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Altiratinib blocks Toxoplasma gondii and Plasmodium falciparum development by selectively targeting a spliceosome kinase Sci. Transl. Med. (IF 19.319) Pub Date : 2022-08-03 Christopher Swale, Valeria Bellini, Matthew W. Bowler, Nardella Flore, Marie-Pierre Brenier-Pinchart, Dominique Cannella, Lucid Belmudes, Caroline Mas, Yohann Couté, Fabrice Laurent, Artur Scherf, Alexandre Bougdour, Mohamed-Ali Hakimi
The Apicomplexa comprise a large phylum of single-celled, obligate intracellular protozoa that include Toxoplasma gondii , Plasmodium , and Cryptosporidium spp., which infect humans and animals and cause severe parasitic diseases. Available therapeutics against these diseases are limited by suboptimal efficacy and frequent side effects, as well as the emergence and spread of resistance. We use a drug
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Triple-negative breast cancer metastasis involves complex epithelial-mesenchymal transition dynamics and requires vimentin Sci. Transl. Med. (IF 19.319) Pub Date : 2022-08-03 Eloïse M. Grasset, Matthew Dunworth, Gaurav Sharma, Melanie Loth, Joseph Tandurella, Ashley Cimino-Mathews, Melissa Gentz, Sydney Bracht, Meagan Haynes, Elana J. Fertig, Andrew J. Ewald
Triple-negative breast cancer (TNBC) is an aggressive subtype associated with early metastatic recurrence and worse patient outcomes. TNBC tumors express molecular markers of the epithelial-mesenchymal transition (EMT), but its requirement during spontaneous TNBC metastasis in vivo remains incompletely understood. We demonstrated that spontaneous TNBC tumors from a genetically engineered mouse model
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Intracavity generation of glioma stem cell–specific CAR macrophages primes locoregional immunity for postoperative glioblastoma therapy Sci. Transl. Med. (IF 19.319) Pub Date : 2022-08-03 Chen Chen, Weiqiang Jing, Yu Chen, Ganyu Wang, Mohnad Abdalla, Lin Gao, Maosen Han, Chongdeng Shi, Anning Li, Peng Sun, Xin Jiang, Zhenmei Yang, Shengchang Zhang, Jing Zhang, Chunwei Tang, Ying Liu, Rui Zhang, Fengbo Xu, Baixiang Dong, Xueen Li, Minglu Liu, Bangming Qiang, Yanhua Sun, Xia Wei, Jun Li, Quanyin Hu, Xinyi Jiang
Glioblastoma multiforme (GBM) remains incurable despite aggressive implementation of multimodal treatments after surgical debulking. Almost all patients with GBM relapse within a narrow margin around the initial resected lesion due to postsurgery residual glioma stem cells (GSCs). Tracking and eradicating postsurgery residual GSCs is critical for preventing postoperative relapse of this devastating
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Polysaccharide and conjugate vaccines to Streptococcus pneumoniae generate distinct humoral responses Sci. Transl. Med. (IF 19.319) Pub Date : 2022-08-03 Leela R. L. Davies, Deniz Cizmeci, Wenyue Guo, Corinne Luedemann, Ronika Alexander-Parrish, Lindsay Grant, Raul Isturiz, Christian Theilacker, Luis Jodar, Bradford D. Gessner, Galit Alter
Streptococcus pneumoniae is a major cause of community-acquired pneumonia, bacteremia, and meningitis in older adults worldwide. Two pneumococcal vaccines containing S. pneumoniae capsular polysaccharides are in current use: the polysaccharide vaccine PPSV23 and the glycoconjugate vaccine PCV13. In clinical trials, both vaccines elicit similar opsonophagocytic killing activity. In contrast to polysaccharide
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Exocrine pancreas regeneration modifies original pancreas to alleviate diabetes in mouse models Sci. Transl. Med. (IF 19.319) Pub Date : 2022-08-03 Xiaoxing Kou, Jin Liu, Dandan Wang, Ming Yu, Can Li, Lu Lu, Chider Chen, Dawei Liu, Wenjing Yu, Tingting Yu, Yao Liu, Xueli Mao, Ali Naji, Tao Cai, Lingyun Sun, Songtao Shi
Diabetes is a major public health issue because of its widely epidemic nature and lack of cure. Here, we show that pancreas-derived mesenchymal stem cells (PMSCs) are capable of regenerating exocrine pancreas when implanted into the kidney capsule of mice with streptozotocin (STZ)–induced diabetes. Mechanistically, we found that the regenerated exocrine pancreas elevated interleukin-6 (IL-6) in PMSC
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Network Tau spreading is vulnerable to the expression gradients of APOE and glutamatergic-related genes Sci. Transl. Med. (IF 19.319) Pub Date : 2022-07-27 Victor Montal, Ibai Diez, Chan-Mi Kim, William Orwig, Elisenda Bueichekú, Raquel Gutiérrez-Zúñiga, Alexandre Bejanin, Jordi Pegueroles, Oriol Dols-Icardo, Patrizia Vannini, Georges El-Fakhri, Keith A. Johnson, Reisa A. Sperling, Juan Fortea, Jorge Sepulcre
A key hallmark of Alzheimer’s disease (AD) pathology is the intracellular accumulation of tau protein in the form of neurofibrillary tangles across large-scale networks of the human brain cortex. Currently, it is still unclear how tau accumulates within specific cortical systems and whether in situ genetic traits play a role in this circuit-based propagation progression. In this study, using two independent
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SARS-CoV-2 S2–targeted vaccination elicits broadly neutralizing antibodies Sci. Transl. Med. (IF 19.319) Pub Date : 2022-07-27 Kevin W. Ng, Nikhil Faulkner, Katja Finsterbusch, Mary Wu, Ruth Harvey, Saira Hussain, Maria Greco, Yafei Liu, Svend Kjaer, Charles Swanton, Sonia Gandhi, Rupert Beale, Steve J. Gamblin, Peter Cherepanov, John McCauley, Rodney Daniels, Michael Howell, Hisashi Arase, Andreas Wack, David L.V. Bauer, George Kassiotis
Several variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged during the current coronavirus disease 2019 (COVID-19) pandemic. Although antibody cross-reactivity with the spike glycoproteins (S) of diverse coronaviruses, including endemic common cold coronaviruses (HCoVs), has been documented, it remains unclear whether such antibody responses, typically targeting the
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Antibody-mediated prevention of vaginal HIV transmission is dictated by IgG subclass in humanized mice Sci. Transl. Med. (IF 19.319) Pub Date : 2022-07-27 Jacqueline M. Brady, Meredith Phelps, Scott W. MacDonald, Evan C. Lam, Adam Nitido, Dylan Parsons, Christine L. Boutros, Cailin E. Deal, Wilfredo F. Garcia-Beltran, Serah Tanno, Harini Natarajan, Margaret E. Ackerman, Vladimir D. Vrbanac, Alejandro B. Balazs
