Evaluated articles

eLife Assessment

This important study addresses the unresolved and long-debated question of whether atypical protein kinase C is required for the maintenance of synaptic potentiation and long-term memory. The convincing results confirm previous findings that persistent activity of PKMζ is required for lasting potentiation of hippocampal synapses and spatial memory. The study also adds new genetic evidence to support the earlier suggestion that enhanced expression of PKC iota/lambda compensates for the genetic reduction of PKM zeta to support synaptic potentiation and memory.

eLife Assessment

This important study implicates that changes in cell regulation may contribute to the evolution of multicellularity. The evidence supporting the conclusions is convincing, with rigorous methods used to test alternative hypotheses. The work will be of broad interest to cell and evolutionary biologists and those studying the cell cycle and cancer.

eLife Assessment

This study presents a valuable finding on the mutational order for common alterations in colorectal cancer. The evidence of in vitro growth assays comparing mutations is solid, although inclusion of biological replicates for the transcriptional assessments and in vivo experiments would have strengthened the study. The work will be of interest to scientists working in the field of colon cancer.

eLife Assessment

This important study identifies the cribriform plate as a key neuroimmune interface that shapes myeloid cell responses during neuroinflammation. Using imaging, flow cytometry, and single-cell approaches in a mouse model of EAE, the authors provide convincing evidence that dendritic cells and macrophages accumulate in PDPN-rich niches and have transcriptional features consistent with tolerogenic or immunosuppressive states. The work is technically strong and novel, and future studies will be needed to define the functional consequences of these myeloid cell states in autoimmunity.

eLife Assessment

This study offers a valuable analysis of how moment-to-moment fluctuations in arousal are associated with structured, non-uniform patterns of brain-wide functional connectivity during wakefulness. Using data-driven analyses of resting-state and naturalistic fMRI with eye tracking, the authors present convincing evidence that arousal is a dynamic, continuous process that shapes brain activity in a structured way beyond a simple global effect. This paper sheds light on the link between brain activity and ongoing fluctuations in arousal and will be of interest to researchers studying large-scale brain functional organization and links between the brain and body.

eLife Assessment

In this important study, DNA and RNA are co-imaged in single cells to show that the proximity of topologically associated domain (TAD) boundaries is uncoupled from the transcriptional activity of nearby genes. The evidence supporting these conclusions is convincing for the regions examined, with high-throughput imaging providing robust statistics. This work will be of interest to researchers studying genome architecture and its relationship to gene regulation.

eLife Assessment

This study provides valuable data regarding gene expression and molecular changes that occur in the mouse spinal cord from exercise and motor activity. Overall, the findings and methods are solid, although additional independent validation experiments would improve the rigor of the study. The work provides resources for neuroscientists who investigate communication between neurons and non-neurons and both basic and translational scientists with interests in how physical activity impacts the nervous system function, with potential therapeutic outcomes.

eLife Assessment

This study provides valuable evidence regarding our expectations about task difficulty and how this might influence proactive attention. The findings suggest that anticipated demands enhance the strength of attentional selection at cued locations. The evidence is solid but not definitive, as the conclusions rely on the absence of changes in spatial breadth. Nevertheless, the manuscript puts forth an informative experiment with a well written and thoughtful discussion of the results.

eLife Assessment

Foucault and colleagues examine how human adaptive learning depends on the structure of the learning task. The authors provide useful findings clarifying the differences in how people learn in environments that are continuously versus discontinuously changing. While they provide solid evidence for most conclusions, support for some of the claims is incomplete in the current form.

eLife Assessment

This important study convincingly demonstrates how bacterial cells can modulate outer membrane-peptidoglycan tethering by expressing two different Lpp homologs with distinct cross-linking efficiencies, revealing that Salmonella typhimurium LppB forms disulfide-based homodimers (or heterotrimers with Lpp when present) and is covalently attached to peptidoglycan primarily via the L,D-transpeptidase LdtB at residue K58. The evidence supporting the authors' claims is solid, including the regulatory role of LppB dimerization for its abundance in E. coli and its ability to inhibit Lpp/A crosslinking to peptidoglycan, although additional analysis and quantification of muropeptides in wild-type E. coli overexpressing LppB would further strengthen the findings. Overall, the work will be of great interest to microbiologists studying cell envelope biogenesis.

eLife Assessment

This fundamental study describes long-range serial dependence of performance on a visual texture discrimination training task that manipulated conditions to induce differing degrees of location transfer of learning. The authors re-analyzed previously-published, behavioral data, generating compelling evidence from converging approaches that the serial dependence effects persist over multiple days of training, and may share a common causal mechanism with training-induced location transfer. By informing our understanding of the importance of temporal integration to long-term perceptual learning and its propensity towards specificity or generalizability, these results should interest neuroscientists who seek to uncover underlying neural mechanisms for these processes.

