Evaluated articles

eLife Assessment

Studying the biological roles of polyphosphates in metazoans has been a longstanding challenge to the field given that the polyP synthase has yet to be discovered in metazoans. This important study capitalizes on the sophisticated genetics available in the Drosophila system and uses a combination of methodologies to start to tease apart how polyphosphate participates in Drosophila development and in the clotting of Drosophila hemolymph. The data validating one of these tools (cyto-FLYX ) are solid and well-documented and they will open up a field of research into the functional roles of polyP in a metazoan model. The other tools for tissue specific knockdown of polyP (Mito-FLYX, ER-FLYX, and Nuc-FLYX) have not yet been validated but will be invaluable to the field when they are.

eLife Assessment

This is a very important study in which the authors have modified ChIP-seq and 4C-seq with a urea step, which drastically changes the pattern of chromatin interactions observed for SATB1, but not other proteins (including CTCF). The study highlights that the urea protocols provide a complementary view of protein-chromatin interactions for some proteins, which can uncover previously hidden, functionally significant layers of chromatin organization. If applied more widely, these protocols may significantly further our understanding of chromatin organization. The study's findings are supported by a wealth of controls, making the evidence compelling.

eLife Assessment

Catani and colleagues provide data on antigenic properties of neuraminidase proteins of pandemic H1N1 and show that antigenic diversity of the neuraminidase from 2009 to 2020 largely falls into two groups. These antigenic groups map to two phylogenetic groups, and substitutions at positions 432 and 321 are likely associated with the antigenic change. These data and results allow useful insights into the antigenic properties of N1 influenza and the evidence supporting the conclusions is solid.

eLife Assessment

This important study investigates the different mechanisms that provide instructions for a missing body part to regenerate its appropriate identity. The authors use two species of planarians to identify a key role for bodywide canonical Wnt gradients in controlling the outcome of regeneration. The study provides convincing evidence for variable regeneration efficiency among planarian species that will be of interest to developmental biologists interested in regeneration. However, some of the results are over-interpreted and the additional experiments could provide better support for the authors' claims.

eLife Assessment

M proteins are essential group A streptococci virulence factors that bind to numerous human proteins; a small subset of M proteins, such as M3, have been reported to bind collagen, which is thought to promote tissue adherence. In this important paper, the authors provide a solid characterization of M3 interactions with collagen. The work raises significant questions regarding the specificity of the structure and its interactions with different collagens, with implications for the variable actions of M protein collagen interactions on biofilm formation.

eLife Assessment

This important work substantially advances our understanding of how accessory olfactory bulb neurons respond to social odor cues across the estrous cycle, showing that responses vary with the strain and sex of the odor source but display no consistent differences between estrous and non-estrous states. It employs a unique electrophysiology preparation that activates the vomeronasal organ pump via electric stimulation, enabling precise recordings of accessory olfactory bulb cell responses to different chemosignals in anesthetized mice. Overall, the study presents convincing findings on the stability and variability of accessory olfactory bulb response patterns, indicating that while accessory olfactory bulb detects social signals, it does not appear to interpret them based on reproductive state. This work will be of interest to those studying olfaction, social behavior, reproductive cycles, and systems neuroscience more broadly.

eLife Assessment

Pinho et al use in vivo calcium imaging and chemogenetic approaches to examine the involvement of hippocampal sub-regions across the different stages of a sensory preconditioning task in mice. They find evidence for sensory preconditioning in male mice. They also find that, in these mice, CaMKII-positive neurons in the dorsal hippocampus encode the audio-visual association that forms in stage 1 of the task. The evidence in support of these findings is convincing. The important study will be of interest to researchers in the fields of learning and memory and/or hippocampus function.

eLife Assessment

The study introduces new tools for measuring the intracellular calcium concentration close to transmitter release sites, which may be relevant for synaptic vesicle fusion and replenishment. This approach yields important new information about the spatial and temporal profile of calcium concentrations near the site of entry at the plasma membrane. This experimental work is complemented by a coherent, open-source, computational model that successfully describes changes in calcium domains. The conclusions are solid and well supported by the data.

