1,720,962 research outputs found
PREreview of "GLUD1 dictates muscle stem cell differentiation by controlling mitochondrial glutamate levels"
No full text<p><strong>This Zenodo record is a permanently preserved version of a PREreview. You can view the complete PREreview at <a href="https://prereview.org/reviews/10066121">https://prereview.org/reviews/10066121</a>.</strong></p>
<p>This review reflects comments and contributions from Marina Schernthanner and Pablo Ranea-Robles. Review synthesized by Pablo Ranea-Robles.</p><p>In this study, the authors studied the role of GLUD1 in satellite cells in the muscle. These cells are responsible for dynamic changes in muscular cells upon different signals, such as exercise. It is well known that metabolic changes play an important role in the fate decision of these cells toward proliferation or differentiation. Here, they found that GLUD1 and glutamine anaplerosis are decreased in differentiation, in contrast to what happens during proliferation. Using inducible KO cells and mice, they show how GLUD1 deficiency induces differentiation to myotubes and imbalance fusion of fibers. This phenotype was associated with an accumulation of glutamate only in mitochondria together with decreased levels of mitochondrial aspartate. In consequence, the malate-aspartate shuttle was inhibited, disturbing the NAD/NADH ratio between the cytosolic and mitochondrial compartments. In conclusion, they establish the role of GLUD1 in muscle satellite cells as a brake on differentiation, allowing proper proliferation using glutamine to feed the TCA cycle. Overall, we found this an excellent study, highly relevant, easy to read, and with multiple techniques and models to sustain their conclusions. Therefore, we would like to congratulate the authors on such a high-impact study. Below, a few comments we think could improve the manuscript and its understanding by the broad scientific community.</p><p>Major comments:</p><ul><li><p>We had no major comments</p></li></ul><p>Minor comments:</p><ul><li><p>Could authors expand on how they know/tested that the custom media they used worked fine on the protocols of differentiation/proliferation? Was it possible to control for the amount of FBS in proliferation vs differentiation media (there appears to be a big difference between 30% and 0.2% FBS) without affecting the maintenance/differentiation of cells? FBS per se contains a number of growth factors, which could influence metabolomic analyses?</p></li><li><p>I would recommend adding some implications/impact of these results more on a big picture over muscular function.</p></li><li><p>The graphical abstract is excellent. I would just recommend to make the changes in NAD/NADH more clear, and indicate better the status of WT cell (quiescent vs prolif)</p></li><li><p>Are there more number of cells after 48h in fig 2?</p></li><li><p>What is the ratio Glu/alpha-kg in the cytosol?</p></li><li><p>Metabolic changes were done with proliferation media, as I understand it, why did the authors not perform metabolomic analysis with the differentiation media?</p></li><li><p>Figure 5D - can the authors show the metabolite levels of the cytosolic fraction as well (maybe in a supplementary figure)? Given that few differences were observed in whole cell lysates, as shown in B, one would expect that mitochondrial and cytosolic metabolite levels display opposite trends that balance each other out, correct?</p></li><li><p>Figure 4 - aren't these minimal differences in transcription upon loss of Glud1 surprising, given the strong phenotypic difference in figure 1? What mediates precocious differentiation if not transcriptional changes? Could it be that the authors are dealing with somewhat heterogeneous populations here and thus relative enrichment of MuSC vs differentiated cell populations might not be readily picked up by bulk RNA-seq?</p></li><li><p>Figure 3C-D - couldn't a reduction in GFP+ cells in theory also be due to increased cell death of GFP+ PAX7+ MuSC? Have the authors excluded this possibility by f.e. showing that there is no difference in TUNEL+(general cell death, DNA damage marker) and Caspase-3+ (apoptotic) cells between KO and WT MuSCs? For D) addition of nuclear signals to indicate cell fusion as expected in muscle fibers/myotubes would be helpful.</p></li></ul><p>Suggestions for future studies:</p><ul><li><p> It would be extremely interesting to evaluate a possible rescue of the phenotype in vivo. Perhaps with alanine supplementation?</p></li></ul>
<h2>Competing interests</h2>
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The author declares that they have no competing interests.