HIV broadly neutralizing antibodies (bNAbs) are capable of both blocking viral entry and driving innate immune responses against HIV-infected cells through their Fc region. Vaccination or productive infection results in a polyclonal mixture of class-switched immunoglobulin G (IgG) antibodies composed of four subclasses, each encoding distinct Fc regions that differentially engage innate immune functions
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Association of a common genetic variant with Parkinson’s disease is mediated by microglia Sci. Transl. Med. (IF 19.319) Pub Date : 2022-07-27 Rebekah G. Langston, Alexandra Beilina, Xylena Reed, Alice Kaganovich, Andrew B. Singleton, Cornelis Blauwendraat, J. Raphael Gibbs, Mark R. Cookson
Studies of multiple neurodegenerative disorders have identified many genetic variants that are associated with risk of disease throughout a lifetime. For example, Parkinson’s disease (PD) risk is attributed in part to both coding mutations in the leucine-rich repeat kinase 2 ( LRRK2 ) gene and to a common noncoding variation in the 5′ region of the LRRK2 locus, as identified by genome-wide association
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Histamine production by the gut microbiota induces visceral hyperalgesia through histamine 4 receptor signaling in mice Sci. Transl. Med. (IF 19.319) Pub Date : 2022-07-27 Giada De Palma, Chiko Shimbori, David E. Reed, Yang Yu, Virginia Rabbia, Jun Lu, Nestor Jimenez-Vargas, Jessica Sessenwein, Cintya Lopez-Lopez, Marc Pigrau, Josue Jaramillo-Polanco, Yong Zhang, Lauren Baerg, Ahmad Manzar, Julien Pujo, Xiaopeng Bai, Maria Ines Pinto-Sanchez, Alberto Caminero, Karen Madsen, Michael G. Surette, Michael Beyak, Alan E. Lomax, Elena F. Verdu, Stephen M. Collins, Stephen
The gut microbiota has been implicated in chronic pain disorders, including irritable bowel syndrome (IBS), yet specific pathophysiological mechanisms remain unclear. We showed that decreasing intake of fermentable carbohydrates improved abdominal pain in patients with IBS, and this was accompanied by changes in the gut microbiota and decreased urinary histamine concentrations. Here, we used germ-free
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SARS-CoV-2 mRNA vaccination elicits robust antibody responses in children Sci. Transl. Med. (IF 19.319) Pub Date : 2022-07-26 Yannic C Bartsch, Kerri J St Denis, Paulina Kaplonek, Jaewon Kang, Evan C Lam, Madeleine D Burns, Eva J Farkas, Jameson P Davis, Brittany P Boribong, Andrea G Edlow, Alessio Fasano, Wayne G Shreffler, Dace Zavadska, Marina Johnson, David Goldblatt, Alejandro B Balazs, Lael M Yonker, Galit Alter
Although children have been largely spared from coronavirus disease 2019 (COVID-19), the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC) with increased transmissibility, combined with fluctuating mask mandates and school re-openings, have led to increased infections and disease among children. Thus, there is an urgent need to roll out COVID-19 vaccines
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Improving the diagnosis of severe malaria in African children using platelet counts and plasma Pf HRP2 concentrations Sci. Transl. Med. (IF 19.319) Pub Date : 2022-07-20 James A. Watson, Sophie Uyoga, Perpetual Wanjiku, Johnstone Makale, Gideon M. Nyutu, Neema Mturi, Elizabeth C. George, Charles J. Woodrow, Nicholas P. J. Day, Philip Bejon, Robert O. Opoka, Arjen M. Dondorp, Chandy C. John, Kathryn Maitland, Thomas N. Williams, Nicholas J. White
Severe malaria caused by Plasmodium falciparum is difficult to diagnose accurately in children in high-transmission settings. Using data from 2649 pediatric and adult patients enrolled in four studies of severe illness in three countries (Bangladesh, Kenya, and Uganda), we fitted Bayesian latent class models using two diagnostic markers: the platelet count and the plasma concentration of P. falciparum
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Interleukin-6–dependent epithelial fluidization initiates fibrotic lung remodeling Sci. Transl. Med. (IF 19.319) Pub Date : 2022-07-20 Ian T. Stancil, Jacob E. Michalski, Corinne E. Hennessy, Kristina L. Hatakka, Ivana V. Yang, Jonathan S. Kurche, Mercedes Rincon, David A. Schwartz
Chronic disease results from the failure of tissues to maintain homeostasis. In the lung, coordinated repair of the epithelium is essential for preserving homeostasis. In animal models and human lung disease, airway epithelial cells mobilize in response to lung injury, resulting in the formation of airway-like cysts with persistent loss of functional cell types and parenchymal architecture. Using live-cell
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Intranasal vaccination with lipid-conjugated immunogens promotes antigen transmucosal uptake to drive mucosal and systemic immunity Sci. Transl. Med. (IF 19.319) Pub Date : 2022-07-20 Brittany L. Hartwell, Mariane B. Melo, Peng Xiao, Ashley A. Lemnios, Na Li, Jason Y.H. Chang, Jingyou Yu, Makda S. Gebre, Aiquan Chang, Laura Maiorino, Crystal Carter, Tyson J. Moyer, Neil C. Dalvie, Sergio A. Rodriguez-Aponte, Kristen A. Rodrigues, Murillo Silva, Heikyung Suh, Josetta Adams, Jane Fontenot, J. Christopher Love, Dan H. Barouch, Francois Villinger, Ruth M. Ruprecht, Darrell J. Irvine
To combat the HIV epidemic and emerging threats such as SARS-CoV-2, immunization strategies are needed that elicit protection at mucosal portals of pathogen entry. Immunization directly through airway surfaces is effective in driving mucosal immunity, but poor vaccine uptake across the mucus and epithelial lining is a limitation. The major blood protein albumin is constitutively transcytosed bidirectionally
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Rescue of autosomal dominant hearing loss by in vivo delivery of mini dCas13X-derived RNA base editor Sci. Transl. Med. (IF 19.319) Pub Date : 2022-07-20 Qingquan Xiao, Zhijiao Xu, Yuanyuan Xue, Chunlong Xu, Lei Han, Yuanhua Liu, Fang Wang, Runze Zhang, Shuang Han, Xing Wang, Geng-Lin Li, Huawei Li, Hui Yang, Yilai Shu
Programmable RNA editing tools enable the reversible correction of mutant transcripts, reducing the potential risk associated with permanent genetic changes associated with the use of DNA editing tools. However, the potential of these RNA tools to treat disease remains unknown. Here, we evaluated RNA correction therapy with Cas13-based RNA base editors in the myosin VI p.C442Y heterozygous mutation
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A hitchhiker’s guide to mucosal and systemic immunity Sci. Transl. Med. (IF 19.319) Pub Date : 2022-07-20 Francis C. Szoka
PEGylated lipid protein immunogens delivered intranasally to mice and macaques drive production of IgG and IgA antibodies at other mucosal sites (Hartwell et al. ).