eLife Assessment

This important theoretical study introduces an extension to the commonly used SIR model for infectious disease dynamics, to explicitly consider the role of larger group sizes. Instead of the commonly used individual-based network models, the authors developed a simplified approach based on group sampling, with discrete high- and low-risk groups, which makes the results easier to produce and interpret, at the cost of less detail in the model. The evidence is convincing in terms of the soundness of the theoretical projections and the impact that accounting for group sizes may have on inferences from surveillance data. However, it has not yet been demonstrated that the predictions provide more realistic projections when based on real-world data.

eLife Assessment

In this convincing work by Yamaguchi et al. the cryo-EM structure of the heterohexameric 3:3 LGI1-ADAM22 complex is presented. The findings suggest that LGI1 can cluster ADAM22 in a trimeric fashion. The clustering of cell surface proteins is important in controlling signaling in the nervous system. This new version of the manuscript has been improved substantially and the figures have been enhanced and clarified.

eLife Assessment

This valuable study characterises the activity of motor units from two of the three anatomical subdivisions ("heads") of the triceps muscle while mice walked on a treadmill at various speeds. Altogether, this is the most thorough characterisation of motor unit activity in walking mice to date, providing convincing evidence for probabilistic recruitment of motor units that differed between the two heads.

eLife Assessment

This important study identifies a novel role for Hes5+ astrocytes in modulating the activity of descending pain-inhibitory noradrenergic neurons from the locus coeruleus during stress-induced pain facilitation. The role of glia in modulating neurological circuits including pain is poorly understood, and in that light, the role of Hes5+ astrocytes in this circuit is a key finding with broader potential impacts. This work is supported by convincing evidence, albeit somewhat limited by the indirect nature of the evidence linking adenosine to nearby neuronal modulation, and possible questions on the population specificity of the transgenic approach.

eLife Assessment

This study presents valuable findings on the high prevalence of pain in women with polycystic ovary syndrome and its association with distinct future health risks across different racial groups. The evidence supporting the conclusions is compelling, utilizing a massive global dataset and rigorous propensity score matching to identify pain as a critical, yet underexplored, clinical marker. The work will be of interest to reproductive endocrinologists, medical biologists, and clinicians involved in the diagnosis and management of polycystic ovary syndrome.

eLife Assessment

This paper presents the important finding that BNIP3/NIX, a mitophagy receptor, and its binding to ATG18 are required for mitophagy during muscle cell reorganization in Drosophila. Although the involvement of the BNIP3-ATG18/WIPI axis in mitophagy induction has been reported in mammalian cell culture systems, this study provides the first compelling evidence for this pathway in vivo in animals. The physiological significance of this BNIP3-dependent mitophagy will require further investigation.

eLife Assessment

This paper provides a compelling and rigorous quantitative analysis of the turnover and maintenance of CD4+ tissue-resident memory T cell clones, in the skin and the lamina propria. It provides a fundamental advance in our understanding of CD4 T cell regulation. Interestingly, in both tissues, maintenance involves an influx from progenitors on the time scale of months. The evidence that is based on fate mapping and mathematical inference is strong, although open questions on the interpretation of the Ki67-based fate mapping remain.

eLife Assessment

The authors of this important study investigate how telomere length regulates hTERT expression via non-telomeric binding of the telomere-associated protein TRF2. They conclusively show that TRF2 binding to long telomeres results in a reduction in its binding to the hTERT promoter, while short telomeres restore TRF2 binding in the hTERT promoter, recruiting repressor complexes like PRC2, and suppressing hTERT expression. There is convincing support for the claims and the findings should be of broad interest for cell biologists and those working in fields where telomeres alter function, such as cancer and aging.

eLife Assessment

This is an important study linking olfactory bulb activity not only to sniffing parameters but also to movement and place. The evidence for odor sampling is mostly solid, but the analysis supporting the potentially exciting result on the encoding of place is currently incomplete.