Evaluated articles

eLife Assessment

This study presents an important finding on the molecular mechanism for transduction of environmentally induced polyphenism. The evidence supporting the claims of the author is solid. This paper would be of interest to those studying aphids wing dimorphism.

eLife Assessment

The authors present a useful agent-based model to study the tensile force generated by myosin mini-filaments in actin systems (bundles and networks); by numerically solving a mechanical model of myosin-II filaments, the authors provide insights into how the geometry of the molecular components and their elastic responses determine the force production. This work is of interest to biophysicists (in particular theoreticians) investigating force generation of motor molecules from a biomechanical engineering and physics perspective. The authors convincingly show that cooperative effects between multiple myosin filaments can enhance the total force generated, but not the efficiency of force generation (force per myosin) if passive cross-linkers are present. This work would benefit from a more extensive discussion of the relevance of the results in view of the existing experimental literature.

eLife Assessment

This important study investigates the propensity of the intravacuolar pathogen, Leishmania, to scavenge lipids which it utilizes for its accelerated growth within macrophages. Although some of the data compellingly links increased lipid acquisition to parasite growth, data to support the underlying mechanism to describe the proposed model is incomplete. The study adds to other work that has implicated pathogen-derived processes in the selective recruitment of vesicles to the pathogen-containing vacuole, based on the content of the cargo.

eLife Assessment

Centromeres are specific sites on chromosomes that are essential for mitosis and genome fidelity. This valuable work extends previous studies to convincingly show that the centromere-histone core contributes to force transduction through the kinetochore. The centromere mainly strengthens one of the two paths of force transduction, influenced by the centromeric DNA sequence, the mechanism for which remains to be determined. This work will be of interest to those studying cell division and chromosome segregation.

eLife Assessment

In this manuscript the authors established a novel three-dimensional culture system for stratified epithelia that allows epithelial cells to undergo epithelial-to-mesenchymal transition (EMT) and subsequent mesenchymal-to-epithelial transition (MET) while migrating through a membrane with 3.0-µm micropores, and, thus, provides a valuable tool to study EMT and possibly wound regeneration or metastasis. Furthermore, a set of experiments provides solid data suggesting that TGF beta signaling and actin polymerization promote movement of epithelial cells into the pores, while Piezo1 and Keratin 6 prevent keratinocyte migration and EMT.

eLife Assessment

This work represents an important contribution to our understanding of how membrane energetics influence protein conformation and function in mechano-sensitive channels. Through extensive molecular dynamics simulations and energetic analysis, the study demonstrates how the channel structure is shaped by a balance of protein and membrane-induced forces, effectively reconciling experimental data from different membrane environments. However, while much of the computational data is convincing, some aspects of the energetic analysis and models employed remain incomplete.

eLife Assessment

This useful study uses the MMTV-Neu-YD5 mouse model for HER2-dependent breast cancer to generate transcriptomic and proteomic datasets from extracted primary tumour samples. The data sets generated appear to be solid and will be useful to the community. However, mechanistic studies to support the conclusion that mitochondrial function is increased in the tumours remain incomplete and would benefit from experiments that would directly interrogate aspects such as cellular heterogeneity, and signalling.

eLife Assessment

This important work substantially advances our understanding of the interaction among gut microbiota, lipid metabolism, and the host in type 2 diabetes. However, some evidence is incomplete, particularly in the mouse experiments with FMT. Additional experiments will be required to strengthen the authors' interesting findings.

eLife Assessment

This valuable work presents an interpretable protein-DNA Energy Associative (IDEA) model for predicting binding sites and affinities of DNA-binding proteins. The study provides a detailed description of the method, making it reproducible. However, the generalizability of the prediction model presents certain concerns, and the supporting evidence appears incomplete. Nonetheless, with a thorough re-examination of the training and testing procedures, this model can be widely applicable for predicting genome-wide protein-DNA binding sites.

eLife Assessment

This is an important study reporting that activation of the presynaptic GPR55 receptor suppresses synaptic transmission by modulating GABA release through the reduction of the readily releasable pool without affecting the presynaptic AP waveform and calcium influx. The evidence supporting this claim is compelling and based on an impressive array of techniques including patch-clamp recordings from the axon terminals of cerebellar Purkinje cells and fluorescent imaging of vesicular exocytosis. However, a few technical issues leave some questions open, these include uncertainty regarding the specificity of pharmacological agents and the nature of the endogenous process that would activate this pathway in vivo. In the current form, the evidence indicating that synaptic vesicles become insensitive to VGCC activation in the presence of GPR55 is weak and would need to be supported with additional experimental data.