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Dendrimer nanotherapy for severe COVID-19 attenuates inflammation and neurological injury markers and improves outcomes in a phase2a clinical trial Sci. Transl. Med. (IF 19.319) Pub Date : 2022-07-20 Aaron M. Gusdon, Nauder Faraday, John S. Aita, Sunil Kumar, Ishan Mehta, HuiMahn A. Choi, Jeffery L. Cleland, Keith Robinson, Louise D. McCullough, Derek K. Ng, Rangaramanujam M. Kannan, Sujatha Kannan
Hyperinflammation triggered by SARS-CoV-2 is a major cause of disease severity, with activated macrophages implicated in this response. OP-101, a hydroxyl-polyamidoamine dendrimer– N -acetylcysteine conjugate that specifically targets activated macrophages, improves outcomes in preclinical models of systemic inflammation and neuroinflammation. In this multicenter, randomized, double-blind, placebo-controlled
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A semaphorin-plexin-Rasal1 signaling pathway inhibits gastrin expression and protects against peptic ulcers Sci. Transl. Med. (IF 19.319) Pub Date : 2022-07-20 Rui Xu, Carsten Höß, Jakub M. Swiercz, Dominique T. Brandt, Veronika Lutz, Natalia Petersen, Rui Li, Dandan Zhao, Arkadiusz Oleksy, Tilbe Creigh-Pulatmen, Martina Trokter, Marina Fedorova, Ann Atzberger, Rune B. Strandby, August A. Olsen, Michael P. Achiam, David Matthews, Magdalena Huber, Hermann-Josef Gröne, Stefan Offermanns, Thomas Worzfeld
Peptic ulcer disease is a frequent clinical problem with potentially serious complications such as bleeding or perforation. A decisive factor in the pathogenesis of peptic ulcers is gastric acid, the secretion of which is controlled by the hormone gastrin released from gastric G cells. However, the molecular mechanisms regulating gastrin plasma concentrations are poorly understood. Here, we identified
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NK cells with tissue-resident traits shape response to immunotherapy by inducing adaptive antitumor immunity Sci. Transl. Med. (IF 19.319) Pub Date : 2022-07-13 Nicole Kirchhammer, Marcel P. Trefny, Marina Natoli, Dominik Brücher, Sheena N. Smith, Franziska Werner, Victoria Koch, David Schreiner, Ewelina Bartoszek, Mélanie Buchi, Markus Schmid, Daniel Breu, K. Patricia Hartmann, Polina Zaytseva, Daniela S. Thommen, Heinz Läubli, Jan P. Böttcher, Michal A. Stanczak, Abhishek S. Kashyap, Andreas Plückthun, Alfred Zippelius
T cell–directed cancer immunotherapy often fails to generate lasting tumor control. Harnessing additional effectors of the immune response against tumors may strengthen the clinical benefit of immunotherapies. Here, we demonstrate that therapeutic targeting of the interferon-γ (IFN-γ)–interleukin-12 (IL-12) pathway relies on the ability of a population of natural killer (NK) cells with tissue-resident
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Miswiring of Merkel cell and pruriceptive C fiber drives the itch-scratch cycle Sci. Transl. Med. (IF 19.319) Pub Date : 2022-07-13 Jing Feng, Yonghui Zhao, Zili Xie, Kaikai Zang, Sanja Sviben, Xueming Hu, James A. J. Fitzpatrick, Lu Wen, Yifei Liu, Ting Wang, Katy Lawson, Qin Liu, Yan Yan, Xinzhong Dong, Liang Han, Gregory F. Wu, Brian S. Kim, Hongzhen Hu
Itch sensation provokes the scratch reflex to protect us from harmful stimuli in the skin. Although scratching transiently relieves acute itch through activation of mechanoreceptors, it propagates the vicious itch-scratch cycle in chronic itch by further aggravating itch over time. Although well recognized clinically, the peripheral mechanisms underlying the itch-scratch cycle remain poorly understood
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An inactivated multivalent influenza A virus vaccine is broadly protective in mice and ferrets Sci. Transl. Med. (IF 19.319) Pub Date : 2022-07-13 Jaekeun Park, Sharon L. Fong Legaspi, Louis M. Schwartzman, Sebastian M. Gygli, Zhong-Mei Sheng, Ashley D. Freeman, Lex M. Matthews, Yongli Xiao, Mitchell D. Ramuta, Natalia A. Batchenkova, Li Qi, Luz Angela Rosas, Stephanie L. Williams, Kelsey Scherler, Monica Gouzoulis, Ian Bellayr, David M. Morens, Kathie-Anne Walters, Matthew J. Memoli, John C. Kash, Jeffery K. Taubenberger
Influenza A viruses (IAVs) present major public health threats from annual seasonal epidemics and pandemics and from viruses adapted to a variety of animals including poultry, pigs, and horses. Vaccines that broadly protect against all such IAVs, so-called “universal” influenza vaccines, do not currently exist but are urgently needed. Here, we demonstrated that an inactivated, multivalent whole-virus
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Targeted inducible delivery of immunoactivating cytokines reprograms glioblastoma microenvironment and inhibits growth in mouse models Sci. Transl. Med. (IF 19.319) Pub Date : 2022-07-13 Filippo Birocchi, Melania Cusimano, Federico Rossari, Stefano Beretta, Paola M. V. Rancoita, Anna Ranghetti, Stefano Colombo, Barbara Costa, Peter Angel, Francesca Sanvito, Marcella Callea, Rossana Norata, Linda Chaabane, Tamara Canu, Antonello Spinelli, Marco Genua, Renato Ostuni, Ivan Merelli, Nadia Coltella, Luigi Naldini
Glioblastoma multiforme (GBM) is the most common and lethal brain tumor characterized by a strongly immunosuppressive tumor microenvironment (TME) that represents a barrier also for the development of effective immunotherapies. The possibility to revert this hostile TME by immunoactivating cytokines is hampered by the severe toxicity associated with their systemic administration. Here, we exploited