</p>
PREreview of "A kidney-hypothalamus axis promotes compensatory glucose production in response to glycosuria"
No full text<p><strong>This Zenodo record is a permanently preserved version of a PREreview. You can view the complete PREreview at <a href="https://prereview.org/reviews/8431146">https://prereview.org/reviews/8431146</a>.</strong></p>
<p>This review reflects comments and contributions from Marina Schernthanner, Femi Arogundade and Pablo Ranea-Robles. Review synthesized by Jonny Coates.</p>
<p>The study leverages the phenotype presented by the renal Glut2 KO mice (glycosuria with normal glycemia) to investigate how the body senses this glucose loss and the mechanisms behind metabolic homeostasis processes that lead to enhanced glucose production so glycemia remains stable. The use of a genetically modified mouse model with renal Glut2 knockout provides a controlled system for studying the specific role of renal glucose transporters in glucose homeostasis. The study involves various methods, including measurements of glucose production, metabolomics, gene expression related to the hypothalamic-pituitary-adrenal axis, afferent renal nerve ablation, and analysis of secreted proteins. The authors point to a kidney/hypothalamus axis and suggest the involvement of different acute phase proteins in this homeostatic response. The limitations of the study are acknowledged, and further research is suggested to delve deeper into the role of secretory proteins and the specific source of endogenous glucose production after afferent renal denervation. The manuscript is well written and the results are potentially of interest. The study's findings have potential implications for the field of diabetes treatment, as they suggest a mechanism that may explain why SGLT2 inhibitors don't achieve their full potential in lowering blood glucose levels. However, we think that some of the conclusions are merely based on descriptive assessments of changes occurring in the renal Glut2 KO mice. There are a lack of details in the reporting of some of the results and, in particular, in the discussion section, that would also require a bit more explanation from the authors. Right now, it could be hard for the reader to place this research in context. We have summarized our comments below</p>
<p>Major comments:</p>
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<p>The study mentions the use of male and female mice, but it's important to know the sample sizes for each experimental group and how gender might influence the results. Additionally, the authors should provide more details about the control groups and their matching criteria to ensure the validity of comparisons. Moreover, the exact genetic information for the knockout mice i.e. what is the CreER driver that makes it kidney-specific? Is missing. It is currently inconsistent in terms of sex and age of mice used for different experiments. </p>
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<p>Minor comments:</p>
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<p>While the metabolomics analysis is described, more information is needed about the biological significance of the changes observed in the metabolites. How do these changes relate to the compensatory glucose production, and are they causally linked?</p>
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<p>The paper would benefit from improved organization and clarity, particularly in the results and discussion sections. </p>
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<p>Crh+ cells in control image of fig 2 are not clear. The authors could consider highlighting the are where these cells are present, or add an inset showing a zoomed image of some positive cells</p>
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<p>How specific is the use of capsaicin to selectively suppress afferent renal nerve activity? Does this impact other neurons? Either citations or experimental data should be included here. </p>
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<p>The conditions of mice in Sup Fig. 1 are not clear and should be stated clearly in this part of the text and in the figure legend.</p>
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<p>The study is transparent about its limitations and raises important questions for future research. This acknowledgment of limitations contributes to the scientific rigor of the work.</p>
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<p>While control groups are mentioned, it's not clear how these controls were chosen or matched to the experimental group. Further information is needed on how these controls were used to make valid comparisons.</p>
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<p>While the study describes the experimental procedures in detail, it's essential to provide information on how many times these experiments were replicated to assess the reproducibility of the results. This is especially crucial given the complex methods used.</p>
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<p>Blocking the HPA axis and assessing responses in KO and WT mice would strengthen the data in Fig 2</p>
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<p>Investigating or showing the levels of glucagon and adrenaline to delineate mechanisms of tissue-specific glucose production would further strengthen the data presented. </p>
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<p>Is it possible to measure glucose production under denervation conditions? That would support the conclusion if the increased glucose production is blunted </p>
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<p>Not everyone might be familiar with the abbreviation 2D-DIGE. Explaining this before first use would be beneficial. </p>
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<p>Supp fig 2 could be fused with Fig 4 to make the argument more convincing.</p>
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<p>The authors state that "It is possible that afferent renal denervation in the present study attenuated only hepatic glucose production through the hypothalamus without affecting the compensatory increase in renal (local) glucose production". Addressing this would significantly strengthen the manuscript, particularly given that the title includes "hypothalamus-kidney axis". </p>
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<p>Comments on reporting:</p>
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<p>The paper mentions the use of statistical tests but lacks information on the specific statistical tests performed for each analysis. It's crucial to provide details on the tests used, assumptions made, and how p-values were adjusted for multiple comparisons, if applicable.</p>
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<p>Suggestions for future studies:</p>
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<p>Extend the research to human subjects, particularly individuals with diabetes treated with SGLT2 inhibitors. Investigate whether similar mechanisms and pathways are at play in humans, and whether these findings have clinical relevance.</p>
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<p>Investigate the specific roles of secreted proteins, such as acute phase proteins and major urinary proteins, in glucose regulation and potential interactions with the kidney-hypothalamus axis.</p>
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<p>Explore how the kidney-hypothalamus axis integrates with other nervous system and endocrine signals involved in glucose regulation, such as insulin and glucagon.</p>
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<p>Conduct in-depth studies on the impact of afferent renal nerve activity on glucose homeostasis and the signaling pathways involved. Investigate the role of sensory nerves in detecting glycosuria and triggering compensatory responses.</p>
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<p>Competing interests</p>
<p>The author declares that they have no competing interests.</p>
PREreview of "Maternal adaptations in mouse lactation are vulnerable to diet-induced excess adiposity"
No full textThis Zenodo record is a permanently preserved version of a PREreview. You can view the complete PREreview at https://prereview.org/reviews/8268259.
