Evaluated articles

eLife Assessment

This important work provides a new method to extract cfDNA from residual plasma from heparin separators for molecular testing. The evidence supporting the authors' claims is convincing, although some further metrics should also be evaluated. This finding will be interesting to people working in epigenomics and infectious disease diagnostics.

eLife Assessment

The characterization of a dissociable Mediator subunit implicated in cellular pathways, particularly lung alveolar function and HIV latency, would be conceptually interesting. The authors have preliminary evidence for a stable Med16 subcomplex that may regulate specific genes. This work is useful in that it points to interactions between Med16 and UBP1, but the evidence is preliminary and incomplete.

eLife Assessment

This work introduces FunC-ESMs, a proteome-scale framework to classify loss-of-function missense variants into distinct mechanistic groups by combining two complementary state-of-the-art machine learning models. The strength of evidence is convincing, supported by solid benchmarking, integration with experimental datasets, and careful methodological design. The significance of the findings is valuable, providing a resource of clear interest to researchers and diagnostic laboratories working on variant interpretation.

eLife Assessment

This study offers a valuable methodological advance by introducing a gene panel selection approach that captures combinatorial specificity to define cell identity. The findings address key limitations of current single-gene marker methods. The evidence is compelling, but would be strengthened by further validation of rare cell states and unexpected marker categories.

eLife Assessment

This study addresses an important question in liver biology: how zonal hepatocytes balance survival and proliferation following injury? The authors propose that a mid-zone Atf4-Chop axis to Btg2 program temporarily suppresses proliferation to promote survival after a variety of chemical and surgical liver injury models. The authors provide evidence that some zones mount tailored stress responses, which ultimately promote regeneration and liver healing; however, the "mid-zone" changes with different injury models, making it difficult to conclude that the ATF4-CHOP response is specific to this zone in all injury contexts. In addition, it is possible that Atf4 and Btg2 overexpression could lead to Cyp2e1 suppression, which could reduce the extent of injury after CCl4 or APAP. To some extent, these points make the strength of the evidence incomplete, but do not entirely detract from the significance of the study, which is underscored by the helpful observation that there are zone-specific stress responses that mediate liver regeneration and survival.

eLife Assessment

This study presents an important finding by identifying OPG as a novel stromal checkpoint influencing T-cell anti-tumor responses, thereby shedding new light on the complex interplay between the tumor microenvironment and immune regulation. The data are robust and the experimental approaches are sound, providing solid support for the study's conclusions; however, there are a number of additional questions raised by the data. Of particular note are the questions raised on the mechanistic effects of TRAIL versus RANKL. In addition, it would broaden the interest in this study to include more translational human data to complement the work presented.

eLife Assessment

Findings from this study are considered fundamental because they identify amino acid uptake, cholesterol synthesis, and protein prenylation as key metabolic regulators of B cell activation, proliferation, and survival, advancing understanding of T-independent immune responses. The study links metabolic reprogramming directly to B cell function, highlighting how cellular metabolism supports immune fitness. The evidence is compelling, combining unbiased proteomic profiling with genetic and pharmacological validation to demonstrate causal roles for these pathways.

eLife Assessment

This is a valuable study that combines biophysical and evolutionary approaches to understand why particular mutations in the SARS-CoV-2 protein N arose during the COVID-19 pandemic. The evidence is solid and supports the conclusions.

eLife Assessment

The study reports a potential pathway for isoleucine biosynthesis mediated by the underground activity of AHASII, which converts glyoxylate and pyruvate to 2-ketobutyrate. While the findings are valuable in revealing a possible alternative route for isoleucine production, the evidence presented remains incomplete. More comprehensive biochemical experiments are required to substantiate the physiological feasibility of this pathway.

eLife Assessment

This fundamental study provides the first genome-wide characterization of H3K115 acetylation and identifies a striking and previously unappreciated association of this globular-domain histone modification with fragile nucleosomes at CpG island promoters, active enhancers, and CTCF binding sites. While the work is largely descriptive and correlative in nature the evidence is compelling. The authors present multiple, orthogonal genomic and biochemical analyses that consistently support their central conclusions.

eLife Assessment

This important manuscript evaluates how sample size and demographic balance of reference cohorts affect the reliability of normative models. The evidence supporting the conclusions is convincing. This work will be of interest to clinicians and scientists working with normative models.

eLife Assessment

This valuable study compares auditory cortex responses to sounds and cochlear implant stimulation measured with surface electrode grids in rats. Beyond the reduced frequency resolution of cochlear implants observed previously, this study suggests key discrepancies between neuronal representations of cochlear stimulations and natural sounds. The evidence for this result is solid but could be strengthened with a clarification of the methodology and an adaptation of the claim to the actual precision of the measurements. This study is of interest to researchers in the auditory neuroscience field and clinicians implementing treatments with cochlear implants.

eLife Assessment

This important study shows that visual search for upright and rotated objects is affected by rotating participants in a VR and gravitational reference frame. However, the evidence supporting this conclusion is incomplete, given the authors' use of normalized response time and the assumption that object recognition across rotations requires mental rotation.

eLife Assessment

This fundamental study uses simultaneous EEG and fMRI recordings to shed light on the relationship between alpha and gamma oscillations and specific cortical layers. The sophisticated methodology provides compelling evidence for correlations between oscillatory power and the strength and contents of fMRI signals in different cortical layers. This paper will be of interest to neuroscientists studying the role and mechanisms of alpha and gamma oscillations.

eLife Assessment

This paper presents an important theory and analysis of the role of neurogenesis and inhibitory plasticity in the drift of neural representations in the olfactory system. For one of the findings, regarding the impact of neurogenesis on the drift, the evidence remains incomplete. The reason lies in the differences in variability/drift of the mitral/tufted cell responses observed in the model compared to experimental observations, where these responses remain stable over extended time scales.

eLife Assessment

This study provides important results with regard to the ongoing debate of the relationship between internalizing psychopathology and learning under uncertainty. The methods and analyses are solid, and the results are backed by a large sample size, yet the study could still benefit from a more detailed discussion about the difference in experimental design and analysis compared to previous studies. If these concerns are addressed, this study would be of interest to researchers in clinical and computational psychiatry for the behavioral markers of psychopathological symptoms.

eLife Assessment

This important study uses innovative microfluidics-based single-cell imaging to monitor replicative lifespan, protein localization, and intracellular iron levels in aging yeast cells. The evidence for the proposed role of Ssd1 and reduced nutrients for lifespan through limiting iron uptake is convincing, even though some mechanistic details remain unclear. This work will be of interest to cell biologists working on aging and iron metabolism.

eLife Assessment

The authors describe an interesting approach to studying the dynamics and function of membrane proteins in different lipid environments. The fundamental findings have theoretical and practical implications beyond the study of EGFR to all membrane signalling proteins. The evidence supporting the conclusions is compelling, based on the use of a nanodisk system to study membrane proteins in vitro, combined with state-of-the-art single-molecule FRET. The work will be of broad interest to cell biologists and biochemists.