170 Matching Annotations
  1. Apr 2024
    1. Lean mass increased sig-nificantly in the exercise group compared with baseline (P # .01)and the usual care group (P , .001). At follow-up, all body com-position variables remained significantly improved in the exercisegroup compared with baseline (P , .001

      interesting how we are looking at body composition, cool if looked at cardiorespiratory fitness

    2. After 5 minutes of quiet sitting, blood pressurewas measured by using the arm contralateral to the affected breastwith an automated sphygmomanometer

      interesting to measure blood pressure in one sitting? Usually will be elevated in this setting, white coat syndrome

    3. Exercise improves individual components ofmetabolic syndrome in survivors of breast cancer7-9;however, consensus is lacking that it improvesmetabolic syndrome as a collective entity, partic-ularly in high-risk survivors of breast cancer—racial and/or ethnic minorities with obesity

      interesting, obesity often occurs here because of lack to proper food/exercise

    4. sarcopenic obesity

      characterized by the combination of obesity, defined by high body fat percentage, AND sarcopenia, defined as low skeletal muscle mass accompanied by low muscle function

  2. Feb 2024
    1. Fig. 3.

      ogether, these results suggest that inhibition of OGT promotes PD-L1 traf- ficking from early endosomes to late endosomes and lysosomes, consistent with the accelerated degradation of PD-L1

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    1. Usewar metaphors with caution; they are an ethical minefield

      war metaphors also seem as though they can narrow the treatment options for patient, explore alternative medicine etc.

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    1. we havenow demonstrated for the first time that patients with PTSD ex-hibit greater vascular a1AR sensitivity, as evidenced by a lowerED50 for the selective a1AR agonist PE.

      lower Ed means increased sensitivity

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  3. Jan 2024
    1. 11

      at pH 0 will have fully protonated form, as increase pH deprotonate one group, lower concentration of fully protonated form, while increasing concentration where carboxyl grpup deprotanted, where cross at blue and green pKa amino group

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  4. Dec 2023
    1. Wheninvestigating the transition between the twoarchitectures, we noted that mosquitoes, whichdisplay type-I features

      when have full set of condensin II subunits they will have territory organization,

    2. ig. 1

      chromosome territories --> intrachromosomal features telomere-to-centromere axis --> intrachromosomal and inter telomere clustering --> intra and inter centromere clustering --> intra and inter

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    1. Early studies focused on histonepost-translational modifications(Barski et al. and Mikkelsen et al.) andtranscription factors (Johnson et al.and Robertson et al.

      possible resources to look into to expand what is said in text, look for how they did it before, how they changed, and how that advanced the field

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    1. Our method is currently limited by the inability to identify candi-dates that contain introns but can be expanded to include modelsof introns in fungi.

      limitation

    2. test the ability to identify novel phero-mones, we verified that deletion of all copies of the candidate far-nesylated pheromone of Yarrowia lipolytica (whose last commonancestor with S. cerevisiae existed more than 300 million yearsago) prevented mating of the a cells of this species.

      cool, are they actually performing a hypothesis driven experiment after the computational to see if they truly did what they were searching for?

    3. Since then, pheromones have beenbiochemically isolated and characterized in laboratory yeasts,filamentous fungi, and crop pathogens by isolation from extra-cellular medium, 2,9,17,18 but this approach depends on discov-ering the environmental conditions that stimulate mating and ob-taining sufficient material to determine the pheromone’s peptidesequence

      limitation

    4. Finding thepheromones of economically important yeast will help to under-stand and control their mating as well as shed light on the evolu-tion of these molecules and the receptors that recognize them

      importnace of the research

    5. we identified strong candidate pheromone genes in241 genomes, covering 13 clades that are each separated from each other by at least 100 million years,the time required for evolution to remove detectable sequence homology among small pheromone genes.For one small clade, the Yarrowia, we demonstrated that our algorithm found the a-factor genes: deletingall four related genes in the a-mating type of Yarrowia lipolytica prevents mating

      conclusions

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    1. ) Project is to enable the scientific and medical communities tointerpret the human genome sequence and apply it to understand human biology and improve health. T

      goal

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  5. Nov 2023
    1. Together, these data indicateda differential reliance on ASCT2 activity across breast cancer celllines, whereby only basal-like cells required ASCT2-mediatedglutamine uptake for cell growth.

