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  1. SntB triggers the antioxidant pathways to regulate development and aflatoxin biosynthesis in Aspergillus flavus

    This article has 12 authors:
    1. Dandan Wu
    2. Chi Yang
    3. Yanfang Yao
    4. Dongmei Ma
    5. Hong Lin
    6. Ling Hao
    7. Wenwen Xin
    8. Kangfu Ye
    9. Minghui Sun
    10. Yule Hu
    11. Yanling Yang
    12. Zhenhong Zhuang
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      In this useful study, the authors investigate the regulatory mechanisms related to toxin production and pathogenicity in Aspergillus flavus. Their observations indicate that the SntB protein regulates morphogenesis, aflatoxin biosynthesis, and the oxidative stress response, however, the data supporting these conclusions are incomplete. The work will be of interest to bacteriologists.

    Reviewed by eLife

    This article has 3 evaluationsAppears in 2 listsLatest version Latest activity
  2. Activating SRC/MAPK signaling via 5-HT1A receptor contributes to the effect of vilazodone on improving thrombocytopenia

    This article has 17 authors:
    1. Ling Zhou
    2. Chengyang Ni
    3. Ruixue Liao
    4. Xiaoqin Tang
    5. Taian Yi
    6. Mei Ran
    7. Miao Huang
    8. Rui Liao
    9. Xiaogang Zhou
    10. Dalian Qin
    11. Long Wang
    12. Feihong Huang
    13. Xiang Xie
    14. Ying Wan
    15. Jiesi Luo
    16. Yiwei Wang
    17. Jianming Wu
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This study presents a valuable finding on the possible use of vilazodone in the management of thrombocytopenia through regulating 5-HT1A receptor signaling. The evidence supporting the claims of the authors is solid, with the combined use of computational methods and biochemical assays. The work will be of broad interest to scientists working in the field of thrombocytopenia.

    Reviewed by eLife

    This article has 3 evaluationsAppears in 2 listsLatest version Latest activity
  3. Germline cis variant determines epigenetic regulation of the anti-cancer drug metabolism gene dihydropyrimidine dehydrogenase (DPYD)

    This article has 14 authors:
    1. Ting Zhang
    2. Alisa Ambrodji
    3. Huixing Huang
    4. Kelly J. Bouchonville
    5. Amy S. Etheridge
    6. Remington E. Schmidt
    7. Brianna M. Bembenek
    8. Zoey B. Temesgen
    9. Zhiquan Wang
    10. Federico Innocenti
    11. Deborah Stroka
    12. Robert B. Diasio
    13. Carlo R. Largiadèr
    14. Steven M. Offer
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This manuscript presents valuable findings on the identification of epigenetically mediated control for the recognition of dihydropyrimidine dehydrogenase (DPYD) gene expression that is linked with cancer treatment resistance using 5-fluorouracil. The evidence is compelling, supported by data from patient-derived specimens and direct assessment of 5-fluorouracil sensitivity, which provides confidence in the proposed mechanisms. The model is additionally supported by genome data from a population with high "compromised allele frequency". This work will interest those studying drug resistance in cancer therapy.

    Reviewed by eLife

    This article has 2 evaluationsAppears in 2 listsLatest version Latest activity
  4. PSTPIP2 ameliorates aristolochic acid nephropathy by suppressing interleukin-19-mediated neutrophil extracellular trap formation

    This article has 13 authors:
    1. Changlin Du
    2. Jiahui Dong
    3. Chuanting Xu
    4. Pengcheng Jia
    5. Na Cai
    6. Qi Wang
    7. Zhenming Zhang
    8. Lingfeng Jiang
    9. Wei Jiang
    10. Rui Feng
    11. Jun Li
    12. Cheng Huang
    13. Taotao Ma
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This paper is of interest to a broad audience of cell biologists, and researchers who work in cell death and the role of NETosis in the pathogenesis of chronic diseases. This study presents valuable new insights to support NETosis plays an important role in the development of aristolochic acid nephropathy (AAN). A series of compelling experiments using in vivo and in vitro model supported that AAN induced NET formation via IL-19-IL20-beta receptor can induce inflammation and cell death. This new knowledge of the interaction between kidney cells and neutrophils could have clinical implications in the treatment of AAN.

