Evaluated articles

eLife Assessment

This study presents valuable findings by demonstrating that specific GPCR subtypes induce distinct extracellular vesicle miRNA signatures, highlighting a potential novel mechanism for intercellular communication with implications for receptor pharmacology within the field. The data is compelling, however, more evidence is needed to determine whether the distinct extracellular vesicle miRNA signatures result from GPCR-dependent miRNA expression or GPCR-dependent incorporation of miRNAs into extracellular vesicles.

eLife Assessment

This important study introduces an advance in multi-animal tracking by reframing identity assignment as a self-supervised contrastive representation learning problem. It eliminates the need for segments of video where all animals are simultaneously visible and individually identifiable, and significantly improves tracking speed, accuracy, and robustness with respect to occlusion. This innovation has implications beyond animal tracking, potentially connecting with advances in behavioral analysis and computer vision. While the strength of support for these advances is solid overall, the presentation could be greatly improved for clarity and broader accessibility; in addition, incorporating more standard metrics in the multi-animal tracking literature would better benchmark the approach against other methods.

eLife Assessment

This useful study presents interesting observations on the potential importance of extracellular transport of human papillomaviruses along actin protrusions by retrograde flow. The focus on the events of HPV infection between ECM binding and keratinocyte-specific receptor binding is unique and interesting. However, the evidence supporting the conclusions is incomplete, and additional experimental support is needed. Because conclusions drawn regarding HS interactions are largely based on experiments using a single HS mAb, the specificity of this mAb needs to be described in more detail, either based on the literature or further experimentation.

eLife Assessment

The authors collected valuable time-course RNA-seq data from four tree species in natural environments and analyzed seasonal patterns of gene expression. The genome assemblies and gene expression data across multiple species and tissues are convincing, but the overarching conclusions are inadequately supported due to weaknesses in the study design, which encompasses three different environments and two distinct time periods. This makes it impossible to disentangle genetic effects - which are critical for evolutionary inferences - from environmental influences on gene expression.

eLife Assessment

The study provides valuable technical advances to generate and isolate neural rosettes. The technique is robust, as indicated by both reviewers. The evidence is solid, as shown in orthogonal characterization by flow cytometry, morphology, and scRNA-seq. Comparison with the manual-rosette-picking protocol will enhance the validity of the claims.

eLife Assessment

This valuable study provides outlines the mechanism by which repeated vaccination broadens the breadth of antibody responses against epitope unmatched virus strains. The authors' mathematical model is solid and incorporates various parameters that regulate B cell activation and antibody response.

eLife Assessment

Cryptovaranoides, an end-Triassic animal (just over 200 Ma old), was originally described as a possibly anguimorph squamate, i.e., more closely related to snakes and some extant lizards than to other extant lizards, making Squamata much older than previously thought and providing a new calibration date inside it. Following a rebuttal and a defense, this fourth important contribution to the debate makes a meticulous and solid argument that Cryptovaranoides is not a squamate. However, further comparisons to potentially closely related animals would greatly benefit this study, and parts of the text require clarification.

eLife Assessment

This important study presents a sequence-based method for predicting drug-interacting residues in intrinsically disordered proteins (IDPs), addressing a significant challenge in understanding small-molecule:IDP interactions. The findings have solid support through examples underscoring the role of aromatic interactions. While predicted binding sites remain coarse, validation was done on a total of 10 IDPs at varying depths. The method builds on the authors' previous work and, with ad hoc modifications, is poised to benefit this emerging field.

eLife Assessment

This fundamental work provides solid evidence that advances our understanding of the physical mechanisms underlying bacterial cell division by examining the role of membrane tension and FtsZ condensation in sequential stages of division. The effect of accDA overexpression on membrane tension was carefully characterized. To further enhance rigor, the authors could consider examining orthogonal perturbations to membrane tension, addressing membrane tension vs. fluidity, and addressing the ability of FtsZ to bend membranes in cells.

eLife Assessment

This important study presents the rational redesign and engineering of interleukin-7. The data from the integrated approach of using computational, biophysical, and cellular experiments are convincing, but this study can further benefit from more quantitative analyses and structural data. This paper is broadly relevant to those studying immunomodulation using biologics.