      figure 1 conclusion

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    1. Myc directly and selectively activates MCT1 tran-scription and that elevated MCT1 levels are a hallmark ofhuman malignancies with MYC or MYCN involvement. Notably,we show that blocking MCT1 function rapidly disables glycol-ysis, leading to reductions in ATP and glutathione (GSH) levels,and that cotreatment with metformin, which forces the gly-colytic phenotype, augments the in vivo efficacy of MCT1inhibitors against MYC-expressing malignances.

      conclusions

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    1. All these data indicate that WZB117, a novel Glut1inhibitor, is effective both in vitro and in vivo in inhibitingcancer cell growth and can serve as a prototypicalcompound for the further development of Glut1 andglucose transport inhibitors as a new group of anticancertherapeutics.

      conclusion

    2. other cellgrowth, survival, and cell death processes were examinedin WZB117-treated cancer cells to identify molecular par-ticipants and consequences of the treatment.

      figure 5 purpose

    3. fter identifying and characterizing some of the bio-logic and biochemical changes in cancer cells related toglucose transport and glucose metabolism

      figure 4 purpose

    4. The possibility of theinvolvement of other mechanisms such as AMP-activatedprotein kinase (AMPK)/mTOR signaling–mediated arrestof protein synthesis cannot be ruled out

      gaps in study

    5. Anaerobe Gas Generating Pouch System with indicator(BD GasPak EZ). The pouch formed an oxygen-free envi-ronment in which the compound-treated cells were incu-bated for 24 hours.

      depriving cells of oxygen

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  6. Oct 2023

    Annotators

    1. (A)

      Consequently, we are able to identify sex-biased gene expres- sion that does not derive from sex differences in cell type abundances. We next modeled sex bias effects across tissues. We discovered a total of 13,294 differentially expressed genes [sex-biased genes; local false sign rate (LFSR) ≤ 0.05], with 473 to 4558 genes discovered per tissue, rep- resenting 1.3% to 12.9% of all tested genes, respectively

    1. In Rett's syndrome, for instance, females that carry a mutated copy of the MECP2 gene on the maternal X are able to survive (although with variable symptoms), because the paternal X has a normal copy that remains active in some cells

      because the X with the mutated is inactive?

  7. watermark.silverchair.com watermark.silverchair.com
    1. tress response correlates with changes in alternative splicingof Jumonji-family histone modifiers, suggesting a relationshipbetween cellular stress and sex-specific gene expressionchanges

      interesting

    2. hanges in methylation at Dmrt1caused by temperature exposure were heritable and capableof over-riding chromosomal sex in the next generation

      causative role of methylation

    3. threshold is reached sufficient to maintain andstabilize one pathway and repress the alternative pathway.

      alternative explanation to metaphors we have seen

    4. sex determination is a synthesis of manymolecular events that drives a community of cells towards a coordinatedtissue fate.

      like this definition of sex determination

    Annotators

    1. As shown here, the maintenance of female gonadal sexrequires continuous expression of FOXL2 to suppress maledevelopment

      usually female is described as the default, now seeing that male is described as the default

    1. Sex determination can be viewed as a battle for primacy in thefetal gonad between a male regulatory gene network in whichSryactivatesSox9 and a female network involving WNT/b-catenin sig-nalling

      opposes 20th century assumptions

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    1. Giventhe importance of R-spondin1 and Wnt4acting via β-catenin in establishing theembryonic ovary, it would be of inter-est to conditionally delete this path-way in adult ovaries to see whether thegonads also show ovary to testis trans-differentiation. In other words, is thiseffect solely mediated by Foxl2, or areother factors of equal importance alsoinvolved?

      possible research question????

    Annotators

    1. He obtained DNAsamples from unusual clinical cases in whichindividuals with two X chromosomes hadbeen designated as males (XX males) andones with an XY chromosomal constitutionhad been designated as females (XY fe-males)

      ?

