Evaluated articles

eLife assessment

In this valuable paper, the authors use an existing theoretical framework relying on information theory and maximum entropy inference in order to quantify how much information single cells can carry, taking into account their internal state. They reanalyze experimental data in this light. Despite some limitations of the data, the study convincingly highlights the difference between single-cell and population channel capacities. This result should be of interest to the quantitative biology community, as it contributes to explaining why channel capacities are apparently low in cells.

eLife assessment

This study presents a novel fluorescence based imaging strategy to investigate the folding status of RNA-binding proteins (RBPs) and their association with molecular chaperones under stress. It provides fundamental findings that will potentially advance our understanding in the folding and aggregation status of RBPs in nuclear stress bodies in a significant manner. However, there is also the concern that the evidence regarding protein fate is incomplete and additional controls are needed to fully support the conclusion. The imaging methodology can be adapted to study many other proteins that undergo liquid-liquid phase separation under specific cellular conditions.

eLife assessment

This is an important study that brings insight into mechanisms that underlie regulation of GABAergic transmission in response to changes in activity. The authors present solid data supporting the premise that action potential firing rather than excitatory synaptic strength is a key determinant of GABAergic synaptic inputs.

eLife assessment

This manuscript describes important findings that will impact our understanding of nuclear pore complex (NPC)-genome interactions and how nuclear pore proteins (nucleoporins) impact super enhancer function. The authors develop a clever new approach termed NPC-DamID to map chromatin-NPC interactions that has several important advantages over existing techniques and may be used in contexts that are incompatible with genetic manipulation. The authors provide compelling evidence that nucleoporins interact with super enhancers in multiple cell types and also suggest that the phase separation behavior of nucleoporins contributes to the hierarchical organization of super enhancers, which is exciting and will stimulate additional work.

eLife assessment

This is an important study highlighting how a single protein transporter dysfunction can significantly alter brain biochemistry, potentially playing a crucial role in the intellectual disability in creatine transporter deficiency (CTD) patients. The evidence is compelling that the new in vitro CTD model using CTD patient's brain organoid cultures will be widely applicable. Despite minor areas for further exploration, the study significantly enhances our understanding of CTD, offering potential therapeutic targets and a robust foundation for continued research in the field.

eLife assessment

This study demonstrates that plasticity of ocular dominance of binocular neurons in the visual thalamus persists in adulthood. The evidence supporting the authors' conclusion is convincing, and the findings are an important contribution to a growing body of work identifying plasticity in the adult visual system. This work will interest those in the field of ocular dominance plasticity in the visual system as well as scientists investigating the function of synaptic plasticity in the brain.

eLife assessment

The bacterial neurotransmitter:sodium symporter homoglogue LeuT is an well-established model system for understanding the fundamental basis for how human monoamine transporters, such as the dopamine and serotonin, couple ions with neurotransmitter uptake. Here the authors provide convincing data to show that K+ binding on the intraceullular side catalyses the return step of the transport cycle in LeuT by binding to one of the two sodium sites. The mechansitic consequences of K+ binding could either facilitate LeuT re-setting and/or prevent the rebinding and possible efflux of Na+ and substrate.

eLife Assessment

This fundamental study examines whether synaptic cell adhesion molecules neuroligin 1-3 resident on astrocytes, rather than neurons, exert effects on synaptic structure and function. With compelling evidence, including rigorous validation of neuroligin deletion efficiency in astrocytes and independent confirmation using human neuron-mouse glia co-cultures, the authors report that deletion of neuroligins 1-3 specifically in astrocytes does not alter synapse formation or astrocyte morphology in the hippocampus or visual cortex. This study provides definitive evidence highlighting the specific role of neuronal neuroligins rather than their astrocytic counterparts in synaptogenesis.

