Evaluated articles

eLife Assessment

This study presents valuable analyses of single neuron activity in the subthalamic nucleus (STN) of monkeys performing a decision-making task that manipulates both perceptual evidence and reward. In particular, the study shows convincing evidence of multiple decision variables being represented in the STN. However, the evidence for sub-populations in STN with distinct involvements in decision-making is incomplete at this stage and requires either further efforts to provide stronger support or refinement of that conclusion.

eLife Assessment

This manuscript presents a novel investigation of organizational principles governing brain activity at both global and local scales during naturalistic viewing paradigms, an important advance for theoretical neuroscience, functional neuroimaging, and neurology. The authors demonstrate that brain activity during naturalistic viewing is dominated by two anti-correlated states that toggle between each other with a third transitional state mediating between them. The evidence supporting this finding is compelling, with the successful replication across three independent datasets (StudyForrest, NarrattenTion, and CamCAN) a particular strength.

eLife Assessment

This valuable study examined how sensory adaptation supports visual perception in the presence of noise. The authors used a combination of human psychophysics, electroencephalography (EEG), and deep neural networks to show that adaptation to noise can improve perception. The results are solid but are, at present, weakened by a number of concerns, including some related to the experimental design and some regarding the interpretation of the results in terms of particular mechanisms. With these concerns adequately addressed, the study and conclusions would be likely to be of broad interest to the neuroscience community.

eLife Assessment

This manuscript describes a series of studies using four different Go/No Go task variants in combination with fast-scan cyclic voltammetry to determine the role of dopamine release in the ventromedial striatum in action selection, controllability of reward pursuit, effort, and reward approach. The authors conclude that dopamine signals in the ventromedial striatum integrate the invigoration of action initiation with continuous estimation of spatial, but not temporal, proximity to rewards. There are, however, a number of concerns regarding methodology that could affect the interpretation of the results. Thus, while the findings are useful, they are considered incomplete, with the primary claims only partially supported.

eLife Assessment

This valuable study investigates whether the activity of an ABC transporter, BmrA, can be modulated by mechanical stimuli. The authors develop a single-molecule experimental system to address this question, although aspects of the methodological framework are incomplete. This work also develops a convincing theoretical model to explain the effect of membrane curvature on the conformational transitions observed during the activity cycle of this membrane protein. This study is of interest to the fields of membrane biophysics and membrane transport.

eLife Assessment

In this important work, it is demonstrated that certain high-resolution cryo-EM structures can be obtained by using concentrated cell extracts without purification. The compelling results with the mammalian ribosomes demonstrate the utility of this approach for this molecule and complexes with elongation factor 2. Moreover, this work also demonstrates the utility of 2D template matching for particle picking for structure determination by single-particle averaging pipelines.

eLife Assessment

The study proposed hemogenic endothelium in adult BM using lineage tracing. Though the study is potentially valuable, the data is incomplete due to the lack of control and insufficient analysis. There is potential for the study to be improved by further revision.

eLife Assessment

This useful study by Palo et al proposes that FRG1 functions as a negative regulator of Nonsense-Mediated mRNA decay (NMD) by associating with the exon junction complex (EJC) and destabilizing UPF1 independently of DUX4. The authors present solid evidence to dissect the relationship between FRG1 and DUX4 in NMD. However, the evidence to support the claim that FRG1 is a component of the EJC or the NMD machinery is incomplete.

eLife Assessment

This study presents a valuable finding on maternal SETDB1 as a key chromatin repressor that shuts down the 2C gene program and enables normal mouse embryonic development. The evidence supporting the claims of the authors is solid, although the inclusion of a causality test, a mechanistic understanding of SETDB1 targeting, and phenotypic quantification would have greatly strengthened the study. The work will be of broad interest to biologists working on embryonic development, stem cells and gene regulation.

eLife Assessment

This manuscript provides valuable insight into how genome organization changes as cells progress through the cell cycle after mitotic exit. The conclusions are supported by solid, rigorous data, and the use of sorted unsynchronized cells rather than cells treated with drugs is a particular strength. Two sharp genome remodeling events are identified at G1-S and to a lesser extent, at S-G2 transitions. A discussion on the limitations of Hi-C and a broader interpretation of results in the context of other mechanistic models would strengthen the overall rigor.

eLife Assessment

This important study addresses the question of how organ-specific blood vessels form during different stages of development, and how specific genes may regulate these processes. New genetic tools were developed to label distinct endothelial cell populations and track them over time in different mutant backgrounds. The results are solid; however, additional data quantification, lineage tracing, and cell autonomy experiments would further strengthen the conclusions.

eLife Assessment

This study presents an important study into the molecular function of AT-HOOK MOTIF NUCLEAR LOCALIZED 15 (AHL15), a member of the AHL protein family, identifying it as a potential regulator of three-dimensional gene-loop organization within transcribed gene bodies. The authors support this claim with compelling genome-wide evidence, integrating AHL15 binding profiles with transcriptional and chromatin accessibility changes, as well as demonstrating overlap with genes known to form loops across transcribed regions. The evidence supporting the claims of the authors is solid. Collectively, these findings will be of broad interest to biologists seeking to understand the core regulatory mechanisms underlying gene expression.