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Targeting KDM4 for treating PAX3-FOXO1–driven alveolar rhabdomyosarcoma Sci. Transl. Med. (IF 19.319) Pub Date : 2022-07-13 Shivendra Singh, Ahmed Abu-Zaid, Hongjian Jin, Jie Fang, Qiong Wu, Tingting Wang, Helin Feng, Waise Quarni, Ying Shao, Lily Maxham, Alireza Abdolvahabi, Mi-Kyung Yun, Sivaraja Vaithiyalingam, Haiyan Tan, John Bowling, Victoria Honnell, Brandon Young, Yian Guo, Richa Bajpai, Shondra M. Pruett-Miller, Gerard C. Grosveld, Mark Hatley, Beisi Xu, Yiping Fan, Gang Wu, Eleanor Y. Chen, Taosheng Chen, Peter
Chimeric transcription factors drive lineage-specific oncogenesis but are notoriously difficult to target. Alveolar rhabdomyosarcoma (RMS) is an aggressive childhood soft tissue sarcoma transformed by the pathognomonic Paired Box 3–Forkhead Box O1 (PAX3-FOXO1) fusion protein, which governs a core regulatory circuitry transcription factor network. Here, we show that the histone lysine demethylase 4B
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A bivalent SARS-CoV-2 monoclonal antibody combination does not impact the immunogenicity of a vector-based COVID-19 vaccine in macaques Sci. Transl. Med. (IF 19.319) Pub Date : 2022-07-12 Joseph P. Nkolola, Jingyou Yu, Huahua Wan, Aiquan Chang, Katherine McMahan, Tochi Anioke, Catherine Jacob-Dolan, Olivia Powers, Tianyi Ye, Abishek Chandrashekar, Daniel Sellers, Julia Barrett, Yueh-Ming Loo, Mark T. Esser, Robert H. Carnahan, James E. Crowe, Dan H. Barouch
Human monoclonal antibodies (mAbs) that target the spike glycoprotein of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) offer a promising approach for the prevention and treatment of coronavirus disease 2019 (COVID-19). Given suboptimal global vaccination rates, waning immunity in vaccinated individuals, and the emergence of SARS-CoV-2 variants of concern, the use of mAbs for COVID-19
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SARS-CoV-2 infection produces chronic pulmonary epithelial and immune cell dysfunction with fibrosis in mice Sci. Transl. Med. (IF 19.319) Pub Date : 2022-07-07 Kenneth H. Dinnon, Sarah R. Leist, Kenichi Okuda, Hong Dang, Ethan J. Fritch, Kendra L. Gully, Gabriela De la Cruz, Mia D. Evangelista, Takanori Asakura, Rodney C. Gilmore, Padraig Hawkins, Satoko Nakano, Ande West, Alexandra Schäfer, Lisa E. Gralinski, Jamie L. Everman, Satria P. Sajuthi, Mark R. Zweigart, Stephanie Dong, Jennifer McBride, Michelle R. Cooley, Jesse B. Hines, Miriya K. Love, Steve
A subset of individuals who recover from coronavirus disease 2019 (COVID-19) develop post-acute sequelae of SARS-CoV-2 (PASC), but the mechanistic basis of PASC-associated lung abnormalities suffers from a lack of longitudinal tissue samples. The mouse-adapted severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain MA10 produces an acute respiratory distress syndrome (ARDS) in mice similar
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Genomic and epigenomic BRCA alterations predict adaptive resistance and response to platinum-based therapy in patients with triple-negative breast and ovarian carcinomas Sci. Transl. Med. (IF 19.319) Pub Date : 2022-07-06 Francesca Menghi, Kalyan Banda, Pooja Kumar, Robert Straub, Lacey Dobrolecki, Isabel V. Rodriguez, Susan E. Yost, Harshpreet Chandok, Marc R. Radke, George Somlo, Yuan Yuan, Michael T. Lewis, Elizabeth M. Swisher, Edison T. Liu
Triple-negative breast cancer (TNBC) and ovarian carcinomas (OvCas) with BRCA1 promoter methylation ( BRCA1 meth) respond more poorly to alkylating agents compared to those bearing mutations in BRCA1 and BRCA2 ( BRCA mut). This is a conundrum given the biologically equivalent homologous recombination deficiency (HRD) induced by these genetic and epigenetic BRCA perturbations. We dissected this problem
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Closed-loop stimulation using a multiregion brain-machine interface has analgesic effects in rodents. Sci. Transl. Med. (IF 19.319) Pub Date : 2022-06-29 Guanghao Sun,Fei Zeng,Michael McCartin,Qiaosheng Zhang,Helen Xu,Yaling Liu,Zhe Sage Chen,Jing Wang
Effective treatments for chronic pain remain limited. Conceptually, a closed-loop neural interface combining sensory signal detection with therapeutic delivery could produce timely and effective pain relief. Such systems are challenging to develop because of difficulties in accurate pain detection and ultrafast analgesic delivery. Pain has sensory and affective components, encoded in large part by
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Metabolic reprogramming of skeletal muscle by resident macrophages points to CSF1R inhibitors as muscular dystrophy therapeutics. Sci. Transl. Med. (IF 19.319) Pub Date : 2022-06-29 Farshad Babaeijandaghi,Ryan Cheng,Nasim Kajabadi,Hesham Soliman,Chih-Kai Chang,Josh Smandych,Lin Wei Tung,Reece Long,Amirhossein Ghassemi,Fabio M V Rossi
The role of tissue-resident macrophages during tissue regeneration or fibrosis is not well understood, mainly due to the lack of a specific marker for their identification. Here, we identified three populations of skeletal muscle-resident myelomonocytic cells: a population of macrophages positive for lymphatic vessel endothelial receptor 1 (LYVE1) and T cell membrane protein 4 (TIM4 or TIMD4), a population
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The fight against malaria: Diminishing gains and growing challenges Sci. Transl. Med. (IF 19.319) Pub Date : 2022-06-29 Justin M. Cohen, Fredros Okumu, Bruno Moonen
Since the year 2000, historic reductions in malaria incidence and mortality have been driven by the widespread distribution of bed nets, drugs, and insecticides for the prevention and treatment of malaria. Scale-up of these tools has been enabled by an increase in malaria financing compounded by price reductions, yet these trends are unlikely to continue at the same rate. Rapid population growth in
