Evaluated articles

eLife assessment

This important study utilizes a viral-mediated short hairpin RNA (shRNA) approach to investigate in a novel way the role of the wild-type PHOX2B transcription factor expressed in critical chemosensory neurons in the brainstem retrotrapezoid nucleus (RTN) region for maintaining normal CO2 chemoreflex control of breathing in adult rats. The convincing results show blunted ventilation during elevated inhaled CO2 (hypercapnia) with knockdown of PHOX2B, accompanied by a reduced expression of Gpr4 and Task2 mRNA for the proposed RTN neuron proton sensor proteins GPR4 and TASK2. These results indicate that maintained expression of wild-type PHOX2B affects respiratory control in adult animals, complementing previous studies showing that PHOX2B-expressing RTN neurons may be critical for chemosensory control throughout the lifespan, and with implications for neurological disorders involving the RTN, which will be of interest to neuroscientists studying respiratory neurobiology as well as the neurodevelopmental control of motor behavior.

eLife assessment

This is an important study that describes an elegant modelling driven approach to design of allosteric antagonists for CXCR4 that have a selective effect on receptor nanocluster formation, cell polarisation and chemotaxis, but spare binding of CXCL12 to the receptor and inhibition of adenylate cyclase. This enables selective targeting of processes dependent upon cell polarisation and chemotaxis without impacting signalling effects and may avoid some of the toxicity associated with antagonists that target CXCL12 binding and thus block all CXCR4 signalling. The revised manuscript offers convincing evidence to support the claims. The modelling work is better described and additional data has been presented that better illustrates the unique features of the new antagonist. The in vivo studies in the zebrafish model open a path to studies in mammalian models.

eLife assessment

This valuable study uses neuroanatomical techniques to investigate somatosensory projections from the elephant trunk to the brainstem. Given its unique specializations, understanding how the elephant trunk is represented within the brain is of general interest to evolutionary and comparative neuroscientists. The authors present solid evidence for the existence of a novel isomorphism in which the folds of the trunk are mapped onto the trigeminal nucleus; however, due to their unusual structure, some uncertainty remains about the identification and anatomical organization of nuclei within the elephant brainstem.

eLife assessment

This paper explores the relationships among evolutionary and epidemiological quantities in influenza, and presents fundamental findings that substantially advance our understanding of the drivers of influenza epidemics. The authors use a rich set of data sources to gather and analyze compelling evidence on the roles of genetic distance, other influenza dynamics and epidemiological indicators in predicting influenza epidemics. The central findings highlight the significant influence of genetic distance on A(H3N2) virus epidemiology and emphasize the role of A(H1N1) virus incidence in shaping A(H3N2) epidemics, suggesting subtype interference as a key factor. This paper also makes relevant data available to the research community.

eLife assessment

This study on the effects of fasting on safety learning rests on basic premises and concepts that both reviewers found difficult to follow. If these can be clarified, the findings may well be useful and of some utility for the field of emotional learning as well as experimental clinical psychology. However, the main claims of the study are only partially supported and are therefore incomplete.

eLife assessment

The authors conduct a valuable GWAS meta-analysis for COVID-19 hospitalization in admixed American populations and prioritized risk variants and genes. The evidence supporting the claims of the authors is solid. The work will be of interest to scientists studying the genetic basis of COVID pathogenesis.

eLife Assessment

This important work presents an example of how genomic data can be used to improve understanding of an ongoing, long-term bacterial outbreak in a hospital with an application to multi-drug resistant Pseudomonas aeruginosa, and will be of interest to researchers concerned with the spread of drug-resistant bacteria in hospital settings. The convincing genomic analyses highlight the value of routine surveillance of patients and environmental sampling and show how such data can help in dating the origin of the outbreak and in characterising the epidemic lineages. These findings highlight the importance of understanding environmental factors contributing to the transmission of P. aeruginosa for guiding and tailoring infection control efforts.

eLife Assessment

This auhors present findings on the role of the sirtuins SIRT1 and SIRT3 during Salmonella Typhimurium infection. This valuable study increases our understanding of the mechanisms used by this pathogen to interact with its host and may have implications for other intracellular pathogens. The reviewers disagreed on the strength of the evidence to support the claims. Although one reviewer found the strength of the evidence convincing, the other found that it was incomplete, and that the main claims are only partially supported, as can be seen from the public reviews.

eLife Assessment

This study provides valuable observations indicating that human pyramidal neurons propagate information as fast as rat pyramidal neurons despite their larger size. Convincing evidence demonstrates that this property is due to several biophysical properties of human neurons. This study will be of interest to neurophysiologists.

