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  1. Minus the Error: Testing for Positive Selection in the Presence of Residual Alignment Errors

    This article has 9 authors:
    1. Avery Selberg
    2. Nathan L Clark
    3. Timothy B Sackton
    4. Spencer V Muse
    5. Alexander G Lucaci
    6. Steven Weaver
    7. Anton Nekrutenko
    8. Maria Chikina
    9. Sergei L Kosakovsky Pond
    This article has been curated by 1 group:
    • Curated by eLife

      eLife Assessment

      Alignment and sequencing errors are a major concern in molecular evolution, and this valuable study represents a welcome improvement for genome-wide scans of positive selection. This new method seems to perform well and is generally convincing, although the evidence could be made more direct and more complete through additional simulations to determine the extent to which alignment errors are being properly captured.

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    This article has 4 evaluationsAppears in 1 listLatest version Latest activity
  2. Design of combination therapeutics from protein response to drugs in ovarian cancer cells

    This article has 9 authors:
    1. Alexandra Franz
    2. Ciyue Shen
    3. Fabian Coscia
    4. Kenneth Munroe
    5. Lea Charaoui
    6. Anil Korkut
    7. Matthias Mann
    8. Augustin Luna
    9. Chris Sander
    This article has been curated by 1 group:
    • Curated by eLife

      eLife Assessment

      In this valuable study, the authors provide a simple yet elegant approach to identifying therapeutic targets that synergize to prevent therapeutic resistance in ovarian cancer using cell lines, data-independent acquisition proteomics, and bioinformatic analysis. The authors convincingly identify several combinations of pharmaceuticals that were able to overcome or prevent therapeutic resistance in culture models of ovarian cancer, a disease with an unmet diagnostic and therapeutic need. However, the extent to which these findings may extend to more complex models of ovarian cancer remains unclear.

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    This article has 3 evaluationsAppears in 1 listLatest version Latest activity
  3. WRN and WRNIP1 ATPases impose high fidelity on translesion synthesis by Y-family DNA polymerases

    This article has 4 authors:
    1. Jung-Hoon Yoon
    2. Karthi Sellamuthu
    3. Louise Prakash
    4. Satya Prakash
    This article has been curated by 1 group:
    • Curated by eLife

      eLife Assessment

      This manuscript reports an important finding for understanding the molecular mechanisms of mutagenesis, carcinogenesis, and senescence. It follows a previous report showing that the Werner syndrome protein WRN and its interacting protein WRNIP1 are indispensable for translesion DNA synthesis (TLS) by Y-family DNA polymerases (Pols). The manuscript provides convincing evidence that WRN and WRNIP1 ATPases, in addition to the previously reported role of the WRN 3'>5' exonuclease activity, are essential for promoting the fidelity of replication through DNA lesions by Y-family Pols in human cells.

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    This article has 5 evaluationsAppears in 1 listLatest version Latest activity
  4. Serum, Cell-Free, HPV-Human DNA Junction Detection and HPV Typing for Predicting and Monitoring Cervical Cancer Recurrence

    This article has 11 authors:
    1. Anne Van Arsdale
    2. Olga Mescheryakova
    3. Sonia Gallego
    4. Elaine C Maggi
    5. Bryan Harmon
    6. Dennis YS Kuo
    7. Koenraad Van Doorslaer
    8. Mark H Einstein
    9. Brian J Haas
    10. Cristina Montagna
    11. Jack Lenz
    This article has been curated by 1 group:
    • Curated by eLife

      eLife Assessment

      This is a valuable study that suggests that HPV-human DNA junctions can be identified from cfDNA in women with cervical cancer and that detection of these junctions is indicative of recurrence. The evidence supporting the conclusions is incomplete, in part because the numbers of reads identifying breakpoints in tumor samples or in circulating cell-free serum samples are not provided. More quantitative analysis will be required to confirm that the breakpoints represented in cell-free DNA can be used as a surrogate to monitor the recurrence of cervical cancer cells, and additional patient studies would also be needed to strengthen the study. This work will be of interest to those who study and treat cervical cancer as well as other HPV-related malignancies.