eLife Assessment

The new development of Neuroplex, a pipeline that links projection-defined neuronal identity to in vivo calcium activity within the same animal, is an important contribution to the field of neuroscience and beyond. The strength of evidence is convincing.

eLife Assessment

This study uses a Bayesian framework to characterize latent brain state dynamics associated with memory encoding and performance in children, as measured with functional magnetic resonance imaging. The novelty of the approach offers valuable insights into memory-related brain activity, but the consideration of developmental changes in memory and brain dynamics, and the evidence to support the proposed mapping between specific states and distinct aspects of memory, are incomplete. This work will be of interest to researchers interested in cognitive neuroscience and the development of memory.

eLife Assessment

This study provides important insights into how working memory shapes perceptual decisions, using a dual-task design, continuous mouse tracking, and hierarchical Bayesian modeling. By dissociating fast attentional capture effects from slower, sustained perceptual biases within single trials, the authors provide compelling evidence that working memory-perception interactions unfold through distinct dynamic processes rather than a single mechanism. This work will be of interest to researchers studying working memory, perception, decision-making, and mouse-tracking methodology.

eLife Assessment

This important study links allelic expression imbalance with replication timing, suggesting a stochastic model for haploinsufficiency in dosage-sensitive disease. The integration of allele-specific RNA-seq and replication timing in clonal systems provides solid evidence for an association between asynchronous replication and allelic imbalance, although the scope and generality should be addressed in future work. This study will interest epigeneticists and genome regulation researchers studying replication timing and monoallelic expression, as well as developmental biologists and human geneticists concerned with clonal heterogeneity, haploinsufficiency, and variable disease penetrance.

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

eLife Assessment

This valuable study demonstrates molecular changes associated with age related impairment in oligodendrocyte differentiation and ability to myelinate. The identification of particular genes that are associated with this decline will provide potential future targets for therapeutic interventions. The reviewers felt that the quality of the evidence was solid while identifying some minor weaknesses that if addressed would enhance the rigor of the study.

eLife Assessment

This study presents a high-quality cryo-EM structure of the human kinase PINK1 in complex with the HSP90-CDC37 chaperone complex, capturing a partially folded intermediate in which the C-lobe and C-terminal extension are structured while the N-lobe remains unfolded and engaged by the HSP90 clamp. The structural data are broadly consistent with a recently published structure of the same complex, providing useful insight into early steps of PINK1 maturation and highlighting residues linked to familial Parkinson's disease. However, the mechanistic conclusions remain incomplete because the manuscript does not experimentally validate key hypotheses raised by the structure, including the functional roles of the C-lobe interface, the HPNI motif, the C-terminal extension, or the proposed competition between HSP90 and TOM20.

eLife Assessment

This study presents valuable findings on the differential effects of RNA on the phase separation, aggregation dynamics, and bioactivity of PSMα3 and LL-37. The authors provide solid evidence from complementary biophysical and cell-based experiments that RNA influences peptide assembly and associated in vitro activities. The study is of interest for understanding interactions between amyloidogenic peptides and nucleic acids.

eLife Assessment

In their valuable study, Beaudet, Berger and Hendricks provide a mechanistic link between disease-associated tau hyperphosphorylation, loss of cooperative tau envelope formation on microtubules, and dysregulation of axonal transport prior to aggregation. Using complementary in vitro reconstitution and human iPSC-derived neuronal assays with phosphodeficient and phosphomimetic tau constructs targeting 14 disease-relevant sites, the authors convincingly show that phosphorylation state alters tau organization on microtubules and differentially impacts kinesin- and lysosome-based transport. The evidence is solid and well aligned with the conclusions, yet the work could be further strengthened by incorporating additional controls and motor-specific assays to refine the mechanistic depth.

eLife Assessment

Kambali et al use optogenetic manipulations to examine whether the ventral hippocampal Schaffer collateral (vCA3-to-vCA1) and temporoammonic (EC-to-vCA1) pathways regulate anxiety- and fear-related behaviors in mice. They find that both pathways regulate the expression of fear (freezing) responses to a context and auditory conditioned stimulus paired with foot shock (trace conditioning protocol), but only the Schaffer collateral pathway regulates the expression of anxiety-related behaviors in the elevated plus maze, open field test, and Vogel conflict test. Overall, the study is valuable: it detects bidirectional effects of optogenetic excitation and inhibition in both pathways. However, the strength of the evidence in support of its main claims is incomplete.