Evaluated articles

eLife Assessment

Graca et al. reports a fundamental missing link in the ethanol metabolism of mycobacteria and illuminates the role of a flavoprotein dehydrogenase that acts as an electron shuttle between an uncommon redox cofactor and the electron transport chain. Overall, the data presented are compelling, supported by a range of well designed and meticulous experiments. The findings will be of broad interest to researchers investigating bacterial metabolism.

eLife assessment

This important study employs an innovative genetic selection-based approach to identify short peptide sequences that target bacterial proteins for degradation. Using random mutagenesis they identified 5 amino acid long "degrons" that target the toxin VapC for degradation permitting survival. They provide compelling data that degrons ending in Ala-Ala are selectively recognized by the ClpXP protease and identify the sequence FKLVA as a particularly significant target. As a whole, there is enthusiasm about the author's findings, although there are also some improvements that could be made to increase the clarity and impact, mostly in the form of revisions to the text.

eLife Assessment

This is a valuable study on the diffusion rates of drug molecules in human-derived cells, presenting convincing data indicating that their diffusion behavior depends on their charged state. It proposes that blocking drug protonation enhances diffusion and fractional recovery, suggesting improved intracellular availability of weakly basic drugs. The findings are significant for drug design and understanding the biophysical behavior of small molecules in cells.

eLife assessment

The manuscript makes an important contribution to antimalarial drug discovery, utilizing diverse systems biology methodologies. It focuses on an improved M1 metalloprotease inhibitor and provides compelling evidence for the utility of chemoproteomics in pinpointing PfA-M1 targeting. Additionally, metabolomic analysis reveals specific alterations in the final steps of hemoglobin breakdown. These findings highlight the potential of the developed methodology not only for PfA-M1 targeting but also for other inhibitors targeting various malarial proteins or pathways.

eLife assessment

The manuscript establishes a sophisticated mouse model for acute retinal artery occlusion (RAO) by combining unilateral pterygopalatine ophthalmic artery occlusion (UPOAO) with a silicone wire embolus and carotid artery ligation, generating ischemia-reperfusion injury upon removal of the embolus. This clinically relevant model is useful for studying the cellular and molecular mechanisms of RAO. The data overall are solid, presenting a novel tool for screening pathogenic genes and promoting further therapeutic research in RAO.

eLife Assessment

This study presents an important set of new tools to facilitate Cre or Dre-mediated recombination in mice. The characterization of these new tools was done using solid and validated methodology. The work convincingly demonstrates the efficient gene knockout capability of these models and will progress the field.

eLife assessment

This important work describes the activation of astrocytes via the nuclear translocation of PKM2 in an animal model of multiple sclerosis. This study provides convincing evidence of the interaction between TRIM21 and PKM2 as the crucial molecular event leading to the translocation of PKM2 and a metabolic shift towards glycolysis dominance, fostering proliferation in stimulated astrocytes. This finding is significant as it underscores the potential of targeting glycolytic metabolism to mitigate neurological diseases mediated by astrocytes, offering a strong rationale for potential therapeutic interventions.

eLife Assessment

This study is a valuable contribution to the field of neuronal modeling by way of providing a method for rapidly obtaining neuronal physiology parameters from electrophysiological recordings. The method is solid as the generated models reproduce both ground-truth simulated data and empirical data, and there is now a quantitative comparison with other approaches.

eLife assessment

The fundamental study by Ding and colleagues identifies subpopulations of neurons recorded in the monkey subthalamic nucleus (STN) with distinct activity profiles and causal contributions during perceptual decision-making. The combination of neuronal recording, microstimulation, and computational methods provides convincing evidence for a heterogenous neural population that could support multifaceted roles in decision formation. This study should be of wide interest to computational and experimental neuroscientists interested in cognitive function.

