Protection against Mitochondrial and Metal Toxicity Depends on Functional Lipid Binding Sites in ATP13A2 by Shaun Martin, Sarah van Veen, Tine Holemans, Seyma Demirsoy, Chris van den Haute, Veerle Baekelandt, Patrizia Agostinis, Jan Eggermont, Peter Vangheluwe

“…ATP13A2 interacts at the N-terminus with the signaling lipids phosphatidic acid (PA) and phosphatidylinositol (3,5) bisphosphate (PI(3,5)P2), which modulate ATP13A2 activity under cellular stress conditions. Here, we analyzed stable human SHSY5Y cell lines overexpressing wild-type (WT) or ATP13A2 mutants in which three N-terminal lipid binding sites (LBS1–3) were mutated. …”
Get full text

Cis‐Regulation of an m6A Eraser by an Insertion Variant Associated with Survival of Patients With Non‐Small Cell Lung Carcinoma by Lei Cheng, Qiangsheng Hu, Yanan Wang, Wei Nie, Haijiao Lu, Bo Zhang, Genming Zhao, Shiyun Ding, Feng Pan, Yinchen Shen, Runbo Zhong, Ruoxin Zhang

“…Abstract N6‐methyladenosine (m6A) serves as one of the crucial RNA modifications for genes involved in cancer progression. Here, 7273 expression quantitative trait loci potentially regulating 30 m6A pathway genes are identified from the GTEx database, with 69 single nucleotide polymorphisms significantly associated with survival of non‐small cell lung carcinoma (NSCLC) patients (n = 1523) from the ongoing genome‐wide association study after false positive probability tests. …”
Get full text

TMEM187-IRAK1 Polymorphisms Associated with Rheumatoid Arthritis Susceptibility in Tunisian and French Female Populations: Influence of Geographic Origin by Olfa Khalifa, Nathalie Balandraud, Nathalie Lambert, Isabelle Auger, Jean Roudier, Audrey Sénéchal, David Geneviève, Christophe Picard, Gérard Lefranc, Isabelle Touitou, Bakridine M’Madi Mrenda, Cécilia Benedito, Etienne Pardoux, Anne-Laure Gagez, Yves-Marie Pers, Christian Jorgensen, Touhami Mahjoub, Florence Apparailly

“…Polymorphisms have been identified in the Xq28 locus as risk loci for rheumatoid arthritis (RA). Here, we investigated the association between three polymorphisms in the Xq28 region containing TMEM187 and IRAK1 (rs13397, rs1059703, and rs1059702) in two unstudied populations: Tunisian and French. …”
Get full text

Metabolic resistance to pyrethroids with possible involvement of non-coding ribonucleic acids in Anopheles funestus, the major malaria vector in western Kenya by Isaiah Debrah, Daibin Zhong, Maxwell G. Machani, Godfrey Nattoh, Kevin O. Ochwedo, Collins M. Morang’a, Ming-Chieh Lee, Linda E. Amoah, Andrew K. Githeko, Yaw A. Afrane, Guiyun Yan

“…However, evidence on the molecular basis of pyrethroid resistance in western Kenya is limited. Here, we reported metabolic resistance mechanisms and demonstrated that multiple non-coding Ribonucleic Acids (ncRNAs) could play a potential role in An. funestus resistance to pyrethroid in western Kenya. …”
Get full text

Immune-checkpoint-inhibitor therapy directed against PD-L1 is tolerated in the heart without manifestation of cardiac inflammation in a preclinical reversible melanoma mouse model by Caroline Schoenherr, Caroline Schoenherr, Stefan Pietzsch, Stefan Pietzsch, Cristina Barca, Franziska E. Müller, Frauke S. Bahr, Martina Kasten, Andre Zeug, Sergej Erschow, Christine S. Falk, Evgeni Ponimaskin, James T. Thackeray, Denise Hilfiker-Kleiner, Denise Hilfiker-Kleiner, Melanie Ricke-Hoch

“…Thus, enabling the study of anti-cancer-therapy effects. Here, we analyzed potential cardiac side effects of antibody-mediated PD-L1 inhibition in the preclinical B16F10-GCV mouse model after tumor elimination and 2 weeks recovery (50 days after tumor inoculation). …”
Get full text

