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  1. Spatial and temporal coordination of Duox/TrpA1/Dh31 and IMD pathways is required for the efficient elimination of pathogenic bacteria in the intestine of Drosophila larvae

    This article has 7 authors:
    1. Fatima Tleiss
    2. Martina Montanari
    3. Olivier Pierre
    4. Julien Royet
    5. Dani Osman
    6. Armel Gallet
    7. C. LĂ©opold Kurz
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This article describes a novel mechanism allowing the insect Drosophila to combat pathogenic enteric pathogens while preserving the beneficial indigenous microbiota. The authors provide compelling evidence that oral infection of Drosophila larvae by pathogenic bacteria activate a valve that traps the intruders in the anterior midgut, allowing them to be killed by antimicrobial peptides. This important work substantially advances our understanding of pathogen clearance in the insect gut.

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    This article has 3 evaluationsAppears in 1 listLatest version Latest activity
  2. Sub-type specific connectivity between CA3 pyramidal neurons may underlie their sequential activation during sharp waves

    This article has 10 authors:
    1. Rosanna P. Sammons
    2. Stefano Masserini
    3. Laura Moreno-Velasquez
    4. Verjinia D. Metodieva
    5. Gaspar Cano
    6. Andrea Sannio
    7. Marta Orlando
    8. Nikolaus Maier
    9. Richard Kempter
    10. Dietmar Schmitz
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This study represents valuable findings on the asymmetric connectivity pattern of two different types of CA3 pyramidal cell types showing that while athorny cells receive strong inputs from all other cell types, thorny cells receive weaker inputs from athorny neurons. Computational modeling is used to evaluate the impact of this connectivity scheme on the sequential activation of different cell types during sharp wave ripples. The experimental evidence supporting the authors' claims is solid, although improvements to the modelling aspect of the study would strengthen the study.

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    This article has 4 evaluationsAppears in 1 listLatest version Latest activity
  3. Local, calcium- and reward-based synaptic learning rule that enhances dendritic nonlinearities can solve the nonlinear feature binding problem

    This article has 4 authors:
    1. Zahra Khodadadi
    2. Daniel Trpevski
    3. Robert Lindroos
    4. Jeanette Hellgren Kotaleski
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This computational modeling study builds on multiple previous lines of experimental and theoretical research to investigate how a single neuron can solve a nonlinear pattern classification task. The study presents valuable insights that the location of synapses on dendritic branches, as well as synaptic plasticity of excitatory and inhibitory synapses, influences the ability of a neuron to discriminate combinations of sensory stimuli. However, the evidence presented is incomplete - the major conclusions are only partially supported by the data presented, and there are identified gaps between the supporting evidence and the major conclusions.

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    This article has 4 evaluationsAppears in 2 listsLatest version Latest activity
  4. Noisy neuronal populations effectively encode sound localization in the dorsal inferior colliculus of awake mice

    This article has 4 authors:
    1. Juan C. Boffi
    2. Brice Bathellier
    3. Hiroki Asari
    4. Robert Prevedel
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      The paper reports the important discovery that the mouse dorsal inferior colliculus, an auditory midbrain area, encodes sound location. The evidence supporting the claims is solid, although how the encoding of sound source position in this area relates to localization behaviors in engaged mice remains unclear. The observations described should be of interest to auditory researchers studying the neural mechanisms of sound localization.

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    This article has 4 evaluationsAppears in 2 listsLatest version Latest activity
  5. Skeletal Muscle Satellite Cells Co-Opt the Tenogenic Gene Scleraxis to Instruct Regeneration

    This article has 5 authors:
    1. Yun Bai
    2. Tyler Harvey
    3. Minjie Hu
    4. Colin Bilyou
    5. Chen-Ming Fan
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This manuscript reports an important finding that the transcription factor Scleraxis regulates regenerative myogenesis by controlling the proliferation and differentiation of muscle stem cells. The evidence presented is compelling and supports the conclusions and the mechanisms by which this gene regulates satellite cell function. These data will be of interest to developmental, transcriptional, and stem cell biologists.