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Delivery of therapeutic carbon monoxide by gas-entrapping materials Sci. Transl. Med. (IF 19.319) Pub Date : 2022-06-29 James D. Byrne, David Gallo, Hannah Boyce, Sarah L. Becker, Kristi M. Kezar, Alicia T. Cotoia, Vivian R. Feig, Aaron Lopes, Eva Csizmadia, Maria Serena Longhi, Jung Seung Lee, Hyunjoon Kim, Adam J. Wentworth, Sidharth Shankar, Ghee Rye Lee, Jianling Bi, Emily Witt, Keiko Ishida, Alison Hayward, Johannes L. P. Kuosmanen, Josh Jenkins, Jacob Wainer, Aya Aragon, Kaitlyn Wong, Christoph Steiger, William
Carbon monoxide (CO) has long been considered a toxic gas but is now a recognized bioactive gasotransmitter with potent immunomodulatory effects. Although inhaled CO is currently under investigation for use in patients with lung disease, this mode of administration can present clinical challenges. The capacity to deliver CO directly and safely to the gastrointestinal (GI) tract could transform the
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Antibody Fc characteristics and effector functions correlate with protection from symptomatic dengue virus type 3 infection Sci. Transl. Med. (IF 19.319) Pub Date : 2022-06-29 Antonio G. Dias, Caroline Atyeo, Carolin Loos, Magelda Montoya, Vicky Roy, Sandra Bos, Parnal Narvekar, Tulika Singh, Leah C. Katzelnick, Guillermina Kuan, Douglas A. Lauffenburger, Angel Balmaseda, Galit Alter, Eva Harris
Preexisting cross-reactive antibodies have been implicated in both protection and pathogenesis during subsequent infections with different dengue virus (DENV) serotypes (DENV1-4). Nonetheless, humoral immune correlates and mechanisms of protection have remained elusive. Using a systems serology approach to evaluate humoral responses, we profiled plasma collected before inapparent or symptomatic secondary
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MECP2-related pathways are dysregulated in a cortical organoid model of myotonic dystrophy Sci. Transl. Med. (IF 19.319) Pub Date : 2022-06-29 Kathryn H. Morelli, Wenhao Jin, Shashank Shathe, Assael A. Madrigal, Krysten L. Jones, Joshua L. Schwartz, Tristan Bridges, Jasmine R. Mueller, Archana Shankar, Isaac A. Chaim, John W. Day, Gene W. Yeo
Myotonic dystrophy type 1 (DM1) is a multisystem, autosomal-dominant inherited disorder caused by CTG microsatellite repeat expansions (MREs) in the 3′ untranslated region of the dystrophia myotonica-protein kinase ( DMPK ) gene. Despite its prominence as the most common adult-onset muscular dystrophy, patients with congenital to juvenile-onset forms of DM1 can present with debilitating neurocognitive
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CKS1 inhibition depletes leukemic stem cells and protects healthy hematopoietic stem cells in acute myeloid leukemia Sci. Transl. Med. (IF 19.319) Pub Date : 2022-06-22 William Grey, Ana Rio-Machin, Pedro Casado, Eva Grönroos, Sara Ali, Juho J. Miettinen, Findlay Bewicke-Copley, Alun Parsons, Caroline A. Heckman, Charles Swanton, Pedro R. Cutillas, John Gribben, Jude Fitzgibbon, Dominique Bonnet
Acute myeloid leukemia (AML) is an aggressive hematological disorder comprising a hierarchy of quiescent leukemic stem cells (LSCs) and proliferating blasts with limited self-renewal ability. AML has a dismal prognosis, with extremely low 2-year survival rates in the poorest cytogenetic risk patients, primarily due to the failure of intensive chemotherapy protocols to deplete LSCs and toxicity of therapy
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B cell targeting in CAR T cell therapy: Side effect or driver of CAR T cell function? Sci. Transl. Med. (IF 19.319) Pub Date : 2022-06-22 Gregory M. Chen, Jan Joseph Melenhorst, Kai Tan
Chimeric antigen receptor (CAR) T cell therapies targeting CD19 and CD22 have been successful for treating B cell cancers, but CAR T cells targeting non–B cell cancers remain unsuccessful. We propose that rather than being strictly a side effect of therapy, the large number of CAR interactions with normal B cells may be a key contributor to clinical CAR T cell responses.
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Elicitation of pneumovirus-specific B cell responses by a prefusion-stabilized respiratory syncytial virus F subunit vaccine Sci. Transl. Med. (IF 19.319) Pub Date : 2022-06-22 Emily Phung, Lauren A. Chang, Maryam Mukhamedova, Lijuan Yang, Deepika Nair, Scott A. Rush, Kaitlyn M. Morabito, Jason S. McLellan, Ursula J. Buchholz, John R. Mascola, Michelle C. Crank, Grace Chen, Barney S. Graham, Tracy J. Ruckwardt
Respiratory syncytial virus (RSV) is a substantial cause of morbidity and mortality globally. A candidate RSV prefusion (pre-F)–stabilized subunit vaccine, DS-Cav1, has previously been shown to elicit potent and durable neutralizing activity in a phase 1 clinical trial in healthy adults. Here, we used fluorescently labeled probes and flow cytometry to evaluate the antigen specificity and phenotype
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Suvorexant ameliorated sleep disturbance, opioid withdrawal, and craving during a buprenorphine taper Sci. Transl. Med. (IF 19.319) Pub Date : 2022-06-22 Andrew S. Huhn, Patrick H. Finan, Charlene E. Gamaldo, Alexis S. Hammond, Annie Umbricht, Cecilia L. Bergeria, Eric C. Strain, Kelly E. Dunn
Increased orexin/hypocretin signaling is implicated in opioid withdrawal, sleep disturbances, and drug-seeking behaviors. This study examined whether a dual-orexin receptor antagonist would improve sleep and withdrawal outcomes when compared with placebo during a buprenorphine/naloxone taper. Thirty-eight participants with opioid use disorder were recruited to a clinical research unit and maintained
