Evaluated articles

eLife assessment

In this valuable study, the authors characterize the role of splicing factor SRSF1 during spermatogenesis with a conditional knockout of Srsf1 in male germ cells. The phenotype and molecular role of SRSF1 in regulating alternative splicing in precursor spermatogonial stem cells in juvenile testes are convincingly supported. The paper also provides convincing evidence that the mRNA encoding Tial, a factor relevant to spermatogonial maintenance and male fertility, is alternatively spliced in testis and that this splicing is regulated by SRSF1. The work will be of interest to the fields of reproductive biology, stem cell biology, and alternative splicing.

eLife assessment

This important study presents findings with broad implications for the use of AlphaFold2 models in ligand binding pose modeling, a common task in protein structure modeling. The computational experiments and analyses provide compelling results for the GPCR protein family data, but the conclusions are likely to apply also to other proteins and they will therefore be of interest to biophysicists, physical chemists, structural biologists, and anyone interested or involved in structure-based ligand discovery.

eLife assessment

The microRNA lin-4, originally discovered in C. elegans, has a key role in controlling developmental timing across species, but how its expression is developmentally regulated is poorly understood. Here, the authors provide convincing evidence that two MYRF transcription factors are essential positive regulators of lin-4 during early C. elegans larval development. These results provide important insight into the molecular control of developmental timing that could have significant implications for understanding these processes in more complex systems.

eLife assessment

Resistance of Plasmodium falciparum to artemisinin, which has become a threat to malaria control, has been linked to mutations in the parasite protein K13. This study provides important new insights into the function of K13 in the endocytosis of hemoglobin, a central process for the activation of artemisinin derivatives. Conditional protein mislocalization combined with high-resolution imaging provides convincing evidence that K13 is involved in the formation of cytostomes, the structures involved in the endocytosis of host cytosol. This study will be of interest to scientists working on parasite biology as well as antimalarial drug resistance.

eLife assessment

This paper reports valuable results regarding the potential role and time course of the prefrontal cortex in conscious perception. Although the sample size is small, the results are convincing, and strengths include the use of several complementary analysis methods. The behavioral test includes subject report such that the study does not allow for distinguishing between (phenomenal) awareness and conscious access; nevertheless, results do advance our understanding of the contribution of prefrontal cortex to conscious perception.

eLife assessment

This paper is of interest to researchers and policy makers involved in cervical cancer prevention. The paper provides insight into how the Covid19 pandemic accelerated changes in organized cervical cancer screening. The claim that self-sampling led to a major improvement of test coverage seems somewhat exaggerated and alternative hypotheses to those provided by the authors on the population who chose self-sampling are possible. Nonetheless, this is a valuable piece of work given the scope of the intervention(s) and the precedent it sets i.e. a crisis can in fact accelerate positive changes in screening that have been academic possibilities rather than practical realities.

eLife assessment

This paper addresses the important question of presynaptic homeostasis and convincingly demonstrates antagonistic interactions between Spinophilin and Syd-1 in this process. It also provides a useful hypothesis for the downstream mechanisms.

eLife assessment

Moises and Harel generate an important set of novel molecular tools in African turquoise killifish, an innovative model to study aging biology. The new solid tools described in this paper can boost this buddying model system for broad biotechnological applications. The authors showcase the efficacy of their tools in the context of peptide hormones involved in growth and gonad development. The killifish community will greatly benefit from these novel tools and the relevance of the developed methods will likely go beyond the killifish community.

eLife assessment

This study addresses an important question in the field of antimicrobial chemotherapy: whether combinations of enzyme inhibitors that select for mutations that confer resistance to one inhibitor and at the same time increased sensitization to the other inhibitor can provide a path towards mitigating resistance risks. The authors here investigated one such combination of inhibitors of Plasmodium falciparum DHODH (dihydroorotate dehydrogenase), finding that despite "collateral sensitivity", it was still possible to select a mutation that mediated resistance to both inhibitors without any change in parasite fitness. Additional cross-susceptibility and structural modeling strengthen this study, which is performed to a high technical standard and presents a convincing body of data.

eLife assessment

The valuable study by Dumeaux et al examines the transcriptional response to antifungal treatment in the major opportunistic human fungal pathogen Candida albicans. Using solid methodology, including a novel droplet-based single cell transcriptomics platform, the authors report that fungal cells exhibit heterogeneity in their transcriptional response to antifungal drug treatment. The ability to study the trajectories of individual cells in a high-throughput manner provides a novel perspective on studying the emergence of drug tolerance and resistance in fungal pathogens.

