Evaluated articles

eLife Assessment

This paper represents a very solid body of work that aims to understand why prostate cancer with CDK12 loss does not respond to HRd-based therapeutics, such as PARP inhibitors. The work is felt to be fundamental given a thorough computational and genomic analysis, the generation of CDK12-adapted cell lines, and potential synthetic vulnerability to CDK13 loss with genetic knockdown or co-inhibition with a CDK12/13 inhibitor. The evidence is compelling given the authors' systematic testing of components of the CDK12/13 pathways in a number of prostate cancer models. Some weaknesses focused on the functional effect of the various mutations found at different CDK12 sites (loss vs. altered), more comprehensive characterization of CDK12 KO lines, and specificity of the CDK12/13 inhibitor and in vivo experimental schema.

eLife Assessment

This valuable study examines the effects of side-wall confinement on the chemotaxis of swimming bacteria in a shallow microfluidic channel. The authors present solid experimental evidence, combined with geometric analysis and numerical simulations of simplified models, showing that chemotaxis is enhanced when the distance between the side walls is comparable to the intrinsic radius of circular swimming near open surfaces. This study should be of interest to scientists specializing in bacteria-surface interactions.

eLife Assessment

This is a convincing paper that addresses topics important in our understanding of how inflammatory markers are modulated in both obesity and type 2 diabetes and their effects on Wnt signaling mediators in human bone. There are changes in bone at the tissue level in these 2 common metabolic disorders that ultimately lead to compromised bone strength. These data will be critical to our understanding of the pathophysiology of skeletal fragility in obesity and diabetes.

eLife Assessment

This article uncovers a new improtant role of STAMBPL1 in promoting angiogenesis in triple-negative breast cancer (TNBC) and elucidates the specific mechanisms by which it activates the GRHL3/HIF1α/VEGFA axis through interaction with FOXO1. The finding that STAMBPL1 mediates GRHL3 transcription through the interaction with FOXO1 is novel. These experimental results corroborate each other, forming a solid foundation of evidence that supports the main findings of the article.

eLife Assessment

This study provides important findings in characterizing dopamine neuron heterogeneity in the ventral midbrain. The strength of evidence is strong for a convincing classification, but claims related to the effects of G2019S-LRRK2 expression were considered more preliminary. The creation of an snRNA-seq exploration tool for these datasets should interest groups interested in understanding dopamine neuron subclass dynamics in behavior and diseases.

eLife Assessment

Sanchez-Vasquez et al establish an innovative approach to induce aneuploidy in preimplantation embryos. This important study extends the author's previous publications evaluating the consequences of aneuploidy in the mammalian embryo. In this work, the authors investigate the developmental potential of aneuploid embryos and characterize changes in gene expression profiles under normoxic and hypoxic culture conditions. Using a solid methodology they identify sensitivity to Hif1alpha loss in aneuploid embryos, and in further convincing experiments they assess how levels of DNA damage and DNA repair are altered under hypoxic and normoxic conditions.

eLife Assessment

This work introduces an important new method for depleting ribosomal RNA from bacterial single-cell RNA sequencing libraries, demonstrating its applicability for studying heterogeneity in microbial biofilms. The findings provide convincing evidence for a distinct subpopulation of cells at the biofilm base that upregulates PdeI expression. Future studies exploring the functional relationship between PdeI and c-di-GMP levels, along with the roles of co-expressed genes within the same cluster, could further enhance the depth and impact of these conclusions.

eLife Assessment

This important paper shows that the acquisition and expression of Pavlovian conditioned responding are lawfully related to temporal characteristics of an animal's conditioning experience. It showcases a rigorous experimental design, several different approaches to data analysis, careful consideration of prior literature, and a thorough introduction. The evidence supporting the conclusions is strong and convincing. The paper will have a general appeal to those interested in the behavioral and neural analysis of Pavlovian conditioning.

eLife Assessment

This study presents important findings on the role of CXXC-finger protein 1 in regulatory T cell gene regulation and function. The evidence supporting the authors' claims is solid, with mostly state-of-the-art technology, although the inclusion of more mechanistic insights would have strengthened the study. The work will be of relevance to immunologists interested in regulatory T cell biology and autoimmunity.

eLife Assessment

This manuscript offers a modeling platform in which horizontal gene transfer (HGT) is incorporated into the ecological dynamics of microbial communities. The investigation is valuable as it brings to the forefront a potentially important process and highlights its implications, however, the investigation in its current form is incomplete because it is based on a narrow range of parameters and assumptions. As a result, the scope and relevance of the findings are not fully clear; a more in-depth description of model assumptions and the formulation structure and a more thorough analysis of the impact of different parameters would strengthen the manuscript. This work will be of interest to microbiologists as well as researchers in ecological and evolutionary biology.