eLife assessment

This valuable study demonstrates that the behavior of the cells in the presomitic mesoderm in zebrafish embryos depend on both an intrinsic program and external information, providing new insight into the biology underlying embryo axis segmentation. There is convincing support for the findings with a thorough and quantitative single-cell real-time imaging approach, both in vitro and in vivo, developed by the authors.

eLife assessment

The authors observed a positive correlation between FSH and fat mass, as well as a negative association with the appendicular lean mass/fat mass ratio. These valuable findings in male subjects within a hypogonadal setting following Degarelix treatment imply that FSH might function as a predictor, similar to observations in women. However, it's important to note that the analysis is incomplete, as other major confounding factors such as testosterone were not included.

eLife assessment

This landmark study presents MetaPathPredict, a method that uses a stacked ensemble of neural networks to predict the presence or absence of KEGG modules based on annotated features in the genome. The evidence supporting the conclusions is compelling, with a tool that allows for prediction of KEGG modules in sparse gene sequence datasets.

eLife assessment

Using single-cell sequencing, high-resolution imaging, and inducible genetic deletion of yolk-sac (YS) derived macrophages, the authors present a useful map of fetal liver macrophage subpopulations and provide important data demonstrating that heterogeneous fetal liver macrophages regulate erythrocyte enucleation, interact physically with fetal HSCs, and may regulate neutrophil accumulation in the fetal liver. These novel findings, although yet incomplete, might provide a solid foundation for further investigating the effects of macrophages on HSC function during fetal hematopoiesis and into adulthood and will be useful for the field of macrophage biology and developmental hematopoiesis.

eLife assessment

The findings are important and would potentially have theoretical and practical implications outside the field. However the strength of evidence presented was assessed as being incomplete in several respects. Major strengths are (1) genetic factors in facial appearance are of broad interest, and the potential influence of possibly identical factors in a serious congenital disorder (cleft lip/palate) heightens that interest further; (2) proving which single nucleotide variants influence phenotypes, and by what mechanisms, is a major challenge for the field as a whole. The weakness, as assessed, was that in its present form the experimental approach was not sufficiently rigorous to support the conclusions unambiguously.

eLife assessment

This important study presents data suggesting that HFD-induced histone epimutations in sperm may impact the transcriptome of the placenta, thereby contributing to the paternal transmission of paternal metabolic disorders to offspring. Although the hypothesis is interesting and the evidence presented is compelling, more careful statistical analyses and functional validation experiments are needed to further strengthen the conclusion.

eLife assessment

In this important study, the authors explore the importance of developmental changes in cortico-DRN innervation in the balance of behavioral control in a foraging task. The authors report somewhat convincing evidence that while juvenile mice and adult mice both perform the task, juveniles exhibit more impulsive behavior due to reduced efficacy of cortico-DRN projections. The authors conclude that the development of cortico-DRN (esp mPFC) projections allows 5HT input to promote perseveration (or exploitation) in the balance of behavioral control. However, reviewers raised issues regarding the strength of the evidence without further experiments.

eLife assessment

This manuscript addresses a non-canonical function of the Class 2 ribonuclease III Drosha in the regulation of adult neural stem cell fate, important for understanding how these cells generate neurons or oligodendrocytic cells.
Overall, this manuscript has many strengths. The authors identify 165 proteins, several of them enriched in neural stem cells, and potentially specific for miRNA dependent or independent Drosha macromolecular complexes.
While the authors provide systematic and convincing evidence on the biochemical interactions among the key players in this cascade, the significance of these interactions for neural stem cell fate determination in vivo remains unclear, as the in vitro cellular systems used to document most of the data reported in the paper may not (fully) represent resident neural stem cells in the adult hippocampus. The in vivo function mediated by Drosha/ Safb1 needs to be substantiated by more evidence and/or complementary approaches.

eLife Assessment

In this valuable technical report, Verma et al. provide convincing evidence that endogenously tagged dynein and dynactin form processive motor complexes that move along microtubules in living cells. Using quantitative fluorescence microscopy, they directly compare the stoichiometry and motility of these complexes to kinesin-1, revealing distinct transport behaviors and regulatory properties. This study offers key methodological and conceptual advance for understanding the dynamics of native motor proteins within the cellular environment and will be of interest to the cell biology community.

eLife assessment

The important study uses a new experimental method to provide compelling evidence on how sense- and anti-sense transcription is differentially regulated. The method described here can generally be used to study the alterations in transcription. This paper will be of interest to scientists working in the gene regulation community.

eLife assessment

This useful manuscript extends prior work to identify OVO as a major transcriptional activator of the female germline gene expression program. Using a combination of solid genomic strategies, the authors demonstrate that OVO binds to the promoters of hundreds of genes in the female germline and promotes their expression.