Evaluated articles

eLife Assessment

This is an important and convincing dataset shedding new light on a role for Malat1 in osteoblast physiology. The work is of value to areas other than the bone field because it supports a role and mechanism for beta-catenin that is novel and unusual. The findings are significant in that they support the presence of another anabolic pathway in bone that can be productively targeted for therapeutic goals. Revisions further improved the paper and addressed the reviewers' concerns.

eLife Assessment

This manuscript applies a theoretical analysis to two published datasets on yeast and bacterial evolution to compare different ways of quantifying fitness. It makes an important advance by clarifying how discrepancies can arise by using different approaches and provides recommendations for best practices. While the evidence is solid, some improvements in the presentation of the data and a greater focus on the causes of the discrepancies between the various fitness estimates would strengthen the paper further.

eLife Assessment

This fundamental article significantly advances our understanding of FGF signalling, and in particular highlights the complex modifications affecting this pathway. The evidence for the authors' claims is convincing, combining state of the art conditional gene deletion in the mouse lens with histological and molecular approaches. This work should be of great interest to molecular and developmental biologists beyond the lens community.

eLife Assessment

This important modeling study alters a previous model of the intact cat spinal locomotor network to simulate a lateral hemi-section of the spinal cord. The modeling and experimental work described provide convincing evidence that this model is capable of qualitatively predicting alterations to the swing and stance phase durations during locomotion at different speeds on intact or split-belt treadmills. This paper will interest neuroscientists studying vertebrate motor systems, including researchers working on motor dysfunction after spinal cord injury.

eLife Assessment

The study by Ma et al. provides fundamental findings and compelling evidence that Pyrotinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (PERSIST): A multicenter phase II trial. The findings enhance the understanding of HER2-positive breast cancer. The claims are fully supported by the types of experiments that were performed.

eLife Assessment

This important study reports on the redundant roles of the decapping activators Edc3 and Scd6 in orchestrating post-transcriptional programs to modulate metabolic responses to nutrients in yeast. The authors employed mutagenesis studies in conjunction with a battery of transcriptome-wide analyses to provide convincing evidence supporting their conclusions. Considering the broad implications of post-transcriptional regulation of gene expression, this study will be of interest across a variety of biomedical disciplines ranging from biochemistry and molecular and cellular biology to those specializing in studying various pathologies.

eLife Assessment

This important study provides compelling evidence for the evolutionary diversification and conserved NFκB-inducing function of RHIM-containing RIP kinase proteins across animal lineages, combining thorough bioinformatic analysis with functional assays in human cells. The findings are of broad interest to immunologists and evolutionary biologists, though some novel observations would benefit from deeper conceptual integration.

eLife Assessment

This study provides important insights into the role of the Mid1 gene in hippocampal development and its implications in Opitz G/BBB syndrome, with much evidence supporting its impact on synaptic plasticity, neural rhythms, and cognitive functions. The methods, data, and analyses are solid, supporting the claims, presenting several minor weaknesses, and establishing Mid1 as a potential therapeutic target for neurological deficits associated with OS. The conclusions are largely supported by the results, but additional data are needed.

eLife Assessment

Understanding how neural circuits mediate decision-making is a core problem in neuroscience. In this interesting and important work, the authors use detailed behavioral analysis and rigorous quantitative modeling to convincingly support the idea that the nematode C. elegans uses an "accept-reject" behavioral strategy, based on learned features of its environment, to make decisions upon encountering food patches. The work expands our understanding of the behavioral repertoire of this species, providing a foundation for future mechanistic studies in this powerful model system.

eLife Assessment

This important study shows that calcium stores in the endoplasmic reticulum of the parasitic protozoan, Toxoplasma gondii play a major role in buffering calcium levels in the cytosol as well as other organelles such as the mitochondrion. Advanced imaging techniques, including use of genetically encoded calcium indicators provide compelling evidence for the role of the SERCA-Ca2+ ATPase pump in regulating organellar calcium levels. However, it remains unclear whether intra-organellar calcium transport occurs via ER-mitochondria membrane contact sites or other mechanisms. This work will be of interest to cell and molecular biologists interested in calcium signalling in divergent eukaryotes.

