Evaluated articles

eLife Assessment

Bowler et al. present a software/hardware system for behavioral control of navigation-based virtual reality experiments, particularly suited for pairing with 2-photon imaging but applicable to a variety of techniques. This system represents a valuable contribution to the field of behavioral and systems neuroscience, as it provides a standardized, easy to implement, and flexible system that could be adopted across multiple laboratories. The authors provide compelling evidence of the functionality of their system by reporting benchmark tests and demonstrating hippocampal activity patterns consistent with standards in the field. This work will be of interest to systems neuroscientists looking to integrate flexible head-fixed behavioral control with neural data acquisition.

eLife Assessment

This important study combines convincing evolution experiments with molecular and genetic techniques to study how a genetic lesion in MreB that causes rod-shaped cells to become spherical, with concomitant deleterious fitness effects, can be rescued by natural selection. The detailed mechanistic investigation increases our understanding of how mreB contributes to cell wall synthesis and shows how compensatory mutations may reestablish its homogeneity.

eLife Assessment

This study presents a method for expressing single-stranded DNA fluorescent aptamers in E. coli using a retron-based strategy. The evidence supporting the successful expression and folding of DNA aptamers is solid, with clear demonstration of fluorescence after extraction, though the aptamers do not function in living cells. The method represents an important technical advance that will likely become standard for DNA aptamer expression in bacterial systems.

eLife Assessment

In this valuable study, Huffer et al posit that non-cold sensing members of the TRPM subfamily of ion channels (e.g., TRPM2, TRPM4, TRPM5) contain a binding pocket for icilin that overlaps with the one found in the cold-activated TRPM8 channel. After examining a body of TRP channel cryo-EM structures to identify the conserved site, this study presents convincing electrophysiological evidence supporting the presence of an icilin binding pocket within TRPM4. This study shows that icilin has modulatory effects on the TRPM4 channel and will be of direct interest to those working in the TRP-channel field, but it also has implications for studies of somatosensation, taste, as well as pharmacological targeting of the TRPM subfamily.

eLife Assessment

This fundamental research conducted a molecular comparison between smooth muscle cells and adjacent fibroblast cells within lung blood vessels affected by pulmonary arterial hypertension. The study identified distinct disease-related states in each cell type and provided deeper insights into their interactions and communication. While certain conclusions should be interpreted with caution due to inherent methodological limitations, the study's findings remain convincing and robust. This is supported by the use of advanced and complementary techniques, as well as the rare isolation of diseased lung blood vessel cells from the same donor, enabling direct comparison.

eLife Assessment

The authors have developed a valuable approach that employs cell-free expression to reconstitute ion channels into giant unilamellar vesicles for biophysical characterisation. The work is convincing and will be of particular interest to those studying ion channels that primarily occur in organelles and are therefore not amenable to be studied by more traditional methods.

eLife Assessment

This important work substantially advances our understanding of RNA structure analysis by introducing an innovative method that extends DMS probing to include guanosine residues, thereby enhancing our ability to detect complex tertiary interactions. The evidence supporting the conclusions is compelling, with detailed analyses demonstrating the method's capacity to differentiate structural contexts and improve RNA structure predictions. This work will be of broad interest to RNA structural biology, biochemistry, and biophysics researchers.

eLife Assessment

This study presents valuable findings, based on solid methods, to link metabolic dysfunction in Wilson's disease to immune cell dysregulation and poor cholecystitis outcomes. The integration of clinical data and single-cell analyses highlights NK cell exhaustion as a key factor, offering insights with potential therapeutic implications. The work will be of interest to colleagues in inflammatory and metabolic diseases.

eLife Assessment

This fundamental work provides new mechanistic insight in regulation of PDGF signaling through splicing controls. The evidence is compelling to demonstrate functional involvement of Srsf3, an RNA binding protein to this new and interesting mechanism. The work will be of broad interest to developmental biologists in general and molecular biologists/biochemists in the field of growth factor signaling and RNA processing.

eLife assessment

The authors combined molecular dynamics simulations and experiments to study the role of ATP as a hydrotrope of protein aggregates. The topic is of major current interest and thus the study potentially makes an important contribution to the community. With the revised version, the level of evidence is considered generally solid, although there remains concern regarding the unusually high ATP concentration used in the simulation.