Sodium arsenite induces islets β-cells apoptosis and dysfunction via SET-Rac1-mediated cytoskeleton disturbance by Tianming Qiu, Yu Zhi, Jingyuan Zhang, Ningning Wang, Xiaofeng Yao, Guang Yang, Liping Jiang, Li Lv, Xiance Sun

“…Even though apoptosis plays a pivotal role in arsenic-induced islet β-cell dysfunction, the explicit underlying mechanisms remain elusive. Here, we have identified that the SET-Rac1 signaling pathway is instrumental in the apoptosis and dysfunction of islet β-cells induced by NaAsO2. …”
Get full text

Hyperleukocytosis in a neuroblastoma patient after treatment with natural killer T cells expressing a GD2-specific chimeric antigen receptor and IL-15 by Xin Xu, Shantan Reddy, Saleh Bhar, Frederic D Bushman, Amy N Courtney, Gabriel A Barragán, Gengwen Tian, Erica J Di Pierro, Leonid S Metelitsa, Antonino Montalbano, Hangjin Yu, Claudia Martinez Amador, Nisha Ghatwai, Michael S Wood, Deborah Schady, Aoife M Roche, David de la Cerda, Donald Williams Parsons, Andras Heczey

“…The ability of immune cells to expand numerically after infusion distinguishes adoptive immunotherapies from traditional drugs, providing unique therapeutic advantages as well as the potential for unmanageable toxicities. Here, we describe a case of lethal hyperleukocytosis in a patient with neuroblastoma treated on phase 1 clinical trial (NCT03294954) with autologous natural killer T cells (NKTs) expressing a GD2-specific chimeric antigen receptor and cytokine interleukin 15 (GD2-CAR.15). …”
Get full text

Protocol for a feasibility study and process evaluation of a psychosocially modelled diabetes education programme for young people with type 1 diabetes: the Youth Empowerment Skill... by Nick Sevdalis, Khalida Ismail, Tayana Soukup, Trevor Murrells, Dulmini Kariyawasam, Stephen Thomas, Judith Parsons, Angus Forbes, Rita Forde, Maria Baldellou Lopez, Marie Jones, Martha Ford-Adams, Nardos Yemane, Siobhan Pender, Alex Silverstien

“…The programme aims to facilitate a positive adaptation to life with diabetes and engagement with diabetes care through peer-based learning, immersive simulations and support from an outreach youth worker. Here, we present a protocol for a feasibility study of the YES programme.Methods and analysis The study was designed following the Medical Research Council Complex Intervention Evaluation Framework to: test the feasibility (acceptance, implementability, recruitment and completion) of the YES programme; and estimate its efficacy in relation to metabolic and psychosocial outcomes. …”
Get full text

ECM-mimicking hydrogel models of human adipose tissue identify deregulated lipid metabolism in the prostate cancer-adipocyte crosstalk under antiandrogen therapy by Agathe Bessot, Joan Röhl, Maria Emmerich, Anton Klotz, Akhilandeshwari Ravichandran, Christoph Meinert, David Waugh, Jacqui McGovern, Jenni Gunter, Nathalie Bock

“…The all-human, all-3D, models presented here provide a significant advance to dissect the role of fat in therapy response for mCRPC.…”
Get full text

Computational and in vitro evaluation of sumac-derived ©Rutan compounds towards Sars-CoV-2 Mpro inhibition by Muzaffar Kayumov, Parthiban Marimuthu, Parthiban Marimuthu, Jamoliddin Razzokov, Jamoliddin Razzokov, Jamoliddin Razzokov, Nurkhodja Mukhamedov, Nurkhodja Mukhamedov, Akmal Asrorov, Nodir S. Berdiev, Jamolitdin F. Ziyavitdinov, Ansor Yashinov, Ansor Yashinov, Yuliya Oshchepkova, Shavkat Salikhov, Sharafitdin Mirzaakhmedov

“…Natural substances started being screened for their antiviral activity by computational and in-vitro techniques. Here, we evaluated the anti-SARS-CoV-2 main protease (Mpro) efficacy of ©Rutan, which contains five polyphenols (R5, R6, R7, R7’, and R8) extracted from sumac Rhus coriaria L. …”
Get full text

