Evaluated articles

eLife Assessment

This manuscript uses modeling approaches to provide mechanistic insight into the structural and dynamic properties of enhancer-promoter interactions in Drosophila. Given the interest in this field, this is a timely approach, and the results give useful insights by providing predictions about the processivity of cohesin loop extrusion in Drosophila and concluding that the compartmental interaction strength is poised near criticality in the coil-globule phase space. The evidence provided to support some of the conclusions is, however, incomplete and would be strengthened by better considering some of the caveats in the data used to constrain the models, such as the use of "homie" genetic elements in the dynamic data. There is insufficient evidence provided for the dynamics being criticality-driven, and in addition, consideration of alternative models would further strengthen the conclusions of the manuscript.

eLife Assessment

This important work describes the adaptation and evaluation of two red-shifted anion channelrhodopsins (RubyACRs) for optogenetic inhibition in Drosophila. The study provides convincing evidence for the effectiveness of RubyACRs in fly neurons, including electrophysiology, calcium imaging, and behavioral analysis. With minor revisions to address potential toxicity and compatibility with 2-photon imaging, this paper and the publicly available fly lines it describes will be resources that are of value to the neuroscience community.

eLife Assessment

The work convincingly demonstrates the role of the mycobacterial secreted effector protein MmpE, which translocates to the host nucleus and exhibits phosphatase activity. The study is particularly valuable in showing that both the nuclear localization signal sequences and residues critical for phosphatase function are essential for host gene regulation, lysosomal biogenesis, and intracellular survival. Future studies will be needed to explore additional host pathways modulated by MmpE, particularly in the context of infection with a fully virulent Mycobacterium tuberculosis strain.

eLife Assessment

Weindel et al examine behavioural and EEG data in an innovative contrast comparison paradigm where they vary mean contrast widely while keeping contrast difference constant. As intended, this allowed an elegant decomposition of processing stages: while sensory encoding shortened with increasing contrast in keeping with Pieron's law, the period of decision formation lengthened, in keeping with Fechner's law, which was applied to drift rates in a diffusion model of that period. This is an important demonstration of how these two laws apply in concert, to two distinct processing levels, and the multivariate topography parsing, mixed effect models and diffusion models are convincing.

eLife Assessment

This manuscript reports the development and characterization of iGABASnFR2, a genetically encoded GABA sensor that demonstrates substantially improved performance compared to its predecessor, iGABASnFR1. The work is comprehensive and methodologically rigorous, combining high-throughput mutagenesis, functional screening, structural analysis, biophysical characterization, and in vivo validation. The significance of the findings is fundamental, and the supporting evidence is compelling. iGABASnFR2 represents a notable advance in GABA sensor engineering, enabling enhanced imaging of GABA transmission both in brain slices and in vivo, and constitutes a timely, technically robust addition to the molecular toolkit for neuroscience research.

eLife Assessment

The study introduces a valuable dataset for investigating the relationship between vision and language in the brain. The authors provide convincing evidence that decoders trained on brain responses to both images and captions outperform those trained on responses to a single modality. The dataset and decoder results will be of interest to communities studying brain and machine decoding.

eLife Assessment

This valuable study uses fiber photometry, implantable lenses, and optogenetics, to show that a subset of subthalamic nucleus neurons are active during movement, and that active but not passive avoidance depends in part on STN projections to substantia nigra. The strength of the evidence for these claims is solid and this paper may be of interest to basic and applied behavioural neuroscientists working on movement or avoidance.

eLife Assessment

This is an important study that takes a key step towards understanding developmental disorders linked to mutations in the O-GlcNAc transferase enzyme by generating a mouse model harboring the C921Y mutation. While the mechanisms remain open, the study thoroughly examines behavioral and anatomical differences in these mice and provides convincing evidence for behavioral hyperactivity and learning/memory deficits, as well as phenotypic differences in skull and brain formation. This study will be of interest to those studying neurodevelopmental disorders and associated mechanisms.

eLife Assessment

This study provides new important insights concerning pathogen variant-specific reproduction parameters from molecular sequencing and case finding. The methods for inferring which variants will likely emerge in subsequent epidemic cycles are solid. This article is of broad interest to infectious disease epidemiology researchers and mathematical modellers of the COVID-19 pandemic.

eLife Assessment

This important study combined careful computational modeling, a large patient sample, and replication in an independent general population sample to provide convincing evidence in support of a computational account of a difference in risk-taking between people who have attempted suicide and those who have not. It is proposed that this difference reflects a general change in the approach to risky (high-reward) options and a lower emotional response to certain rewards. While the findings advance our understanding of cognitive mechanisms at the group level, the observation that computational phenotype is predictive of suicidal behavior only in the clinical sample and not in the online sample limits its applicability for individual prediction, early detection and prevention of suicidality.