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    This article has 3 evaluationsAppears in 1 listLatest version Latest activity
  5. SMC5/6-Mediated Plasmid Silencing is Directed by SIMC1-SLF2 and Antagonized by LT

    This article has 4 authors:
    1. Martina Oravcová
    2. Minghua Nie
    3. Takanori Otomo
    4. Michael N Boddy
    This article has been curated by 1 group:
    • Curated by eLife

      eLife Assessment

      This Research Advance manuscript further elucidates the roles of SMC5/6 loader proteins and associated factors in the silencing of extrachromosomal circular DNA by the SMC5/6 complex. While the findings are largely in line with expectations, they are useful, representing a meaningful advance beyond the recent study (reference 33), contributing to a growing foundation for further comparative and mechanistic investigations. Solid evidence is presented for a role for SIMC1/SLF2 in the localization of the SMC5/6 complex to plasmid DNA, and the distinct requirements, as compared to the recruitment of SMC5/6 to chromosomal DNA lesions.

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    This article has 5 evaluationsAppears in 1 listLatest version Latest activity
  6. HIV-specific CD8+ T-cell responses soon after treatment initiation during acute HIV infection are associated with viral reservoir decline

    This article has 19 authors:
    1. Pien M van Paassen
    2. Alexander O Pasternak
    3. Karel A van Dort
    4. Ad C van Nuenen
    5. Irma Maurer
    6. Brigitte Boeser-Nunnink
    7. Ninée VEJ Buchholtz
    8. Tokameh Mahmoudi
    9. Cynthia Lungu
    10. Reinout van Crevel
    11. Casper Rokx
    12. Jori Symons
    13. Monique Nijhuis
    14. Annelou van der Veen
    15. Liffert Vogt
    16. Michelle J Klouwens
    17. Jan M Prins
    18. Neeltje A Kootstra
    19. Godelieve J de Bree
    This article has been curated by 1 group:
    • Curated by eLife

      eLife Assessment

      This valuable paper used a longitudinal cohort of individuals initiating ART to suggest that CD8+ T cells may contribute to the clearance of intact HIV DNA during long-term antiretroviral therapy (ART) for HIV, which is relevant to our understanding of the mechanisms driving reservoir persistence in people living with HIV. The reviewers concluded that the evidence presented is incomplete to fully support these claims, as the cohort sampling is relatively infrequent, and the association direction could be bi-directional or due to other confounding variables.

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    This article has 4 evaluationsAppears in 1 listLatest version Latest activity
  7. FGF and MafB regulated cadherin expression drives lamina formation in the auditory hindbrain

    This article has 6 authors:
    1. Rosanna CG Smith
    2. Maryam Clark
    3. Mireya Vazquez-Prada
    4. Marc Astick
    5. Kristina C Tubby
    6. Stephen R Price
    This article has been curated by 1 group:
    • Curated by eLife

      eLife Assessment

      The authors conducted a valuable study that investigates a molecular pathway mediating the transformation of a cell aggregate into a sheet known as the nucleus laminaris, a crucial site for auditory processing. While the study offers a comprehensive view of the sequence of developmental events and suggests possible roles for FGF signaling, the transcription factor Mafb, and the cell surface adhesive molecule Cadherin-23 in this process, the current data were considered incomplete.

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    This article has 3 evaluationsAppears in 1 listLatest version Latest activity
  8. Deployment of endocytic machinery to periactive zones of nerve terminals is independent of active zone assembly and evoked release

    This article has 5 authors:
    1. Javier Emperador-Melero
    2. Steven J Del Signore
    3. Kevin M De León González
    4. Pascal S Kaeser
    5. Avital A Rodal
    This article has been curated by 1 group:
    • Curated by eLife

      eLife Assessment

      This is a valuable and rigorous study that addresses the question of what determines the spatial organization of endocytic zones at synapses. The authors use compelling approaches, in both Drosophila and rodent model systems, to define the role of activity and active zone structure on the organization of the peri-active zone. While the findings are primarily negative, they are carefully executed and contribute to the field by refining existing models of presynaptic organization.