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    This article has 4 evaluationsAppears in 2 listsLatest version Latest activity
  6. SLC35G1: A highly chloride-sensitive transporter responsible for the basolateral membrane transport in intestinal citrate absorption

    This article has 10 authors:
    1. Yoshihisa Mimura
    2. Tomoya Yasujima
    3. Katsuhisa Inoue
    4. Shogo Akino
    5. Chitaka Namba
    6. Hiroyuki Kusuhara
    7. Yutaro Sekiguchi
    8. Kinya Ohta
    9. Takahiro Yamashiro
    10. Hiroaki Yuasa
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This work identifies the molecular function of an orphan human transporter, SLC35G1, providing convincing but incomplete evidence that this protein is involved in intestinal citrate absorption. This work provides important insight into transporter function and human physiology.

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    This article has 4 evaluationsAppears in 1 listLatest version Latest activity
  7. Formation of multinucleated osteoclasts depends on an oxidized species of cell surface associated La protein

    This article has 6 authors:
    1. Evgenia Leikina
    2. Jarred M. Whitlock
    3. Kamran Melikov
    4. Wendy Zhang
    5. Michael P. Bachmann
    6. Leonid V. Chernomordik
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This manuscript provides an important advance in our understanding of the molecular events that promote osteoclast fusion. Compelling data support the conclusion that an oxidized form of the ubiquitous protein La promotes osteoclast fusion following enrichment at the cell surface of osteoclast progenitors. These data improve our understanding of the processes that regulate bone resorption and will be of broad interest to researchers in the fields of cell biology and musculoskeletal physiology.

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    This article has 3 evaluationsAppears in 1 listLatest version Latest activity
  8. Temporally controlled nervous system-to-gut signaling bidirectionally regulates longevity in C. elegans

    This article has 5 authors:
    1. Lingxiu Xu
    2. Chengxuan Han
    3. Lei Chun
    4. X.Z. Shawn Xu
    5. Jianfeng Liu
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This study reports that the timing of 'brain-to-gut' signaling influences the lifespan of the C. elegans model. The main finding, that modulating the same neurotransmitter, Acetylcholine, at different ages elicits lifespan shortening - or extending - effects utilizing different receptors, is important and of broad interest to the longevity field as recognized by all the reviewers. The data is largely consistent with the authors' model, but the strength of the evidence is incomplete. The study requires several rigorous experiments detailed by the reviewers to substantiate the main conclusions.

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    This article has 5 evaluationsAppears in 1 listLatest version Latest activity
  9. ScRNA-seq and scATAC-seq reveal that sertoli cell mediate spermatogenesis disorders through stage-specific communications in non-obstructive azoospermia

    This article has 6 authors:
    1. Shimin Wang
    2. Hongxian Wang
    3. Bicheng Jin
    4. Hongli Yan
    5. Qingliang Zheng
    6. Dong Zhao
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This study provides valuable scRNA-seq and scATAC-seq data for testicular tissues from patients with spermatogenesis disorders. By examining the transcriptomic and epigenetic changes in Sertoli cells, the authors uncovered key regulatory mechanisms underlying male infertility and identified potential therapeutic targets. While some of the cellular profiling results are convincing, the analyses for differential profiling of NOA cases and epigenomics data remain incomplete in their current form.

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    This article has 4 evaluationsAppears in 1 listLatest version Latest activity
  10. The Drosophila EcR-Hippo component Taiman promotes epithelial cell fitness by control of the Dally-like glypican and Wg gradient

    This article has 3 authors:
    1. Colby K. Schweibenz
    2. Victoria C. Placentra
    3. Kenneth H. Moberg
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      The authors study how cells with lower levels of the conserved steroid hormone signaling component Taiman (tai) are out-competed by neighboring wild-type cells with higher fitness in Drosophila imaginal discs. The findings are useful since they uncover an unexpected link between tai and Wingless signaling in cell competition. The evidence however is incomplete, since the tai loss-of-clone phenotype is based on one allele and the mechanism involved in cell competition through Dlp and Wg lacks adequate supporting data.

