Evaluated articles

eLife assessment

This is an important study of the dimensionality and synchrony of calcium responses in Purkinje cells measured across a large region of the cerebellar cortex over the course of learning. This work has the potential to inform our understanding of the functional organization of the cerebellum and longstanding hypotheses about the role of cerebellar climbing fibers in the induction of learning and in the timing of movement, but the evidence provided for the many sweeping claims is incomplete. The paper would benefit from additional statistical analyses to more rigorously evaluate the central claims, with consideration of appropriate comparison groups and potential confounds.

eLife assessment

This important study uses mathematical modelling to demonstrate that conformational autoinhibition of the RAF kinase is an important feature of its paradoxical activation by pharmacological inhibitors. This part of the theoretical analysis is highly compelling but its extension to the investigation of how the binding of 14-3-3 adaptors additionally contributes to the paradoxical activation phenomenon is incomplete and would benefit from more rigorous experimental validation. With the experimental part addressing 14-3-3-dependent regulation strengthened or the 14-3-3 part completely removed, this paper would be of considerable interest to cell biologists and cancer biologists, ultimately paving the way for improved RAF therapeutics.

eLife assessment

This is a descriptive paper in the field of metascience, which documents levels of accessibility and reproducible research practices in the field of cardiovascular science. As such, it does not make a theoretical contribution, but it argues, first, that there is a problem for this field, and second, it provides a baseline against which the impact of future initiatives to improve reproducibility can be assessed. The study was pre-registered and the methods and data are clearly documented. This kind of study is extremely labour-intensive and represents a great deal of work.

eLife assessment

This study presents important evidence of the impact of the covid pandemic on breast cancer screening globally but with important variations by healthcare setting. The data analysis is comprehensive, using solid systematic review methods. The results will be of interest to public health policymakers and health care and cancer control practitioners and researchers across the globe.

eLife assessment

TP73 is a member of the p53 family of tumor suppressors. The authors provide compelling evidence that a TAp73-alpha to TAp73-gamma switch could be a frequent phenomenon in human cancers and provide novel evidence that TAp73-gamma has oncogenic functions via Leptin. The authors provide a substantial amount of high-quality data and convincingly demonstrate a novel function of this specific isoform of p73 in lipid metabolism and tumorigenesis.

eLife assessment

This is a valuable contribution to the effort to provide genetic access to and characterization of the major classes of interneurons in the mammalian neocortex. The authors develop an improved strategy for intersectionally targeting a fourth (and final) major category of diverse interneurons in the mouse, including the previously studied neurogliaform cells. They provide a detailed characterization of these cells and show convincingly that their genetic strategy can be used to identify and manipulate these cells, both in vitro and in vivo.

eLife assessment

In this important study, the authors present evidence for the novel involvement of a scavenger receptor in tubular morphogenesis. Using a convincing set of data, the authors propose that the Drosophila scavenger receptor Emp (homologous to human CD36 ) couples endocytosis of luminal molecules and regulates tube length via controlling Crumbs and Src. This work will be of broad interest to cell and development biologists as well as cancer biologists.

eLife assessment

This manuscript is important as it showed an establishment of a method for looking a neuronal activity in embryos which can support the previously reported laterality in chick thalamofugal system. However, the evidence the author provided was incomplete as no actual data was provided.

eLife assessment

This important study provides a substantial advance with a method by which a protein target resistant to therapeutic approaches can be uniquely modulated by a cellular protein kinase ferried by nanobodies to a precise molecular site of recruitment. Evidence for this major claim is compelling, but evidence for some of the minor claims seems incomplete. The work will be of broad interest to cell biologists, cardiovascular researchers, and drug developers.

eLife assessment

This important study provides a state-of-the-art framework to explore the coupling of complementary cerebral measures (neural, hemodynamic, and metabolic) during development by providing an interesting roadmap for multimodal neuroimaging in infants. The methodological contribution is compelling with an original setup for simultaneous EEG and NIRS recording and solid data analyses. However, the claims about functional specialization and the role of the temporal-parietal junction in social processing are only partially supported by the results. This work will be of interest to a broad audience of scientists interested in multimodal neuroimaging and cognitive development.

eLife assessment

Overall, this is an important study that characterizes human oral lichen planus via single-cell analysis. Although the work is descriptive, it can represent an important resource for future studies and highlights potentially relevant biology. However, the claims are a bit overstated and some of the analyses that lead to interpretations remain incomplete.

eLife assessment

This study is a valuable contribution to our understanding of vocal variation in acoustic displays of male baleen whales, part of a developing story about cultural change in songs in species other than the relatively well studied humpback whales. The authors present solid evidence of changes at various timescales in 20-Hz song note intervals and call center frequency over decadal time scales and large spatial scales.

eLife assessment

This study presents important findings regarding the local dynamics at the anion binding site in the SLC26 transporter prestin that is responsible for electromotility in outer hair cells. The authors reveal critical differences to homologous proteins and thereby provide insight into prestin's unique function. The evidence is generally convincing, although orthogonal evidence would be required to fully support the claims concerning the mechanistic basis for voltage sensitivity.

eLife assessment

This paper is a valuable step in multi-subject behavioral modeling using an extension of the Variational Autoencoder (VAE) framework. Using a novel partition of the latent space and in tandem with a recently proposed regularization scheme, the paper provides a rich set of computational analyses analyzing social behavior data of mice with results that represent the state-of-the-art in this subfield. The strength of evidence is convincing, with the methodology being well documented and the results being reproducible, although some additional quantifications would have been helpful to fully gauge the circumstances where the approach would be most effectively applied.

eLife assessment

This is a valuable study of Eph-Ephrin signaling mechanisms generating pathological changes in amyotropic lateral sclerosis. There are exciting findings bearing on the role of glial cells in this pathology. The study emerges with solid evidence for a novel astrocyte-mediated mechanism for disease propagation. It may help identify potential therapeutic targets.

eLife assessment

This is an important study that revealed a new noncoding RNA regulatory circuit involved in T cell function. The authors provide compelling evidence, that is more rigorous than the state-of-the-art, using genetically engineered mice and cell-based experiments. The interpretation of the results should be tempered due to the small effect size observed.

eLife assessment

In this important study, Lui and colleagues examine whether the locus coeruleus is involved in extinction of an appetitive conditioned response. Using a set of optogenetic approaches aimed at manipulating the activity of locus coeruleus cells, the authors provide solid evidence that these neurons regulate the extinction of conditioned responses. Overall this study further highlights the key role of noradrenaline in cognitive processes and will be of interest to those interested in associative learning, extinction, noradrenaline, associated brain systems and translational endpoints.

eLife Assessment

This study aggregates across five fMRI datasets and reports that a network of brain areas previously associated with response inhibition processes, including several in the basal ganglia, are more active on failed stop than successful stop trials. This study is valuable as a well-powered investigation of fMRI measures of stopping, and following revisions provides solid evidence for its conclusions.

eLife assessment

Based on a technological advance which couples onboard calcium imaging with in vivo electrophysiology in freely behaving mice, this important work presents data about the modulation of some long range brain activity correlations during social interactions. Solid evidence shows that neural activity across cerebellum and cingulate cortex is more correlated during social behaviors than during non-social epochs. This study is of interest for a broad range of neurophysiologists.

eLife assessment

This important study reveals the use of an allocentric spatial reference frame in the updating perception of the location of a dimly lit target during locomotion. The evidence supporting this claim is compelling, based on a series of cleverly and carefully designed behavioral experiments. The results will be of interest not only to scientists who study perception, action and cognition but also to engineers who work on developing visually guided robots and self-driving vehicles.