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    This article has 4 evaluationsAppears in 1 listLatest version Latest activity
  9. Weak evidence for heritable changes in response to selection by aphids in Arabidopsis accessions

    This article has 5 authors:
    1. Marc W. Schmid
    2. Klara Kropivšek
    3. Samuel E. Wuest
    4. Bernhard Schmid
    5. Ueli Grossniklaus
    This article has been curated by 1 group:
    • Curated by eLife

      eLife Assessment

      This paper examines selection on induced epigenetic variation ("Lamarckian evolution") in response to herbivory in Arabidopsis thaliana. The authors find weak evidence for such adaptation, which contrasts with a recently published study that reported extensive heritable variation induced by the environment. The authors convincingly demonstrate that the findings of the previous study were confounded by mix-ups of genetically distinct material, so that standing genetic variation was mistaken for acquired (epigenetic) variation. Given the controversy surrounding the influence of heritable epigenetic variation on phenotypic variation and adaptation, this study is an important, clarifying contribution; it serves as a timely reminder that sequence-based verification of genetic material should be prioritized when either genetic identity or divergence is of importance to the conclusions.

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    This article has 4 evaluationsAppears in 1 listLatest version Latest activity
  10. Inhibitory circuits generate rhythms for leg movements during Drosophila grooming

    This article has 3 authors:
    1. Durafshan Sakeena Syed
    2. Primoz Ravbar
    3. Julie H Simpson
    This article has been curated by 1 group:
    • Curated by eLife

      eLife Assessment

      Using a combination of connectomics, optogenetics, behavioral analysis, and modeling, this study provides important findings on the role of two populations of inhibitory neurons in the generation of leg grooming movements in Drosophila. The data as presented provide incomplete evidence that the identified neuronal populations contribute to the alternation of flexion and extension by inhibiting specific sets of motor neurons while disinhibiting their counterparts. While the manuscript provides comprehensive details about the 13A/B neuronal populations involved in grooming control, updates on statistics, and explicit mentioning of experimental/modeling caveats would strengthen the study. The work will interest neuroscientists, and particularly those working on motor control.

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    This article has 5 evaluationsAppears in 1 listLatest version Latest activity
  11. Dynamic fMRI networks of emotion

    This article has 4 authors:
    1. Niels Janssen
    2. Uriel KA Elvira
    3. Joost Janssen
    4. Theo GM van Erp
    This article has been curated by 1 group:
    • Curated by eLife

      eLife Assessment

      This manuscript provides valuable information on the neurodynamics of emotional processing while participants were watching movie clips. The methods and results were solid in deciphering the temporal-spatial dynamics of emotional processing. This work will be of interest to affective neuroscientists.

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    This article has 3 evaluationsAppears in 1 listLatest version Latest activity
  12. Gamma Synchrony Mediates Figure-Ground Perception

    This article has 4 authors:
    1. Maryam Karimian
    2. Mark J Roberts
    3. Peter De Weerd
    4. Mario Senden
    This article has been curated by 1 group:
    • Curated by eLife

      eLife Assessment

      Karimian et al. present a valuable new model to explain how gamma-band synchrony (30-80 Hz) can support human visual feature binding by selectively grouping image elements, countering recent criticisms that the stimulus dependence of gamma oscillations limits their functional role. Grounded in the theory of weakly coupled oscillators and informed by primate electrophysiology, the model captures behavioural patterns observed in human psychophysics, offering support for the potential role of synchrony-based mechanisms, but incomplete evidence for a specific role of gamma oscillations. This work could be strengthened by more direct evidence for the proposed mechanism, and expanding beyond figure-only model inputs with limited ecological validity.