eLife assessment

This valuable study investigates how hierarchies are processed in the brain, using a paradigm that intends to bridge disparate domains (e.g., language/music and memory). The main findings are that hippocampus and medial prefrontal cortex are sensitive to hierarchy position, while the response in inferior frontal gyrus seems to vary with amount of experience with the hierarchy. Evidence supporting these claims is solid, and would be strengthened by additional methodological clarifications (e.g., as to why the particular analyses are most appropriate for the research question) and further discussion of limitations related to the study design (e.g., the possibility that the task does not require hierarchical representations).

eLife assessment

The manuscript describes the synergy among PI3Kbeta activators, providing compelling results concerning the mechanism of their activation. The particular strengths of the work arise to a great extend from the reconstitution system better mimicking the natural environment of the plasma membrane than previous setups have. The study will be a landmark contribution to the signaling field.

eLife assessment

This manuscript describes a fundamental strategy for developing isozyme-selective inhibitors of inositol hexakisphosphate kinases. The compelling evidence that subtle changes to the gatekeeper position can sensitize the inositol hexakisphosphate kinase mutant to allosteric inhibitors will undoubtedly inspire other analog-sensitive inhibitor studies. This manuscript will be of interest to researchers focusing on kinase regulation and inhibitor design.

eLife assessment

This is an important study highlighting a distinct role of WASP dependent actin foci in B cell antigen receptor signalling. The evidence supporting the conclusions is compelling. The proposal of higher molecular density in B cell receptor clustering leading to kinase exclusion and attenuated signalling is provocative as it contrasts with models for other antigen receptors.

eLife assessment

This study presents fundamental findings on the role of transcription readout and intron retention in transposon expression during aging in mammals. The evidence supporting the claims of the authors is compelling, strongly supporting the authors' claims. The work will be of interest to scientists studying aging, transcription regulation, and epigenetics.

eLife assessment

There was a range of opinion among three highly expert reviewers from different perspectives in the field. This is a significant topic and it was felt that the contribution at present is valuable to those in the field. However, it was agreed after consultation that the description of the simulation methodology was inadequate.

eLife assessment

This important study advances our understanding of the potential mechanisms of deep-sea adaptation and sheds light on the evolutionary history of hadal snailfish. Through comparative genomic analysis, the authors provide convincing evidence and propose hypotheses on the timing of trench colonization, population structure, and adaptations to the hadal snailfish genome in response to their environment.

eLife assessment

The authors pair single-cell sequencing technology with the LoopSeq synthetic long-read method to examine samples of hepatocellular carcinoma and benign liver, with the goal of identifying mutations and fusion transcripts specific to cancer cells. The authors present a valuable resource and the overall support for the major claims is solid.

eLife assessment

The authors present a solid statistical framework for using sibling phenotype data to assess whether there is evidence for de-novo or rare variants causing extreme trait values. Their valuable method is promising and will be of interest to researchers studying complex trait genetics.

eLife Assessment

This useful study examines relationships between tumor mutational burden and the response to immunotherapy, using new data sets along with publicly available data sets. The authors conclude that tumor mutational burden cut-offs are unreliable proxies for predicting the response to therapy, underpinned by solid evidence, but with several caveats and assumptions that leave the central question subject to further inquiry. In summary, this is an interesting study that adds to a growing body of work investigating the particular conditions governing the effectiveness of immunotherapy.

eLife assessment

This work presents important findings on the cellular and ultrastructural organization of the nervous system in the freshwater polyp Hydra. The authors present outstanding imaging data with convincing evidence to support their claims. The manuscript provides a starting point for further functional in vivo studies. The work will be of interest to developmental biologists and neurobiologists.

eLife assessment

This important study reports on a new method for the fabrication and the analysis of the transport through nuclear pore complexes mimic. Methods, data and analyses are convincing and show a clear correlation between the size of the nuclear pore complex mimic and its transport selectivity. This work will be of high interest to biologists and biophysicists working on the mechanosensitivity of nucleocytoplasmic transport.