Evaluated articles

eLife assessment

This important work provides evidence that artificial recurrent neural networks can be used to investigate neural mechanisms underlying reversible remapping of spatial representations. Authors perform convincing state of the art analyses showing how population activity preserves the encoding of spatial position despite remappings due to the tracking of an internal variable. This paper will be of interest to neuroscientists studying contextual computations, neural representation of space and links between artificial neural networks and the brain.

eLife assessment

This behavioral modeling study investigates how humans make decisions on the difficulty of perceptual categorization tasks. The study finds that such judgments are best described by an evidence-accumulation model that includes a dynamic comparison of difficulty-related evidence, which terminates when the difference in evidence between two tasks reaches a predetermined bound – a valuable finding for research in perceptual decision-making. The paper provides compelling behavioral evidence for the proposed model through: 1) quantitative model selection/validation procedures, and 2) qualitative analyses of the relation between the optimal model of the task and the human data (and the proposed model).

eLife assessment

This paper presents an important finding: that Styxl2, a poorly characterized pseudo-phosphatase, plays a role in the sarcomere assembly by promoting the degradation of non-muscle myosins. The genetic evidence supporting the conclusions is compelling, although future work will be needed to elucidate the functional role and biochemical mechanism of autophagic degradation of non-muscle myosins. This work will be of interest to biologists studying muscle development, cell biology, and proteolysis.

eLife assessment

This valuable work fills a gap in the mapping of gene expression patterns in the early embryo of C. elegans. The presented data are solid and provides a resource for future analysis.

eLife assessment

In this important study, the authors provide convincing evidence that current DNA-based microbial genomics for skin bacteria cannot always detect the source of sequenced DNA and whether it originated from viable or non-viable bacteria. Additionally, the authors demonstrated in humans and mice that most of the viable bacteria reside inside hair follicles rather than the surface of the skin per se. Overall, the work has significance beyond a single discipline and will be of interest to those studying microbiomes.

eLife assessment

This important study highlights a potential connection between fatty acid intrusion into myocytes and increases in mitochondrial ceramide that cause deficits in coenzyme Q and consequent insulin resistance. The authors primarily use the L6 myocyte model, which may not fully recapitulate in vivo conditions, however, the manuscript shows compelling data in mice that substantially supports the L6 cell results. Overall, this study provides a strong framework for a compelling pathway of myocyte dysfunction and for continued efforts to test the important hypotheses that are presented.

eLife assessment

This paper introduces the python software package Pynapple and a separate package of more advanced routines (Pynacollada) to the Neuroscience/Neural Engineering community. Pynapple provides a set of data objects and methods that have the potential to simplify data analysis for neural and behavioral data types. This represents a valuable contribution to the field. With more examples and as a live coding notebook, the evidence was judged to be compelling.

eLife assessment

The authors provide a new powerful tool as well as a large database that should be useful to the neuroscience community, but not only. The authors developed and applied a methodology to automatically estimate the volume, cell number, and density of mice brains from multiple regions, by detecting the native fluorescence of the cell nuclei. Using this platform, they analyzed an existing dataset containing multiple mouse brains, available in the Allen Mouse Connectivity project. The data provides a comprehensive neuroanatomical comparison of brain nuclei between males and females, between hemispheres, and between 2 strains of lab mice.

eLife assessment

In its current form, the reviewers felt that the work describing the use of a CycleGAN for alignment of neural activity from a neural interface across sessions was useful, with solid evidence showing that it improved performance over similar-concept previous approaches.

eLife assessment

This is an interesting and valuable study describing the importance of a focal adhesion protein vinculin in osteocytes in controlling bone formation by regulating the expression of sclerostin, which inhibits bone formation. The data are generally convincing and support the conclusions. Some additional investigation and discussions are required to further strengthen the conclusion and interpretation.

eLife assessment

Small subthreshold dendritic-somatic depolarizations can propagate to presynaptic nerve endings and may modulate transmitter release, but the mechanisms of this modulation remain poorly understood because the technical challenge of recording from small bouton synapse. Here the authors directly record from small cerebellar bouton terminals In paired somatic and presynaptic recordings, they demonstrate that small synaptic potentials can travel within 2 to 3 ms to the bouton and arrive there with an amplitude attenuated by 20 to 70% with respect to the somatically recorded potential. As expected, this amplitude attenuation depends on axon length. In recordings of MLI-Purkinje cell pairs the authors further demonstrate that small somatic subthreshold depolarizations of about 20 mV size can enhance AP-triggered IPSCs recorded in the Purkinje cells and change synaptic plasticity during AP trains. In order to address mechanisms of such presynaptic modulation, the authors measure presynaptic AP waveforms via cell attached recordings and found these very stable. On the other hand, presynaptic ICa(V) directly recorded in voltage-clamped MLI boutons facilitated in response to small pre-depolarizations and such facilitated ICa(V) produced larger IPSCs in paired recordings of MLI boutons and coupled Purkinje cells. The authors propose that an accumulation of partially gated channels during small presynaptic depolarizations is able to produce more rapid gating of VGCCs during the AP waveform on arrival of an invading presynaptic AP.