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    This article has 3 evaluationsAppears in 1 listLatest version Latest activity
  13. Coenzyme A governs proinflammatory macrophage metabolism

    This article has 13 authors:
    1. Greg. A. Timblin
    2. Kevin. M. Tharp
    3. Johanna ten Hoeve
    4. Daniel S. Kantner
    5. Ilayda Baydemir
    6. Eric A. Noel
    7. Chandra Khantwal
    8. Pankaj K. Singh
    9. Joshua N. Farahzad
    10. Jorge Domínguez-Andrés
    11. Russell E. Vance
    12. Nathaniel W. Snyder
    13. Valerie M. Weaver
    This article has been curated by 1 group:
    • Curated by eLife

      eLife Assessment

      This important study looks into the effect of exogenous CoA on the response of TLR4-activated macrophages. Specifically, CoA enhances the LPS response by examining metabolomics, 13C tracing, and assessments of transcription and acetylation. Together, these provide a compelling series of findings that show exogenous CoA is taken up by macrophages, and this facilitates histone acetylation and transcription associated with activation and antimicrobial activity.

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    This article has 3 evaluationsAppears in 1 listLatest version Latest activity
  14. Cell surface localisation of GPI-anchored receptors in Trypanosoma brucei

    This article has 7 authors:
    1. Sourav Banerjee
    2. Nicola Minshall
    3. Alex Cook
    4. Olivia Macleod
    5. Helena Webb
    6. Matthew Higgins
    7. Mark Carrington
    This article has been curated by 1 group:
    • Curated by eLife

      eLife Assessment

      This valuable manuscript investigates the localisation of nutrient receptors in bloodstream stage trypanosomes, with implications for both nutrient uptake and immune evasion. Results after direct fixation of the cells in culture medium provide convincing evidence that the amounts of receptors on the surface of the cell, as opposed to the flagellar pocket, have previously been severely underestimated. Some results were essentially confirmatory, and there are questions regarding the quantitation of ligand binding by transferring receptors.

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    This article has 4 evaluationsAppears in 1 listLatest version Latest activity
  15. Midbrain somatostatin-expressing cells control pain-suppression during defensive states

    This article has 15 authors:
    1. Nanci Winke
    2. Frank Aby
    3. Daniel Jercog
    4. Thomas Bienvenu
    5. Coline Riffault
    6. Rabia Bouali-Benazzouz
    7. Juliette Viellard
    8. Delphine Girard
    9. Zoé Grivet
    10. Marc Landry
    11. Laia Castell
    12. Emmanuel Valjent
    13. Stephane Valerio
    14. Pascal Fossat
    15. Cyril Herry
    This article has been curated by 1 group:
    • Curated by eLife

      eLife Assessment

      The study is a timely and important contribution to our knowledge of the circuit mechanisms of fear analgesia. The novel cue-induced analgesia paradigm allowed a compelling identification of a brainstem circuit element, i.e., somatostatin-expressing neurons within the ventrolateral periaqueductal grey that project to the rostroventral medulla, in mediating fear analgesia. The vlPAG is a known region of pain modulation, and this study adds key insight to the circuit involved in fear-associated analgesia. This work will be of interest to systems and behavioral neuroscientists, especially those interested in emotional behavior, pain, and/or brainstem function.

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    This article has 4 evaluationsAppears in 1 listLatest version Latest activity
  16. RBMX2: A Pivotal Regulator Linking Mycobacterium bovis Infection to Epithelial-Mesenchymal Transition and Lung Cancer Progression

    This article has 13 authors:
    1. Chao Wang
    2. Yongchong Peng
    3. Hongxin Yang
    4. Yanzhu Jiang
    5. Abdul Karim Khalid
    6. Kailun Zhang
    7. Shengsong Xie
    8. Luiz Bermudez
    9. Yong Yang
    10. Lei Zhang
    11. Huanchun Chen
    12. Aizhen Guo
    13. Yingyu Chen
    This article has been curated by 1 group:
    • Curated by eLife

      eLife Assessment

      The study presents a comprehensive multi-approach and functional investigation of RBMX2 as a host factor involved in Mycobacterium bovis pathogenesis and its potential role in promoting epithelial-mesenchymal transition and lung cancer progression. The findings are valuable since the possible connection between M. bovis and lung cancer and the underlying mechanisms provides a promising direction for future research. The evidence is solid with methods, data, and analyses broadly supporting the claims, albeit with minor weaknesses that, if addressed, will make the evidence stronger. The study remains of great interest to microbiology, oncology, and drug discovery scientists.

