Evaluated articles

eLife assessment

This manuscript used the sci-Plex system for screening compounds to improve the Ascl1-induced reprogramming from Müller glia to bipolar neurons in vitro, followed by in vivo characterization of two promising compounds in mice. The findings are valuable for future studies to develop cell replacement strategies for treatment of retinal degeneration. The strength of evidence is solid, featuring a scalable drug screening design, albeit with limited mechanistic insights.

eLife assessment

This manuscript reports a valuable computational study of the effects of axon de-myelination and re-myelination on action potential speed and propagation failure. The manuscript presents solid evidence for the effects of de- and re-myelination in different models of working memory, with potential implications in disorders such as multiple sclerosis. The exposition of the manuscript is targeted for researchers interested in biophysical models of cognitive deficits.

eLife assessment

This manuscript describes an important web resource for kinases connected to cytokines. The compelling information will be used by researchers across a number of fields including analysts, modelers, wet lab experimentalists and clinician-researchers, who are looking to improve our understanding of pathologies and means to correct them through modulating the immune response.

eLife assessment

The findings of this study are valuable as they provide new insights into the role of acetylcholine in modulating sensory processing in the auditory cortex. This paper reports a systematic measurement of cell activity in the auditory cortex before and after the microiontophoretic application of Ach during an oddball and cascade sequence of auditory stimuli. The evidence presented is convincing, as the study used a rigorous experimental design and statistical analysis. The manuscript will interest researchers in auditory neuroscience and neuromodulation, as well as clinicians and individuals with auditory processing disorders.

eLife assessment

This fundamental study explored the impact of migraine-related cortical spreading depression (CSD) on the firing of nerves innervating the coverings of the brain that are considered the putative source of migraine-related pain. Using convincing approaches they show that these responses are altered in response to mechanical deformation of the brain coverings. Given that migraine is characterized by worsening head pain in response to movement, the findings offer a potential mechanism that may explain this clinical phenomenon.

eLife Assessment:

This study presents valuable findings that add to our understanding of cortical astrocytes, which respond to synaptic activity with calcium release in subcellular domains that can proceed to larger calcium waves. The proposed concept of a spatial "threshold" is based on solid evidence from in vivo and ex vivo imaging data and the use of mutant mice. Details of the specific threshold must be taken with caution and are necessarily incomplete, but may be supported by additional experiments with higher resolution in space and time in the future.

eLife assessment

This important study reports comprehensive multi-omics data on the changes induced in young and aged male mouse tail fibroblasts after treatment with chemical reprogramming factors. The authors provide solid evidence to support their claim that chemical reprogramming factors induce changes consistent with a reduction of cellular 'biological' age (e.g., correlations with established aging markers in whole tissues).

eLife assessment

The authors provide an important series of metabolic measurements characterizing group dynamics in fish, rationalizing that schooling behavior presents several benefits. The strength of evidence supporting this conclusion is solid, but the specific methodological and analytical approaches taken should be considered for further interpretation.

eLife Assessment

This valuable study investigates evolutionary aspects around a single amino acid polymorphism, known to be under long-term balancing selection, in an immune peptide of Drosophila melanogaster. Using alleles with different substitutions, the investigators demonstrate that while one allele provides better survival after systemic infections by a bacterial pathogen, the alternative allele endows its carriers with a longer lifespan under certain conditions. The authors suggest that these contrasting fitness effects of the two alleles contribute to balancing their long-term evolutionary fate. While the work is very interesting, the strength of the provided evidence is still incomplete, and the study would benefit from more rigorous approaches.

eLife assessment

The study presents important findings regarding a transcription-independent component of the early recovery of proteasome activity from a short pulse of proteasome inhibitor treatment, which has not been appreciated before and which is independent of the DDI2-NRF2 axis. While the evidence is in principle solid, with recapitulation in several cell line models, the proposed alternative underlying mechanism, namely regulation at the level of proteasome assembly, lacks experimental support, and at this point remain speculative.

eLife Assessment

This is a valuable study of the role that life history differences might play in determining population size and demography. While concerns about generation times and population structure leave the evidence for the claims in parts incomplete, the work is of considerable interest to anyone who tries to understand evolutionary consequences of life history changes.