    2. can the nucleus of a fully differen-tiated cell, if placed in an undivided egg cell,direct the development of a complete andwell-formed new organism, or as they say inthe trade, do nuclei from differentiated cellsremain totipotent?

      research question

    3. We are vertebrates because our motherswere vertebrates and produced eggs of thevertebrate pattern; but the color of ourskin and hair and eyes, our sex, statureand mental peculiarities were determinedby the sperm as well as by the egg fromwhich we came

      interesting, I feel like this is finally putting more emphasis on the female

    4. The nucleusmay contain genes, but if all cells contain thesame set of genes, how indeed could differ-ent cell types arise during embryonic devel-opment?

      answer is a highly complex and differentiated egg cytoplasm

    5. specific base sequences in aDNA molecule, which is in higher organismsorganized into complex arrangements of pro-tein and nucleic acid called chromosomes.

      definition of gene

    6. The basic assumption of scholars in this areais that scientific research forms an integralpart of our cultural, social, and political sys-tems.

      assumptions of the field "social studies of science"

    7. I will discuss the devel-opment of two central concepts in develop-mental biology - differential gene expressionand the continuity of the germ line; I arguethat social and political factors combinedwith particular experimental results to shapethe ideas which have come now, in the lasthalf of the 1980sto be accepted into the bio-logical canon.

      connection between science and society, how science influences society and how society influences science

    8. Now finally the father'sheirs, the "hip, young gunslingers of moderndevelopmental biology" have returned to res-cue the stunted offspring and help it, withthe heavenly blessing of the Father, to growto manhood.

      interesting metaphor

    Annotators

    1. (A)

      Hypothesis: This figure is highlighting the outcomes that resulted from different combinations of DMRt1 and E2 in chickens. The hypothesis of the paper was that DMRT1 plays a key role in sex determination and essential for testis development and the production of estrogen is important in sex determination and is linked to DMRT1 expression. Methods: DMRT1-Mutant birds were generated using a surrogate host. These DMRT1 knockout chickens were generated using CRISPR-Cas9 to target the DMRT1 gene in cultured chicken primordial germ cells. ZD+ZD- and ZD+ZD+ are male chickens and ZD+W and ZD-W are female chickens , with the - indicating DMRT1 knockout. These genotypes were the result of crossing a wild type hen with a male chicken heterozygous for functional DMRT1. The effects of blocking estrogen synthesis (E2) on gonadal development where assessed by injecting eggs with an inhibitor of aromatase activity (fadrozole), indicated by FAD. The then looked at the presence of medullary sex cords and cortex development. Results: For the DMRT1 column, the ++ indicates 2 copies the + indicates 1 copy and the - indicates 0 copies. For the E2 and cortex column the + indicated present and the - indicates absent. The medulla column is looking at the development of the medullary sex cords into ovary or testis. Conclusions: This figure helps support the finding of the whole paper, which are the DMRT1 dosage is the driving factor of sex determination, and that gonadal hormones have little to no effect on external secondary sexual characteristics. The loss of a single copy of DMRT1 in male birds results in ovarian rather than testicle development and give proof of a DMRT1-dependent dosage-based mechanism of sex determination in birds. Connection to Arnold 2012: The theory that is discussed as incorrect in the Arnold paper is also proven wrong in this paper. The theory of sex determination is that 'the sexual phenotype of individuals is dependent on the gonad: male and female somatic cells and tissues are initially sexually indifferent and sexual dimorphism is imposed by the type of gonad that develops.' This places the differentiation of the gonads at the center of sexual determination. However; in this paper explaining avian sex determination, we see that gonads and their hormones have little or no effect on external secondary sexual characteristics.

    2. Our analysis shows that DMRT1 is the key sex determinationswitch in birds and that it is essential for testis development, butthat production of estrogen is also a key factor in primary sexdetermination in chickens, and that this production is linked toDMRT1 expression

      results

    1. applied CRISPR/Cas9 to isolatedchicken germ cells that were injected intosurrogate embryos. Those embryos hadbeen genetically modified such that theylacked their own germ cells, and this greatlyenhanced the rate of germline transmission,in itself a highlight of the pape

      methods

    2. romosomal sex directs theembryonic gonads to form ovaries ortestes, which then secrete hormones tofeminise or masculinise the rest of thebody.

      long held belief in animal biology

    Annotators

  8. Sep 2023
    1. The mole

      Central question: Why and how to ovotestes develop in female moles? not very hypothesis driven, but had some preconceived ideas based on other work in mammals, genes already known to have roles in sex differentiation

      focus on regulatory regions, ovary part vs. testes, some relationship there worth considering, comparison also with testes and testes part, ovary part and testes part

      identifying genes of interest based on primarily chromosomal rearrangements

      CYP17A1 and FGF9 enhancer fusion androgen production grip strength gonad masculinization meiosis TAD changes

    2. (A) Strategy used to identify genes withaltered 3D chromatin organization as aresult of species-specific rearrangements.

