Evaluated articles

eLife Assessment

This work presents important findings regarding the interaction of the monkeypox virus (MPXV) attachment H3 protein with the cellular receptor heparan sulfate and the use of this information to develop antivirals potentially effective against all orthopoxviruses. Using a combination of state-of-the art computational and wet experiments the authors present convincing evidence to sustain their claims. These results will interest those working on basic orthopoxviruses biology and antiviral development.

eLife Assessment

This valuable study investigates the selectivity of neuronal responses in the neocortex and thalamus to visual stimuli presented far outside their receptive fields. The study shows convincing evidence for a long-latency surround-induced response in primary visual cortex that is absent in the dorsal lateral geniculate nucleus and does not depend strongly on the visual characteristics of the surround stimulus. The paper should be of interest to neurophysiologists interested in vision and contextual modulations.

eLife Assessment

This important study identified a molecular mechanism linking diabetes to AD risk and the data presented are convincing. The authors investigated the role of kallistatin in metabolic abnormalities associated with AD and identified that Kallistatin is a key player that mediates Aβ accumulation and tau hyperphosphorylation in AD. This manuscript provides novel insights into the pathogenesis of AD, indicating that the hypolipidemic drug fenofibrate attenuates AD-like pathology in Kallistatin transgenic mice.

eLife assessment

This important study examines E. coli growth and division, suggesting that inhomogeneous organization of ribosomes in the cytoplasm results in cell size-dependent growth rate perturbations. The work is conceptually appealing, but incomplete due to shortcomings in the experiments and modeling.

eLife Assessment

This important work proposes a neural network model of interactions between the prefrontal cortex and basal ganglia to implement adaptive resource allocation in working memory, where the gating strategies for storage are adjusted by reinforcement learning. Numerical simulations provide convincing evidence for the superiority of the model in improving effective capacity, optimizing resource management, and reducing error rates, as well as for its human-like performance. This work will be of broad interest to computational and cognitive neuroscientists, and may also interest machine-learning researchers who seek to develop brain-inspired machine-learning algorithms for memory.

eLife Assessment

Rachubinski and colleagues provide an important manuscript that includes two major advances in understanding immune dysregulation in a large cohort of individuals with Down syndrome. The work comprises compelling, comprehensive, and state-of-the-art clinical, immunological, and autoantibody assessment of autoimmune/inflammatory manifestations. Additionally, the authors report promising results from a clinical trial with the JAK inhibitor tofacitinib for individuals with dermatological autoimmune disease.

eLife assessment

The manuscript presents a machine-learning method to predict protein hotspot residues. The validation is incomplete, along with the misinterpretation of the results with other current methods like FTMap.

eLife assessment

Ctnnb1 encodes β-catenin, an essential component of the canonical Wnt signaling pathway. In this important study, the authors identify an upstream enhancer of Ctnnb1 responsible for the specific expression level of β-catenin in the gastrointestinal track. Deletion of this enhancer in mice and analyses of its association with human colorectal tumors provide compelling support that it controls the dosage of Wnt signaling critical to the homeostasis in intestinal epithelia and colorectal cancers.

eLife Assessment

This useful study examines the neural activity in the motor cortex as a monkey reaches to intercept moving targets, focusing on how tuned single neurons contribute to an interesting overall population geometry. The presented results and analyses are solid, though the investigation of this novel task could be strengthened by clarifying the assumptions behind the single neuron analyses, and further analyses of the neural population activity and its relation to different features of behaviour.

eLife Assessment

This valuable study presents a deep learning framework for predicting synergistic drug combinations for cancer treatment in the AstraZeneca-Sanger (AZS) DREAM Challenge dataset. The level of evidence seems solid, although performance on some datasets seems unconvincing and further validation would be required to demonstrate the generalizability of the model and, in turn, its clinical relevance. The reported tool, DIPx, could be of use for personalized drug synergy prediction and exploring the activated pathways related to the effects of drug combinations.

eLife Assessment

This valuable study by Cui et al. investigates mechanisms generating sighs, which are crucial for respiratory function and linked to emotional states. Utilizing advanced methods in mice, they provide solid evidence that increased excitability in specific preBötzinger complex neuronal subpopulations expressing Neuromedin B receptors, gastrin-releasing peptide receptors, or somatostatin can induce sigh-like large amplitude inspirations. With additional technical clarifications and further elaboration of the limitations in terms of how the results are interpreted in the revised manuscript, the study will interest neuroscientists studying respiratory neurobiology and rhythmic motor systems.