eLife Assessment

This valuable study concerns a highly interesting and biologically relevant topic, the regulation of the PIN auxin transporter, which is of broad interest to the plant biology community. The authors propose NPY1 to act downstream of PID in auxin-mediated development by modulating PIN phosphorylation, which, if experimentally solidified, would expand our understanding of PIN regulation. While the genetic evidence is solid, the mechanistic role of NPY1 and the functional relevance of phosphorylated PIN residues are still uncertain. There are also concerns regarding experimental rigor and methodological transparency.

eLife Assessment:

This study addresses valuable questions about the neural mechanisms underlying statistical learning of room acoustics, combining robust behavioral measures with non-invasive brain stimulation. The behavioral findings are strong and extend previous work in psychoacoustics, but the TMS results are modest, with methodological limitations and over-interpretation that weaken the mechanistic conclusions. The strength of evidence is therefore incomplete, and a more cautious interpretation of the stimulation findings, alongside strengthened analyses, would improve the manuscript.

eLife Assessment

This important study presents a cross-species and cross-disciplinary analysis of cortical folding. The authors use a combination of physical gel models, computational simulations, and morphometric analysis, extending prior work in human brain development to macaques and ferrets. The findings support the hypothesis that mechanical forces driven by differential growth can account for major aspects of gyrification. The evidence presented is overall strong and convincingly supports the central claims; the findings will be of broad interest in developmental neuroscience.

eLife Assessment

This important study characterises the morphogenesis of cortical folding in the ferret and human cerebral cortex using complementary physical and computational modelling. Notably, these approaches are applied to charting, in the ferret model, known abnormalities of cortical folding in humans. The study finds convincing evidence that variation in cortical thickness and expansion account for deviations in morphology, and supports these findings using cutting-edge approaches from both physical gel models and numerical simulations. The study will be of broad interest to the field of developmental neuroscience.

eLife Assessment

This is an important study reporting a new phenotype for a gene cluster that has previously been associated with the responses of the Gram-negative opportunistic pathogen Pseudomonas aeruginosa to flow fluid. Expression of the froABCD gene cluster is induced by HOCl in vitro and by activated immune cells, which produce these types of reactive chlorine species. Overall, the evidence presented by the authors is solid; however, the mechanism of fro-induction by HOCl remains unclear, and the evidence in support of the authors' claims is descriptive, which needs to be improved. This study is of interest to infection biologists interested in mechanisms of bacterial pathogenicity.

eLife Assessment

The authors develop an important microfluidic microvascular model called "Vessel-on-Chip", which they use to study Neisseria meningitidis interactions within this in vitro vascular system. Compelling evidence shows that the fabricated channels are lined by endothelial cells, and these can be colonized by N. meningitidis that in turn triggers neutrophil recruitment. This model has advantages over the human skin xenograft mouse model, which requires complex surgical techniques, however, it also carries limitations in that only endothelial cells and supplied specific immune cells in the microfluidics are present, while true vasculature contains a number of other cell types including smooth muscle cells, pericytes, and components of the immune system.

[Editors' note: this paper was reviewed by Review Commons.]

eLife Assessment

Yabaji et al. reports a fundamental study highlighting the mechanistic connection for susceptibility to TB infection via the sst1 locus, this was shown to involve increased IFN and Myc production causing the down-regulation of anti-oxidant defence genes and chronic lipidation. Ultimately, lipid peroxidation may underlie infectivity and macrophage dysfunction. Overall, the data presented are compelling, supported by a well designed multi-omics approach and the findings will be of broad interest to researchers investigating the molecular mechanisms of TB infection.

[Editors' note: this paper was reviewed by Review Commons.]

eLife Assessment

This useful study shows that stimuli of a certain size elicit theta oscillations in V1 neurons both in spikes and local field potentials, and monkeys performing a dot detection task on these stimuli show theta rhythmicity in their response times. This replicates previous findings showing rhythmic theta activity in V4 and behaviour when stimuli are presented in the receptive field along with a surrounding flanker stimulus. However, there is incomplete evidence that rhythmicity in neural activity is related to the rhythmicity in behavior, and the mechanisms underlying these oscillations remain unclear.

eLife Assessment

This important study reports that an oncogenic population in an epithelium can either be repressed or spread, depending on the tissues. This work provides convincing evidence, supported by pharmacological perturbations and numerical simulations using the vertex model, that the principle of "high heterotypic interfacial tension" that appears to drive cell sorting and tissue segregation in embryonic models similarly applies to cancer cell behaviour.

eLife Assessment

This important study provides compelling evidence that fever-like temperatures enhance the export of Plasmodium falciparum transmembrane proteins, including the cytoadherence protein PfEMP1 and the nutrient channel PSAC, to the red blood cell surface, thereby increasing cytoadhesion. Using rigorous and well-controlled experiments, the authors convincingly demonstrate that this effect results from accelerated protein trafficking rather than changes in protein production or parasite development. These findings significantly advance our understanding of parasite virulence mechanisms and offer insights into how febrile episodes may exacerbate malaria severity.