Evaluated articles

eLife assessment

Using extensive atomistic molecular dynamics simulations, the authors analyzed the TCR/pMHC interface with different peptide sequences and protein constructs. The results provide important insights into the catch-bond phenomenon in the context of T-cell activation. In particular, the analysis points to convincing evidence that supports the role of force in further discriminating different peptides during the activation process beyond structural considerations.

eLife assessment

This study presents a valuable inventory of immune responses to the BTN162b2 mRNA COVID-19 vaccination in 20 hemodialyses (HD) patients and controls at different time courses. The transcriptomic sequencing data were collected and analyzed using a solid and validated methodology. The data analysis and clinical predictors to predict anti-Spike IgG titers in HD can be a starting point for further studies characterizing the immune dysregulation seen in ESRD.

eLife assessment

This work is a valuable presentation of sharp-wave-ripple reactivation of hippocampal neural ensemble activity recorded as animals explored two different environments. It attempts to use the fact that the ensemble code remaps between the two mazes to identify the best replay-detection procedures for analyzing this type of data. The reviewers found the evidence for a prescriptive conclusion inadequate, while still appreciating the concept of comparing maze-identity discrimination with replay.

eLife assessment

This work is a valuable presentation of sharp-wave-ripple reactivation of hippocampal neural ensemble activity recorded as animals explored two different environments. It attempts to use the fact that the ensemble code remaps between the two mazes to identify the best replay-detection procedures for analyzing this type of data. The reviewers found the evidence for a prescriptive conclusion inadequate, while still appreciating the concept of comparing maze-identity discrimination with replay.

eLife Assessment

This useful study examines patterns of diversity and divergence in two closely related sub-species of Zea mays, patterns that have bearings on local adaptation in maize and teosinte at intermediate geographic scales. The authors suggest that convergent evolution has been facilitated by both standing variation and gene flow, with independent selective sweeps in the two species. While the data themselves are solid, there are limitations concerning population sampling, false positive rates in sweep detection and integration of phenotypic data, which make it difficult to draw definitive conclusions. The work should in principle be of broad interest to colleagues studying the relationship between domesticated species and their progenitors, as well as those studying instances of parallel evolution.

eLife assessment

This landmark study sheds light on a long-standing puzzle in Protein kinase A activation in Trypanosoma. Extensive experimental work provides exceptional evidence for the conclusions of the work, which represents a significant advancement in our understanding of the molecular mechanism of cyclic nucleotide binding domains. The work is relevant for researchers with interests in kinases and their mechanistic study.

eLife assessment

This study in budding yeast (S. cerevisiae) presents important findings demonstrating that the exonuclease Xrn1 regulates autophagy in response to methionine deprivation through effects on TORC1. There is solid evidence that the impact of Xrn1 on TORC1 is contingent on its catalytic activity rather than the degradation of any specific category of mRNAs. A major strength is the novel mechanism, in which Xrn1 modulates the nucleotide-binding state of the Gtr1/2 complex.

eLife assessment

This fundamental study employs a combination of cryo-electron microscopy, molecular dynamics, and mass spectrometry to elucidate the role of α-tubulin acetylation at the lumenal lysine 40 residue (αK40) within the cilium. Compelling evidence shows αK40 acetylation to impact the structure and stability of doublet microtubules in cilia by affecting the lateral rotational angle. The work will be of relevance to those interested in cytoskeleton and structural biology.

eLife assessment

This important study provides insights into the role of FBXO24 in controlling spermiogenesis and male fertility in mice. The mouse models used and the data are convincing. This paper will interest biomedical researchers working on reproductive biology and fertility control.

eLife assessment

The intrinsic chirality of actin filaments (F-actin) is implicated in the chiral arrangement and movement of cellular structures, but it was unknown how opposite chiralities can arise when the chirality of F-actin is invariant. Kwong et al. present evidence that two actin filament-based cytoskeletal structures, transverse actin arcs and radial stress fibers, drive clockwise and anti-clockwise rotation, respectively. This fundamental work, which has broad implications for cell biology, is supported by compelling data.