    Reviewed by eLife

    This article has 3 evaluationsAppears in 2 listsLatest version Latest activity
  5. Discovery and biological evaluation of a potent small molecule CRM1 inhibitor for its selective ablation of extranodal NK/T cell lymphoma

    This article has 11 authors:
    1. He Liu
    2. Meisuo Liu
    3. Xibao Tian
    4. Haina Wang
    5. Jiujiao Gao
    6. Hanrui Li
    7. Zhehuan Zhao
    8. Yu Liu
    9. Caigang Liu
    10. Xuan Chen
    11. Yongliang Yang
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This study reports a valuable finding on the discovery and evaluation of a potent small molecule inhibitor for CRM1 that may be important to treat extranodal NK/T cell lympohma (ENKTL). The evidence supporting the claims of the authors is solid that reflects an important finding for novel CRM1 inhibitors to treat ENKTL, although additional experimental evidence is needed. The work will be of interest to cancer biologists working on ENKTL.

    Reviewed by eLife

    This article has 4 evaluationsAppears in 2 listsLatest version Latest activity
  6. A novel triptolide analog downregulates NF-κB and induces mitochondrial apoptosis pathways in human pancreatic cancer

    This article has 11 authors:
    1. Qiaomu Tian
    2. Peng Zhang
    3. Yihan Wang
    4. Youhui Si
    5. Dengping Yin
    6. Christopher R Weber
    7. Melissa L Fishel
    8. Karen E Pollok
    9. Bo Qiu
    10. Fei Xiao
    11. Anita S Chong
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This useful manuscript presents a new therapeutic formulation and these solid findings have potential clinical significance as the efficacy of CK21 is relevant in various pancreatic cancer models.Further validation studies would help to strengthen the findings.

    Reviewed by eLife

    This article has 5 evaluationsAppears in 2 listsLatest version Latest activity
  7. Death by a thousand cuts through kinase inhibitor combinations that maximize selectivity and enable rational multitargeting

    This article has 6 authors:
    1. Ian R Outhwaite
    2. Sukrit Singh
    3. Benedict-Tilman Berger
    4. Stefan Knapp
    5. John D Chodera
    6. Markus A Seeliger
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This study presents a valuable finding on an alternative method that combines multiple inhibitors to maximize on-target inhibition and minimize off-target inhibition. The evidence supporting the claims of the authors is solid, although a proper validation of the methodology could strengthen the paper. The work will be of interest to scientists working in the field of drug discovery, particularly in the field of kinase inhibitors.

    Reviewed by eLife

    This article has 5 evaluationsAppears in 2 listsLatest version Latest activity
  8. Assessing drug safety by identifying the axis of arrhythmia in cardiomyocyte electrophysiology

    This article has 3 authors:
    1. Stewart Heitmann
    2. Jamie I Vandenberg
    3. Adam P Hill
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This compelling and novel mathematical method assesses drug pro-arrhythmic cardiotoxicity by examining the electrophysiology of untreated cardiac cells. It will be valuable for future drug safety design.

    Reviewed by eLife

    This article has 8 evaluationsAppears in 2 listsLatest version Latest activity
  9. Local generation and efficient evaluation of numerous drug combinations in a single sample

    This article has 2 authors:
    1. Vlad Elgart
    2. Joseph Loscalzo
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      In this manuscript, a method to test a large number of drug combinations in a single cell culture sample is presented. The strength of the evidence lies in their multiple experiments with different combinations of agents. The paper suggests that results from this application are feasible and the methodology could be applied in other laboratories to use drug combinations for defined outcomes.

    Reviewed by eLife

    This article has 5 evaluationsAppears in 2 listsLatest version Latest activity
  10. A generic binding pocket for small molecule IKs activators at the extracellular inter-subunit interface of KCNQ1 and KCNE1 channel complexes

    This article has 9 authors:
    1. Magnus Chan
    2. Harutyun Sahakyan
    3. Jodene Eldstrom
    4. Daniel Sastre
    5. Yundi Wang
    6. Ying Dou
    7. Marc Pourrier
    8. Vitya Vardanyan
    9. David Fedida
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      By combining electrophysiological analysis of mutant channels and molecular dynamics simulations, this important study identifies a common binding site for two structurally distinct activators of KCNQ1-KCNE1 channels. The findings represent an important advance for the field, with convincing functional and computational data to support the claims. The work will be of interest to those studying the binding of small molecule drugs to membrane protein complexes.