eLife assessment

This manuscript addresses the important issue of hemodynamic response function (HRF) variability across brain areas and will be valuable to researchers who use fMRI and other types of functional imaging that rely on neurovascular coupling. Using simulations and experiments, the authors provide solid evidence that differences in the HRF can impact spectrum-based metrics such as ALFF and fALFF. A better understanding of the variability of the HRF is critical for the proper interpretation of activation onset times and of differences observed in clinical populations where both neural and vascular alterations can be expected.

eLife assessment

This valuable study shows that Rab12 is required for LRRK2 activation. However, while some of the data are compelling, some claims, especially the ones related to LRRK2's membrane association are not supported. Addressing discrepancies between figures (pointed out by reviewers) and re-writing certain sections will greatly improve this manuscript.

eLife assessment

This exceptional work substantially advances our understanding of the mechanics of the Reissner's fibre (RF) by performing in-vivo experiments that track and analyze the behavior of the RF when it is cut and the behavior of ciliated cells touching the RF when contact is interrupted. The data is valuable and the conclusions are compelling. The work will be of broad interest to many research communities including developmental neuroscience and cilia biology.

eLife assessment

This manuscript reports the fundamental finding that an oligomeric protein kinase, CaMKII, can be phosphorylated by another molecule of the holoenzyme in a manner that does not involve subunit exchange. The evidence for the main conclusion is compelling, supported by several independent experiments. If independently confirmed in future, the study will stand as having provided a novel regulatory mechanism for the autophosphorylation of this kinase. The work will be of broad interest to molecular and cellular neuroscientists as well as biochemists.

eLife assessment

This is an important analysis of two sleep datasets in children and adolescents that contributes to our understanding of sleep spindle and slow oscillation dynamics during development and is expected to be of interest to interdisciplinary fields including development and sleep. The analyses are solid and adequately complex to capture the changes in sleep spindle to slow oscillation coupling between the age groups. However, the paper would be strengthened by performing the same analyses in an adult sample to sufficiently characterize the maturation of sleep spindles and their coupling to slow oscillations.

eLife assessment

This study presents a valuable finding on the associations and causal relationship between second primary cancers and the initial diagnosis of a primary cancer via using a large database. The evidence supporting the claims of the authors is solid. The work will be of interest to cancer clinicians.

eLife assessment

This important study combines engineered mesenchymal stem cells together with mouse models of kidney injury to determine the ability of these cells to reduce kidney damage upon acute kidney injury. The evidence supporting the claims is solid, although the inclusion of more than one type of stem cell and the use of male mice which are more prone to acute kidney injury, would strengthen the study. This work will be of interest to both basic scientists and clinicians working on mechanisms of kidney injury and repair.

eLife assessment

This important study identifies the functional consequence of myelination of interneuronal axons on circuit function by showing that 4.1B deletion leads to altered myelination in a subset of interneurons and altered intrinsic and synaptic physiological parameters. The authors' conclusions about how myelination of inhibitory axons affects physiological properties are based on solid evidence using a combination of imaging and electrophysiological approaches.

eLife assessment

This is an important study that uses chromatin accessibility as a measure to determine the impact of neuronal activity on the state of chromatin regulatory elements in striatal neurons. The authors provide convincing evidence of how Pdyn gene expression is highly dependent on a distal regulatory genomic region both at basal and upon neuronal activation in this particular system, a mechanism conserved as well in human neuronal cells. Although the basic idea of accessibility changes have been studied before, this paper ties previous findings all together in one place and uses the analysis to identify a functionally relevant and conserved enhancer for the prodynorphin gene with potential relevance for neuropsychiatric disorders beyond basic cellular neuroscience. The study will be of interest to neuroscientists studying the striatum, neuronal plasticity, or related neuropsychiatric disorders.

eLife assessment

This study characterized the activity of optogenetically identified dopaminergic and GABAergic neurons in the ventral tegmental area in mice performing a memory-guided T-maze task, and shows that subpopulations of dopaminergic and GABAergic neurons exhibited choice-related activity during the delay period, consistent with some previous studies (e.g. Morris et al., 2006, Parker et al., 2016). The authors demonstrate that these delay-period activities were enhanced when the task requires short-term memory. The results are convincing and this study provides important results regarding the nature of delay-period activity in the task.