Evaluated articles

eLife assessment

Münker and colleagues use an optical tweezer setup to apply oscillatory forces to endocytosed/phagocytosed glass beads over a wide frequency range (from ~1 to 1000 Hz) and probe cytoplasmic material properties at multiple time scales in six different cell types. Using statistical methods and principal component analysis, they find that the active and passive mechanical properties of cells can be described by 6 parameters (from power law fits) that allow characterizing the viscous and elastic nature of the cytoplasmic material as well as an effective active energy driven by cellular metabolism. Overall, this is very well done and important work, using convincing and state-of-the-art methods, albeit with some limitations related to the way the beads are internalized.

eLife Assessment

This valuable work provides novel insights into the substrate binding mechanism of a tripartite ATP-independent periplasmic (TRAP) transporter, which may be helpful for the development of specific inhibitors. The structural analysis is convincing, but additional work will be required to establish the transport mechanism as well as well as binding sites for all ligands. This study will be of interest to the membrane transport and bacterial biochemistry communities.

eLife Assessment

van Vliet and colleagues show a useful correlation between internal states of a convolutional neural network (CNN) trained on visual word stimuli with three specific components of evoked MEG potentials during reading in humans. The findings are solid, though quantitative evidence that model can produce any of the phenomena that the human visual system is known to have (e.g., feedback connections, sensitivity to word frequency), or that it has comparable performance to human behaviour (i.e., similar task accuracy with a comparable pattern of mistakes) would make the conclusions much stronger.

eLife Assessment

This paper advances an important new concept in psoriasis pathogenesis and implicates Sema4a as a homeostatic regulator that is highly epithelial-specific. The findings are convincing and lend support for the biology described here as a mechanism with therapeutic implications.

eLife Assessment

This study presents a useful pipeline for de novo design of antimicrobial peptides active both against bacteria and viruses. The method is based on deep learning, using a GAN generator and a regression tasked to predict antimicrobial activity. The experimental evidence supporting the conclusions is solid, with 24 validated peptides, although some additional justifications of the computational strategy would be a plus. This work will be of interest to the community working on machine learning for biomedical applications and specifically on antimicrobial peptides.

eLife Assessment

This important study of artificial selection in microbial communities shows that the possibility of selecting a desired fraction of slow and fast-growing types is impacted by their initial fractions. The evidence, which relies on mathematical analysis and simulations of a stochastic model, is compelling. It highlights the tension between selection at the strain and the community level. This study should be of interest to researchers interested in ecology, both theoretical and experimental.

eLife Assessment

In this valuable study, the authors studied a novel Zn2+- and NAD+-independent KDAC protein, AhCobQ, in Aeromonas hydrophila, which lacks homology with eukaryotic counterparts, thus underscoring its unique evolutionary trajectory within the bacterial domain. They attempt to demonstrate deacetylase activity, however, whilst the revised manuscript has been improved, significant aspects of the data are still incomplete and require further refinement. The work will be of interest to microbiologists studying metabolism and post-translational modifications.

eLife Assessment

This useful study reports how neuronal activity in the prefrontal cortex maps time intervals during which animals wait to reach a reward, with this mapping remaining consistent across days. While most claims are supported by solid evidence, the study could have benefitted from an improved experimental design to more clearly disambiguate correlations between neuronal patterns and not only time but also stereotypical behaviors and restraint from impulsive decisions. This study will be of particular interest to neuroscientists focused on decision-making and motor control.

eLife assessment

This revised study presents valuable evidence that a combination of endothelial cells, astrocytes, and neuroblastoma cells of human origin can integrate to form an in vitro brain blood barrier, that recapitulates key aspects of its natural counterpart, especially at short times. Convincingly, the mechanism by which neuroblastoma-secreted GDNF increases Claudin-5 and VE-cadherin is described. To substantiate the role of GDNF in vivo, authors demonstrated that knock-down of this neurotrophic factor, increased the permeability of the brain blood barrier in mice. This in vitro system can be used to study the permeability of the human brain blood barrier to different drugs.

eLife Assessment

This valuable study describes a software package in R for visualizing metabolite ratio pairs. The evidence supporting the claims of the authors is solid and broadly supports the authors' conclusions. This work would be of interest to the mass spectrometry community.

