Evaluated articles

eLife Assessment

The ability to measure autophagic flux in vivo in response to physiological stresses remains a challenge for investigators in the field; the novel mouse model present in this work is significant and should prove valuable to investigators in addressing shortcomings of existing models. In addition, the development of the microplate reader approach to permit semi-high-throughput analysis of samples is convincing and a significant advance. The application of these approaches to measuring autophagy in multiple tissues is appreciated but raises some questions that need to be answered and highlighted, including what new biological insight has been generated for tissues under study, how overall autophagy versus rates of flux are determined, and how the sex of the animal affects outcomes. The neuronal populations under study should be reassessed.

eLife Assessment

This manuscript presents valuable experimental results describing the localisation and regulation of casein kinase CK1δ during the cell cycle. During the G2 phase of the cell cycle, the autophosphorylation of the C-terminal tail stabilises and inhibits the kinase which might protect CK1δ in the subsequent G1 phase. The results may be of interest to researchers working on casein kinase function and regulation but due to lack of some controls remain incomplete.

[Editors' note: this paper was reviewed by Review Commons.]

eLife Assessment

This study provides a useful single-cell atlas of the Clytia hemisphaerica planula, complemented by an updated medusa dataset, ultrastructural analyses and in situ validation of expression patterns. The cross-stage comparison and cluster-similarity framework offer a promising basis for investigating cellular diversification across the life cycle. The evidence is currently incomplete due to documentation deficits and insufficient cross-referencing with prior work. It should be relatively easy to address these issues, which should make this a valued resource for cnidarian researchers and for colleagues studying cell-type evolution.

eLife Assessment

This study offers valuable insights into the genetic and evolutionary basis of the starvation response by confirming the hypothesis about the mito-nuclear etiology of this trait. The level of evidence is currently incomplete but could be improved if controls were designed better, particularly by including analysis of variation in the initial, common population prior to all treatments. Overall, this work would be interesting to a broad audience, beyond the Drosophila community, if the analysis of the candidate genes against Human ortholog loci were to be conducted with more careful controls.

eLife Assessment

This valuable study combines a chromosome-level genome assembly with population resequencing and demographic modelling to reassess the status of the Formosan landlocked salmon, a critically endangered salmonid at the southern edge of the genus. The assembly and the evidence for extensive lineage-specific chromosomal fusions are genuinely well done, and the discovery of an overlooked, genetically distinct population in Hehuan Creek is sound and of clear management relevance. Evidence for the headline claims is incomplete: species rank is asserted but nowhere argued, and gene flow is excluded using a coalescent model that contains no migration parameter. Support for the population-viability conclusions is also not complete, as the demographic mechanisms invoked in the discussion are not borne out by the supplementary tables.

eLife Assessment

This valuable study uses genetic, behavioural, neuronal activity and cell-based assays to show that the Drosophila ionotropic receptor IR20a contributes to the detection of arginine and low-sodium salt, and suggests that peripheral receptor combinations may help integrate these nutrient cues. The evidence for a role for IR20a and associated co-receptors in these responses is solid, but the evidence that distinct receptor assemblies mediate receptor-level multimodal integration is incomplete, as this central model is inferred from functional data and leaves some discrepancies between behaviour, physiology and prior work unresolved. The study will be of interest to sensory neuroscientists and chemosensory biologists.

eLife Assessment

This important study provides a contribution to retinal regeneration research by using overexpression of pro-neural factors to reprogram fetal human RPE cells into retinal neurons. The authors provide solid evidence of fetal RPE reprogramming into neural and photoreceptor-like states using scRNA-seq and imaging validation. There remains concerns regarding comparisons between the effectiveness of different combinatorial transcription factor codes.

eLife Assessment

This important study presents an ultrastructural atlas of extracellular vesicles and non-vesicular particles in Drosophila olfactory sensilla, using cryofixation-based serial block-face electron microscopy to catalogue roughly 7,800 particles across four antennal regions. The evidence is compelling: the cryofixation minimizes fixation artifacts, and the rigorous, well-validated methodology and morphometric analyses provide strong support for the structural classifications and spatial distributions, though some conclusions require moderation or additional evidence. The work provides a potentially foundational resource for researchers studying extracellular-particle signaling in sensory organs.

eLife Assessment

This study presents valuable findings on the functional consequences of nuclear envelope rupture caused by the depletion of nuclear pore complex subunits on the behaviour and organisation of chromosomes during mitosis in C. elegans embryos. The experiments are generally well-designed and executed; however, the evidence for some of the main conclusions is incomplete. This work is of potential interest to cell biologists working on cell division.

eLife Assessment

In this important study, Lau et al. identify non-conserved nucleotides within the common binding motifs of BLIMP1 and IRF4 that provide a molecular mechanism for their distinct roles as crucial transcription factors during the antibody-secreting cell differentiation. The major strength of this manuscript is the solid and detailed characterization of human in vitro plasma cell differentiation. However, several overstatements exist, therefore requiring careful revision to improve the manuscript.

eLife Assessment

Using sci-L3-Strand-seq, this study shows genome-wide, single-cell evidence that DSBs triggered by CRSIPR/Cas9 are frequently resolved through sister chromatid exchange (SCE), which is undetectable with conventional whole genome sequencing approaches. This important work provides helpful metrics quantifying the occurrence of SCE events at targeted and repetitive genomic loci that are of particular interest to those working in gene editing, DNA repair, genome instability, or repetitive genomic loci. The analysis of reciprocal daughter-cell pairs provides compelling evidence for SCE events, providing evidence consistent with CDK1-TTF2-TRAIP mediated cell-cycle regulated CMG helicase disassembly and fork cleavage at unreplicated regions.