eLife Assessment

This work presents valuable new information on the microtubule-binding mode of the microtubule kinesin-13, MCAK, the authors use quantitative single-molecule studies to propose that MCAK preferentially binds to a GDP-Pi-tubulin portion of the microtubule end. However, the evidence provided to support this claim remains incomplete and would benefit from more rigorous methodology particularly the diffraction limited experiments do not provide sufficient spatial resolution to support the authors' conclusions. In addition, a more through discussion of the existing literature would further strengthen the manuscript.

eLife Assessment

This important study provides data that challenges the standard model that binding of Type 2 Nuclear Receptors to chromatin is limited by the available pool of their common heterodimerization partner Retinoid X Receptor. The evidence supporting the conclusions is compelling, utilizing state-of-the-art single-molecule microscopy. This work will be of broad interest to cell biologists who wish to determine limiting factors in gene regulatory networks.

eLife assessment

This study by Sheng and colleagues provides valuable insights into the mechanism of competitive inhibitors of P2X receptors. The structural and functional evidence supporting the subtype specificity of pyridoxal-5'-phosphate derivatives is compelling and provides information for designing drugs that selectively target different subtypes of P2X receptor channels. The work will be of interest to biochemists, structural biologists, and pharmacologists.

eLife assessment

This important manuscript details the characterization of ClpL from L. monocytogenes as an effective and autonomous AAA+ disaggregase that provides enhanced heat resistance to this food-borne pathogen. Supported by compelling evidence, the authors demonstrate that ClpL has DnaK-independent disaggregase activity towards a variety of aggregated model substrates, which is more potent than that observed with the endogenous canonical DnaK/ClpB bi-chaperone system. The work will be of broad interest to microbiologists and biochemists.

eLife Assessment

This important study examines the role of Microrchidia (MORC) proteins in the human malaria parasite Plasmodium falciparum. Solid experimental results, including genome editing and chromatin profiling methods (ChIP-seq and Hi-C), provide a comprehensive picture of the critical role MORC plays in shaping parasite chromatin. Depletion of MORC results in a lethal collapse of heterochromatin and parasite death, nominating the factor as a new target of antimalarial therapies.

eLife Assessment

This study makes an important contribution by characterizing the role of the exocyst in secretory granule exocytosis in the Drosophila larval salivary gland. The results are solid and lead to the novel interpretation that the exocyst participates not only in exocytosis, but also in earlier steps of secretory granule biogenesis and maturation. However, the authors are urged to provide additional proof that the exocyst subunit knockdowns were effective and to acknowledge the possibility that inactivation of an essential exocytosis component could indirectly affect other parts of the secretory pathway.

eLife assessment

The manuscript provides convincing evidence that both circulating omega-6 and omega-3 PUFAs are associated with lower all-cause, cancer, and cardiovascular mortality in the UK BioBank population and that omega-3s have a stronger effect than omega-6s. The findings have important public health implications.

eLife assessment

This important study combines experimental infections with laboratory and field Plasmodium falciparum isolates to quantify the force of human malaria parasite transmission. By using compelling methodological approaches, the authors establish clear positive correlations between mosquito infection levels (as determined by oocyst numbers), sporozoite loads in salivary glands, and sporozoites expelled during feeding. The link between heterogenous infection levels in the mosquitoes and malaria transmission would be of interest to vector biologists, parasitologists, immunologists, and mathematical modellers.

eLife Assessment

The authors adapt a previously-established method that permits detection of in vivo extracellular levels of two distinct enkephalin opioid peptides in response to stressful experiences in mice. The present study highlights the potential of measuring actual peptides by microdialysis-LC-MS. They use this approach in conjunction with fiber photometric calcium imaging to correlate enkephalin neuron activity and enkephalin release in response to repeated stress, providing convincing evidence that this improved approach can provide new insights into opioid signaling in-vivo. This important study provides a means to understand various behavioral states controlled by endogenous opioids and the nucleus accumbens, including hedonic and stress responses, in health and disease. This work will be of broad interest to the neuroscientific community.