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    This article has 5 evaluationsAppears in 1 listLatest version Latest activity
  11. Srs2 binding to PCNA and its sumoylation contribute to RPA antagonism during the DNA damage response

    This article has 5 authors:
    1. Jiayi Fan
    2. Nalini Dhingra
    3. Tammy Yang
    4. Vicki Yang
    5. Xiaolan Zhao
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This manuscript reports valuable findings on the role of the Srs2 protein in turning off the DNA damage signaling response initiated by Mec1 (human ATR) kinase. The data provide solid evidence that Srs2 interaction with PCNA and ensuing SUMO modification is required for checkpoint downregulation. However, experimental evidence with regard to the model that Srs2 acts at gaps after camptothecin-induced DNA damage is currently lacking. The work will be of interest to cell biologists studying genome integrity but would be strengthened by considering the possible role of Rad51 and its removal.

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    This article has 5 evaluationsAppears in 1 listLatest version Latest activity
  12. Establishing the foundations for a data-centric AI approach for virtual drug screening through a systematic assessment of the properties of chemical data

    This article has 6 authors:
    1. Allen Chong
    2. Ser-Xian Phua
    3. Yunzhi Xiao
    4. Woon Yee Ng
    5. Hoi Yeung Li
    6. Wilson Wen Bin Goh
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This study presents a valuable finding on how data quality and data representation are key to obtain predictive machine learning models, even without resorting to complex machine learning approaches. The evidence supporting the claims of the authors is, however, incomplete, as their conclusions are drawn from a single dataset of big size, similarity analysis within and between subsets is lacking, and there are concerns regarding the composition of the training and holdout sets (active:inactive ratio, possible triviality of decoys). If the results were expanded to other quality datasets of different compositions to demonstrate robustness, the manuscript would be of wide interest in the machine learning and drug discovery fields

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    This article has 4 evaluationsAppears in 1 listLatest version Latest activity
  13. MftG is crucial for alcohol metabolism of mycobacteria by linking mycofactocin oxidation to respiration

    This article has 12 authors:
    1. Ana Patrícia Graça
    2. Vadim Nikitushkin
    3. Mark Ellerhorst
    4. Cláudia Vilhena
    5. Tilman E. Klassert
    6. Andreas Starick
    7. Malte Siemers
    8. Walid K. Al-Jammal
    9. Ivan Vilotijevic
    10. Hortense Slevogt
    11. Kai Papenfort
    12. Gerald Lackner
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This valuable work examines the role of the oxidoreductase MftG in Mycolicibacerium smegmatis alcohol metabolism. A solid set of data is presented to show that, in the context of ethanol metabolism, MftG couples electrons derived from the oxidation of redox cofactor mycofactocin to mycobacterial respiratory chain. The theoretical and functional analyses could benefit from more rigour to expand on hypotheses that already exist in the field. This work highlights the metabolic flexibility of mycobacteria, but it will also be of interest to the broader field of bacterial metabolism.

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    This article has 3 evaluationsAppears in 1 listLatest version Latest activity
  14. Toxin-based screening of C-terminal tags in Escherichia coli reveals the exceptional potency of ssrA-like degrons

    This article has 2 authors:
    1. Patrick C. Beardslee
    2. Karl R. Schmitz
    This article has been curated by 1 group:
    • Curated by eLife

      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.

