Evaluated articles

eLife Assessment

This study presents a valuable finding on the importance of the plasma metabolome in glaucoma risk prediction. The evidence supporting the claims of the authors is solid and the work offers insights for the design of protective therapeutic strategies for glaucoma. The authors have addressed the concerns of the reviewers and reported on the limitations of the study.

eLife Assessment

In this valuable study, Seidel et al. identify and characterize a novel subset of hepatocellular carcinoma patient-derived xenograft models defined by active Jagged 1-Notch2 signaling and a distinctive progenitor-like gene expression profile. Within the limitations of the PDX system they used, their methods are state-of-the-art, their data are strong and believable, and their conclusions are convincing. However, the ability to identify HCC patients that might respond is limited, and the mechanistic assessment downstream of JAG1/NOTCH2 is relatively descriptive. Some additional clarifications and experiments would strengthen the paper.

eLife Assessment

The authors have demonstrated the use of adenine base editors delivered via adeno-associated viruses to introduce edits in the mitochondrial genome. The manuscript describes the methodology well, and the conclusions are convincingly supported by the results. The valuable results highlight the potential of these base editors to model mtDNA variations in somatic tissues in animal models.

eLife Assessment

The manuscript contains important findings regarding inflammatory macrophage subsets that have theoretical and/or practical applications beyond the field of rheumatology. The authors demonstrate with compelling evidence the effects of PGE2 on TNF signaling. This work will be of broad interest to immunologists and cell biologists.

eLife Assessment

The manuscript presents a useful analysis of the relationship between climate variables and malaria incidence, for local temperature and rainfall and the global climate driver of ENSO from 2008 to 2019 in a lowland region of East Africa, with wavelet analyses and linear regressions after time series decomposition. The paper is convincing albeit not novel in its application of wavelets to the analysis of this type of time series data for a vector-borne infection. It is less persuasive on what is learned about the role of climate variability (non-seasonal climate effects), and it is also unclear how the analysis informs climate change and malaria, and this motivation for the work is not warranted as it pertains to longer time scales than those considered. The work should be better placed in the context of what is known for malaria in East Africa and in different transmission settings.

eLife Assessment

This manuscript offers important insights into how polyphosphate (polyP) influences protein phase separation differently from DNA. The authors present compelling evidence that polyP distinguishes among protein conformational ensembles, leading to divergent condensate maturation behaviors that include unfolding and polyproline II formation. In response to reviewer feedback, the authors addressed key concerns by incorporating charge-equivalent DNA controls and extending structural analysis to FruR variants, further reinforcing the polymer-specific effects of polyP. While some discrepancies between protein systems remain unresolved, the study enhances our understanding of how biopolymers influence protein assembly and conformational transitions.

eLife Assessment

Shah and colleagues take advantage of the presence of maternal and somatic ribosomes in zebrafish and confirm their differential expression during development. The authors convincingly show that ribosomes previously found expressed during oogenesis are also expressed in primordial germ cells and that hybrid maternal and somatic ribosomes are formed during development. The question of ribosome heterogeneity, the expression and function of maternal versus somatically provided ribosomes are of broad interest and this fundamental work sets new directions for future functional studies of this interesting phenomenon.

eLife Assessment

This work derives a valuable general theory unifying theories of efficient information transmission in the brain with population homeostasis. The general theory provides an explanation for firing rate homeostasis at the level of neural clusters with firing rate heterogeneity within clusters. Applying this theory to the primary visual cortex, the authors present solid evidence that accounts for stimulus-specific and neuron-specific adaptation. Reviewers have provided additional suggestions for improving the readability of the manuscript, as well as discussing previous results on adapting coding as well as those aspects of experimental data that are not fully explained by the present theory.

eLife Assessment

This fundamental study reports the effects of the psychedelic drug psilocin on iPSC-derived human cortical neurons, analyzing different aspects of structural and functional neuronal plasticity. The evidence is convincing, integrating a comprehensive characterization of 5-HT2A expression and its subcellular distribution upon treatment with psilocin at different time points. The study supports the value of using iPSC-derived human cortical neurons for testing the potentially translational effects of psilocin and other psychedelic-related compounds.

