Evaluated articles

eLife assessment

Force generation by the myosin motor plays an important role during cell division. Myosin activity is regulated by phosphorylation, which activates myosin in animals but was thought to inactivate it in yeast. In this valuable study, the authors use a combination of convincing approaches to show that under some growth conditions, dependent on the carbon source of the growth medium, phosphorylation becomes essential for myosin function.

eLife assessment

The fundamental work by Starret et al advances the understanding of the etiological roles of viruses and other environmental factors in bladder cancers after solid organ transplantation. The evidence is compelling using cutting edge sequencing approaches of patient samples. This work will be immediately interesting to multiple fields (of viral oncogenesis, BK polyomavirus (BKPyV) and JC polyomavirus (JCPyV), solid organ transplantation and whole genome and transcriptome sequencing) and may eventually influence care after organ transplantation.

eLife assessment

This study addresses a fundamental question about the spatiotemporal location of neurotransmitter release in a synapse with essential implications for postsynaptic signaling and neural excitability in general. The authors provide convincing evidence on non-overlapping nanometer scale organization of the two primary forms of evoked vesicle fusion (synchronous and asynchronous) in the synapse. They utilize tools for super-resolution assessment of synaptic transmission that were previously developed in their lab, in this way they help bridge earlier work based on imaging approaches that lack temporal resolution and electrophysiological results lacking spatial resolution.

eLife assessment

This is an important and valuable paper that uses H2B overexpression to quantify changes to chromatin compaction using elegant in vivo imaging approaches in the live epidermis in stem cells undergoing epidermal differentiation. The results confirm in vitro findings that changes to chromatin compaction precede cell fate commitment during epidermal stem cell differentiation. These conclusions are mostly supported by solid and convincing experimental and quantitative evidence and the recapitulation of chromatin and transcriptional phenomena in a live tissue setting using careful in vivo imaging and quantification is of value.

eLife assessment

This manuscript details the valuable development of population genetics theory that can be used to infer past changes in the selfing rate in natural populations. The inference procedure is solid, although the comparison to previous estimates can be improved, and deeper insight could be gained from further theoretical exploration. The work will be of broad interest to the field of mating systems evolution.

eLife assessment

Based on a large set of complementary experiments, the authors propose that the lncRNA LNCSOX17 regulates human definitive endoderm differentiation, although its function is not related to the adjacent SOX17 gene in the same topological domain (TAD). The findings are important and supported by convincing data, although the molecular mechanism by which LNCSOX17 regulates endoderm differentiation stays unresolved.

eLife assessment

This fundamental study presents a crystal structure of two proteins catalyzing histone H2B ubiquitination. Findings from the structural study are further validated by mutagenesis and functional assays. This is a well-executed study providing useful information to the field.

eLife assessment

This important work provides knowledge regarding how neuropeptides, which are highly expressed in the brain, can influence cortical plasticity. The conclusions are supported by compelling evidence from both in vitro and in vivo assays, although some control experiments are needed to further strengthen the conclusions. This paper will be of interest to neuroscientists studying cortical processing and neural plasticity, as well as cell biologists and biochemists interested in peptide function in general.

eLife assessment

This fundamental study substantially advances our understanding of interactions of consecutive memory tasks by identifying responsible molecules and neurons. The evidence supporting the claims of the authors is generally solid, although further contextualization of the interferences in memory consolidation and more rigorous measurements of the effects of genetic manipulation would have strengthened the study. The work will be of broad interest to neuroscientists working on learning and memory as well as learning psychologists.

eLife assessment

In this study, the authors provide important findings supporting a key role for TLP2 as a regulator of neurotoxic and pro-inflammatory cytokine and chemokine release following acute and chronic neuroinflammation. They provide convincing data supporting that the abrogation of TPL2 kinase activity ameliorates disease pathogenesis in a mouse model of tauopathy. This manuscript will be of broad interest to readers in the fields of neuroimmunology and neurodegenerative disease who are interested in the pathogenic effects of innate immune signaling pathways in disease.

eLife assessment

Rett syndrome is one of the most frequently diagnosed neurodevelopmental conditions. The gene mutated in the condition, Mecp2, encodes for a transcriptional repressor, but genes functioning downstream of Mecp2 have remained difficult to clarify. Here the authors identify an important candidate gene, Growth Differentiation Factor 11 (GDF11) regulated by Mecp2 via epigenetic mechanisms. Further studies in mouse models demonstrate that genetic reduction of Gdf11 ameliorates behavioral deficits of Mecp2 duplication mice, and can function to produce neurobehavioral deficits in mice alone. These findings will be of interest to scientists working in mouse cognition, behavior, neurodevelopment, transcriptional and epigenetics.