eLife Assessment

This study examines a valuable question regarding the developmental trajectory of neural mechanisms supporting facial expression processing. Leveraging a rare intracranial EEG (iEEG) dataset including both children and adults, the authors reported that facial expression recognition mainly engaged the posterior superior temporal cortex (pSTC) among children, while both pSTC and the prefrontal cortex were engaged among adults. However, the sample size is relatively small, with analyses appearing incomplete to fully support the primary claims.

eLife Assessment

This work presents a useful investigation of functional and structural brain changes following navigation and verbal memory training. The analyses of whole-brain structural changes are incomplete and would benefit from a more comprehensive approach to support the study's main conclusion regarding the lack of a structural whole-brain plasticity effect. However, some analyses are exhaustive and compelling in demonstrating the presence of longitudinal behavioural effects, the presence of functional activation changes, and the lack of hippocampal volume changes.

eLife Assessment

The authors developed a fundamental computational method, which is intended to automatically process bioluminescence imaging-derived tumour images across anatomical regions and over time. This allows quantitative analysis of such data, and the authors applied it to describe the spatiotemporal distribution of tumour cells in response to CD19-targeted CAR-T cells that contained either CD28 or 4-1BB costimulatory domains. Some operational limitations were identified, which relate to the pipeline's reliance on predefined regions of interest instead of aligning signal sites with anatomical information, scaling, and not taking animal pose into account. Overall, the authors provide compelling evidence for the functionality of their computational approach towards automated analysis of bioluminescence imaging data, while applying it to a current topic of wide interest in cell therapy research.

eLife Assessment

This important study investigates changes in oscillatory activity across cortical and subcortical areas during stroke recovery in a nonhuman primate model. The authors distinguish between global and local oscillatory bursts, providing solid evidence that these two types of bursts correlate with distinct aspects of movement; additionally, they show that the likelihood of these bursts occurring follows opposing trends during recovery. The study could be further improved by accounting for inter-individual differences and by some technical improvements, such as employing more robust burst detection methods and more stringent analyses.

eLife Assessment

This manuscript describes solid and very interesting findings that substantially advance our understanding of a major research question on the role of Cx32 hemichannels in the Schwann cell paranode. It provides an interdisciplinary integration of imaging, in silico approaches, and functional data. This important study proposes a new mechanism with profound physiological relevance and provides new insights into glial modulation of electrical conduction in sensory/motor myelinated nerves.

eLife Assessment

The article presents important findings of a dissociation between phasic and tonic pain functions in adaptive behavior, combining immersive VR, computational modeling, skin conductance, and EEG data. The methodology used is solid. Its ecological design and sophisticated computational modeling are major strengths. The article would benefit from adding details on hypotheses, VR implementation, sample size determination, modeling, analysis, and pain specificity.

eLife Assessment

The study presents valuable theoretical insights by attempting to classify pattern-forming gene subnetworks and exploring their potential mechanisms. However, the results are incomplete, as they rely on oversimplified models, limited classifications, and assumptions that may not hold in more complex or realistic scenarios.

eLife Assessment

This work provides valuable insights by introducing a post-translational extrusion mechanism that could reshape how we understand the coupling between DnaA activity and DNA-replication initiation. While solid evidence is presented for some of the key results, other claims rest on indirect proxies and could be improved.

eLife Assessment

This well-designed, valuable study uses isotope tracing to analyse how iron limitation alters TCA cycle metabolism in Mycobacterium tuberculosis, revealing potential antibiotic targets for non-replicating bacteria in the host. The findings provide insights into metabolic remodelling under iron-limited conditions. Whilst some of the evidence is solid, the data around the GABA shunt is incomplete, requiring genetic validation, as was done for the glyoxylate shunt. Questions remain about the underlying mechanisms and their specific role in M. tuberculosis pathogenesis.

eLife Assessment

This paper reports the development of proteins and small molecules that drive bridge LMO2, an oncogenic transcription factor in T-ALL, to E3 ligases (Cereblon and VHL), and demonstrates their effectiveness in degrading FMO2, causing growth arrest and inducing apoptosis in T cell lines in vitro. The findings are valuable because they provide evidence that intrinsically disordered proteins can be targeted for degradation by PROTAC-type chemicals. The paper also provides a route for rational PROTAC design based on intracellular antibody paratopes. Overall, the paper is supported by solid evidence and will be of interest to chemical biologists and cancer pharmacologists.