eLife Assessment

This is an important study that utilizes proteomic and genetic approaches to identify the glycoprotein quality control factor malectin as a pro-viral host protein involved in the replication of coronavirus. The evidence supporting this conclusion is convincing, although continued elucidation of the mechanistic basis of malectin-mediated viral replication would further strengthen these findings. This work will be of interest to cell biologists studying the molecular mechanisms of glycoprotein quality control and virologists studying the host-pathogen interactions.

eLife Assessment

This is a useful paper regarding the roles of brown adipose tissue and skeletal muscle in thermogenesis in mice, with potential significance for the field. The overall approach is innovative but on balance the evidence for the claim is incomplete, as cast immobilization, while innovative, is likely stressful, may impact muscle and BAT directly, and imposes an energetic cost of motion on the animal that is not accounted for. Further experiments are also needed to directly assess the role of adipose-derived BCAAs in thermogenesis. The authors have done a good job of textually editing their manuscript to clarify the findings and limitations of the study.

eLife assessment

This work describes how the toxin-antitoxin (TA) system, which uses the cyclic di-GMP as an antitoxin, controls both the persistence of antibiotics linked to biofilms and the integrity of the bacterial genome. The authors present solid evidence linking cyclic di-GMP and the toxin HipH. The work is valuable because it establishes the relationship between bacterial persistence and biofilm resilience, which lays a strong basis for future research on the formation of bacterial biofilms and antibiotic resistance.

eLife assessment

The authors provide useful data to support the existence of a regulatory pathway starting with SPI1-driven ZFP36L1 expression, that goes on to downregulate HDAC3 expression at the transcript level, leading to PD-L1 upregulation due to implied enhanced acetylation of its promoter region. This is therefore an interesting pathway that adds to our understanding of how PD-L1 expression is controlled in gastric cancer. However, this is likely one of many possible pathways that impact PD-L1 expression, and the data are currently incomplete to support the claims made.

eLife Assessment

This is an important study that connects the polymerase-associated factor 1 complex (Paf1C) with Histone 2B monoubiquitination and the expression of genes key to virulence in Cryptococcus neoformans. The provided information is convincing and has the potential to open several opportunities to further understand the basic biology of this significant human fungal pathogen.

eLife Assessment

In this manuscript the authors examine correlations between intrinsic electrophysiological properties of HVC neurons projecting to Area X and the temporal structure of the birds' song. The study provides important insights into how the structure of vocalization can relate to intrinsic physiological properties of the neurons that are essential for learning the behavior. The evidence supporting the idea that song temporal structure is related to intrinsic physiology is solid and this research will be of general interest to researchers in the field and neurophysiologists.

eLife Assessment

Giamundo et al. present fundamental data with new insights into the role of Ezrin, a major membrane-actin linker that assembles signaling complexes, in the spatial regulation of EGF signaling mediators. The use of multiple state-of-the-art microscopy techniques, multiple cell lines and inhibitors, together with in vivo models convincingly supports the majority of their conclusions. The findings are helpful for understanding EGF/mTOR signal transduction and support a critical role for the scaffolding protein Ezrin in the upstream regulation of EGFR/AKT activity, TSC subcellular localization and mTORC1 signaling. These findings contribute substantially to understanding how endo-lysosomal signaling are regulated, alterations which are implicated in many human diseases.

eLife Assessment

This study retrospectively analyzed clinical data to develop a risk prediction model for pulmonary hypertension in high-altitude populations. The evidence is solid, and the findings are useful and hold clinical significance as the model can be used for intuitive and individualized prediction of pulmonary hypertension risk in these populations.

eLife Assessment

This study reports a fundamental observation concerning cell death regulation by the anti-apoptotic BCL2 family NOXA. The authors convincingly demonstrate that NOXA is destabilized through the interaction with WSB2, a substrate receptor in CRL5 ubiquitin ligase complex, sensitizing the cells to treatments. These are key findings for cell biologists and cancer researchers as they identified a new target impacting drug responsiveness in cancer therapies.