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Molecular signatures of long-term hepatocellular carcinoma risk in nonalcoholic fatty liver disease Sci. Transl. Med. (IF 19.319) Pub Date : 2022-06-22 Naoto Fujiwara, Naoto Kubota, Emilie Crouchet, Bhuvaneswari Koneru, Cesia A. Marquez, Arun K. Jajoriya, Gayatri Panda, Tongqi Qian, Shijia Zhu, Nicolas Goossens, Xiaochen Wang, Shuang Liang, Zhenyu Zhong, Sara Lewis, Bachir Taouli, Myron E. Schwartz, Maria Isabel Fiel, Amit G. Singal, Jorge A. Marrero, Austin J. Fobar, Neehar D. Parikh, Indu Raman, Quan-Zhen Li, Masataka Taguri, Atsushi Ono, Hiroshi
Prediction of hepatocellular carcinoma (HCC) risk is an urgent unmet need in patients with nonalcoholic fatty liver disease (NAFLD). In cohorts of 409 patients with NAFLD from multiple global regions, we defined and validated hepatic transcriptome and serum secretome signatures predictive of long-term HCC risk in patients with NAFLD. A 133-gene signature, prognostic liver signature (PLS)–NAFLD, predicted
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Granzyme K+ CD8 T cells form a core population in inflamed human tissue. Sci. Transl. Med. (IF 19.319) Pub Date : 2022-06-15 A Helena Jonsson,Fan Zhang,Garrett Dunlap,Emma Gomez-Rivas,Gerald F M Watts,Heather J Faust,Karishma Vijay Rupani,Joseph R Mears,Nida Meednu,Runci Wang,Gregory Keras,Jonathan S Coblyn,Elena M Massarotti,Derrick J Todd,Jennifer H Anolik,Andrew McDavid,,Kevin Wei,Deepak A Rao,Soumya Raychaudhuri,Michael B Brenner
T cell-derived pro-inflammatory cytokines are a major driver of rheumatoid arthritis (RA) pathogenesis. Although these cytokines have traditionally been attributed to CD4 T cells, we have found that CD8 T cells are notably abundant in synovium and make more interferon (IFN)-γ and nearly as much tumor necrosis factor (TNF) as their CD4 T cell counterparts. Furthermore, using unbiased high-dimensional
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Sex-specific effects of daily tadalafil on diabetic heart kinetics in RECOGITO, a randomized, double-blind, placebo-controlled trial Sci. Transl. Med. (IF 19.319) Pub Date : 2022-06-15 Riccardo Pofi, Elisa Giannetta, Tiziana Feola, Nicola Galea, Federica Barbagallo, Federica Campolo, Roberto Badagliacca, Biagio Barbano, Federica Ciolina, Giuseppe Defeudis, Tiziana Filardi, Franz Sesti, Marianna Minnetti, Carmine D. Vizza, Patrizio Pasqualetti, Pierluigi Caboni, Iacopo Carbone, Marco Francone, Carlo Catalano, Paolo Pozzilli, Andrea Lenzi, Mary Anna Venneri, Daniele Gianfrilli, Andrea
Cyclic GMP–phosphodiesterase type 5 (PDE5) inhibition has been shown to counteract maladaptive cardiac changes triggered by diabetes in some but not all studies. We performed a single-center, 20-week, double-blind, randomized, placebo-controlled trial (NCT01803828) to assess sex differences in cardiac remodeling after PDE5 inhibition in patients with diabetic cardiomyopathy. A total of 122 men and
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The balance between protective and pathogenic immune responses to pneumonia in the neonatal lung is enforced by gut microbiota Sci. Transl. Med. (IF 19.319) Pub Date : 2022-06-15 Joseph Stevens, Shelby Steinmeyer, Madeline Bonfield, Laura Peterson, Timothy Wang, Jerilyn Gray, Ian Lewkowich, Yan Xu, Yina Du, Minzhe Guo, James L. Wynn, William Zacharias, Nathan Salomonis, Lisa Miller, Claire Chougnet, Dennis Hartigan O’Connor, Hitesh Deshmukh
Although modern clinical practices such as cesarean sections and perinatal antibiotics have improved infant survival, treatment with broad-spectrum antibiotics alters intestinal microbiota and causes dysbiosis. Infants exposed to perinatal antibiotics have an increased likelihood of life-threatening infections, including pneumonia. Here, we investigated how the gut microbiota sculpt pulmonary immune
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Calreticulin mutant myeloproliferative neoplasms induce MHC-I skewing, which can be overcome by an optimized peptide cancer vaccine Sci. Transl. Med. (IF 19.319) Pub Date : 2022-06-15 Mathieu Gigoux, Morten O. Holmström, Roberta Zappasodi, Joseph J. Park, Stephane Pourpe, Cansu Cimen Bozkus, Levi M. B. Mangarin, David Redmond, Svena Verma, Sara Schad, Mariam M. George, Divya Venkatesh, Arnab Ghosh, David Hoyos, Zaki Molvi, Baransel Kamaz, Anna E. Marneth, William Duke, Matthew J. Leventhal, Max Jan, Vincent T. Ho, Gabriela S. Hobbs, Trine Alma Knudsen, Vibe Skov, Lasse Kjær, Thomas
The majority of JAK2 V617F -negative myeloproliferative neoplasms (MPNs) have disease-initiating frameshift mutations in calreticulin ( CALR ), resulting in a common carboxyl-terminal mutant fragment (CALR MUT ), representing an attractive source of neoantigens for cancer vaccines. However, studies have shown that CALR MUT -specific T cells are rare in patients with CALR MUT MPN for unknown reasons
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Chronologically modified androgen receptor in recurrent castration-resistant prostate cancer and its therapeutic targeting Sci. Transl. Med. (IF 19.319) Pub Date : 2022-06-15 Mithila Sawant, Kiran Mahajan, Arun Renganathan, Cody Weimholt, Jingqin Luo, Vandna Kukshal, Joseph M. Jez, Myung Sik Jeon, Bo Zhang, Tiandao Li, Bin Fang, Yunting Luo, Nicholas J. Lawrence, Harshani R. Lawrence, Felix Y. Feng, Nupam P. Mahajan
Resistance to second-generation androgen receptor (AR) antagonists such as enzalutamide is an inevitable consequence in patients with castration-resistant prostate cancer (CRPC). There are no effective therapeutic options for this recurrent disease. The expression of truncated AR variant 7 (AR-V7) has been suggested to be one mechanism of resistance; however, its low frequency in patients with CRPC