eLife assessment

This important study uses state-of-the-art, multi-region two-photon calcium imaging to characterize the statistics of functional connectivity between visual cortical neurons. While the evidence supporting the conclusions is solid, alternative interpretations of the results cannot be ruled out due to the limitations of calcium imaging, the use of noise correlations as a measure of functional connectivity and putative confounds of behavioural state modulations.

eLife Assessment

So et al. present an optimized protocol for single-nuclei RNA sequencing of adipose tissue in mice, ensuring better RNA quality and nuclei integrity. The authors use this protocol to explore the cellular landscape in both lean and diet-induced obese mice, identifying a dysfunctional hypertrophic adipocyte subpopulation linked to obesity. The data analyses are solid, and the findings are supported by the evidence presented. This study provides valuable information for the field of adipose tissue biology and will be particularly helpful for researchers using single-nuclei transcriptomics in various tissues.

eLife Assessment

This study reveals a novel mechanism of glutamine synthetase (GS) regulation in Methanosarcina mazei, demonstrating that 2-oxoglutarate (2-OG) directly promotes GS activity by stabilizing its dodecameric assembly. Using mass photometry, activity assays, and cryo-electron microscopy, the authors show that GS transitions from a dimeric, inactive form at low 2-OG concentrations to a fully active dodecameric complex at saturating 2-OG levels, highlighting 2-OG as a key effector in C/N sensing. The findings are valuable, supported by solid data, and provide new insights into archaeal GS regulation, though further clarification of interactions with known partners like Glnk1 and sp26 is needed.

eLife assessment

This is a valuable paper that identifies a potential challenge for embryos during fertilization: holding sperm contents in the fertilized embryos away from the oocyte meiotic spindle so that they don't get ejected into the polar body during meiotic chromosome segregation. The authors identify proteins involved in cytoplasmic streaming and maintaining the grouping of paternal organelles as being critical for this process. There remain minor weaknesses in the data presented but the paper provides solid evidence for the majority of its claims, and while the findings may pertain to a narrow audience the tools used and basic characterization shown will likely be relied upon by many in the community and therefore is of high value.

eLife Assessment

This important study identifies biallelic variants of DNAH3 in unrelated infertile men and reports infertility in DNAH3 knockout mice. The authors demonstrate that compromised DNAH3 activity decreases the expression of IDA-associated proteins in the spermatozoa of human patients and knockout mice, providing convincing evidence that DNAH3 is a novel pathogenic gene for asthenoteratozoospermia and male infertility. The study will be of substantial interest to clinicians, reproductive counselors, embryologists, and basic researchers working on infertility and assisted reproductive technology.

eLife Assessment

This study investigates the role of the Cadherin Flamingo (Fmi) in cell competition in developing tissues in Drosophila melanogaster. The findings are valuable in that they show that Fmi is required in winning cells in several competitive contexts. The evidence supporting the conclusions is solid, as the authors identify Fmi as a potential new regulator of cell competition, however, they don't delve into a mechanistic understanding of how this occurs.

eLife assessment

This valuable study shows how an intersecting network of regulators acting on genes with differences in their RNA metabolism explains why the loss of some regulators of RNAi in C. elegans can selectively impair the silencing of some target genes. The evidence presented is convincing, as the authors use a combination of computational modeling and RNAi assays to support their conclusions.

eLife assessment

This paper reports a large drug repurposing screen based on an in vitro culture platform to identify compounds that can kill Plasmodium hypnozoites. This valuable work adds to the current repertoire of anti-hypnozoites agents and uncovers targetable epigenetic pathways to enhance our understanding of this mysterious stage of the Plasmodium life cycle. The data presented here are based on solid methodology and represent a starting point for further investigation of epigenetic inhibitors to treat P. vivax infection. This paper will be of interest to Plasmodium researchers and more broadly to readers in the fields of host-pathogen interactions and drug development.

eLife assessment

This manuscript presents important observations on the early changes that occur in calcium signaling, TMEM16a channel activation, and mitochondrial dysfunction in salivary gland cells in a murine model of autoimmune Sjögren's disease. The study reports that in response to DMXAA treatment which induces a murine model of Sjögren's disease, salivary gland cells show significant changes in saliva release, calcium signaling, TMEM16a activation, mitochondrial function, and sub-cellular morphology of the endoplasmic reticulum. The work is compelling and will be of strong interest to physiologists working on secretion, calcium signaling, and mitochondria.