eLife Assessment

This potentially valuable work aimed at a better understanding of the mechanisms of response and resistance to androgen deprivation therapy in prostate cancer using genetically engineered mouse models. A key observation relates to the timing of TNF blockage therapy and the concept of a "TNF switch." The solid data were collected using conventional approaches and the conclusions are mostly justified, particularly with the inclusion of more detailed statistics in the revision. The work will be of interest to the prostate cancer research community.

eLife Assessment

This study provides valuable insights into the influence of sex on bile acid metabolism and the risk of hepatocellular carcinoma (HCC). The data to support that there are inter-relationships between sex, bile acids, and HCC in mice are convincing, although this is a largely descriptive study. Future studies are needed to understand the interaction of sex hormones, bile acids, and chronic liver diseases and cancer at a mechanistic level. Also, there is not enough evidence to determine the clinical significance of the findings given the differences in bile acid composition between mice and men.

eLife assessment

This study presents a valuable finding on the precision conferred by dynamical interpretation of morphogen gradients. The evidence supporting the claims of the authors is convincing, with compelling theoretical analysis and solid yet incomplete experimental data. With the experimental part strengthened, the work could be of interest to the developmental biology and developmental systems biology communities.

eLife assessment

This manuscript probes the ways in which a protein tag might influence the structure, dynamics and stability of a covalently-attached substrate protein. Such findings are of important significance to several fields, particularly in understanding how these influences control the abundance of proteins within a cell. The evidence provided to support the authors' conclusions are, however, incomplete and further control experiments are necessary to fully support the proposed model.

eLife Assessment

This valuable study reports on electrophysiological recording of the spiking activity of single neurons in the entopeduncular nucleus (EPN) in freely-moving mice performing an auditory discrimination task. The data show that the activity of single EPN neurons is modulated by reward and movement kinematics, with the latter further affected by task contexts (e.g. movement toward or away from a reward location). The results provide solid evidence for the conclusions. There is some ambiguity as to whether the data contain the population of EPN neurons characterized in previous studies that obtained different results. Investigations separating confounding factors would be of benefit. Nonetheless, the work is overall of interest to those who study how the basal ganglia, particularly the EPN, contribute to behavior.

eLife assessment

This important paper shows that the anti-gremlin-1 (GREM1) antibody is not effective at treating liver inflammation or fibrosis. Critically, the evidence also challenges existing data on the detection of GREM1 by ELISA in serum or plasma by demonstrating that high-affinity binding of GREM1 to heparin would lead to localisation of GREM1 in the ECM or at the plasma membrane of cells. The conclusions are supported by a convincing, well-controlled set of experiments.

eLife assessment

This fundamental state-of-the-art modeling study explores neural mechanisms underlying walking control in cats, demonstrating the probability of three different states of operation of the spinal circuitry generating locomotion at different speeds. The authors' biophysical modeling sufficiently reproduces and provides explanations for experimental data on how the locomotor cycle and phase durations depend on treadmill walking speed and points to new principles of circuit functional architecture and operating regimes underlying how spinal circuits interact with supraspinal signals and limb sensory feedback signals to produce different locomotor behaviors at different speeds, which are major unresolved problems in the field. The modeling evidence is compelling, especially in advancing our understanding of locomotion control mechanisms and will interest neuroscientists studying the neural control of movement.

eLife Assessment

This important study is an advancement towards the understanding of animal nervous system organization and evolution by providing an exceptional, high-quality and detailed description of the entire connectome of the 3-day larva of the marine annelid Platynereis dumerilii. It provides a wealth of data on cell type diversity and the modules that interconnect them. Its strength is the massive amount of high-quality data, although this is also partly a weakness as it can make the work difficult to read and digest scientifically. This work lays the foundations for studies on cell type diversity, segmental vs. intersegmental connectivity, and mushroom bodies, but will certainly also be of use to scientists interested in other nervous systems parts, their functions, and evolution.

eLife Assessment

This study presents a valuable methodological advancement in quantifying thoughts over time. A novel multi-dimensional experience-sampling approach is presented, identifying data-driven patterns that the authors use to interrogate fMRI data collected during naturalistic movie-watching. The experimentation is inventive and the analyses carried out and results presented are convincing.

eLife Assessment

This important study provides new insights into the mechanisms that underlie perceptual and attentional impairments of conscious access. The paper presents convincing evidence of a dissociation between the early stages of low-level perception, which are impermeable to perceptual or attentional impairments, and subsequent stages of visual integration which are susceptible to perceptual impairment but resilient to attentional manipulations. This study will be of interest to scientists working on visual perception and consciousness.