eLife Assessment

This valuable paper explores the idea that transient modulations of neural gain promote switches between distinct perceptual interpretations of ambiguous stimuli. The authors provide solid evidence for this idea by pupillometry (an indirect proxy of neuromodulatory activity), fMRI, neural network modeling, and dynamical systems analyses. The highly integrative nature of this approach is rare in the field.

eLife Assessment

This is a valuable study, tackling the long-standing issue of the difficulty in imaging the inferior olive and addressing the most relevant questions with a rigorous approach. The technological advance allowed the authors to generate solid experimental evidence with high-quality data. The results are presented clearly and the analyses are rigorous.

eLife Assessment

This valuable study presents findings on the developmental roles of Nup107, a key nucleoporin, in regulating the larval-to-pupal transition in Drosophila melanogaster through its involvement in ecdysone signaling. The evidence supporting the authors' claims is solid, with robust experimental approaches including RNAi knockdown and rescue experiments. The authors propose that Nup107 influences EcR localization indirectly by reducing the expression of Halloween genes, a consequence of impaired Torso signaling. However, it remains uncertain whether Torso is the sole receptor tyrosine kinase involved, and this disruption ultimately leads to decreased ecdysone production. In addition, finding a mechanism would strengthen the findings as the currently proposed mechanism is not completely supported by the data.

eLife Assessment

This is a valuable study that explores the function of CCP5 in mouse ependymal cells. The methods, data, and analyses broadly support the claims. However, the study is incomplete as it stands. Minor weaknesses remain and the authors may wish to address them.

eLife Assessment

This is an important study with convincing evidence that multi-voxel fMRI activity patterns for threat-conditioned stimuli are altered by learning CS-US contingencies. The analyses are dense, but rigorous. The protocol is quite nuanced and complex, but the authors have done a fair job of explaining and presenting the results. The work is relevant for our understanding of how effective learning changes neural stimulus representation in the human brain.

eLife Assessment

This study presents useful findings on the differences between male and hermaphrodite C. elegans connectomes and how they may result in changes in locomotory behavioural outputs. However, the study appears incomplete with respect to the relationship between sex-specific AVA wiring and male mate-finding. Another area of concern is that the analysis does not consider animal-to-animal variability in the wiring when attempting to identify significant differences between the male and hermaphrodite.

eLife Assessment

This study investigates trial-by-trial inter-areal interactions in the visual cortex of the mouse and the monkey by analyzing two previously published datasets. The authors find that activity in one layer (in mice) or one area (in monkeys) can partially predict neural activity in another layer or area on the single-trial level in different experimental contexts. This valuable finding expands previously known contributions of stimulus-independent downstream activity to neural responses in the visual cortex by demonstrating how these change under varying visual stimuli as well as in the absence of visual stimulation. While the methodology is solid, the analysis for the monkey data is incomplete and would benefit from including a second animal.

eLife Assessment

The paper addresses the question of gene epistasis and asks what is the correct null model for which we should declare no epistasis. By reanalyzing synthetic gene array datasets regarding single and double-knockout yeast mutants, and considering two theoretical models of cell growth, the authors reach the valuable conclusion that the product function is a good null model. While the justification of some assumptions is incomplete, the results have the potential to be of value to the field of gene epistasis.

eLife Assessment

This study provides a fundamental analysis of the EmrE efflux pump, highlighting the role of the C-terminal domain in influencing uncoupled proton leak. The integration of biophysical techniques with molecular dynamics simulations offers solid support for the key findings and adds substantial evidence toward a definitive understanding of EmrE transport mechanism.

eLife Assessment

This important study offers a molecular characterization of neurons and glia in the adult nervous system of the fruit fly Drosophila melanogaster. The study focuses on the progeny of a specific set of neural stem cells that contribute to the central complex, a conserved brain region that plays key roles in sensorimotor integration. The data are convincing and collected using validated methodology, generating an invaluable resource for future studies. The study will be of interest to developmental neurobiologists.

eLife assessment

The study presents a useful computational analysis of how the ratio between excitatory and inhibitory neural numbers affects coding capacity. The authors show that increasing the proportion of inhibitory neurons (as observed in upper cortical layers compared to the input recipient layer 4) increases the dimensionality of neural activity and improves the encoding of time-varying stimuli. However, the evidence about the role of the inhibitory population in coding is incomplete because numerical results are neither supported by analytical mathematical results nor include controls for changes in firing thresholds or subtypes of inhibitory neurons.