Evaluated articles

eLife assessment

This important study offers new and convincing support for the idea that about a third of mouse liver DNAse hypersensitivity sites (DHS) showing male-biased chromatin opening are sex-biased because of the male-specific cyclic action of growth hormone pulses to alter chromatin accessibility, as compared to the relative ineffectiveness of the more static pattern of growth hormone secretion in females. Supporting evidence is found in the impact of hypophysectomy and growth hormone treatment on chromatin accessibility, and the binding of specific transcription factors and epigenetic marks at STAT5-sensitive sites. This work uncovers mechanisms underlying sex differences in liver function and will be of broad interest to endocrinologists and hepatologists.

eLife assessment

This study investigated the role of specific proteins in a mouse model of developmental epilepsy. The significance of the work is important because a new mouse model was used to simulate a type of developmental epilepsy. The work is also significant because the deletion of two proteins together, but not separately, improved the symptoms, and data were convincing.

eLife assessment

This useful study uses a microfluidic method to evaluate the ability of single human white blood cells to produce combinations of cytokines and the evidence that this takes place is solid. The paper highlights polyfunctionality using data that are similar to a prior dataset from the same group. The authors comment that, in analysis of larger panels, single cells rarely make more than 2 or 3 cytokines so that investigation of 3 cytokines at a time is sufficient to investigate this phenomenon. Coupling this approach to other modes of single cell analysis may provide greater insight into what limits simultaneous production of multiple cytokines.

eLife assessment

This paper presents valuable findings that shed light on the mental organisation of knowledge about real-world objects. It provides diverse, if incomplete and tentative, evidence from behaviour, brain, and large language models that this knowledge is divided categorically between relatively small objects (closer to the relevant scale for direct manipulation) and larger objects (further from the typical scope of human affordances for action).

eLife assessment

The authors present a valuable work suggesting that the superficial, retinorecipient layers of the mouse superior colliculus (SC) may participate in figure-ground segregation and object recognition. These data are based largely on optogenetic perturbations of SC but the strength of evidence is currently incomplete: although the effects are statistically significant, there are significant technical limitations that are not adequately addressed via controls.

eLife assessment

This study presents important findings linking structural and functional changes in frontotemporal dementia to underlying neurotransmitter systems. The evidence to support the claims is solid, however, relationships are relatively modest and there are limitations regarding the neurotransmitter data. This study will appeal to clinicians and neuroscientists who are interested in the potential effects of certain neurotransmitter systems on clinical features of frontotemporal dementia.

eLife assessment

This is a valuable report that describes that ACE2 expression is upregulated by SARS-CoV-2 infection via activation of transcription factor Sp1 and inhibition of HNF4α through the PI3K/AKT pathway. Inhibition of Sp1 reduces SARS-CoV-2 infection in vitro and in an animal model. This work is solid and will be of interest to those interested in ACE2 biology and its impact in COVID-19.

eLife assessment

This fundamental work substantially advances our understanding of how cells can tightly modulate small GTPase activity to build and maintain neighboring cytoskeletal structures, in this case microvilli. The evidence supporting these claims is compelling and is supported by both protein-protein interaction assays as well as cell biological studies. The work will be of interest to cell biologist studying the cytoskeleton as well as those interested in G-protein mediated regulation.

eLife Assessment

This is a useful analysis of STORM data that characterizes the clustering of active zones in retinogeniculate terminals across ages and in the absence of retinal waves. The design makes it possible to relate fixed time point structural data to a known outcome of activity-dependent remodeling. However, the evidence is incomplete, weakening the claims the authors make regarding how activity influences the clustering of these synapses.

eLife assessment

The ExA-SPIM methodology developed will be important to the field of light sheet microscopy as the new technology provides an impressive field of view making it possible to image the entire expanded mouse brain at cellular and subcellular resolution. The authors provide solid evidence that mostly supports the conclusions.

eLife assessment

This study provides useful findings on how phonetic properties of words, i.e., their difficulty and prior knowledge, influence the outcome of targeted memory reactivation (TMR) during sleep. While these findings are supported by solid evidence, they are based on a small sample size warranting future work to shed further light on the impact of TMR in language learning.

