Evaluated articles

eLife Assessment

This manuscript tackles a significant problem in addiction science: how interdependent are measures of "addiction-like" behavioral phenotypes? The manuscript provides compelling evidence that, under these experimental conditions, escalation of intake, punishment-resistant responding, and progressive ratio break points reflect a single underlying construct rather than reflect distinct unrelated measures. The exceptionally large sample size and incorporation of multiple behavioral endpoints add strength to this paper, and make it an important resource for the field.

eLife assessment

The study investigates the functional impact of cranial irradiation in mouse and proposes PAK3 as molecular element involved in radiation-induced cognitive decrement. The significance of the findings is useful for fields covering radiation, brain tumor and cognition. The strength of evidence is solid, although the referees expressed divergent views on the manuscript.

eLife assessment

Multimodal experiences that for example contain both visual and tactile components are encoded as associative memories. This manuscript is a valuable contribution supporting structural and functional brain plasticity following associative training protocols that pair together different types of sensory stimuli. The results provide solid support for this plasticity being a basis for cross-modal associative memories.

eLife assessment

This study builds upon previous work which demonstrated that brain injury results in the entry of a protein called albumin into the brain which then causes diverse effects. The present study shows that prolonged stimulation of a forelimb in a rat leads to albumin entry, and is associated with effects that suggest plasticity is enhanced in the stimulated side of the brain. The strength of evidence was convincing and results are important because they suggest a previously-considered pathological process may be relevant to the normal brain and have benefits.

eLife assessment

Chang et al. provide glutamate co-expression profiles in the central noradrenergic system and test the requirement of Vglut2-based glutamatergic release in respiratory and metabolic activity under physiologically relevant gas challenges. Their experiments provide compelling evidence that conditional deletion of vesicular glutamate transporters from noradrenergic neurons does not impact steady-state breathing or metabolic activity in room air, hypercapnia, or hypoxia. This study provides an important contribution to our understanding of how noradrenergic neurons regulate respiratory homeostasis in conscious adult mice.

eLife assessment

This paper presents a valuable pipeline based on state-of-the-art analytical software that was used to study genetic pleiotropy between neuropsychiatric disorders. The presented evidence supporting the claims is convincing and now includes an appropriate comparison to previously published methods as well as a detailed exploration of the findings. The created pipeline can thus be used by researchers from diverse fields to study different combinations of diseases and traits.

eLife assessment

This study presents valuable new insights from the protist Tetrahymena regarding radial spokes, conserved protein complexes that are relevant for cilia motility. The work employs interdisciplinary approaches to provide convincing support for radial spoke composition with some experiments, but there are weaker areas with partially incomplete support, such as relying on knockouts alone rather than including localization studies of tagged proteins.

eLife assessment

This important study presents convincing evidence for the use of orangutan teeth as terrestrial proxies to reconstruct rainfall regimes, while exploring the potentially conflicting impact of breastfeeding signals. The findings will be of broad interest for those using and developing methods and tools to reconstruct environmental conditions in the historical and archaeological past.

eLife assessment

This fundamental study provides a unique tool for assessing the range of phosphorylation in insulin reactions due to genetic variation and dietary influence through the utilization of genetically distinct mouse strains. The discoveries of this study hold substantial importance, as they shed light on the interplay between genetic attributes and environmental conditions in shaping the insulin-signaling network within skeletal muscle, a crucial regulator of metabolism. The supporting evidence presented is compelling, and the work is anticipated to captivate a wide audience within the metabolism discipline due to its extensive appeal and by providing inspiration for further hypothesis-driven research.

eLife assessment

This fundamental work uses computational network models to suggest a possible origin of the wide range of time scales observed in cortical activity. This claim is supported by convincing evidence based on comparisons between mathematical theory, simulations of spiking network models, and analysis of recordings from the orbitofrontal cortex. This manuscript will be of interest to the broad community of systems and computational neuroscience.

eLife assessment

This valuable work explores how transcription factors regulate transcription through cooperative binding to enhancers. Through experiments and modeling, the authors show convincingly that the cooperativity of transcription factor binding regulates transcriptional bursting and the extent of the amount of time that the target promoter remains in an active state.