eLife assessment

This important study addresses the problem of detecting weak similarity between protein sequences, a procedure commonly used to infer homology or assign putative functions to uncharacterized proteins. The authors present a convincing approach that combines recently developed protein language models with well-established methods. The benchmarks provided show that the proposed tool is fast and accurate for remote homology detection, making this paper of general interest to all researchers working in the fields of protein evolution and genome annotation.

eLife assessment

This fundamental study addresses a long-standing mystery in splicing regulation: does splicing occur co- or post-transcriptionally? The authors provide compelling evidence demonstrating that splicing can occur post-transcriptionally at a transcription site proximal zone, changing the way we think about splicing.

eLife assessment

The study is an important advancement to the consideration of antimalarial drug resistance: the authors make use of both modelling results and supporting empirical evidence to demonstrate the role of malaria strain diversity in explaining biogeographic patterns of drug resistance. The theoretical methods and the corresponding results are compelling, with the novel model presented moving beyond existing models to incorporate malaria strain diversity and antigen-specific immunity. This work is likely to be interesting to malaria researchers and others working with antigenically diverse infectious diseases.

eLife assessment

This study presents useful results on glutamine-rich motifs in relation to protein expression and alternative genetic codes. The solid data are based on bioinformatic approaches that are employed to systematically uncover sequence features associated with proteome-wide amino acid distribution and biological processes.

eLife assessment

This valuable study sheds light on the pivotal role of alterations in chondrocyte glycan metabolism in two contexts: The onset of cartilage degeneration and early onset of osteoarthritis (OA). The action is through hypertrophic differentiation of chondrocytes, a finding that provides insights into the identification of nascent markers for early-stage OA. The evidence supporting the claims is solid, with the authors clearly demonstrating the role of articular cartilage corefucosylation in the development of OA. The authors' inferences would be further enhanced through future experiments aimed at analyzing the mechanisms underlying the changes in glycometabolism in cartilage.

eLife Assessment

This is an important study that characterizes a surprising interaction between two different cytokine/hormone receptors using nanoscale resolution (dSTORM) microscopy. The study provides solid evidence that the interaction is ligand-dependent, and is mediated by the receptor-associated intracellular signalling molecule JAK2. While at present limited to growth hormone and prolactin receptors in a limited number of cell lines, there are potentially broad implications for cytokine signalling, as such JAK2-mediated interactions could occur between a range of different cytokines. Moreover, the specific hormone interactions shown in the manuscript may have significant implications for understanding how these hormones can have differential effects in breast cancer, under different conditions.

eLife assessment

This valuable study asks how Promyelocytic leukemia protein (PML) becomes associated with the nucleoli of cells (PML Nucleolar Associations, PNAs) upon various genotoxic stimuli. Using immunostaining analysis with induced DNA double-strand breaks (DSBs) in rDNA repeats, the authors provide solid evidence that PNAs are triggered mostly by the inhibition of topoisomerase and RNA polymerase I, which is augmented by homologous recombination but not by the non-homologous end joining double-strand break repair pathway. The findings have potential implications for a better understanding of how DNA damage in ribosomal DNA is repaired for genome stability. This paper is of interest to researchers in the fields of nuclear structure and DNA repair.

eLife assessment

This important study could potentially represent a step forward towards personalized medicine by combining cell-based data and a prior-knowledge network to derive Boolean-based predictive logic models to uncover altered protein/signaling networks within cancer cells. The level of evidence supporting the conclusions is solid, as the authors present analyses on independent, real-world data to validate their approach. These findings could be of interest to medical biologists working in the field of cancer, as the work should inform drug development and treatment choices in the field of oncology.

eLife assessment

This study provides the fundamental insight that TGN46, a single-pass membrane protein, acts as a cargo receptor for proteins at the Trans-Golgi Network. The authors demonstrate that the luminal domain of TGN46 is crucial for the incorporation of the soluble secretory protein PAUF into CARTS, a class of vesicles mediating TGN to surface traffic. The data presented are compelling, yielding a clear model for the sorting of cargos destined for secretion.