      Hypothesis: Scientists predicted that rearrangements in 3D chromatin organization can alter regulatory domains and affect gene expression. Methods: In genome comparisons, synteny breaks can identify rearrangements. Mole genomes were compared with full-chromosome assemblies from human, mouse, and shrew. These were used for comparison as they are the closest taxonomical outgroup with normal ovarian development. These comparisons were performed to identify rearrangements specific to moles. Moreover, Hi-C domain predictions were used to identify genes located in topologically associating domains (TAD) that were affected by a synteny break. They then filtered the located genes according to Gene Ontology (GO terms). Results: They found 286 synteny breaks, and 2,595 genes with altered 3D chromatin organization. Conclusion: After filtering candidates based on GO terms, the list was restricted to 39 genes that were possibly effected. Concept from Ainsworth 2015: A made a connection between female mole's genitalia and the DSD called, congenital adrenal hyperplasia, which causes the body to produce excessive amounts of male sex hormones. If you have this condition and are XX, you are born with an enlarged clitoris and fused labia that resemble a scrotum. In the study they compared the mole genome with humans, so I find this interesting. Concept from Ridnik 2021: In this paper, TAD's are described in a bit more detail, as well as the Hi-C domain. Hi-C is a genome-wide chromosome conformation capture technique. Investigation of Hi-C interaction maps reveled that genome is further organized into megabase-scale units. These are called TADs. TADs there are regulatory elements (enhancers) and they are predicted to interact with their promoters by forming a loop to control gene expression. In the Real paper, they use both Hi-C and TAD predictions for their 3D chromatin organization.

    3. caf-folded using Hi-C data

      what order are the contigs within the chromosome, call scaffolds when put them together, get organizational structure for it.

      more transcripts than genes because of alternative splicing

    4. B) Strategy used to assign regulatoryelements to candidate genes. Number ofactive enhancers is correlated to geneexpression levels for each tissue

      question: Where are footprints of altered gene regulation that might be the consequence of mole specific rearrangements? methods: used the functional datasets that they used in figure 2A. They also used the TAD predictions and rearranged them to delimit a possible region of new interactions for each candidate gene (identified in 2A), and figure out the number of active regulatory elements. results: 17 genes were predicted to gain de novo interaction with regions containing active enhancers. Also there is a correlation between the number of active enhancers and the gene expression levels for each tissue. conclusion: This data helped the scientists draw their conclusion that there is a positive correlation between active enhancers and gene expression amongst 10 genes. For further experiment, they selected the androgen-related gene CYP17A1 and the pro-testicular growth factor gene FGF9. These were selected because they displayed higher expression. Concept from Ainsworth 2015: There have been 25 genes identified that are involved in differences or disorders of sex development. Also, in the past few years, next-generation DNA sequencing has uncovered a wide range of variations in these genes that may cause mild effects of sex differences on individuals but not cause DSDs. This helps point to how sex is a spectrum, something that is seen and studied in moles. Concept from Ridnik 2021: Past studies also looked at rearranged TAD. Looking at gene regulation of the X-inactivation centre (Xic) locus, the importance of TAD partitioning and structures in regulating proper gene expression during development was demonstrated.

    5. A positive correla-tion between active enhancers and gene ex-pression was found for 10 genes. Among thetop-ranked candidates, we selected those dis-playing higher expression for subsequent func-tional validation: the androgen-related geneCYP17A1 and the pro-testicular growth fac-tor gene FGF9

      greater conclusion from all of figure 2

    6. AD predictions,to delimit a potential region of new interac-tions for each candidate gene and determinethe number of active regulatory elements con-tained within

      question for 2B

    7. Using our functional datasets, we thensearched for footprints of altered gene regu-lation that might be the consequence of mole-specific rearrangements

      functional datasets described above, methods for how gathered data for figure 2B

    8. To identify mole-specific rearrangements, we compared themole genomes (T. occidentalis and C. cristata)with full-chromosome assemblies from human,mouse, and shrew, as the closest taxonomicaloutgroup with normal ovarian development

      purpose of figure 2A

    9. no relevant candidates were found,we searched for changes in 3D chromatinorganization, on the basis of the hypothesisthat rearrangements can alter regulatory do-mains and affect gene expression

      hypothesis for why looking into 3D chromatin organization

    10. Our anal-ysis confirms moles as a distinct family in theorder Eulipotyphla, with shrews and hedge-hogs being the most closely related species(15) (supplementary text)

      hypothesis?