    Reviewed by eLife

    This article has 10 evaluationsAppears in 2 listsLatest version Latest activity
  11. The generation of HepG2 transmitochondrial cybrids to reveal the role of mitochondrial genotype in idiosyncratic drug-induced liver injury

    This article has 6 authors:
    1. Amy Louise Ball
    2. Carol E Jolly
    3. Mark G Lennon
    4. Jonathan J Lyon
    5. Ana Alfirevic
    6. Amy E Chadwick
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This paper is of potential interest to scientists within the field of drug-induced liver injury. The concept of the study is interesting by generating mitochondrial genotype-specific liver cell lines to evaluate idiosyncratic hepatotoxicity. While the proof-of-concept is clearly presented, the current data do not yet allow to draw broad conclusions about the significance of the study in terms of drug effects.

    Reviewed by eLife

    This article has 4 evaluationsAppears in 2 listsLatest version Latest activity
  12. Pharmacological hallmarks of allostery at the M4 muscarinic receptor elucidated through structure and dynamics

    This article has 24 authors:
    1. Ziva Vuckovic
    2. Jinan Wang
    3. Vi Pham
    4. Jesse I Mobbs
    5. Matthew J Belousoff
    6. Apurba Bhattarai
    7. Wessel AC Burger
    8. Geoff Thompson
    9. Mahmuda Yeasmin
    10. Vindhya Nawaratne
    11. Katie Leach
    12. Emma T van der Westhuizen
    13. Elham Khajehali
    14. Yi-Lynn Liang
    15. Alisa Glukhova
    16. Denise Wootten
    17. Craig W Lindsley
    18. Andrew Tobin
    19. Patrick Sexton
    20. Radostin Danev
    21. Celine Valant
    22. Yinglong Miao
    23. Arthur Christopoulos
    24. David M Thal
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This fundamental study is important and carefully executed, providing important insights into the allosteric regulation of GPCRs with exceptional strength of evidence. This work will be of interest to a wide audience in drug discovery and receptor biology. The major strengths are the comprehensive structural and pharmacological characterization with only minor weaknesses, most notably a concern regarding the approach used to quantify efficacy.

    Reviewed by eLife

    This article has 5 evaluationsAppears in 2 listsLatest version Latest activity
  13. Population dynamics of immunological synapse formation induced by bispecific T cell engagers predict clinical pharmacodynamics and treatment resistance

    This article has 6 authors:
    1. Can Liu
    2. Jiawei Zhou
    3. Stephan Kudlacek
    4. Timothy Qi
    5. Tyler Dunlap
    6. Yanguang Cao
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      The authors have developed a useful model for how proteins that mediate a connection between invariant components of the T cell antigen receptor and leukaemic cells antigens, called bispecific engagers (BiTEs), mediate immunological synapse formation and impact T cell search for tumour cells in vivo. The model was compared against the in vitro experiments and in vivo data following a solid approach. The developed framework could provide a direction for employing computational mechanistic models for evaluating various strategies for BiTE treatments.

    Reviewed by eLife

    This article has 5 evaluationsAppears in 2 listsLatest version Latest activity
  14. A mechanism of uncompetitive inhibition of the serotonin transporter

    This article has 10 authors:
    1. Shreyas Bhat
    2. Ali El-Kasaby
    3. Ameya Kasture
    4. Danila Boytsov
    5. Julian B Reichelt
    6. Thomas Hummel
    7. Sonja Sucic
    8. Christian Pifl
    9. Michael Freissmuth
    10. Walter Sandtner
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This study presents the important finding of an unusual uncompetitive inhibitor (ECSI#6) of the serotonin transporter that removes the neurotransmitter serotonin from the synaptic cleft. Through careful and comprehensive analysis, the authors convincingly show that the molecule most likely binds to the inward-facing and K+-bound state and that it assists in folding and targeting the transporter. The work will be of interest to those engaged in biophysical analyses of the serotonin transporter, and colleagues developing pharmacological chaperoning strategies for transporters in general.