eLife assessment

This study provides important new insights into iron sulfur biosynthesis in the human malaria parasite Plasmodium falciparum. The work is based on elegant and robust genetic approaches, and not only confirms the essentiality of the plastid-hosted Suf iron-sulfur cluster synthesis pathway, but also highlights an important additional role for the cysteine desulfurase SufS in apicoplast maintenance via tRNA modification. The work provides compelling evidence for a dual function of parasite SufS, although impact on tRNA has not been established directly. These findings reveal a potential new target for metabolic intervention, and will be of interest to researchers studying apicomplexan parasites, and more broadly, in the field of plastid biology.

eLife assessment

There are no known effective treatments available to date for the treatment of osteosarcomas, the earliest identified bone cancer that can spread to other tissues. In this study, the authors have used novel approaches to identify calreticulin and procollagen C-endopeptidase enhancer (PCOLCE) as osteosarcoma tumor suppressor proteins that inhibit osteosarcoma growth both in animal and in vitro cell culture models. These important findings may provide a basis for the future development of more efficient targeted therapies for the treatment of osteosarcomas.

eLife assessment

This is an important and significant study that focuses on deriving ovarian granulosa-like cells from hiPSC lines. The strengths of the study include bioinformatics analysis to identify relevant candidate transcription factors that drive the iPSCs into the ovarian granulosa pathway, an attempt to derive ovaroid model by combining human PGC-like cells with the iPSC-derived granulosa-like cells, and a variety of endpoint analysis including hormone measurements. Some limitations of the study include poor quality of images, lack of convincing demonstration that follicle-like structures are indeed derived in vitro, lack of clear rationale for using different cell lines with different endpoints chosen for analysis, and lack of clear methods indicating stepwise which transcription factors were used.

eLife assessment

Cover et al., examine the pathway from the intralaminar nucleus of the thalamus (rILN) to the dorsal striatum (DS) in the reinforcement of behavior/actions. The rILN sends a large glutamatergic projection to the DS, but its role in action selection was unknown. The authors found that the rILN neurons that project to the DS were activated at both action initiation and with the reward. Activation and inhibition of this pathway increased the success or decreased the success of reward acquisition, respectively. The findings are an important advance our understanding of the function of rILN to DS projection in reward-based behavior. The manuscript has provided convincing evidence with the appropriate methodologies to support these claims.

eLife assessment

This study presents a valuable finding in identifying the roles of the pericytes in maintaining vascular volume and integrity of spiral ganglion neurons (SGNs) in the cochlea, the main hearing organ. The evidence supporting the authors' claims is solid using an inducible and conditional pericyte depletion mouse model and the co-culture models. While the study provides a modest translational contribution, understanding the roles of organ-specific pericytes is paramount, making this study timely and significant. The work will be interesting for biomedical biologists working on hearing, blood vessels, signaling, and cell-to-cell interactions.

eLife assessment

Illingworth et al. investigate the effectiveness of ribavirin and favipiravir on the treatment of a paediatric patient with chronic RSV and identify an increase in mutations caused by ribavirin while favipiravir had no apparent mutagenic effect. Strength of evidence is incomplete for the mathematical model and solid for the mutational load analysis with potential for improvement in both cases with clarification of the methods. Major strengths are an interesting hypothesis and appropriate modeling methodology that will be of interest to virologists, clinicians and evolutionary biologists. Weaknesses in methodology pertain to mutational load measures possibly also capturing clonal expansion of new mutants and lack of clarity about how viral fitness is related to viral load in the mathematical model.

eLife assessment

This study presents the important finding of an unusual uncompetitive inhibitor (ECSI#6) of the serotonin transporter that removes the neurotransmitter serotonin from the synaptic cleft. Through careful and comprehensive analysis, the authors convincingly show that the molecule most likely binds to the inward-facing and K+-bound state and that it assists in folding and targeting the transporter. The work will be of interest to those engaged in biophysical analyses of the serotonin transporter, and colleagues developing pharmacological chaperoning strategies for transporters in general.

eLife assessment

In this important paper, the authors have developed an approach for simultaneously optimizing the conformational ensemble and degrees of oligomerization, and this has been tested by applying it to a specific protein (SPOP). Comparison of the quality of fits with different models also provides valuable insights into structural features important to the assembly of oligomers. The approach, presented with compelling experimental support, is potentially applicable to other systems as well.

eLife assessment

This valuable study combines live cell imaging and mathematical modeling to show how an emerging model fungus engages in an oscillatory chemical dialogue to prepare for cell-cell fusion. Cell data and modeling are in compelling agreement but leave many open questions as to the nature of coordination between cells and the significance of oscillations, rendering the strength of evidence in support of the authors' inferences incomplete.