eLife Assessment

This important study compares the cortical projections to primary motor and sensory areas originating from the ipsilateral and contralateral hemispheres. They find that, while there is substantial symmetry between the two hemispheres regarding the areas sending projections to these primary cortical areas, contra-hemispheric projections had more inputs from layer 6 neurons than ipsi-projecting ones. The evidence is convincing and most of the conclusions are supported by rigorous analyses.

eLife Assessment

This valuable study characterizes the molecular signatures and function of a type of enteric neuron (IPAN) in the mouse colon, identifying molecular markers (Cdh6 and Cdh8) for these cells. A battery of solid experimental findings suggest data from other species are likely translatable to mice, bridging the abundant literature from humans and other mammals into this experimentally tractable animal model, but the data establishing the role of Cdh6 in synapses among IPANs and in cell-cell contacts with non-neuronal cells is incomplete. This work will be of interest to scientists studying the motor control of the colon and more generally the enteric neuromuscular system.

eLife Assessment

The authors use a multidisciplinary approach to provide a useful link between Beta-alanine and S. Typhimurium (STM) infection and virulence. The work shows how Beta-alanine synthesis mediates zinc homeostasis regulation, possibly contributing to virulence. However, the work is incomplete and requires additional data to firmly establish the connection between Beta-alanine synthesis and zinc homeostasis. Measuring the source and zinc content of STM in vivo and examining mechanisms in human clinical strains and other serovars would be essential.

eLife Assessment

This important study reports on a basis for neurabin-mediated specification of substrate choice by protein phosphatase-1. The data from the comprehensive approach using structural, biochemical, and computational methods are compelling, but the role of the crucial tryptophan residue in the recognition motif can be further tested to strengthen the main argument. This paper is broadly relevant to those investigating various cellular signaling cascades that entail phosphorylation as the main mechanism.

eLife Assessment

This solid paper reports on the use of artificial intelligence to assess bone marrow adipose tissue in the skull. The method employing MRI is novel and that approach allows for the identification of genetic loci that regulate this trait as well as others using data from the UK biobank. Overall this is an important contribution although the authors should consider several points: 1-validation of the T1-weighted MRI signal intensity; 2-further discussion of the sex differences; and 3-cross-trait linkage disequilibrium score regression (LDSC) for osteoporosis, Parkinson's disease, and cognitive function.

eLife Assessment

This article reports a useful set of findings on how electrophysiological response properties of neurons correlate with their position in the brain. The evidence currently remains incomplete, with reviewers making specific suggestions for how clustering needs to be redone. The manuscript would also benefit from a more focused presentation of results and the removal of incorrect claims about recording biases.

eLife Assessment

This valuable study clarifies the mechanism by which the kinesin-10 motor protein, chromosome-associated kinesin, Kid (KIF22), enables chromosome movement during mitosis, demonstrating that human and Xenopus Kid proteins function as processive, homodimeric kinesins capable of processive microtubule plus-end motility. The convincing work highlights that Kid can recruit and transport duplex DNA along microtubules via its conserved C-terminal DNA binding domain, revising our understanding of chromokinesins' role in chromosome motility during mitosis. Although the data are robust, the manuscript would benefit from some editing for clarity.

eLife Assessment

This important study uses Mendelian Randomisation to show that early life phenotypes (i.e. onset of age at menarche and age at first birth) have an influence on a multitude of health outcomes later in life. The provided empirical evidence supporting the antagonistic pleiotropy theory is solid. However, some additional analyses and a more comprehensive discussion of the findings are needed to make the study stronger.

eLife Assessment

The manuscript by Guo and colleagues reports valuable findings about the inhibitory activity of caffeic acid phenethyl ester (CAPE) against TcdB, a key toxin produced by Clostridioides difficile. C. difficile infections are a major public health concern, and this manuscript provides interesting data on toxin inhibition by CAPE, a potentially promising therapeutic alternative for this disease. The strength of the evidence to support the conclusions is solid, with some concerns about the moderate effects on the mouse infection model and direct binding assays of CAPE to the toxin.

eLife Assessment

This important work combines self-report, neural and physiology data to examine the efficacy and mechanisms of counter conditioning versus extinction in reducing re-emergence of conditioned threat responses and show that this appears to rely on the nucleus accumbens rather than the ventromedial prefrontal cortex. These findings are supported by convincing evidence, though some areas could benefit from added clarity and a few targeted refinements and justifications of analytical choices. Results will be of interest to researchers across multiple subfields, including neuroscientists, cognitive theory researchers, and clinicians, particularly those with an interest in clinical applications in trauma therapies.