    Reviewed by eLife

    This article has 5 evaluationsAppears in 2 listsLatest version Latest activity
  15. Metformin protects trabecular meshwork against oxidative injury via activating integrin/ROCK signals

    This article has 11 authors:
    1. Lijuan Xu
    2. Xinyao Zhang
    3. Yin Zhao
    4. Xiaorui Gang
    5. Tao Zhou
    6. Jialing Han
    7. Yang Cao
    8. Binyan Qi
    9. Shuning Song
    10. Xiaojie Wang
    11. Yuanbo Liang
    This article has been curated by 1 group:
    • Curated by eLife

      eLife assessment

      This manuscript proposes that metformin protects against elevated intraocular pressure and oxidative injury by regulating cytoskeleton remodeling through the integrin/ROCK pathway, thus providing a new direction for further exploration toward the treatment of primary open-angle glaucoma as well as investigation of oxidative injury in multiple settings.

    Reviewed by eLife

    This article has 3 evaluationsAppears in 2 listsLatest version Latest activity
  16. Modeling osteoporosis to design and optimize pharmacological therapies comprising multiple drug types

    This article has 7 authors:
    1. David J Jörg
    2. Doris H Fuertinger
    3. Alhaji Cherif
    4. David A Bushinsky
    5. Ariella Mermelstein
    6. Jochen G Raimann
    7. Peter Kotanko
    This article has been curated by 1 group:
    • Curated by eLife

      Evaluation Summary:

      This paper will be of interest to the pharmacology community with interest in available drug treatments for osteoporosis and how to optimize these. The key findings of the paper are based on in silico results and indicate that combined drug treatments may be more efficient in treatment of osteoporosis. This could have a significant impact on clinical management of osteoporosis patients.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

    Reviewed by eLife

    This article has 3 evaluationsAppears in 2 listsLatest version Latest activity
  17. This article has 14 authors:
    1. Guang Wang
    2. Yong-Feng Wang
    3. Jiang-Lan Li
    4. Ru-Ji Peng
    5. Xin-Yin Liang
    6. Xue-Dong Chen
    7. Gui-Hua Jiang
    8. Jin-Fang Shi
    9. Yang-Hu Si-Ma
    10. Shi-Qing Xu
    11. 苏州大学苏州医学院基础医学与生物科学学院, 江苏 苏州215123, 中国
    12. 苏州大学第一附属医院临床检验科, 江苏 苏州215006, 中国
    13. School of Biology and Basic Medical Sciences, Suzhou Medical College, Soochow University, Suzhou, Jiangsu 215123, China
    14. Department of Clinical Laboratory, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China
    This article has been curated by 1 group:
    • Curated by eLife

      Evaluation Summary:

      The authors present a manuscript addressing an important unmet need, specifically focused on understanding the effects of high protein on hematopoiesis. This information can be of interest to basic biologists and clinicians who specialize in the areas of various diseases associated with elevated protein concentration (e.g. infections, inflammation, multiple myeloma, renal failure, etc). This is in part what makes for the complexity in studying this entity as the consequences of such disparate diseases are difficult to parcel out as causes of which specific disease manifestations. Furthermore, the presented work is done in an invertebrate model without additional confirmation in other model systems. Taken together, the work, which is plentiful in experiments, provides an incomplete understanding of cause and effect, leading to overinterpretation of results and overstating of derived conclusions.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

    Reviewed by eLife

    This article has 3 evaluationsAppears in 2 listsLatest version Latest activity
  18. Robust and Efficient Assessment of Potency (REAP) as a quantitative tool for dose-response curve estimation

    This article has 9 authors:
    1. Shouhao Zhou
    2. Xinyi Liu
    3. Xinying Fang
    4. Vernon M Chinchilli
    5. Michael Wang
    6. Hong-Gang Wang
    7. Nikolay V Dokholyan
    8. Chan Shen
    9. J Jack Lee
    This article has been curated by 1 group:
    • Curated by eLife

      Evaluation Summary:

      This article proposes methodology and accompanying software for robustly fitting dose-response curves where response is a number between 0 and 1. When response is transformed using the common logistic transformation, values close to 0 or 1 become large in magnitude, unduly influencing the fitted curve after back-transformation and introducing bias in the estimate of certain parameters. The proposed approach, called Robust and Efficient Assessment of Potency, is less perturbed by these extreme measurements.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

    Reviewed by eLife

    This article has 3 evaluationsAppears in 2 listsLatest version Latest activity
  19. FSH-blocking therapeutic for osteoporosis

    This article has 46 authors:
    1. Sakshi Gera
    2. Tan-Chun Kuo
    3. Anisa Azatovna Gumerova
    4. Funda Korkmaz
    5. Damini Sant
    6. Victoria DeMambro
    7. Karthyayani Sudha
    8. Ashley Padilla
    9. Geoffrey Prevot
    10. Jazz Munitz
    11. Abraham Teunissen
    12. Mandy MT van Leent
    13. Tomas GJM Post
    14. Jessica C Fernandes
    15. Jessica Netto
    16. Farhath Sultana
    17. Eleanor Shelly
    18. Satish Rojekar
    19. Pushkar Kumar
    20. Liam Cullen
    21. Jiya Chatterjee
    22. Anusha Pallapati
    23. Sari Miyashita
    24. Hasni Kannangara
    25. Megha Bhongade
    26. Puja Sengupta
    27. Kseniia Ievleva
    28. Valeriia Muradova
    29. Rogerio Batista
    30. Cemre Robinson
    31. Anne Macdonald
    32. Susan Hutchison
    33. Mansi Saxena
    34. Marcia Meseck
    35. John Caminis
    36. Jameel Iqbal
    37. Maria I New
    38. Vitaly Ryu
    39. Se-Min Kim
    40. Jay J Cao
    41. Neeha Zaidi
    42. Zahi A Fayad
    43. Daria Lizneva
    44. Clifford J Rosen
    45. Tony Yuen
    46. Mone Zaidi
    This article has been curated by 1 group:
    • Curated by eLife

      Evaluation Summary:

      The authors describe a comprehensive characterization of a new humanized FSH blocking antibody (MS-Hu6), which they have studied in-depth in terms of its efficacy on bone and fat tissues. They provide compelling data on mouse and monkey species with a complete evaluation of its pharmacokinetics and biodistribution and characterize its effect for the treatment of obesity and bone loss. It is an important contribution and will be useful to a general readership in endocrinology, bone and fat metabolism.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

    Reviewed by eLife

    This article has 3 evaluationsAppears in 2 listsLatest version Latest activity
  20. Effector membrane translocation biosensors reveal G protein and βarrestin coupling profiles of 100 therapeutically relevant GPCRs

    This article has 20 authors:
    1. Charlotte Avet
    2. Arturo Mancini
    3. Billy Breton
    4. Christian Le Gouill
    5. Alexander S Hauser
    6. Claire Normand
    7. Hiroyuki Kobayashi
    8. Florence Gross
    9. Mireille Hogue
    10. Viktoriya Lukasheva
    11. Stéphane St-Onge
    12. Marilyn Carrier
    13. Madeleine Héroux
    14. Sandra Morissette
    15. Eric B Fauman
    16. Jean-Philippe Fortin
    17. Stephan Schann
    18. Xavier Leroy
    19. David E Gloriam
    20. Michel Bouvier
    This article has been curated by 1 group:
    • Curated by eLife

      Evaluation Summary:

      A challenge to understanding the physiology and therapeutic potential of G protein-coupled receptors (GPCRs) is to understand the range of their couplings to different G proteins. Avet et al developed of a novel set of biosensors to assess the coupling specificity of 100 therapeutically relevant G protein-coupled receptors (GPCRs) to various G protein isoforms and arrestins. The novel screen and results obtained with reference ligands will have broad use for researchers studying GPCRs, potentially impacting discovery of new physiological pathways, understanding adverse effects of currently marketed therapeutics, and discovery of novel, safer therapeutics.

      (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

    Reviewed by eLife

    This article has 4 evaluationsAppears in 2 listsLatest version Latest activity