    11. nexception to this paradigm occurs in moles(family Talpidae), in which XX-genotypic fe-males have an intersex phenotype in at leasteight species

      unlike other mammals in which sex is determined by genetics

    1. non-cod-ing, cis-acting gene regulatory elements and discuss howthey may control transcriptional programmes that underpinsex determination in the context of the 3-dimensional fold-ing of chromatin.

      connecting to how real did same thing

    Annotators

    1. Such surgery is contro-versial because it is usually performed on babies, who are too youngto consent, and risks assigning a sex at odds with the child’s ultimategender identity

      part of me thinks, that if you are going to say this is controversial, where is the line in deciding a babies gender based on sex if the baby is too young to decide for themselves

    2. A study in 1996 recorded womenwith fetal cells in their blood as many as 27 yearsafter giving birth13; another found that maternalcells remain in children up to adulthood14. Thistype of work has further blurred the sex divide,because it means that men often carry cells fromtheir mothers, and women who have been preg-nant with a male fetus can carry a smattering ofits discarded cells.

      would this change an individual after being pregnant?

    3. A DSD called congenital adrenal hyperplasia(CAH), for example, causes the body to produceexcessive amounts of male sex hormones; XXindividuals with this condition are born withambiguous genitalia (an enlarged clitoris andfused labia that resemble a scrotum).

      similar to moles

    4. “I think there’s much greater diversity within male or female,and there is certainly an area of overlap where some people can’t easilydefine themselves within the binary structure,”

      kinda weird to give cells male or female

    1. endothelial cells, fibroblasts, andblood-derived cells such as macrophages, lymphocytes,plasma cells, monocytes, and mast cells.

      other interstitial cell types

    2. Moreover, it is unclearwhether a single factor induces the migration of one ormore precursor cell types that subsequently differentiateinto the different testicular cell populations by direct

      possible research proposal

    3. The initial phase is characterized by theemergence of the so-called indifferent, bipotential gonad,or genital ridge, which is identical in males and females.

      first stage is present in females and males

    4. owever, varia-tions in mammalian sexual differentiation are known toexist, and this needs to be kept in mind when extrapolat-ing from one species to another.

      much research on sex determination done with mice

    Annotators

    1. describessubsequent steps in developmental pathways, dur-ing which the male and female phenotypes are pro-gressively built up, according to the initial decision

      sex differentiation

    2. meant to designate thedevelopmental step at which an individual fate isirremediably directed towards either the male orthe female condition

      sex determination

    3. a single eggis more costly to produce than a single sperm cell,female fecundity is limited mainly by her ability toproduce eggs, while male reproductive success islimited by the number of females he can insemin-ate.

      interesting to think about after reading the sperm and the egg

    4. haplodiploidy

      sex-determination system in which mlaes develop from unfertilized eggs and are haploid, and females develop from fertilized eggs and are diploid

    5. separate sexes, biparentalism, parental controlover sex ratios, Mendelian segregation of sex-ratioalleles, random mating in an infinite population,and no environmentally induced sex differencesin fitness

      assumptions for Fisherian model on sex ratios

    6. Such damaging changes cannot be repairedin unicellular haploid organisms; if non-lethal, theywill be transmitted to daughter cells and progres-sively accumulate through generations.

      caused by reactive oxygen species in environmental stress

    7. Given its early origin in eukaryotes and near-ly universal distribution, it might seem that sexshould provide large and obvious evolutionary ad-vantages. However, it turns out that costs are mucheasier to identify than are benefits

      is sex not needed?

    8. sex to be determined bythe mother’s nutrition during the first three monthsof pregnancy; a poor diet was thought to result inmales, and a better diet in females

      theories, you kinda feel like you still hear some of these today

    9. Aristotle proposed that males are character-ized by an abundance of fire (the superior element),and for this reason are hot and dry, while females,with an abundance of water, are rather cold andwet

      interesting how elements are considered here, also see how this idea from the sperm and the egg of power to the male could have formed through these early philosophies

    10. The dispute about theexact nature of spermatozoa was settled in 1841 bythe Swiss embryologist Albert von Kölliker

      concluded that spermatozoa were not independent animals but the products of cells in the testis, and that contact with the egg was needed for fertilization

    Annotators