eLife assessment

This fundamental study has the potential to substantially advance our understanding of human locomotion in complex real-world settings and opens up new approaches to studying (visually guided) behavior in natural settings outside the lab. The evidence supporting the conclusions is overall compelling. Whereas detailed analyses represent multiple ways to visualize and quantify the rich and complex natural behavior, some of the specific conclusions remain more suggestive at this point. The work will be of interest to neuroscientists, kinesiologists, computer scientists, and engineers working on human locomotion.

eLife assessment

This important study advances our understanding of the machinery that couples DNA synthesis with the deposition of histone proteins onto newly synthesized DNA. A convincing array of experiments combines NMR, protein biochemistry, and in vivo analyses of Chromatin Assembly Factor-1 of fission yeast. The work is of interest to researchers in the field of chromosome/chromatin biology as well as epigenetics.

eLife assessment

This important work shows compelling evidence that Chandelier cells in the visual cortex receive inputs most prominently from local layer 5 pyramidal neurons, only mildly inhibit L2/3 pyramidal neurons, and respond massively to visuomotor mismatch. It also indicates that visual experience in the virtual tunnel activates a plasticity mechanism in Chandelier cells which could be due to the particular visuo-motor coupling experienced in this setting, although a specific control is lacking for this conclusion. This study will be of interest to neuroscientists involved in cortical circuits, visual processing, and predictive coding research.

eLife assessment

This important study assesses anatomical, behavioral, physiological, and neurochemical effects of early-life seizures in rats, describing a striking astrogliosis and deficits in cognition and electrophysiological parameters. The solid results come from a wide range of convergent techniques that were used to understand the effects of early-life seizures on behavior as well as hippocampal prefrontal cortical dynamics. This paper will be of interest to neurobiologists, epileptologists, and behavioral scientists.

eLife assessment

This is an important study examining the neural profile of weak and strong fear memories using a variety of imagining and interrogation neural techniques. The data are convincing in detailing the neural profile of neutral, aversive and fear conditioned stimuli in the LC and its input to the dorsal hippocampus and support the conclusion that dopaminergic input from the LC is the key instigator of trace fear conditioning in hippocampus. This paper is of interest to behavioural and neuroscience researchers studying learning, memory and neural networks.

eLife Assessment

This study presents an important investigation of water coordination in a specific kinase family with a focus on the regulation of osmosensing protein kinases. X-ray crystallographic approaches combined with functional assays are used to address the hypothesis that bound water participates in the osmosensing mechanism as an allosteric kinase inhibitor. The evidence for changes in kinase conformation and space group of the crystal as a function of added low molecular weight polyethylene glycol is solid. The work will be of considerable interest to the kinase field as well as colleagues studying allosteric regulation of protein function.

eLife assessment

This paper seeks to understand how the presentation of peptides by medullary thymic epithelial cells may be regulated by the MHCII peptide loading modulator, H2-O, and how this may affect the selection of regulatory T (Treg) cells. Further work is needed to ensure that the findings are robust: currently the analysis of data is inadequate and inconsistencies in the reported findings are not placed in context with results from other groups. The current version does not provide sufficient support for the claims regarding the effects on Treg cell selection.

eLife assessment

This paper reports useful findings regarding gut bacteria that metabolize dietary flavonoids, which can enhance, reduce, or otherwise alter the flavonoid bioactivities. With a newly developed bioinformatics tool, the authors predict bacterial species that can metabolize parts of the flavonoid tilianin. Formal proof of concept is missing, but if experimentally confirmed, the study will change the way we think about metabolism of flavonoids and would be of broad interest regarding gut bacterial metabolism. Most of the analyses are compelling, but others require further inquiry.

eLife assessment

This important study uses a multi-pronged empirical and theoretical approach to advance our understanding of animal cognition. It presents convincing data on how differences in learning relate to differences in the ways that male versus female animals cope with urban environments, and more generally how reversal learning may benefit animals in urban habitats.