Evaluated articles

eLife Assessment

This manuscript presents important information as to how adolescent alcohol exposure (AIE) alters pain behavior and relevant neurocircuits, with convincing data. The manuscript focuses on how AIE alters the basolateral amygdala, to the PFC (PV-interneurons), to the periaquaductal gray circuit, resulting in feed-forward inhibition. The manuscript is a detailed study of the role of alcohol exposure in regulating the circuit and reflexive pain, however, the role of the PV interneurons in mechanistically modulating this feed-forward circuit could be more strongly supported.

eLife Assessment

This is a valuable report of a spatially-extended model to study the complex interactions between immune cells, fibroblasts, and cancer cells, providing insights into how fibroblast activation can influence tumor progression. The model opens up new possibilities for studying fibroblast-driven effects in diverse settings, which is crucial for understanding potential tumor microenvironment manipulations that could enhance immunotherapy efficacy. While the results presented are convincing and follow logically from the model's assumptions, some of these assumptions, as acknowledged by the authors, may oversimplify certain aspects in light of complex experimental findings, system geometry, and general principles of active matter research. Nonetheless, the authors provide justification for their work as a meaningful step towards more comprehensive modeling approaches.

eLife Assessment

This paper identifies a crucial step in the regulation of tight junction formation by identifying Rho-ROCK activity-dependent activation of the serine protease Matriptase, making Claudins available for tight junction formation. The reviewers were satisfied with the revisions and found the work important and the approach convincing.

eLife Assessment

The ingenious design in this study achieved the observation of 3D cell spheroids from an additional lateral view and gained more comprehensive information than the traditional one angle of imaging. This extended the methods to investigate cell behaviors in the growth or migration of tumor organoids in a time-lapse manner and these extensions should be important to the field. The authors provide compelling evidence that the methods work as described.

eLife Assessment

In this valuable study, the authors used an elegant genetic approach to delete EED at the post-neural crest induction stage. The usage of the single-cell RNA-seq analysis method is extremely suitable to determine changes in the cell type-specific gene expression during development. Results backed by solid evidence demonstrate that Eed is required for craniofacial osteoblast differentiation and mesenchymal proliferation after the induction of the neural crest.

eLife Assessment

This study introduces an important approach using selection linked integration (SLI) to generate Plasmodium falciparum lines expressing single, specific surface adhesins PfEMP1 variants, enabling precise study of PfEMP1 trafficking, receptor binding, and cytoadhesion. By moving the system to different parasite strains and introducing an advanced SLI2 system for additional genomic edits, this work provides compelling evidence for an innovative and rigorous platform to explore PfEMP1 biology and identify novel proteins essential for malaria pathogenesis including immune evasion.

eLife Assessment

This study makes the important finding that pleiotropy is positively associated with parallelism of evolutionary responses in gene expression. This finding, if true, runs counter to current expectations in the field. The analysis uses state-of-the art experimental evolution approach to study the genetic basis of adaptation of Drosophila simulans to a hot environment. Although the experimental results are convincing, the theoretical model is incomplete, due to several unusual assumptions. It remains to be seen whether the main conclusion can be replicated in other contexts.

eLife Assessment

Liang et al. have conducted a small pilot study investigating the feasibility and tolerability of a regimen of neoadjuvant chemo-immunotherapy for non-small cell lung cancer, with lower cumulative dose of chemotherapy and with the immunotherapy delivered on D8 of each cycle. The clinical data are interesting and novel, and overall the findings of the study are valuable. However, the translational data and analyses are incomplete and do not support key claims in the title.

eLife Assessment

In this important paper, the authors use single-cell RNA sequencing to understand post-mitotic cone and rod developmental states and identify cone-specific features that contribute to retinoblastoma genesis. The authors report findings that have practical implications for retinal development, gene expression, and cell fate specification. The evidence is compelling as the experimental design and analysis are exceptionally rigorous.

eLife Assessment

This potentially valuable study investigates the interaction of two integral membrane proteins (Cdhr1a and Pcdh15b) and their roles in cone-rod dystrophy. Convincing evidence using loss-of-function mutants demonstrates that both proteins are required for cone maintenance and survival. There is insufficient evidence to support the subcellular localization and the proposed heterodimeric interaction of the two proteins from distinct subcellular compartments. The methodologies are unclear, and the statistical methods and analysis are improperly applied.

eLife Assessment

Using multiple techniques previously validated by the authors, this study identified INTS12, a component of the Integrator complex involved in 3' processing of small nuclear RNAs U1 and U2, as a factor promoting HIV-1 latency. The work is valuable, based on a sound strategy for screening targets to activate HIV latency and the solid mechanistic insights it provides on INTS12 repression of transcriptional elongation. Future studies are needed to explore INTS12 as a drug target against HIV/AIDS.

eLife Assessment

The paper is a fundamental study examining the role of CDK12 loss in prostate cancer. While previous studies have suggested that CDK12 loss confers HRD phenotypes, clinical trials using PARPi in CDK12 altered patients have not demonstrated significant benefit. This work investigates these mechanisms in depth and provides compelling evidence. A comprehensive genomic analysis serves an excellent resource to the field, showing that biallelic CDK12 alterations do not have genomic features of HRd. Moreover, the study explored both acute and chronic deletion of CDK12, with data suggestive of CDK12-altered cells being uniquely sensitive to CDK13 inhibition. While some minor weaknesses have been previously noted by the reviewers, the authors have adequately addressed these concerns with appropriate rigor.

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

The study conducted by Fang et al. offers significant and fundamental insights, notably enhancing our understanding of angiogenesis. While some of the claims are supported by convincing experimental approaches, others lack sufficient validation. Additionally, there are instances where critical experimental controls appear to be absent.

eLife Assessment

This important study combines single nucleus transcriptional profiling with spatial transcriptomics to identify and map heterogeneity among dopamine neurons in the mouse ventral midbrain. The compelling results separate dopamine neurons into three broad families that have unique (yet overlapping) spatial distribution within the ventral tegmental area and substantia nigra, and also identify population-specific changes in a LRRK2 mouse model of Parkinson's Disease. The creation of a public-facing app where the snRNA-seq data can be investigated by anyone is a major strength.

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 paper presents fundamental research showing 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 compelling. 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 convincing, with mostly state-of-the-art technology. The work will be of relevance to immunologists interested in regulatory T cell biology and autoimmunity.