eLife assessment

In this important study, Esmaily and colleagues investigate the "confidence matching" between two agents and present a useful exploration of its computational and physiological correlates. Further analyses would be helpful to provide a tighter link between fluctuations of confidence, pupil size, EEG response, and computational variables, to delineate the causal relations between these quantities, which are nevertheless incompletely documented at present.

eLife assessment

This manuscript reports important new results, but it provides incomplete support for its claims. Recent data has shown that schizophrenia-related synaptic alterations induce changes in neural network synchrony, and this manuscript provides the first theoretical understanding of the underlying network mechanisms. Proper support for this result, however, requires a tighter link between the computational model and the experimental data and a more in-depth understanding of the model mechanisms.

eLife assessment

This study provides a potentially useful assessment of the effect of testing contacts of cases in school classes when identified, rather than at the end of quarantine, on both the number of secondary infections and other outcomes including tracing delay and identification of the possible source of infection. The authors find that the intervention likely led to a decrease in tracing delay and an increase in the number of possible sources of infection, though were unable to determine whether secondary transmission decreased, due in part to unmeasured confounding. While the surveillance system described provides a solid dataset appropriate for this analysis, the description of methods, study outcomes, and consideration of potential confounding factors is incomplete.

eLife assessment

This study reveals a novel mechanism of Acetylcholine- Acetylylcholine receptor signaling in regulating gut barrier function in Drosophila, which provides important implications on the pathway played in human diseases, such as Chronic Obstructive Pulmonary DiseaseCOPD. The evidence supporting the claims of the authors is solid.

eLife assessment

The present study provides a valuable new perspective on the optomotor response based on an inversion of the behavior under specific (non-natural) conditions that may help elucidate the principles of this specific behavior. The evidence provided is convincing.

eLife assessment

This elegantly performed and rigorous study generates new and conceptually important insights into the interaction between an essential malaria parasite invasion ligand (and vaccine candidate) called PfRH5, and its erythrocyte surface integral membrane receptor basigin. The authors provide compelling evidence based on rigorous biochemical assays that erythrocyte basigin is predominantly expressed in a complex with one of two distinct erythrocyte membrane proteins called PMCA and MCT1 and that PfRH5 binds to these complexes better than to isolated basigin. Certain invasion-inhibitory antibodies, that do not prevent binding of PfRH5 to isolated basigin, do in contrast prevent binding to the basigin complexes, explaining the mode of action of these previously enigmatic antibodies and providing valuable data towards the improved design of vaccines based on PfRH5.

eLife assessment

Using a novel micropipette-based, minimally invasive approach in combination with theoretical and computational analysis, this important work probes tissue mechanics in the Drosophila embryo. The authors provide compelling evidence for the applicability of their method, which reveals important differences between the mechanical properties on the apical and basal tissue sides. This work should be of broad interest to scientists studying tissue mechanics, membranes, and developmental processes.

eLife assessment

The manuscript describes a set of detailed modeling and experimental studies to disentangle the respective roles of gap junctional electrical vs. metabolic coupling mechanisms in the synchronization of islet activity. This is of interest due to the importance of islet synchronization and generally islet network properties in the regulation of insulin secretion from the pancreas. The significance of the findings was judged to be mostly important and the strength of evidence provided was judged to be mostly solid overall.

eLife assessment

In this study, Sparta et al., generated and employed a battery of fluorescent reporters that allowed them to perform time-resolved monitoring of mechanistic target of rapamycin complex 1 (mTORC1) responses to stimuli including glucose, amino acids, and insulin at the single cell resolution. The results of this elegant approach support a model of graded mTORC1 activation in response to the aforementioned stimuli when applied individually or in combination. This model is consistent with continuous adjustment of mTORC1 signaling to changes in cellular environment and opposed to the "on/off" model of mTORC1 function. Considering the pivotal role of mTORC1 in integrating signals such as nutrients, hormones, growth factors, oxygen, and energy status with a plethora of outputs that affect cell fate and organismal physiology, it was thought that this study will be of interests across a variety of biomedical disciplines. Overall, the elegance and robustness of the approach was highly appreciated, though the paper would be strengthened by addressing some technical issues and concerns regarding the positioning of the proposed model of mTORC1 regulation in the field.