Evaluated articles

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.

eLife assessment

This important study offers new and convincing support for the idea that about a third of mouse liver DNAse hypersensitivity sites (DHS) showing male-biased chromatin opening are sex-biased because of the male-specific cyclic action of growth hormone pulses to alter chromatin accessibility, as compared to the relative ineffectiveness of the more static pattern of growth hormone secretion in females. Supporting evidence is found in the impact of hypophysectomy and growth hormone treatment on chromatin accessibility, and the binding of specific transcription factors and epigenetic marks at STAT5-sensitive sites. This work uncovers mechanisms underlying sex differences in liver function and will be of broad interest to endocrinologists and hepatologists.

eLife assessment

This study investigated the role of specific proteins in a mouse model of developmental epilepsy. The significance of the work is important because a new mouse model was used to simulate a type of developmental epilepsy. The work is also significant because the deletion of two proteins together, but not separately, improved the symptoms, and data were convincing.

eLife assessment

This useful study uses a microfluidic method to evaluate the ability of single human white blood cells to produce combinations of cytokines and the evidence that this takes place is solid. The paper highlights polyfunctionality using data that are similar to a prior dataset from the same group. The authors comment that, in analysis of larger panels, single cells rarely make more than 2 or 3 cytokines so that investigation of 3 cytokines at a time is sufficient to investigate this phenomenon. Coupling this approach to other modes of single cell analysis may provide greater insight into what limits simultaneous production of multiple cytokines.

eLife assessment

This paper presents valuable findings that shed light on the mental organisation of knowledge about real-world objects. It provides diverse, if incomplete and tentative, evidence from behaviour, brain, and large language models that this knowledge is divided categorically between relatively small objects (closer to the relevant scale for direct manipulation) and larger objects (further from the typical scope of human affordances for action).

eLife assessment

The authors present a valuable work suggesting that the superficial, retinorecipient layers of the mouse superior colliculus (SC) may participate in figure-ground segregation and object recognition. These data are based largely on optogenetic perturbations of SC but the strength of evidence is currently incomplete: although the effects are statistically significant, there are significant technical limitations that are not adequately addressed via controls.

eLife assessment

This study presents important findings linking structural and functional changes in frontotemporal dementia to underlying neurotransmitter systems. The evidence to support the claims is solid, however, relationships are relatively modest and there are limitations regarding the neurotransmitter data. This study will appeal to clinicians and neuroscientists who are interested in the potential effects of certain neurotransmitter systems on clinical features of frontotemporal dementia.

eLife assessment

This is a valuable report that describes that ACE2 expression is upregulated by SARS-CoV-2 infection via activation of transcription factor Sp1 and inhibition of HNF4α through the PI3K/AKT pathway. Inhibition of Sp1 reduces SARS-CoV-2 infection in vitro and in an animal model. This work is solid and will be of interest to those interested in ACE2 biology and its impact in COVID-19.

eLife assessment

This fundamental work substantially advances our understanding of how cells can tightly modulate small GTPase activity to build and maintain neighboring cytoskeletal structures, in this case microvilli. The evidence supporting these claims is compelling and is supported by both protein-protein interaction assays as well as cell biological studies. The work will be of interest to cell biologist studying the cytoskeleton as well as those interested in G-protein mediated regulation.

eLife Assessment

This is a valuable analysis of STORM data that characterizes the clustering of active zones in retinogeniculate terminals across ages and in the absence of retinal waves. The design makes it possible to relate fixed time point structural data to a known outcome of activity-dependent remodeling. The latest revision has tempered the causal claims made in previous versions. The result provides solid structural support for the hypotheses regarding how activity influences the clustering of these synapses.

eLife Assessment

The ExA-SPIM methodology developed here and characterized and supported by convincing evidence is an important development for the field of light sheet microscopy as the new technology provides an impressive field of view making it possible to image the entire expanded mouse brain at cellular and subcellular resolution.

eLife assessment

This study provides useful findings on how phonetic properties of words, i.e., their difficulty and prior knowledge, influence the outcome of targeted memory reactivation (TMR) during sleep. While these findings are supported by solid evidence, they are based on a small sample size warranting future work to shed further light on the impact of TMR in language learning.