Farm-to-fork changes in poultry microbiomes and resistomes in Maputo City, Mozambique by Natalie Olson, Frederica Lamar, Hermógenes Mucache, José Fafetine, Joaquim Saíde, Amélia Milisse, Denise R. A. Brito, Kelsey J. Jesser, Karen Levy, Matthew C. Freeman, Maya L. Nadimpalli

“…., scavenger) chicken breeds. Here, we performed metagenomic sequencing of total DNA from banked ChEEP ChEEP samples to characterize fecal and carcass microbiomes and resistome diversity between chicken breeds and along the supply chain. …”
Get full text

Estimating the global cost of vision impairment and its major causes: protocol for a systematic review by Nathan Congdon, Thomas Butt, Peng Tee Khaw, Andrew Bastawrous, Tasanee Braithwaite, Rupert R A Bourne, Matthew J Burton, Serge Resnikoff, Jacqueline Ramke, Kevin Frick, Hugh Taylor, Iris Gordon, Ana Patricia Marques, John Cairns, Justine H Zhang, Hannah B Faal, Iain Jones, Marty Jovic, Allyala Nandakumar

“…To perform such a study, a systematic review of the literature is needed. Here we outline the protocol for a systematic review to describe and summarise the costs associated with VI and its major causes.Methods and analysis We will systematically search in Medline (Ovid) and the Centre for Reviews and Dissemination database which includes the National Health Service Economics Evaluation Database. …”
Get full text

Dynamic analysis of growth characteristics, secondary metabolites accumulation, and an in-depth understanding of anthraquinones biosynthesis in Rubia cordifolia Linn. by Conglong Lian, Conglong Lian, Conglong Lian, Xiuyu Liu, Xiuyu Liu, Kaihua Guo, Kaihua Guo, Hao Yang, Hao Yang, Jingfan Yang, Jingfan Yang, Jinxu Lan, Jinxu Lan, Suiqing Chen, Suiqing Chen, Suiqing Chen, Suiqing Chen

“…With the current depletion of natural resources of R. cordifolia, it is critical to conduct cultivation studies on the R. cordifolia. Here, we report on the dynamic growth characteristics and secondary metabolite accumulation of cultivated R. cordifolia, as well as the discovery of important genes involved in anthraquinone biosynthesis. …”
Get full text

Detection of a New GeV Source in the Outer Region of the Coma Cluster: A Signature of External Accretion Shock? by Xiao-Bin Chen, Kai Wang, Yi-Yun Huang, Hai-Ming Zhang, Shao-Qiang Xi, Ruo-Yu Liu, Xiang-Yu Wang

“…Recent studies have found a spatially extended GeV source within the virial radius, consistent with the internal shock origin. Here, we report the detection of a new GeV source at a distance of about 2 $\mathop{.}…”
Get full text

Prevalence and clinical correlates of Gardnerella spp., Fannyhessea vaginae, Lactobacillus crispatus and L. iners in pregnant women in Bukavu, Democratic Republic of the Congo by Lisa Himschoot, Guy Mulinganya, Guy Mulinganya, Guy Mulinganya, Tess Rogier, Ghislain Bisimwa, Ghislain Bisimwa, Freddy Kampara, Freddy Kampara, Yvette Kujirakwinja, Yvette Kujirakwinja, Jules Mongane, Jules Mongane, Innocent Mubalama, Steven Callens, Mario Vaneechoutte, Piet Cools

“…A logistic regression model and ROC curves were calculated to determine the best diagnostic marker for BV.ResultsHere, L. iners (75.8%) was the most prevalent species and G. vaginalis (36.0%) the most common Gardnerella species. …”
Get full text

Dissolved Mn(III) is a key redox intermediate in sediments of a seasonally euxinic coastal basin by R. Klomp, R. Klomp, O. M. Żygadłowska, M. S. M. Jetten, V. E. Oldham, N. A. G. M. van Helmond, N. A. G. M. van Helmond, C. P. Slomp, C. P. Slomp, W. K. Lenstra, W. K. Lenstra

“…The role of organically complexed dissolved Mn(III) (dMn(III)-L) as an electron acceptor and donor in marine environments is still incompletely understood. Here, we use geochemical depth profiles of solutes and solids for the sediment and overlying waters and a reactive transport model to reconstruct the seasonality in sedimentary dMn(III)-L dynamics and benthic Mn release in a eutrophic, seasonally euxinic coastal basin (Lake Grevelingen, the Netherlands). …”
Get full text