eLife Assessment

This important study shows that cave-adapted Astyanax mexicanus have shifted from avoiding alarm and decay odors to being attracted by them, alongside sex-specific responses to social odors. The evidence for the behavioral and heritability claims is convincing, supported by analyses of different cave populations and F2 hybrids, as well as starvation-induced plasticity experiments. Whole-brain pERK mapping offers suggestive mechanistic insight, although uncertainties in anatomical assignments and aspects of statistical and ethogram reporting temper the strength of the neurobiological conclusions. The work will be of interest to anyone working on the evolution of behavior.

eLife Assessment

This valuable study provides insights into the developmental regulation of the unusual form of holometabolous metamorphosis that occurs in the black soldier fly, in which a distinct prepupal stage is interposed between the final larval instar and pupation. This type of life history strategy is similar to what is seen in insects at the hemimetabolous-holometabolous boundary, but, given the phylogenetic position of dipterans, it is likely to be a derived trait. The combination of developmental characterization, gene expression profiling, and RNAi-mediated functional analyses provides solid evidence supporting the authors' conclusions and will be of interest to researchers studying insect development and the evolution of metamorphosis.

eLife Assessment

This study addresses a valuable question with implications for the development of EEG-based neurofeedback interventions for pain. However, the strength of evidence is incomplete because the principal conclusions rely on post hoc responder analyses and methodological ambiguities that weaken the support for the claimed causal relationship between gamma modulation and pain reduction.

eLife Assessment

This fundamental study reveals a new downstream mechanism that mediates mTOR's effect on lifespan in C. elegans. Using a combination of genetic, genomic, and functional analyses, the authors uncovered that a bile acid-like hormone, dafachronic acid (DA), acts downstream of mTOR to modulate lifespan. The reviewers found the evidence provided to be compelling.

eLife Assessment

This important study uses the Cntnap2 mouse model of autism to investigate how reduced activity in the dorsal CA1 region of the hippocampus contributes to impaired temporal binding and memory flexibility. The authors combined trace conditioning and radial maze assays with fibre photometry, optogenetic rescue, and brain-wide c-Fos mapping to provide convincing evidence that dorsal CA1 hypoactivity limits the retention of temporally separated associations and biases learning towards less flexible strategies. The work advances understanding of hippocampal contributions to cognitive alterations associated with autism and will be of broad interest to researchers studying memory, hippocampal function, and neurodevelopmental disorders.

eLife Assessment

This important study combines crystallographic fragment-based screening with fluorescence-polarization competition assays to demonstrate that the SARS-CoV-2 accessory protein ORF9b, and its interface with the mitochondrial import receptor TOM70, is accessible to small-molecule binding. This is a result with practical implications beyond coronavirus biology for efforts to restore interferon signalling and the antiviral response. The structural evidence is convincing, resting on an unusually large body of ligand-bound crystal structures whose fragment hotspots are independently corroborated by orthogonal biophysical approaches including fluorescence polarization and SPR. This study will be of interest to the broad readership of eLife, spanning structural biology, drug discovery, and coronavirus communities.

eLife Assessment

This valuable study provides key insights into the role of the G protein-coupled receptor GPR34 in an Alzheimer's disease (AD) model. Notably, its findings differ, at least in part, from those of previous studies, although the underlying reasons for these discrepancies are not investigated or discussed. The data show that GPR34 deficiency enhances the transcriptional disease-associated microglia signature in microglia and provide solid evidence that myelin is a GPR34 ligand, although the relevance of myelin engulfment in AD is unclear. This study would be of interest for neuro-immunologists and AD clinicians.

eLife Assessment

This valuable study addresses two debates about how confidence is computed: whether it continues the accumulation process that produced the initial choice or reflects a separate one, and whether that accumulation stops at a time limit or an evidence boundary. The evidence is solid, combining systematic model comparison with an independent neural marker of evidence accumulation to adjudicate between models that behaviour alone cannot separate. Support for the boundary-based stopping rule is stronger than for the single-process account, as the neural comparison is qualitative rather than quantified and the alternatives tested cover only a narrow range of plausible two-stage architectures. The work will be of interest to researchers studying decision-making and metacognition.

eLife Assessment

This important study shows that nutrient resorption efficiency in the widespread wetland grass Phragmites australis varies with population origin and remains largely stable under experimentally imposed salt stress, supporting limited short-term plasticity and a role for genetic differentiation. The findings suggest that predictions of wetland nutrient cycling under increasing salinization should account for intraspecific variation and phylogeographic composition, the evidence is compelling, based on a common-garden experiment involving 110 genotypes, paired control and salinity treatments, and convergent metabolomic, ionomic, and whole-plant evidence confirming substantial physiological stress. The revised manuscript clarifies the partial overlap between ecotype and phylogeographic lineage and appropriately qualifies the modest explanatory contribution of latitude, conclusions remain restricted to one species, one growing season, and a single moderate salinity treatment; an ecotype-specific nitrogen resorption response also indicates that plasticity is not entirely absent and the physiological mechanisms and responses to chronic, stronger, or multigenerational salinity exposure remain unresolved. The study will interest researchers working on plant functional ecology, nutrient cycling, and wetland responses to global change.