eLife Assessment

This study presents a useful finding that targeting amino acid metabolism can overcome Trastuzumab resistance in HER2+ breast cancer. The evidence supporting the claims of the authors is solid and the authors may want to validate their results in additional cell lines to strengthen their conclusions. Moreover, the authors should clarify the source of patient samples and why the manuscript focused on epigenetic regulations instead of major transcription factors. The work will be of interest to scientists working in the field of breast cancer.

eLife Assessment

Overall, this is an important work: the new methodology of hamFISH is a key additional tool for the assessment of the expression of multiple genes simultaneously. The authors provide convincing evidence of the utility of this approach on Medial Amygdala (MeA) tissue leveraging previous a transcriptomic dataset for gene selection. The authors also present a deeper dive into putative relationships between the on-tissue expression of subsets of genes and connectivity and behavioral regulation. The putative biological insights are intriguing, although preliminary, but notably they set up questions for future studies.

eLife Assessment

In this valuable contribution, the authors present an approach based on a complex systems theoretical framework to characterize diet-host-microbe interactions and to develop targeted bacteriotherapies using a three-phase workflow. Overall, the solid results provide a reference for microbial community research and insights to guide future studies. However, the theoretical systems approach would benefit from further description, and some claims regarding oxalate bacterial metabolism in complex microbial communities could be strengthened. This study will interest researchers working on gut microbiomes specifically those seeking to modulate host-microbial interactions.

eLife Assessment

This study presents an important methodological advance to improve the sensitivity of PCR for detecting Trypanosoma cruzi in blood, combining DNA fragmentation, deep sampling, and blood cell pellet analysis. The findings offer solid evidence of enhanced detection sensitivity and shed light on parasite load dynamics during chronic infection in mammalian reservoirs. The evidence is sound for macaques and the method shows promise in expanding detection limits, but there is some variability in the limits of detection and small sample size of human samples. This work will be of interest to parasitologists, epidemiologists, and clinicians using molecular diagnostics to monitor responses to etiological treatments for Chagas disease.

eLife Assessment

This study investigated the influence of genomic information and timing of vaccine strain selection on the accuracy of influenza A/H3N2 forecasting. The authors utilised appropriate statistical methods and have provided solid evidence that is an important contribution to the evidence base. While the study addresses a key aspect of public health, the impact is rather limited by its exclusive reliance on predictive methods using genomic information, without incorporating phenotypic data.

eLife Assessment

This important study investigates the implications of human endogenous retrovirus (HERV) activity in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM). These findings indicate significant associations that coincide with previous literature, which has suggested roles for differential HERV activity in degenerative, inflammatory, and aging-related pathologies of the central nervous system (CNS), as well as neurotropic infections. These seminal studies can be strengthened with minor improvements to the methodologies of characterizing differential HERV activity, further characterizing downstream mechanisms by which HERV activity impacts disease and by an expansion of the datasets utilized to include additional cohorts. These compelling findings are of immediate importance to clinicians, policymakers, and researchers interested in the underlying etiology of human health and disease.

eLife Assessment

This useful study investigates the impact of disrupting the interaction of RAS with the PI3K subunit p110α in macrophage function in vitro and inflammatory responses in vivo. Solid data overall supports a role for RAS-p110α signalling in regulating macrophage activity and so inflammation, however for many of the readouts presented the magnitude of the phenotype is not particularly pronounced. Further analysis would be required to substantiate the claims that RAS-p110α signalling plays a key role in macrophage function. Of note, the molecular mechanisms of how exactly p110α regulates the functions in macrophages have not yet been established.

eLife Assessment

This paper addresses the important question of quantifying epistasis patterns, which affect the predictability of evolution, by reanalyzing a recently published combinatorial deep mutational scan experiment. The findings are that epistasis is fluid, i.e. strongly background dependent, but that fitness effects of mutations are predictable based on the wild-type phenotype. However, these potentially interesting claims are inadequately supported by the analysis, because measurement noise is not accounted for, arbitrary cutoffs are used, and global nonlinearities are not sufficiently considered. If the results continue to hold after these major improvements in the analysis, they should be of interest to all biologists working in the field of fitness landscapes.

eLife Assessment

This study makes a valuable contribution to understanding Bayesian inference in dynamic environments by demonstrating how humans integrate prior beliefs with sensory evidence, revealing an overestimation of environmental volatility while accurately tracking noise. The evidence is solid, supported by robust model fitting and principled factorial model set analyses, though limitations in sample size and inconclusive findings on memory capacity tradeoffs reduce the overall impact. Future work should expand validation across datasets, enhance model comparisons, and explore the generalizability of reduced Bayesian frameworks to strengthen the conclusions and broader relevance of the study.

eLife Assessment

This important study uses diffusion magnetic resonance imaging to non-invasively map the white matter fibres connecting the zona incerta and cortex in humans. The authors present convincing evidence to indicate that these connections are organized along a rostro-caudal axis. The findings will be of interest to researchers interested in neuroanatomy and cortico-subcortical connectivity.