Evaluated articles

eLife assessment

This important study uses elegant in vivo experiments combined with expression data on an imprinted gene, Dlk1, to demonstrate its role in pituitary gland size in mice. The evidence supporting the claims of the authors is solid, although the inclusion of both sexes and a rescue model would have strengthened the study. The work will be of interest to developmental biologists working on the pituitary and hypothalamus.

eLife assessment

This study represents an important step toward unifying two strains of inquiry, one related to the functional role of hippocampal theta oscillations and one related to the behavioral impact of engram reactivation, and thus the findings have implications for our understanding of memory that will impact multiple subfields. In combination with additional context from the literature, the important findings are supported by solid evidence supporting the conclusion that memory recall operations occur preferentially at a specific phase of theta.

eLife assessment

This is an interesting study investigating a mechanism for the elimination of aberrant cells from epithelial tissues dependent on the contractility of the interface between cells with different fates regulated by JNK activity. This work offers insights into robustness and error correction mechanisms that help understand cell-cell competition and the origin of tumors. The study should be relevant for cell, developmental and cancer biologists.

eLife assessment

The paper aims to provide structural and functional information on the hepatitis E virus replication complex. The study will be of interest to a broad number of people studying at virus replication, since the replication complex are targets for therapeutic interventions.

eLife assessment

As digested food moves through the intestines specialized epithelial cells (called Enterochromaffin Cells or EECs) sense and respond to the constituent chemicals. The current work utilizes single-cell transcriptomic analyses and intersectional approaches to define and genetically manipulate subsets of EECs. Key findings are that direct stimulation of EEC subtypes influences key aspects of feeding, specifically gut transit, ingestion, and food preference.

eLife assessment

This study provides evidence that the Stromalin Antigen (SA) proteins known to ubiquitously interact with cohesins, retain their capacity to bind CTCF and chromatin in the absence of RAD21 cohesin component. Authors imply that SA has an independent function in addition to its joint role with RAD21 and CTCF, providing experiments that make them suggest that SA proteins organize around RNA:DNA regions in the absence of cohesin, contributing to R-loop regulation and linking chromatin on structure to cohesin loading. The paper is a nice piece of work of interest to readers in the field of cohesin biology and genome organization. However, additional, experiments would be required to strengthen some of the conclusions.

eLife assessment

Signaling mediated by Semaphorins and their receptors Nrp1 and Nrp2 is crucial for regulating the morphology of dendritic spines and dendritic arborization during development. In this manuscript, the authors found that the post-translational modification of S-palmitoylation dictates the subcellular localization and trafficking of Nrp2, but not Nrp1, and is required for Sema3F-dependent pruning of spines on the apical dendrites of layer V cortical neurons. The study provides important insights into how semaphorin signaling achieves spatial specificity on diverse downstream cellular events.

eLife assessment

This fundamental study from Gold and colleagues substantially advances our understanding of the synaptic targeting of a major postsynaptic protein kinase, CaMKII, which is the basis for the persistence of excitatory synaptic strength in synaptic plasticity. The evidence supporting the claims of the authors is convincing, with cell biological, biochemical, as well as structural biological approaches. This work will be of interest to cell and computational biologists working on learning/memory.

eLife assessment

This study advances the understanding of metabolic regulation underpinning self-renewal of stem cells. The authors report that glutamine-dependent acetylation of the kinase PASK regulates its nuclear localization. Evidence is provided that nuclear PASK binds and disrupts Wdr5 association with the anaphase-promoting complex/cyclosome and is a trigger for the activation of myogenic programs in cultured cells. The study will be of interest to an audience in the areas of stem cells, regeneration and metabolic signalling.

eLife assessment

In this work, Verstegen and colleagues established an in vitro system and describe human B cell differentiation pathways via germinal center B cells towards plasma cells by performing single-cell analysis of in vitro stimulated human B cells. The study provides solid evidence toward establishment of in vitro model for B cell differentiation. This study may be valuable in differentiation of primary naive B cells into ASC ex vivo and will be of interest for immunologists with emphasis in B cell biology.