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    This article has 5 evaluationsAppears in 1 listLatest version Latest activity
  17. Addressing cultural and knowledge barriers to enable preclinical sex inclusive research

    This article has 8 authors:
    1. Brianna N Gaskill
    2. Benjamin Phillips
    3. Jonathan Ho
    4. Holly Rafferty
    5. Oladele Olajide Onada
    6. Andrew Rooney
    7. Amrita Ahluwalia
    8. Natasha A Karp
    This article has been curated by 1 group:
    • Curated by eLife

      eLife Assessment

      The authors quantified intentions and knowledge gaps in scientists' use of sex as a biological variable in their work, and used a workshop intervention to show that while willingness was high, pressure points centered on statistical knowledge and perceived additional monetary costs to research. These important findings demonstrate the difficulty in changing understanding - while interventions can improve knowledge and decrease perceived barriers, the impact was small. The evidence was solid, although the sample size was small for the intervention.

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    This article has 5 evaluationsAppears in 1 listLatest version Latest activity
  18. Progressive remote memory decline coincides with parvalbumin interneuron hyperexcitability and enhanced inhibition of cortical engram cells in a mouse model of Alzheimer’s disease

    This article has 6 authors:
    1. Julia J. van Adrichem
    2. Rolinka J. van der Loo
    3. Romina Ambrosini Defendi
    4. August B. Smit
    5. Michel C. van den Oever
    6. Ronald E. van Kesteren
    This article has been curated by 1 group:
    • Curated by eLife

      eLife Assessment

      This valuable study explores changes in remote memory impairment in an amyloid pathology mouse model, demonstrating that progressive deficits coincide with inhibitory interneuron alterations. While the findings shed light on circuit remodeling in this model, the mechanistic links between heightened inhibition and memory loss are currently incomplete. Additional data and deeper analysis may be needed to fully substantiate the authors' interpretations.

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    This article has 3 evaluationsAppears in 1 listLatest version Latest activity
  19. Altair-LSFM: A High-Resolution, Easy-to-Build Light-Sheet Microscope for Sub-Cellular Imaging

    This article has 3 authors:
    1. John Haug
    2. Seweryn Gałecki
    3. Kevin M Dean
    This article has been curated by 1 group:
    • Curated by eLife

      eLife Assessment

      This useful study presents Altair-LSFM, a solid and well-documented implementation of a light-sheet fluorescence microscope (LSFM) designed for accessibility and cost reduction. While the approach offers strengths such as the use of custom-machined baseplates and detailed assembly instructions, its overall impact is limited by the lack of live-cell imaging capabilities and the absence of a clear, quantitative comparison to existing LSFM platforms. As such, although technically competent, the broader utility and uptake of this system by the community may be limited.

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    This article has 5 evaluationsAppears in 1 listLatest version Latest activity
  20. Cryo-EM structure revealed a novel F-actin binding motif in a Legionella pneumophila lysine fatty-acyltransferase

    This article has 5 authors:
    1. Wenjie W Zeng
    2. Garrison Komaniecki
    3. Jiaze Liu
    4. Hening Lin
    5. Yuxin Mao
    This article has been curated by 1 group:
    • Curated by eLife

      eLife Assessment

      This important study identifies a novel Legionella effector, Lfat1, which binds F-actin via a coiled-coil domain and structurally resembles the RID toxin, with cryo-EM revealing key interactions mediated by a hydrophobic helical hairpin. While the study is mostly complete and has compelling data, a few minor changes are recommended.

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    This article has 4 evaluationsAppears in 1 listLatest version Latest activity