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The anti-SARS-CoV-2 monoclonal antibody, bamlanivimab, minimally impacts the endogenous immune response to COVID-19 vaccination Sci. Transl. Med. (IF 19.319) Pub Date : 2022-06-09 Robert J. Benschop, Jay L. Tuttle, Lin Zhang, Josh Poorbaugh, Nicole L. Kallewaard, Peter Vaillancourt, Melissa Crisp, Thi Ngoc Vy Trinh, Joshua J. Freitas, Stephanie Beasley, Montanea Daniels, Natalie Haustrup, Richard E. Higgs, Ajay Nirula, Myron S. Cohen, Mary Marovich
As the coronavirus disease 2019 (COVID-19) pandemic evolves and vaccine rollout progresses, the availability and demand for monoclonal antibodies for the prevention and treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are also accelerating. This longitudinal serological study evaluated the magnitude and potency of the endogenous antibody response to COVID-19 vaccination
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Epigenetic reactivation of transcriptional programs orchestrating fetal lung development in human pulmonary hypertension. Sci. Transl. Med. (IF 19.319) Pub Date : 2022-06-08 Prakash Chelladurai,Carsten Kuenne,Alice Bourgeois,Stefan Günther,Chanil Valasarajan,Anoop V Cherian,Robbert J Rottier,Charlotte Romanet,Andreas Weigert,Olivier Boucherat,Christina A Eichstaedt,Clemens Ruppert,Andreas Guenther,Thomas Braun,Mario Looso,Rajkumar Savai,Werner Seeger,Uta-Maria Bauer,Sébastien Bonnet,Soni Savai Pullamsetti
Phenotypic alterations in resident vascular cells contribute to the vascular remodeling process in diseases such as pulmonary (arterial) hypertension [P(A)H]. How the molecular interplay between transcriptional coactivators, transcription factors (TFs), and chromatin state alterations facilitate the maintenance of persistently activated cellular phenotypes that consequently aggravate vascular remodeling
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Gene therapy targeting protein trafficking regulator MOG1 in mouse models of Brugada syndrome, arrhythmias, and mild cardiomyopathy. Sci. Transl. Med. (IF 19.319) Pub Date : 2022-06-08 Gang Yu,Susmita Chakrabarti,Miroslava Tischenko,Ai-Lan Chen,Zhijie Wang,Hyosuk Cho,Brent A French,Sathyamangla V Naga Prasad,Qiuyun Chen,Qing K Wang
Brugada syndrome (BrS) is a fatal arrhythmia that causes an estimated 4% of all sudden death in high-incidence areas. SCN5A encodes cardiac sodium channel NaV1.5 and causes 25 to 30% of BrS cases. Here, we report generation of a knock-in (KI) mouse model of BrS (Scn5aG1746R/+). Heterozygous KI mice recapitulated some of the clinical features of BrS, including an ST segment abnormality (a prominent
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Risk assessment with gut microbiome and metabolite markers in NAFLD development. Sci. Transl. Med. (IF 19.319) Pub Date : 2022-06-08 Howell Leung,Xiaoxue Long,Yueqiong Ni,Lingling Qian,Emmanouil Nychas,Sara Leal Siliceo,Dennis Pohl,Kati Hanhineva,Yan Liu,Aimin Xu,Henrik B Nielsen,Eugeni Belda,Karine Clément,Rohit Loomba,Huating Li,Weiping Jia,Gianni Panagiotou
A growing body of evidence suggests interplay between the gut microbiota and the pathogenesis of nonalcoholic fatty liver disease (NAFLD). However, the role of the gut microbiome in early detection of NAFLD is unclear. Prospective studies are necessary for identifying reliable, microbiome markers for early NAFLD. We evaluated 2487 individuals in a community-based cohort who were followed up 4.6 years
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Preclinical and clinical evaluation of the LRRK2 inhibitor DNL201 for Parkinson's disease. Sci. Transl. Med. (IF 19.319) Pub Date : 2022-06-08 Danna Jennings,Sarah Huntwork-Rodriguez,Anastasia G Henry,Jennifer C Sasaki,René Meisner,Dolores Diaz,Hilda Solanoy,Xiang Wang,Elvira Negrou,Vitaliy V Bondar,Rajarshi Ghosh,Michael T Maloney,Nicholas E Propson,Yuda Zhu,Romeo D Maciuca,Laura Harris,Angela Kay,Peter LeWitt,T Alex King,Drew Kern,Aaron Ellenbogen,Ira Goodman,Andrew Siderowf,Jason Aldred,Omid Omidvar,Shababa T Masoud,Sonnet S Davis,Annie
Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common genetic risk factors for Parkinson's disease (PD). Increased LRRK2 kinase activity is thought to impair lysosomal function and may contribute to the pathogenesis of PD. Thus, inhibition of LRRK2 is a potential disease-modifying therapeutic strategy for PD. DNL201 is an investigational, first-in-class, CNS-penetrant, selective, ATP-competitive
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Delivery of an ectonucleotidase inhibitor with ROS-responsive nanoparticles overcomes adenosine-mediated cancer immunosuppression. Sci. Transl. Med. (IF 19.319) Pub Date : 2022-06-08 Chengqiong Mao,Stacy Yeh,Juan Fu,Mercedes Porosnicu,Alexandra Thomas,Gregory L Kucera,Konstantinos I Votanopoulos,Shaomin Tian,Xin Ming
Tumor evasion of immune destruction is associated with the production of immunosuppressive adenosine in the tumor microenvironment (TME). Anticancer therapies can trigger adenosine triphosphate (ATP) release from tumor cells, causing rapid formation of adenosine by the ectonucleotidases CD39 and CD73, thereafter exacerbating immunosuppression in the TME. The goal of this study was to develop an approach
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A step forward for LRRK2 inhibitors in Parkinson's disease. Sci. Transl. Med. (IF 19.319) Pub Date : 2022-06-08 Patrick A Lewis
A phase 1 clinical trial for kinase inhibitors targeting LRRK2 provides the foundation for testing the efficacy of LRRK2 kinase inhibitors in Parkinson's disease.