This review reflects comments and contributions by Aude Angelini, Marina Schernthanner, Shaunak Deota, Pablo Ranea-Robles, Luciana Gallo and Femi Arogundade. Synthesized by Pablo Ranea-Robles.
This study explores how a high-calorie diet-induced increase in body fat impacts the way mothers' bodies adapt during lactation in a mouse model. The results revealed that this excess body fat caused changes in the structure of the intestines, the types of immune cells present, and how well the intestinal barrier worked. Another focus of this study was whether these changes persist after lactation and how a HC-diet affects them. The study highlights the implications of excess adiposity for maternal health during the periconceptual/perinatal period and emphasizes the need for further research to understand its effects on postpartum health. Overall, the crowd reviewers found that the conclusions of this manuscript are well-supported by the data, and that this is a relevant topic of research that deserves more attention. Below, we provide our major and minor comments for this study.
Major comments:
The study addresses an important and relevant topic by examining the impact of excess adiposity during lactation, a period often understudied, on maternal health. This has significant implications for understanding postpartum health and potential interventions. This paper is very informative in terms of characterizing changes in tissue-resident and circulating immune cell populations, intestinal tissue morphology, metabolism, intestinal permeability etc. in lactating females when exposed to a high-calorie diet. The use of a mouse model allows for controlled experiments and observations that can help elucidate complex interactions between diet, adiposity, and maternal adaptations. The study employs a longitudinal approach by examining the effects of excess adiposity both during lactation and up to two months post-lactation. This contributes to a better understanding of the persistence and resolution of maternal adaptations.
The authors make experimental data available on a public platform (figshare), allowing other researchers to verify the results and perform further analyses, promoting transparency and reproducibility.
In Fig. 9, the authors should compare the HC-diet lactation and post-lactation groups with a HC-diet fed non-pregnant female group to assess the differential effect of diet vs lactation. We think this is a crucial aspect that should be included in this manuscript. In Fig. 9d, the authors compare to a control diet-non-pregnant female group, which is not ideal. The diet by itself can cause most of the dysregulation and may have an overwhelming effect, especially considering that the authors have reported that HC diet itself increases intestinal permeability in a recent publication.
Following up on Figure 9, the effects observed in the post-lactation group in Fig. 9d seems caused by an apparent outlier in that group. Have the authors evaluated that possibility? If so, this should be accounted for in the discussion of the results.
Minor comments:
We think the introduction is overall okay, but perhaps is missing a bit of focus on the difference between physiological adaptations to pregnancy and pathophysiological adaptations to pregnancy when fed a high-caloric diet. Authors are experts in this topic, but we found this aspect was only well-described in the discussion. A specific mention to the changes in intestinal permeability during physiological pregnancy-lactation in the introduction could improve the understanding of the topic while reading the introduction, especially to differentiate the results of this paper to the ones found in the recent Plos one from the same authors, where they studied these changes during gestation.
Authors may want to include details regarding the live/dead gate in their gating strategy to gate out dead cells.
