Evaluated articles

eLife assessment

This valuable study confirms the association between the human leukocyte antigen (HLA)-II region and tuberculosis (TB) susceptibility in genetically admixed South African populations, specifically identifying a near-genome-wide significant association in the HLA-DPB1 gene, which originates from KhoeSan ancestry. Whilst some of the evidence supporting the association between the HLA-II region and TB susceptibility is solid, the analysis is incomplete and requires further work for the study to achieve its full value. The work will be of interest to those studying the genetic basis of tuberculosis susceptibility/infection resistance.

eLife Assessment

This paper reports the synthesis of covalent inhibitors bearing a unique fragment as a protected covalent warhead for irreversible binding to histidine in carbonic anhydrase (CA) enzymes. These findings are important due to the broad utility of the approach for covalent drug discovery applications and could have long-term impacts on related covalent targeting approaches. The data convincingly support the main conclusions of the paper.

eLife assessment

This study presents an important platform for mapping mutation effects onto higher-level protein structural information, addressing a significant gap in current research. While the work is ambitious and incorporates often-overlooked aspects of higher-order structure, the strength of the evidence supporting some results seems incomplete. The quaternary structure modeling appears to underestimate oligomeric proteins compared to previous studies, and the mutation analysis lacks crucial baseline information. Despite these limitations, the method has potential for broader applications and generalization to additional organisms, warranting further development and refinement.

eLife assessment

This important study reveals a novel mechanism by which hypoxia-ischemia damages the neonatal brain and how hypothermia protects from brain injury. The paper presents an interesting combination of state-of-the-art optical measurements, mitochondrial assays, and the use of various control experiments providing solid evidence for the derived conclusions. Reviewers caution that possible adverse effects of prolonged anesthesia, as well as pain and stress after a major surgical procedure might influence the outcomes and should be carefully considered. This work will be of interest to the fields of hypoxia and brain metabolism research.

eLife assessment

This work presents a valuable mouse model for a liver-specific depletion of the Survival Motor Neuron (SMN) protein, where the liver retains 30% of functional full-length SMN protein. The authors provide a profile of phenotypic changes in liver-specific SMN depleted mice: while evidence supporting their claims are generally solid, the phenotype is mild and mechanistic understanding remains to be determined.

eLife assessment

This important work has substantially advanced our understanding of the molecular basis of symmetry breaking and lineage specification in preimplantation mammalian embryos. The results generated using live imaging are compelling. Quantification of the functional assays is convincing and would be improved by increasing the number of embryos in the evaluations and clearly stating how many embryos are evaluated per experiment.

eLife assessment

This important study advances our understanding of the role energy metabolism, specifically anaerobic glycolysis, plays during development. Convincing genetic and pharmacological evidence demonstrates that glycolytic flux is not only necessary during retinogenesis but also controls the rate of retinal progenitor cell proliferation and photoreceptor maturation. Interesting evidence suggests potential downstream roles for intracellular pH and Wnt/β-catenin signaling; however, more direct evidence is needed to show they are the key mediators of glycolysis. This work is expected to stimulate broad interest and possible future studies investigating the link between metabolism and development in other tissue systems.

eLife assessment

This valuable study investigates how inter-organ communication between the tracheal stem cells and the fat body plays a key role in the directed migration of tracheal stem cells in Drosophila pupae. While the experimental data are extensive and complementary, the evidence presented to substantiate some of the conclusions appears incomplete and requires further clarification and additional experiments. The work would be of interest to researchers in the fields of developmental biology and cancer biology.

eLife assessment

This important study identifies a new class of small molecules that activate the integrated stress response via the kinase HRI. Solid evidence indicates that two of these compounds promote mitochondrial elongation. The findings would be strengthened if the mutant cells with reduced fusion activity of Mfn2 were analyzed for the rescue of mitochondrial functions.

eLife assessment

This important study explores the impact of pH changes and cancer mutations on nucleosome interactions and higher-order chromatin structures. The evidence supporting the main conclusions is solid, based on rigorous computational methods, including pKa prediction, electrostatic force calculation, and molecular dynamics simulations. The findings provide insights into how protonation states and cancer-associated mutations affect nucleosome electrostatics and chromatin organization, making this work of broad interest to chromatin biologists, cancer researchers, and computational biophysicists.

eLife assessment

This study presents valuable findings on the relative cerebral blood volume of non-human primates that move us closer to uncovering the functional and architectonic principles that govern the interplay between neuronal and vascular networks. The evidence of areal variations is solid, but that of vessel counting and laminar analysis is incomplete. The lack of a direct comparison of their approach against better-established MRI-based methods for measuring hemodynamics and vascular structure weakens the evidence provided in the current paper version. The work will be of interest to NHP imaging scientists.