eLife assessment

The phenomenon of summit disease, where complex animal behaviours are controlled by single-celled parasites, captivates biologists and non-scientists alike. In this valuable study, the authors use a laboratory model (Drosophila melanogaster infected with Entomophthora muscae) for this disease to provide compelling evidence for the neuroanatomical and physiological underpinnings of summit disease. This is an excellent example of how seemingly intractable questions in behavioural ecology can be effectively addressed in laboratory settings using decades of work in creating 'models' for biology.

eLife assessment

This is an important report on the discovery of a strong sensitizing effect of cannabidiol on the activation of TRPV2 channels by 2-APB. The conclusions are convincingly supported by solid electrophysiological recordings and cryo-EM structures, but identification of a clear molecular mechanism will require additional structural work. The paper will be of interest to the ion channel research community.

eLife assessment

This valuable paper uses a cohort of SARS-CoV-2 infected people to link immune signatures 3 months post-infection with persistent, long COVID-19 symptoms. The strength of the evidence presented is solid based on a wide array of immunologic assays and a strategically designed cohort, with some claims that are incomplete based on a lack of specifically designed endpoints, lack of analysis of regulatory signals, and incomplete use of control samples. A couple of findings are novel and will be of interest to clinicians and immunologists, particularly that degree of inflammation at 3 months does not impair the generation of SARS-CoV-2 humoral and cellular memory responses and that cellular immune signatures are only somewhat correlated with long COVID-19 symptoms.

eLife assessment

Protein abundance is the result of many layers of regulation, including at the levels of transcription, mRNA stability, translation and protein degradation. Many transcripts contain short upstream ORFs (uORFS), but their effects on the translation of the main ORFs are difficult to predict as they are sometimes negative, positive and of different magnitudes. Here, the authors identify features of uORFs using massively parallel reporter assays, and these features help predict uORF effects on translation of main ORFs. The results will be an important resource for the community of researchers using this model organism and for the molecular and cell biology community in general as they allow to better understand how genes are regulated. There are also areas in which the authors' claims or conclusions are not fully justified and require either additional statistical analysis or new experimentation.

eLife assessment

This valuable study presents presents solid evidence that an anti-CTLA-4 antibody drug conjugate transiently depletes circulating B cells in a mouse model, showing how dysregulation of the T cell immune system can impact B cell homeostasis. The work will be of broad interest to immunologists and medical biologists, but a major limitation is that the mechanism of B-cell reduction remains unclear, as evidence of killing of B-cells by T-cells is not presented.

eLife assessment

This important study was designed to examine the bypass of Ras/Erk signaling defects that enable limited regeneration in a mouse model of hepatic regeneration. This hepatocyte proliferation is associated with the expression by groups of cells of mRNA-loaded CD133+ intracellular vesicles that mediate an intercellular signaling pathway that supports proliferation. These are new observations, supported by convincing data, that have broad significance to the fields of regeneration and cancer.

eLife assessment

This valuable study presents a novel and theoretically interesting model to account for viral diversity within hosts in evolutionary and genomic analyses of pathogens. The simulation results presented are solid, although there are some aspects of the methodology that require further investigation in order to establish their validity. The application to SARS-CoV-2 shows promise, but would benefit from further evaluation.

eLife assessment

This study presents the important finding that gene editing could be used to activate delta-globin expression to treat disorders of red blood cell synthesis. The evidence supporting the claims of the authors is solid, particularly in the immortalized cell lines, although inclusion of a larger number of donor patient samples may have strengthened the conclusions that were able to be drawn from the primary cell experiments. The data show this approach to have promise and identify avenues of effort that could be pursued to advance it to a clinical strategy for hemoglobinopathy treatment.

eLife assessment

Early life stress can have profound effects on animal behavior, including potential influences on individuality. In this valuable work, the authors use a rich new dataset to solidly demonstrate that the behavioral consequences of early life stress in C. elegans can be buffered by neuromodulators previously implicated in patterns of individuality. While much remains to be learned about the mechanisms by which stress might influence individuality, these studies provide an important entry point that will be of interest to neurobiologists studying interactions between behavior, neuromodulation, stress, and individuality.