Evaluated articles

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).

eLife assessment

The manuscript proposes a mechanism by which different S-adenosylmethionine (SAM) synthase enzymes exhibit specificity towards target sequences, thereby proposing a novel layer of control over H3K4 trimethylation (H3K4me3). Such specificity is demonstrated in the context of responses to heat stress for two Caenorhabditis elegans SAM synthase enzymes, supporting the existence and importance of this novel mechanism of epigenetic control.

eLife assessment

The authors document an in-depth analysis of introduction patterns of 5 variant waves in Mexico. This is an important analysis and dataset since the genomic epidemiology of SARS-CoV-2 in Mexico is generally understudied, and this paper contributes important missing information. The phylogenetic analyses are solid and well-presented, but the lack of detail regarding the collection of samples across Mexican states makes it difficult to evaluate conclusions about the relationship between observed viral lineages and local case counts. Additionally, in its current form, the manuscript is mostly descriptive, without clear hypotheses tested or discussion of implications.

eLife assessment

This important work advances our understanding of the factors that affect the speed of colour evolution in birds and the resulting diversification patterns. It provides compelling evidence that more complex plumage coloration can lead to rapid colour evolution in kingfishers, and could pave the way for more comprehensive analyses that fully embrace the multidimensional nature of colour variation. Hence, the results will be of broad interest to ornithologists and evolutionary biologists in general, once the authors have streamlined the theoretical framework and explained the novel methodological approaches in more detail.

eLife assessment

This valuable manuscript describes a fully automated touchscreen cognitive testing system for rats that reduces the length of training required to learn a task and eliminates the need for daily handling. These features make it possible to assess cognitive behaviors in conjunction with other neurobehavioral paradigms during adolescence, an important advance in the field. The data convincingly show that cognitive flexibility does not promote susceptibility to severe weight loss in the activity-based anorexia (ABA) paradigm. However, support for the claim that cognitive deficits seen in rats that had been exposed ABA adequately capture an important clinical feature of the pathophysiology of anorexia nervosa is incompletely supported.

eLife assessment

This study provides fundamental insights into the relationship between single neuron activity in superficial layers of the cortex and electrical signals recorded at the cortical surface. Based on solid measurements, the results indicate a weak correlation between individual layer 2/3 neuron activity and multiunit activity recorded at the surface, whose interpretation could be reinforced. In particular, a strong contribution of layer 1 axons to surface signals is suggested but relies on incomplete evidence.

eLife assessment

This manuscript provides valuable insight into the molecular mechanism by which destabilized mitochondrial proteins 'clog' import channels and contribute to the pathologic mitochondrial and cellular dysfunction implicated in human disease. The evidence supporting this conclusion is solid, utilizing yeast, mammalian cell culture, and mouse models. However, additional characterization of import clogging in the mammalian model systems would strengthen this study. This work will be of broad interest to researchers in the fields of mitochondrial biology, protein quality control and proteostasis.

eLife assessment

This study describes an interesting approach using PEGylated isoprenaline to selectively activate beta-adrenergic receptors in the surface sarcolemma of ventricular myocytes. While the concept is compelling, and the core of an interesting and impactful study is presented, the results are preliminary and incomplete at this stage, and would benefit from more rigorous validation of the approach. The work will be of interest to cardiac cell biologists and pharmacologists.

eLife assessment

This manuscript tests an important assumption about how sensory information is processed and used to guide motor choices. The widely held assumption is that sensory-motor circuits are capable of integrating evidence, but the validity and generality of this 'principle' have been recently questioned by studies suggesting that other computational operations may lead to similar psychophysical results, mimicking integration without actually performing it. This study makes a compelling case that the integration assumption was likely correct all along and that the model mimicry can be easily disambiguated by using appropriate sensory stimuli and task designs that permit rigorous analyses.

eLife assessment

This important study provides convincing evidence that locus coeruleus is activated during visuomotor mismatches. Gain of function optogenetic experiments complement this evidence and indicate that locus coeruleus could be involved in the learning process that enables visuomotor predictions. This study, therefore, sets the groundwork for the circuit dissection of predictive signals in the visual cortex. Loss-of-function experiments would strengthen the evidence of the involvement of locus coeruleus in prediction learning. These results will be of interest to systems neuroscientists.

eLife assessment

The paper provides a valuable, in-depth mathematical analysis of the coevolutionary dynamics resulting from a coupling of players' strategies and (collective) risk, as well as illustrative numerical simulations of the system's trajectories for different starting conditions. It is therefore a solid contribution to our understanding of how cooperation can be sustained when there is feedback between individual decisions and the global risk of disaster. This paper will be of interest to scientists working on mathematical biology/ecology, and more generally various aspects of human decision-making, the interplay between human decisions and the environment, and public goods provision.

eLife assessment

This study addressed a long-standing question in biology - the role of fever during infections. Using innovative research strategy, the authors provide compelling evidence for the positive impact of higher body temperature on both pathogen clearance and tissue repair. This study thus provides important advances in our understanding of host defense and its connection with physiology and behavior.

eLife assessment

This manuscript reports novel and important findings on the mechanisms of regulation of CRAC channels. Collectively, the work represents an important conceptual advancement, showing that stromal interaction molecule-1 is not necessary for Ca2+-dependent inactivation of the Orai1 channel and that Orai1 likely contains a Ca2+ sensor for autoregulatio. The experiments are carefully conducted, and the data is of high quality and support the major conclusions of the authors.

eLife assessment

This important paper advances the understanding, in the model plant Arabidopsis thaliana, of the molecular basis of the promotion of flowering in the spring by exposure to winter cold through a process known as vernalization. In Arabidopsis, there are two classes of long non-coding RNAs produced only when plants are in the cold, and this work provides compelling evidence that the cold-induced expression of one of these (COOLAIR) involves C-repeat binding factor proteins that bind to cognate binding elements in the COOLAIR promoter, but also that COOLAIR is not required for the vernalization-mediated promotion of flowering under standard laboratory conditions in which the vernalization response is measured.

eLife assessment

This study provides fundamental insight into the functional impact of CDK4 inhibition on cells in the tumor microenvironment, which is of high importance and interest to the field. The compelling conclusion that proliferative exhausted T cells are associated with response in HPV+ head and neck cancer is supported by the cohort of 14 patients with paired tumor and adjacent normal tissue and rigorous bioinformatic analysis of nearly 50,000 single CD3+ T cell transcriptomes. This work will be of interest to researchers across tumor types and in other immunological fields of study.

eLife assessment

This paper will be of considerable interest to researchers studying the psychological and neural basis of variation in prosocial behavior. The authors use a sophisticated combination of computational modeling and EEG to show that variation in generosity produced by changes in context (i.e., disadvantageous vs. advantageous inequality) and variation due to individual differences in concern for others both seem to occur early, during the perceptual or valuation stage of a choice, rather than later on during choice comparison. However, these two sources of variation also appear to operate through distinct mechanisms during this stage of processing, which spurs further questions about the drivers of human prosocial behavior.

eLife assessment

The authors examine the function of Tomosyn, in dense core vesicle fusion in neuronal cultures from mice expressing conditional alleles of tomosyn and tomosyn-2. The authors show here that while loss of tomosyns did not affect dense core vesicle exocytosis, it reduced the expression of several key dense core cargos, including BDNF. However, "rescue" experiments are needed to validate the specificity of the effects.