The increase in body weight is clear in Figure 2a. However, when looking at the body weight over time in Supp Fig 2, BW during lactation does not seem to change between the two diet groups. This can be confusing for the reader. It could probably be related to the different type of statistical analysis, but, we think, at least, that authors could include the p-value at day p21 in the Supp 2a body weight graph.
The expression of several tight junction proteins such as occludin (Ocln), claudins (Cldn-1, -2, -3, -4, -5, -7, -8) and zonula occludens (Z0)/tight junction proteins (Tjp1) are downregulated in the gut during metabolic disorders and inflammation. Assessing their expression can be an additional proof that the gut barrier integrity is affected.
The change in select macrophage populations in intestinal tissue is interesting - did the authors check if those populations localize differently (relative to the crypt) in mice fed a control versus a high calorie diet?
Did the authors observe general changes (increase?) in gut-homing signals such as a4b7 integrin, CCR9 on immune cells or CCL25 on intestinal epithelial cells upon high-calorie diet? We were curious about changes in gut-homing signals, since they observed changes in the number of certain immune subsets (f.e. the change in monocyte-derived macrophages) between their two diets. Which could be due to changes of immune cell proliferation in the tissue or a change in recruitment of immune cells to the tissue. Or decreased exit of immune cells through lymphatics (but that would be mostly for dendritic cells and T cells, for which they don't see such drastic changes in number). Technically a4b7 integrin (on immune cells) is less of a gut-homing signal and rather facilitates exit of immune cells out of the blood vessel and into the tissue, so we think checking for chemokines (f.e. CCL25 expressed by the epithelium, which would recruit immune cells into the tissue) would make more sense.
The authors observed a change in mesenteric fat weight and later on in selected immune cell populations. Did they check for differences in the number and composition of lymphoid structures (f.ex. Peyer's patches in the small intestine) or composition and size of the draining mesenteric lymph nodes?
For all of their immune cell isolations from intestinal tissue - were those done after removing secondary lymphoid structures such as Peyer's patches?
Given the reported differences in crypt length - did the authors observe differences in proliferation (EdU pulse, Ki67 staining etc.) and the number of intestinal stem cells as assessed via canonical stem cell markers such as Lgr5 (for both, small and large intestine) or Olfm4 (only in the small intestine)?
Comments on reporting:
We agree with the authors choice of the dam as biological replicate, not the offspring, for analysis
We missed more details regarding euthanasia methods, both for the pups and the adult animal at the end-point of the study, as well as regarding sample size for each experiment in material and methods / figure legends.
Even though Figure 1 was quite informative regarding the experimental design, we think it would be useful to indicate the age of the dams at the point when they were allocated to one of the diets, to facilitate the understanding of the experimental design.
Figure legend of fig. 2 would be more clear if authors add the information on the lactation endpoint used here, i.e P21-23 as explained in the text
We think that Supp figure 2b does not add anything informative to what is already present in Supp 2a.
It is crucial to include a dedicated section within the preprint that thoroughly discusses the limitations of the study. This comprehensive discussion of limitations is essential to provide a well-rounded and balanced interpretation of the results presented.
Suggestions for future studies
It remains unclear how exposure to a high-fat diet during pregnancy might change the susceptibility of those female mice to f.ex. intestinal infections, acute inflammatory insults etc. A follow-up challenge model in previously pregnant mice would have been interesting to see and would have perhaps helped to shed more light on long-lasting immune cell phenotypes following exposure to a high-fat diet. Alternatively, similar characterization studies of intestinal tissue morphology, function and immune landscape, as done for lactating and post-lactating mice in this study, would have been interesting to see in the mice's offspring upon reaching adulthood. Body weight of the offspring coming from these dams was already increased at p21, suggesting transgenerational changes happen in this model.
Following up on future studies on offspring, authors may want to assess if the high-caloric diet also affects the cytokine levels or bacterial products in breast milk, as this could have a major effect on offspring
We found intriguing the possibility that the changes in immune cells may have an effect on the adipose tissue of these dams, could be a nice addition for future experiments.
The fact that the cecal weight is different might suggest an altered microbial composition following a high calorie diet. Did the authors look into this? Alternatively, it could be related to differences in fiber content of the diets, which vary quite a bit in carbohydrate amounts etc. Is it known whether the source and composition of fibers is comparable between the high calorie and control diets used in this study?
Competing interests
The author declares that they have no competing interests
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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