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The mechanosensitive ion channel PIEZO1 is expressed in tendons and regulates physical performance Sci. Transl. Med. (IF 19.319) Pub Date : 2022-06-01 Ryo Nakamichi, Shang Ma, Takayuki Nonoyama, Tomoki Chiba, Ryota Kurimoto, Hiroki Ohzono, Merissa Olmer, Chisa Shukunami, Noriyuki Fuku, Guan Wang, Errol Morrison, Yannis P. Pitsiladis, Toshifumi Ozaki, Darryl D’Lima, Martin Lotz, Ardem Patapoutian, Hiroshi Asahara
How mechanical stress affects physical performance via tendons is not fully understood. Piezo1 is a mechanosensitive ion channel, and E756del PIEZO1 was recently found as a gain-of-function variant that is common in individuals of African descent. We generated tendon-specific knock-in mice using R2482H Piezo1 , a mouse gain-of-function variant, and found that they had higher jumping abilities and faster
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Targeting C3b/C4b and VEGF with a bispecific fusion protein optimized for neovascular age-related macular degeneration therapy Sci. Transl. Med. (IF 19.319) Pub Date : 2022-06-01 Shiqi Yang, Tong Li, Huixun Jia, Min Gao, Yiming Li, Xiaoling Wan, Zhen Huang, Min Li, Yuanqi Zhai, Xiaomeng Li, Xiaotong Yang, Tao Wang, Jian Liang, Qing Gu, Xueting Luo, Lei Qian, Shujie Lu, Junjian Liu, Yanping Song, Fenghua Wang, Xiaodong Sun, Dechao Yu
Antiangiogenesis therapies targeting vascular endothelial growth factor (VEGF) have revolutionized the treatment of neovascular ocular diseases, including neovascular age-related macular degeneration (nAMD). Compelling evidence has implicated the vital role of complement system dysregulation in AMD pathogenesis, implying it as a potential therapeutic strategy for geographic atrophy in dry AMD and to
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Gepotidacin is efficacious in a nonhuman primate model of pneumonic plague Sci. Transl. Med. (IF 19.319) Pub Date : 2022-06-01 Charles Jakielaszek, Mohammad Hossain, Lian Qian, Cindy Fishman, Katherine Widdowson, Jamese J. Hilliard, Frank Mannino, Aparna Raychaudhuri, Elisabeth Carniel, Samandra Demons, Henry S. Heine, Jeremy Hershfield, Riccardo Russo, William M. Mega, David Revelli, Karen O’Dwyer
Gepotidacin is a first-in-class triazaacenaphthylene antibacterial agent that selectively inhibits bacterial DNA gyrase and topoisomerase IV through a unique binding mode and has the potential to treat a number of bacterial diseases. Development of this new agent to treat pneumonic plague caused by Yersinia pestis depends on the U.S. Food and Drug Administration Animal Rule testing pathway, as testing
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Reversal of synapse loss in Alzheimer mouse models by targeting mGluR5 to prevent synaptic tagging by C1Q Sci. Transl. Med. (IF 19.319) Pub Date : 2022-06-01 Joshua Spurrier, LaShae Nicholson, Xiaotian T. Fang, Austin J. Stoner, Takuya Toyonaga, Daniel Holden, Timothy R. Siegert, William Laird, Mary Alice Allnutt, Marius Chiasseu, A. Harrison Brody, Hideyuki Takahashi, Sarah Helena Nies, Azucena Pérez Cañamás, Pragalath Sadasivam, Supum Lee, Songye Li, Le Zhang, Yiyun H. Huang, Richard E. Carson, Zhengxin Cai, Stephen M. Strittmatter
Microglia-mediated synaptic loss contributes to the development of cognitive impairments in Alzheimer’s disease (AD). However, the basis for this immune-mediated attack on synapses remains to be elucidated. Treatment with the metabotropic glutamate receptor 5 (mGluR5) silent allosteric modulator (SAM), BMS-984923, prevents β-amyloid oligomer–induced aberrant synaptic signaling while preserving physiological
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SARS-CoV-2 transmission, persistence of immunity, and estimates of Omicron’s impact in South African population cohorts Sci. Transl. Med. (IF 19.319) Pub Date : 2022-05-31 Kaiyuan Sun, Stefano Tempia, Jackie Kleynhans, Anne von Gottberg, Meredith L McMorrow, Nicole Wolter, Jinal N. Bhiman, Jocelyn Moyes, Mignon du Plessis, Maimuna Carrim, Amelia Buys, Neil A Martinson, Kathleen Kahn, Stephen Tollman, Limakatso Lebina, Floidy Wafawanaka, Jacques D. du Toit, Francesc Xavier Gómez-Olivé, Thulisa Mkhencele, Cécile Viboud, Cheryl Cohen
Understanding the build-up of immunity with successive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and the epidemiological conditions that favor rapidly expanding epidemics will help facilitate future pandemic control. We analyzed high-resolution infection and serology data from two longitudinal household cohorts in South Africa to reveal high cumulative infection rates and
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Lysine acylation causes collateral damage in inborn errors of metabolism Sci. Transl. Med. (IF 19.319) Pub Date : 2022-05-25 Eric S. Goetzman, Jerry Vockley
Posttranslational modifications contribute to the pathology of methylmalonic acidemia and may be targetable via an acylation-resistant sirtuin (Head et al. , this issue).
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MAIT and Vδ2 unconventional T cells are supported by a diverse intestinal microbiome and correlate with favorable patient outcome after allogeneic HCT Sci. Transl. Med. (IF 19.319) Pub Date : 2022-05-25 Hana Andrlová, Oriana Miltiadous, Anastasia I. Kousa, Anqi Dai, Susan DeWolf, Sara Violante, Hee-Yon Park, Sudha Janaki-Raman, Rui Gardner, Sary El Daker, John Slingerland, Paul Giardina, Annelie Clurman, Antonio L. C. Gomes, Chi Nguyen, Marina Burgos da Silva, Gabriel K. Armijo, Nicole Lee, Roberta Zappasodi, Ronan Chaligne, Ignas Masilionis, Emily Fontana, Doris Ponce, Christina Cho, Amy Bush, Lauren
Microbial diversity is associated with improved outcomes in recipients of allogeneic hematopoietic cell transplantation (allo-HCT), but the mechanism underlying this observation is unclear. In a cohort of 174 patients who underwent allo-HCT, we demonstrate that a diverse intestinal microbiome early after allo-HCT is associated with an increased number of innate-like mucosal-associated invariant T (MAIT)
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Schwann cells in the subcutaneous adipose tissue have neurogenic potential and can be used for regenerative therapies Sci. Transl. Med. (IF 19.319) Pub Date : 2022-05-25 Rhian Stavely, Ryo Hotta, Nicole Picard, Ahmed A. Rahman, Weikang Pan, Sukhada Bhave, Meredith Omer, Wing Lam N. Ho, Richard A. Guyer, Allan M. Goldstein
Stem cell therapies for nervous system disorders are hindered by a lack of accessible autologous sources of neural stem cells (NSCs). In this study, neural crest–derived Schwann cells are found to populate nerve fiber bundles (NFBs) residing in mouse and human subcutaneous adipose tissue (SAT). NFBs containing Schwann cells were harvested from mouse and human SAT and cultured in vitro. During in vitro
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Aberrant methylmalonylation underlies methylmalonic acidemia and is attenuated by an engineered sirtuin Sci. Transl. Med. (IF 19.319) Pub Date : 2022-05-25 PamelaSara E. Head, Sangho Myung, Yong Chen, Jessica L. Schneller, Cindy Wang, Nicholas Duncan, Pauline Hoffman, David Chang, Abigael Gebremariam, Marjan Gucek, Irini Manoli, Charles P. Venditti
Organic acidemias such as methylmalonic acidemia (MMA) are a group of inborn errors of metabolism that typically arise from defects in the catabolism of amino and fatty acids. Accretion of acyl-CoA species is postulated to underlie disease pathophysiology, but the mechanism(s) remain unknown. Here, we surveyed hepatic explants from patients with MMA and unaffected donors, in parallel with samples from