eLife assessment

The authors state that there is scant experimental evidence of divisive normalization of neural responses in the human brain. They used fMRI BOLD response to high-level stimuli to explore normalization in V1, object-selective (LO and pFs) and category-selective regions (EBA and PPA) as well effects of attention on cortical responses. Specifically, the authors first test the degree to which BOLD responses to body parts and houses exhibit responses predicted by a non-linear normalization model, compared to two linear models (weighted sum and weighted average). They find that responses, when considering responses to one vs two stimuli, are best fit with the normalization model. They then suggest that object-based attention effects can be better accounted for by a normalization model of attention, compared to attention variants of the aforementioned models. The paper could potentially be an important contribution to the fields of perceptual and cognitive neuroscience, but the conclusions are not sufficiently supported by the data at this stage. Several theoretical and methodological concerns limit the conclusions of this study.

eLife assessment

This manuscript describes a mouse model of a human mitofusin 2- related lipodystrophy, generated by knockin of Mfn2 R707W, and reports data suggesting adipocyte-specific effects involving the integrated stress response, mTorc signaling, and epithelial-mesenchymal transition pathways. The data will be important for understanding how mitochondria can be affected in tissue-specific manner to contribute to metabolic disease.

eLife assessment

This fundamental and timely study provides insights into the structural dynamics of several relevant mutant forms of SARS-CoV-2 spike protein, including the most recent omicron variant. The hydrogen/deuterium-exchange studies provide compelling evidence for the stabilization of the spike stalk in conjunction with increased dynamics of the N-terminal domain, where binding to the ACE2 receptor occurs. These results have profound implications for the development of small molecule inhibitors of the spike protein-ACE2 receptor interaction.

eLife assessment

This paper reports a bet hedging strategy in bacteria based on chromosomal duplications and rearrangements that confer advantages in certain growth conditions. The work is of fundamental importance for understanding the role of genetic and biological variation in bacteria. The experimental work is exceptionally strong and convincing. The paper will be of interest to a broad audience including bacteriologists, geneticists and evolutionary biologists.

eLife assessment

This study provides potentially important insights into the role of mesenchymal stem cells in CAR-T therapy, and suggest that the STC1 gene could be a key factor in influencing the efficacy of this treatment. This finding has the potential to improve current therapeutic strategies based on cell therapy and may indicate new biology related to how mesenchymal stem cells affect the immune state within the tumor microenvironment. Further research is necessary to clarify the signaling pathways, but the data presented by the authors are generally well-supported and convincing.

eLife assessment

This manuscript makes a valuable contribution to the field. The authors have developed a compelling network model to study mechanisms for the emergence of oscillations in the beta range in the primary motor cortex during movement preparation, and their propagation as traveling waves across the cortical sheet. The model is able to recapitulate several features of motor cortical activity acquired experimentally. Due to the recent results suggesting a functional role for traveling waves, it is of great interest to discover the mechanisms underlying such phenomena, and this work is an interesting step in that direction. However, the evidence for the reported new insights is incomplete at this stage, due to some weaknesses that remain to be addressed.

eLife assessment

This paper will be of fundamental interest to many sub-disciplines of neuroscience, ranging from cognitive neuroscientists to cellular neuroscience. It provides compelling and substantial brain and behavioral evidence of a novel intervention that can boost long-term memory. The key claims of the manuscript are generally well supported by the data, though the correlational nature of the data in different types of experiments raises some issues about interpretation.

eLife assessment

The authors present interesting information regarding the possibility of targeting the oncogenic K-Ras(G13C) mutant with nucleotide competitors. The experiments represent a solid support of the claims and show that this approach can work despite concerns about the high affinity of GTP and its high cellular concentration. These results will be of high interest for all working in the Ras field and in targeting oncogenes with small molecules. A weakness of the manuscript is the lack of direct physiological insights.

eLife assessment

This study thoroughly characterizes the morphology of an interesting folded membrane structure that links the epidermis to the cuticle in C. elegans. This structure, here named the meiosome, has been noted by several previous researchers. The study would be strengthened by providing additional support to the notion that the VHA-5::GFP transgenic reporter, used by the authors, faithfully labels the meisosome, and by stronger evidence that meiosomes indeed serve as attachment platforms between the cuticle and the epidermis.

eLife assessment

This manuscript will be of interest to a wide range of cell biologists interested in understanding cell-cell communication. The discovery that an engulfing cell can control the extrusion and degradation of large vehicles from its target cell is important and intriguing. The authors present compelling data that show that exophers (large neuronal extrusions proposed to discard toxic cargo) are taken up by adjacent hypodermal cells, split into smaller fragments, and eventually degraded by lysosome fusion. The authors identify a number of small GTPases and accessory components, as well as the phagocytic receptor (CED-1) and the likely eat-me signal (phosphatidylserine).