eLife Assessment

This important work advances our understanding of the aging trajectory and heterogeneity of hippocampal microglia. The authors provide an in-depth characterization of microglia in young and old mice as well as at intermediate time points, which reveals the existence of intermediate states characterized by a distinct transcriptional signature. The experimental approach is solid, especially with the validation of scRNA-seq findings with other methods. The study should be of interest to neuroimmunologists and biologists interested in aging

eLife Assessment

This important study showing that sleep deprivation increases functional synapses while depleting silent synapses supports previous findings that excitatory signaling increases during wakefulness. This manuscript focuses in particular on AMPA/NMDA ratios. An interesting, although speculative, aspect of the manuscript is the inclusion of a model for the accumulation of sleep needs that is based upon the MEF2C transcription factor but also links to the sleep-regulating SIK3-HDAC4/5 pathway. The authors have clarified some questions raised in the previous review, rendering this a solid piece of work that poses questions for future studies.

eLife Assessment

This paper makes a valuable contribution to our understanding of the tradeoffs in eye design - specifically between improvements in optics and in photoreceptor performance. The authors successfully build a formal theory that enables comparisons across a wide range of species and eye types. One notable example is that how space should be allocated to optics and photoreceptors depends on eye type - with particularly notable differences between compound and simple eyes. The framework introduced to compare different design properties is convincing and provides a nice example of how to study tradeoffs in seemingly disparate design properties.

eLife Assessment

This valuable study by Wu and Zhou combines neurophysiological recordings and computational modelling to address an interesting question regarding the sequence of events from sensing to action. Neurophysiological evidence remains incomplete: explicit mapping of saccade-related activity in the same neurons and a better understanding of the influence of the spatial configuration of stimulus and targets would be required to pinpoint whether such activity might contribute, even partially, to the observed results and interpretations. These results are of interest for neuroscientists investigating decision-making.

eLife Assessment

This important study uses calcium imaging to show an increase in the selectivity of the sensory-evoked response in the apical dendritic tuft of layer 5 barrel cortex neurons as mice learn a whisker-dependent discrimination task. The evidence supporting the conclusions is compelling, and this work will be of great interest to neuroscientists working on reward-based learning and sensory processing.

eLife assessment

This is an important study to reveal local circuit mechanisms in the POA that control body temperature and also highlight how neurotransmitter GABA and neuropeptide NTS from the same neurons differentially modulate temperature. This study was carefully executed, providing convincing evidence for the conclusions in this paper. The findings have emphasized the importance of considering multiple diverse functions of the same neuron populations and will be of interest to neuroscientists working on central regulations of energy metabolism and temperature homeostasis.

eLife Assessment

This phenomenological study reported that cold exposure induced mRNA expression of genes related to lipid metabolism in the paraventricular nucleus of the hypothalamus (PVH). While the paper does not address cell-type specificity or the functional role of lipids in PVH, the findings might still serve as a useful basis for others to explore their relevance to brain responses to cold. In the revised manuscript, the authors made adequate editions, such as new immunostaining and immunoblotting of AGTL and HSL in the PVH, and pharmacological inhibition of lipid peroxidation and lipolysis. The authors also increased the sample size of some experiments and revised the text to limit their data interpretation. Thus, the reviewers considered that these studies are solid in conclusively describing how the PVH is reprogrammed at the level of gene expression by cold exposure.

eLife assessment

In this work, the authors put forward a valuable methodological advancement for imaging deeper in the intact spinal cord of anaesthetized mice. The authors measured blood flow across different vessel types within the spinal cord and observed the cellular responses following venule occlusion. The demonstration is solid, although, a more quantitative comparison with state-of-the-art two-photon excited fluorescence microscopy and a discussion about applicability to functional imaging (e.g., calcium imaging) would have strengthened the study.

eLife Assessment

This technical study presents a novel sampling strategy for detecting synaptic coupling between neurons from dual pipette patch-clamp recordings in acute slices of mammalian brain tissue in vitro. The authors present solid evidence that this strategy, which incorporates automated patch clamp electrode positioning and cleaning for reuse with strategic neuron targeting, has the potential to substantially improve the efficiency of neuronal sampling with paired recordings. This technique and the extensions discussed will be useful for neuroscientists wanting to apply or already conducting automated multi-pipette patch clamp recording electrophysiology experiments in vitro for neuron connectivity analyses.

eLife Assessment

This valuable study describes an apparatus, workflow, and proof-of-concept data for a system to study social cooperation in marmosets, an increasingly popular primate model for neuroscience. The apparatus and methodology have clear and convincing advantages over conventional methods based on manual approaches. However, claims of faster social learning or of finer-grained behavioural analysis in this setup will require further corroboration.