one of the solutions that can reduce CO2 emissions. Buying used cars can reduce the production of new cars, and buying in bulk can also reduce the number of packaging bags needed.

It's important to remember that aircraft contribute significantly to global warming due to their proximity to the atmosphere, which means the carbon dioxide they release has a greater impact. What if we reduced air travel and opted for train travel instead? This shift could lead to a substantial decrease in carbon dioxide emissions.

Improving infrastructure construction can effectively help reduce carbon dioxide emissions by using high-quality building materials that provide better insulation. However, the mining of minerals and the manufacturing of construction materials can also cause pollution, so it's essential to develop a more efficient and environmentally friendly construction process.

Since it's impossible for humans to completely eliminate the use of resources like oil and carbon, carbon dioxide emissions are inevitable. Our best course of action is to explore and utilize alternative renewable energy sources such as wind, water, and tidal energy to substitute for oil and carbon resources.

I believe that cars play a crucial role in causing global warming. Every day, hundreds of millions of people rely on cars, leading to an immense release of carbon dioxide. To combat this issue, many car manufacturers are advocating for the use of battery-powered vehicles with the aim of mitigating the impact of climate change. This highlights the urgency of addressing the potential crisis of global warming.

The rising temperatures of the climate will result in abnormal seasonal changes in certain regions and contribute to an increase in natural disasters.

Scientists anticipate that annual temperatures will increase by at least 1.5 to 5 degrees Fahrenheit by the year 2100.

Carbon dioxide traps more heat than the atmosphere can release, leading to an increase in global temperatures.

The Earth's atmosphere shields life on our planet by absorbing heat from the sun and reflecting the majority of ultraviolet rays.

An obvious and simple explanation of climate warming

看着这些书的名字都听映射现实的，这意思是是很多人都「没有」软技能，「没有」意志力，「没有」心流，「没有」好睡眠，也「没有好习惯」。。。

打工人的书单就需要从工作中来挖掘了

这跟做完笔记之后就懒得看了的现象是类似的，写完之后就很难找到它，因此做笔记是应该要有策略，当然搜索联想功能也很重要

这就是不同的阅读策略，有些人喜欢列书单，一本一本的读过去，有些人就会随性一点。

很难说哪种会更好，但是为了达成某种目的去读，跟按照自己想法来读，可能的确需要不同的选书策略

甚至可以是小黄书

因为放开了题材的限制，作者反而可以发挥得更加自如。

有时候人们说戴着镣铐跳舞还能跳得好的，才体现真正的技术。但是我想如果没那么多镣铐，是否能够创造出更多的璀璨作品呢

是否有明确的现实压力可以当作读哪些书的一种标准。

例如工作中需要某种技能，那就明确需要通过任何方式来获取这项技能，甚至不能局限于书籍这种形式。当然可以用视频，网络文章来帮助学习。

也就是说这些是取决于看书是为了看了爽，还是为了具体的一个目标。毕竟带着填充闲暇时间的目的来看书，跟要完成某个工作任务，升职加薪来看书，可是有很大不同。

的确很多人都会纠结于采用哪种媒介，甚至电子书还要区分格式，版本，纸书还要细究书籍版次。。

总的来说完全可以采用舒服，方便的原则来选择介质。

例如我就是喜欢电子书的便于获取，方便的搜索存档，还不占地方。kindle，iPad，MacBook Pro我都有，所以重点在于选好书，抽出时间来读，以及读得爽

过往经验的综合造就了现在的人，而书籍是一种具备无限魅力的丰富体验的方式

这也是我看到第一版书单时的想法：太多了。

我觉得人的时间是有限的，工作中的写代码只是一部分。

这可能是不同阶段会有不同的想法。

for - Oded Rechavi - neurobiology - gene centrism - critique - from - youtube podcast interview - book - Understanding Living Systems - Ray Noble - Denis Noble

summary - Rechavi performed experiments with C Elegan and demonstrated that it possesses a type of neuron that - produces RNA that in response to elevated temperature change is transmitted to reproductive cells so that the offsprings encode it in the genome, and it is better adapted to deal with elevated temperatures

question - How many species do this? Is it generally found throughout nature?

from - outube podcast interview - book - Understanding Living Systems - Ray Noble - Denis Noble - https://hyp.is/OUlGVBXrEe-iaBeZhH_4DQ/docdrop.org/video/oHZI1zZ_BhY/

• 时间是有限的，要找好书。
• 好书要反复读
• 好书能够穿越时间的限制，这也意味着其承载了能够穿越时间的内容

Moverse-con estas voces nos permite sentir que las relaciones afectivas que nos (con)mueves son inseparables de nuestros cuerpos-mentes. De esta manera, mi práctica investigación apunta a la (re)valoración del conocimiento corporal.

Al sumergirnos en estas voces, podemos experimentar empatía, compasión, dolor o alegría a medida que nos conectamos con las emociones y los relatos de los demás, y estas experiencias resonarán dentro de nosotros de manera tangible y visceral.

En este sentido, la práctica de investigación desafía las jerarquías tradicionales de conocimiento y presenta una perspectiva más holística e inclusiva que reconoce la interconexión entre el cuerpo, la mente y las emociones en la producción y comprensión del conocimiento.

La emoción es una sensación, experimentada en el cuerpo, a la cual se le da un nombre para entenderla en el lenguaje (discurso).

Las plataformas digitales ofrecen un espacio de expresión de emociones que son compartidas y entendidas de maneras nuevas:

Primero, las narrativas digitales tienen la capacidad de transmitir emociones a través de una variedad de medios, como texto, imágenes, videos y sonidos. Estos elementos pueden combinarse para crear experiencias inmersivas que evocan emociones intensas en el espectador o lector. Por ejemplo, un video que muestra testimonios de personas que han pasado por experiencias difíciles puede provocar empatía y compasión en el espectador, mientras que una serie de imágenes evocadoras puede despertar nostalgia o melancolía.

En el ámbito de la investigación y el análisis de datos, las narrativas digitales también pueden utilizarse para explorar y comprender las emociones de las personas en un contexto más amplio. Mediante el análisis de grandes cantidades de datos, como publicaciones en redes sociales o comentarios en blogs, los investigadores pueden identificar patrones y tendencias en las emociones de las personas en respuesta a eventos o temas específicos.