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    This article has 4 evaluationsAppears in 1 listLatest version Latest activity
  15. Reversing protonation of weakly basic drugs greatly enhances intracellular diffusion and decreases lysosomal sequestration

    This article has 7 authors:
    1. Debabrata Dey
    2. Shir Marciano
    3. Anna Poryvai
    4. Ondřej Groborz
    5. Lucie Wohlrábová
    6. Tomás Slanina
    7. Gideon Schreiber
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This is a valuable study on the diffusion rates of drug molecules in human-derived cells, highlighting 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 correlation between pKa and intracellular diffusion is well-supported, but the study would benefit from a more rigorous statistical treatment and a balanced comparison across different types of compounds. Despite these limitations, the findings are significant for drug design and understanding the biophysical behavior of small molecules in cells.

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    This article has 3 evaluationsAppears in 2 listsLatest version Latest activity
  16. Chemoproteomics validates selective targeting of Plasmodium M1 alanyl aminopeptidase as an antimalarial strategy

    This article has 18 authors:
    1. Darren Creek
    2. Carlo Giannangelo
    3. Matthew Challis
    4. Ghizal Siddiqui
    5. Rebecca Edgar
    6. Tess Malcolm
    7. Chaille Webb
    8. Nyssa Drinkwater
    9. Natalie Vinh
    10. Christopher MacRaild
    11. Natalie Counihan
    12. Sandra Duffy
    13. Sergio Wittlin
    14. Shane Devine
    15. Vicky Avery
    16. Tania de Koning-Ward
    17. Peter Scammells
    18. Sheena McGowan
    This article has been curated by 1 group:
    • Curated by eLife

      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.

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    This article has 9 evaluationsAppears in 1 listLatest version Latest activity
  17. Silicone Wire Embolization-induced Acute Retinal Artery Ischemia and Reperfusion Model in Mouse: Gene Expression Provide Insight into Pathological Processes

    This article has 13 authors:
    1. Yuedan Wang
    2. Ying Li
    3. Jiaqing Feng
    4. Chuansen Wang
    5. Yuwei Wan
    6. Bingyang Lv
    7. Yinming Li
    8. Hao Xie
    9. Ting Chen
    10. Faxi Wang
    11. Ziyue Li
    12. Anhuai Yang
    13. Xuan Xiao
    This article has been curated by 1 group:
    • Curated by eLife

      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.

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    This article has 4 evaluationsAppears in 1 listLatest version Latest activity
  18. The robust, high-throughput, and temporally regulated roxCre and loxCre reporting systems for genetic modifications in vivo

    This article has 10 authors:
    1. Mengyang Shi
    2. Jie Li
    3. Xiuxiu Liu
    4. Kuo Liu
    5. Wenjuan Pu
    6. Wendong Weng
    7. Shaohua Zhang
    8. Huan Zhao
    9. Kathy O. Lui
    10. Bin Zhou
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment:

      This study describes a new set of genetic tools for optimized Cre-mediated gene deletion in mice. The advances are substantial and will facilitate biomedical research. Although the tools have been validated using solid methodologies, the quantitative assessment of their recombination efficiency is not yet sufficiently described. Evaluating their ability to mediate the deletion of multiple alleles in a mosaic setting would also be a highly valuable addition.

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    This article has 5 evaluationsAppears in 1 listLatest version Latest activity
  19. Upregulated expression of ubiquitin ligase TRIM21 promotes PKM2 nuclear translocation and astrocyte activation in experimental autoimmune encephalomyelitis

    This article has 12 authors:
    1. Luting Yang
    2. Chunqing Hu
    3. Xiaowen Chen
    4. Jie Zhang
    5. Zhe Feng
    6. Yanxin Xiao
    7. Weitai He
    8. Tingting Cui
    9. Xin Zhang
    10. Yang Yang
    11. Yaling Zhang
    12. Yaping Yan
    This article has been curated by 1 group:
    • Curated by eLife

      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 solid 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. However, control experiments and imaging analyses with higher magnification images should be performed to better support the main claims of the study.

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    This article has 5 evaluationsAppears in 1 listLatest version Latest activity