eLife Assessment

This study makes a valuable advance in our understanding of defensive symbionts in insects. It uses a meta-analysis to quantify the magnitude of change in host fitness components when symbionts are present in hosts exposed to natural enemies. The evidence supporting the study conclusions is solid, with analyses confirming common assumptions that symbionts generally provide defence at low cost to hosts.

eLife Assessment

Aging reduces tissue regeneration capacity, posing challenges for an aging population. In this fundamental study, Reeves et al. show that by combining Wnt-mediated osteoprogenitor expansion (using a special bandage) with intermittent fasting, calvarial bone healing can be restored in aged animals. Intermitted fasting improves osteoprogenitor function by rescuing aging-related mitochondrial dysfunction, which can also be achieved by nicotinamide mononucleotide (NMN) supplementation or by modulating the gut microbiome. By employing rigorous histological, transcriptomic, and imaging analyses in a clinically relevant model, the authors provide compelling evidence supporting the conclusions. The therapeutic approach presented in this study shows promise for rejuvenating tissue repair, not only in bones but potentially across other tissues.

eLife Assessment

This important study uses C. elegans to provide new insights into the role of the conserved protein FLWR-1/Flower in synaptic transmission. Employing a variety of techniques, including calcium imaging, ultrastructural analysis, and electrophysiology, the paper provides convincing evidence that challenges some previous thinking about FLWR-1 function. This work will be of particular interest to neuroscientists studying synaptic physiology and plasticity.

eLife Assessment

This important study investigates nerve-injury-induced allodynia by studying the role of a subpopulation of excitatory dorsal horn CCK+ neurons that express the estrogen receptor GPR30 and potentially modulate nociceptive sensitivity via direct inputs from primary somatosensory cortex. In this revised version, the authors addressed many of the critiques raised through added analyses that convincingly support the notion that spinal GPR30 neurons are indeed an excitatory subpopulation of CCK+ neurons that contribute to neuropathic pain. While evidence of a direct functional corticospinal projection to CCK+/GPR30+neurons is not fully demonstrated, this work will be of broad interest to researchers interested in the neural circuitry of pain.

eLife Assessment

This compelling study introduces a set of novel genetically encoded tools for the selective and reversible ablation of excitatory and inhibitory synapses. These new tools enable selective and efficient ablation of excitatory synapses, and photoactivatable and chemically inducible methods for inhibitory synapse ablation in specific cell types, providing valuable methods for disrupting neural circuits. This approach holds broad potential for investigating the roles of specific synaptic input onto genetically determined cells.

eLife Assessment

This manuscript represents a fundamental contribution demonstrating that fentanyl-induced respiratory depression can be reversed with a peripherally-restricted mu opioid receptor antagonist. The paper reports compelling and rigorous physiological, pharmacokinetic, and behavioral evidence supporting this major claim, and furthers mechanistic understanding of how peripheral opioid receptors contribute to respiratory depression. These findings reshape our understanding of opioid-related effects on respiration and have significant therapeutic implications given that medications currently used to reverse opioid overdose (such as naloxone) produce severe aversive and withdrawal effects via actions within the central nervous system.

eLife Assessment

The findings of this study are valuable, offering insights into the neural representation of reversal probability in decision-making tasks, with potential implications for understanding flexible behavior in changing environments. The study contains interesting comparisons between neural data and models, including evidence for partial consistency with line attractor models in this probabilistic reversal learning task. However, it remains incomplete due to issues related to how the RNN training and the analysis of its dynamics, which renders the evidence as not complete.

eLife Assessment

This valuable study by Xu and colleagues investigates brainstem circuits mediating evoked respiratory reflexes that they define as cough-like in a freely behaving mouse model. They have applied multiple circuit mapping and manipulation approaches to suggest that the caudal spinal trigeminal nucleus (SP5C) nucleus can play a novel role in generating a reflex cough-like behavior in mice. The authors give incomplete evidence that the reflex behavior produced in their mouse model is definitively cough, limiting functional interpretation of the putative circuit identified and requiring more thorough experimental interrogation of the behavior studied.

eLife Assessment

This paper is an important overview of the currently published literature on low-intensity focused ultrasound stimulation (TUS) in humans, providing a meta-analysis of this literature that explores which stimulation parameters might predict the directionality of the physiological stimulation effects. The overall synthesis is convincing. The database proposed by the paper has the potential to become a key community resource if carefully curated and developed.