eLife assessment

This work presents valuable findings of a modulatory effect of yohimbine, an alpha2-adrenergic antagonist that raises noradrenaline levels, on the reconsolidation of emotionally neutral word-picture pairs, depending on the hippocampal and cortical reactivation during retrieval. The evidence supporting the conclusion is incomplete so far, particularly considering concerns about the median-splitting approach for reaction times and hippocampal activity. The work will be of broad interest to researchers working on memory.

eLife assessment

In this elegant and thorough study, Sánchez-León et al. investigate the effects of tDCS on the firing of single cerebellar neurons in awake and anesthetized mice. They find heterogeneous responses depending on the orientation of the recorded Purkinje cell. The paper is important in that it may well explain part of the controversial and ambiguous outcomes of various clinical trials. It is a well-written paper on a deeply analyzed dataset and the methods in the paper are generally convincing, with the current version having some weaknesses in statistical reporting and power.

eLife assessment

In this important study, Bu et al investigate how cell overcrowding triggers a mechano-transduction pathway involving TRPV4 channels, focusing on high-grade ductal carcinoma in situ (DCIS) cells. The authors show that cell crowding in these malignant cells leads to a reduction in cell volume and promotes a pro-invasive phenotype through calcium homeostasis and TRPV4 channel trafficking to the plasma membrane; this phenomenon is specific to invasive cell lines like MCF10CA and DCIS and is corroborated by patient tissue samples. The work suggests the role of TRPV4 in cell motility and mechanical sensing, offering potential therapeutic insights for targeting cancer metastasis. While the study presents robust and convincing data, the absence of TRPV4 genetic ablation is a critical limitation, which would further confirm its role in these processes.

eLife assessment

This study provides valuable evidence on the relationship between morphine-induced social deficits, corticotropin-releasing factor receptors, and alterations in neuronal activity in the paraventricular nucleus of the hypothalamus of mice (PVN). Convincing approaches and methods were used to show that the CRF1 receptor plays a role in sociability deficits occurring after acute morphine administration. Conclusions regarding mechanistic connections between the effect of modulation of CRF 1 receptor on sociability and PVN neuronal firing are, however, incompletely supported.

eLife assessment

This valuable study characterises receptors for calcitonin-related peptides from a deuterostomian animal, the echinoderm Apostichopus japonicus, by a combination of heterologous expression, pharmacological experiments, and the quantification of gene-expression levels. The authors provide solid evidence for a functional calcitonin-related peptide system in the sea cucumber, but some of the phylogenetic and statistical analyses and the evidence of a physiological function are incomplete. This work should be of interest to scientists studying the signaling pathways, functions, and evolution of neuropeptides, and could be of relevance to improving the culture conditions of this economically key species.

eLife Assessment

This valuable study compares ChIP-seq and ChEC-seq2 techniques to investigate RNA polymerase II (RNAPII) binding patterns in yeast, revealing that ChEC-seq2 captures distinct regulatory events associated with active transcription missed by ChIP-seq. The authors use ChEC-seq2 data to build a stochastic model of RNAPII kinetics, providing convincing new insights into transcription regulation and the role of the nuclear pore complex. The paper highlights the importance of careful methodological comparisons in understanding RNAPII dynamics.

eLife assessment

In this valuable study, García-Vázquez et al. provide solid evidence suggesting that G2 and S phases expressed protein 1 (GTSE1), is a previously unappreciated non-pocket substrate of cyclin D1-CDK4/6 kinases. To this end, this study holds a promise to significantly contribute to an improved understanding of the mechanisms underpinning cell cycle progression. Notwithstanding these clear strengths of the article, it was thought that the study may benefit from establishing the precise role of cyclin D1-CDK4/6 kinase-dependent GTSE1 phosphorylation in the context of cell cycle progression, obtaining more direct evidence that cyclin D1-CDK4/6 kinase phosphorylate indicated sites on GTSE1 (e.g., S454) and mapping a degron in GTSE1 whose function may be blocked by cyclin D1-CDK4/6 kinase-dependent phosphorylation.

eLife assessment

The manuscript by Li and coworkers analyzed astrocytic differentiation of midbrain floor plate-patterned neural cells originating from human iPS cells, with a LMX1A reporter. This valuable work identifies transcriptomic differences at the single-cell level, between astrocytes generated from LMX1A reporter positive or negative cells, as well as non-patterned astrocytes and neurons. The evidence is solid, but the paper can be strengthened by further analyses of the transcriptomic data, and astrocytic morphology; also, searching for some of the differentially expressed genes by immunohistochemistry in different regions of the mammalian brain, or in human specimens, would be very informative.

eLife assessment

This useful study characterises motor and somatosensory cortex neural activity during naturalistic eating and drinking tongue movement in nonhuman primates. The data, which include both electrophysiology and nerve block manipulations, will be of value to neuroscientists and neural engineers interested in tongue use. However, data analysis needs to be improved to strengthen the inadequate support for some of the main claims in the paper.