eLife Assessment

This important work demonstrates the role of physically linking the core and CTD kinase modules of TFIIH via separate domains of subunit Tfb3 in confining RNA Polymerase II Serine 5 CTD phosphorylation to promoter regions of transcribed genes in budding yeast. The main findings, resulting from analyses of viable Tfb3 mutants in which the linkage between TFIIH core and kinase modules has been severed, are supported by solid evidence from in vitro and in vivo experiments. There is an intriguing possibility that the Tfb3-mediated connection between core and kinase modules of TFIIH is an evolutionary addition to an ancestral state of physically unconnected enzymes, which could be examined more rigorously with additional evolutionary analyses.

eLife Assessment

This study investigated the dynamics of human cortical network activity with functional magnetic resonance imaging during movie watching and studied the modulation of these dynamics by subcortical areas using an energy landscape mapping method. The authors identified a set of brain states defined at the level of canonical functional networks, quantified how the brain transitions between these states, and related transition probabilities to inter-subject correlations in evoked brain activity. A major emphasis of the work concerns the role of the thalamus, which shows transition-linked activity changes and dynamic connectivity patterns, including differential involvement of parvalbumin- and calbindin-associated thalamic subdivisions. The analytical strategy developed in this study is applicable to other task- and resting-state fMRI data and would be useful for many researchers in the field; however, the evidence supporting the overall conclusions remains incomplete due to limitations associated with fMRI data preprocessing, analysis, and cross-validation.

eLife Assessment

This study provides valuable mechanistic insight into the mutually exclusive distributions of the histone variant H2A.Z and DNA methylation by testing two hypotheses: (i) that DNA methylation destabilizes H2A.Z nucleosomes, thereby preventing H2A.Z retention, and (ii) that DNA methylation suppresses H2A.Z deposition by ATP-dependent chromatin remodelling complexes. Through a series of well-designed and carefully executed experiments, findings are presented in support of both hypotheses. However, the evidence in support of either hypothesis is incomplete, so that the proposed mechanisms underlying the enrichment of H2A.Z on unmethylated DNA remain somewhat speculative.

eLife Assessment

This is an important work implementing data mining methods on IMC data to discover spatial protein patterns related to the triple-negative breast cancer patients' chemotherapy response. The evidence supporting the claims of the authors is solid, although more detailed methodology clarification and validation are needed. While the accuracy of the methods is not very high, the work shows potential for translational application.

eLife Assessment

This study investigates low-affinity Ca2+ binding by WT calreticulin and mutant calreticulin associated with type I myeloproliferative neoplasms, as well as the impact on Ca2+ fluxes in suspension cultures of megakaryocyte-like cells in vitro in response to ER Ca2+ ATPase inhibitors that deplete endoplasmic reticulum (ER) Ca2+ store and open plasma membrane Ca2+ channels through STIM1-Orai interactions. The results are important in that they show that Ca2+ binding by calreticulin and store-operated Ca2+ entry are not fundamentally impacted by the type I deletion mutation in calreticulin, which rules out a direct effect of the calreticulin mutation on its own low-affinity Ca2+ binding and any broad impact on ER Ca2+ regulation. The strength of the data and methods used ranges from solid to convincing, although the use of suspension-based flow cytometric assays to investigate ER Ca2+ levels and Ca2+ entry can be challenged. High-affinity Ca2+ binding sites could be further considered, and possible confounding effects of Abl kinase activity in the megakaryocyte-like cell lines could be offset.

eLife Assessment

This important study combines a two-person joint hand-reaching paradigm with game-theoretical modeling to examine whether, and how, one's reflexive visuomotor responses are modulated by a partner's control policy and cost structure. The study provides a solid and novel set of behavioral findings suggesting that involuntary visuomotor feedback is indeed modulated in the context of interpersonal coordination. The work will be of interest to cognitive scientists studying the motoric and social aspects of action control.

eLife Assessment

This important study addresses a classic debate in visual processing, using a strong method applied to a rare clinical population to evaluate hierarchical models of visual object perception. The paper finds only partial support for the hierarchical model: as expected, neural responses in ventral visual cortex show increased representational selectivity for faces along the posterior-anterior axes, but the onsets of the signals do not show a temporal hierarchy, indicating more parallel processing. The iEEG dataset is impressive, but the evidence for lack of temporal hierarchy is incomplete: essential quality checks need to be performed, and statistical analyses adapted to ensure that the data and analyses would be able to reveal temporal hierarchy if it were present in the data.

eLife Assessment

This article reports an algorithm for inferring the presence of synaptic connection between neurons based on naturally occurring spiking activity of a neuronal network. One key improvement is to combine self-supervised and synthetic approaches to learn to focus on features that generalize to the conditions of the observed network. This valuable contribution is currently supported by incomplete evidence.