Maternal phthalates exposure promotes neural stem cell differentiation into phagocytic astrocytes and synapse engulfment via IRE1α/XBP1s pathway by Fengzhen Cui, Shiyu Deng, Yan Fu, Tongtong Xu, Shuangshuang Bao, Siyi Wang, Yahang Lin, Xianghui Wang, Faming Zhao, Tingting Zhang, Shunqing Xu, Zhijun Zhang, Wanlu Li, Guo-Yuan Yang, Huanwen Tang, Jixian Wang, Xia Sheng, Yaohui Tang

“…However, the molecular mechanism remains unclear. Here, we demonstrate that maternal exposure to MBP enhances neural stem cell (NSC) differentiation into astrocytes with highly expressed C3 and LCN2 in mouse offspring, resulting in increased synapse phagocytosis and cognitive dysfunction. …”
Get full text

Depression symptom severity and behavioral impairment in school-going adolescents in Uganda by Ronald Anguzu, Catherine Abbo, Julia Dickson-Gomez, Max Bobholz, Arthur Kiconco, Abdul R. Shour, Richard Kabanda, Kenneth Kalani, Laura D. Cassidy

“…Depressive symptoms are more prevalent in adolescents than in other age groups which may affect socio-emotional and behavioral development including academic achievement. Here, we determined the association between depression symptom severity and behavioral impairment among adolescents enrolled in secondary schools of Eastern and Central Uganda. …”
Get full text

The oncolytic adenovirus TILT-123 with pembrolizumab in platinum resistant or refractory ovarian cancer: the phase 1a PROTA trial by Matthew Stephen Block, James Hugo Armstrong Clubb, Johanna Mäenpää, Santeri Pakola, Dafne Carolina Alves Quixabeira, Tatiana Kudling, Elise Jirovec, Lyna Haybout, Mirte van der Heijden, Sanae Zahraoui, Susanna Grönberg-Vähä-Koskela, Sini Raatikainen, Victor Arias, Saru Basnet, Nea Ojala, Teijo Pellinen, Annabrita Hemmes, Katja Välimäki, Annukka Pasanen, Tuomo Alanko, Daniel Adamo, Susan Ramadan, Jorma Sormunen, Juha Kononen, Julia Wanda Cohen, Michael Jon Chisamore, John Goldfinch, Suvi Sorsa, Riikka Havunen, Claudia Kistler, Aino Kalervo, Víctor Cervera-Carrascon, João Manuel dos Santos, Akseli Hemminki

“…Originally developed to improve efficacy of T-cell therapies such as immune checkpoint inhibitors and adoptive cell transfer, TILT-123 (Ad5/3-E2F-D24-hTNFα-IRES-hIL-2) is a serotype chimeric oncolytic adenovirus encoding tumor necrosis factor alpha and interleukin-2. Here we report results from phase 1a of PROTA, a single-arm, multicentre dose escalation trial with TILT-123 and pembrolizumab in female patients with platinum resistant or refractory ovarian cancer (NCT05271318). …”
Get full text

The Manufacture of GMP-Grade Bone Marrow Stromal Cells with Validated In Vivo Bone-Forming Potential in an Orthopedic Clinical Center in Brazil by Rhayra B. Dias, João A. M. Guimarães, Marco B. Cury, Leonardo R. Rocha, Elaine S. da Costa, Liebert P. Nogueira, Camila Hochman-Mendez, Anneliese Fortuna-Costa, Anna Karoline F. Silva, Karin S. Cunha, Sergio A. L. de Souza, Maria Eugênia L. Duarte, Rafaela C. Sartore, Danielle C. Bonfim

“…Although a wide variety of methods have been used to expand BMSCs on a large scale by using good manufacturing practice (GMP), little attention has been paid to whether the expansion procedures indeed allow the maintenance of critical cell characteristics and potency, which are crucial for therapeutic effectiveness. Here, we described standard procedures adopted in our facility for the manufacture of clinical-grade BMSC products with a preserved capacity to generate bone in vivo in compliance with the Brazilian regulatory guidelines for cells intended for use in humans. …”
Get full text