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Nature Medicine

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https://www.readbyqxmd.com/read/28436958/local-clearance-of-senescent-cells-attenuates-the-development-of-post-traumatic-osteoarthritis-and-creates-a-pro-regenerative-environment
#1
Ok Hee Jeon, Chaekyu Kim, Remi-Martin Laberge, Marco Demaria, Sona Rathod, Alain P Vasserot, Jae Wook Chung, Do Hun Kim, Yan Poon, Nathaniel David, Darren J Baker, Jan M van Deursen, Judith Campisi, Jennifer H Elisseeff
Senescent cells (SnCs) accumulate in many vertebrate tissues with age and contribute to age-related pathologies, presumably through their secretion of factors contributing to the senescence-associated secretory phenotype (SASP). Removal of SnCs delays several pathologies and increases healthy lifespan. Aging and trauma are risk factors for the development of osteoarthritis (OA), a chronic disease characterized by degeneration of articular cartilage leading to pain and physical disability. Senescent chondrocytes are found in cartilage tissue isolated from patients undergoing joint replacement surgery, yet their role in disease pathogenesis is unknown...
April 24, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28436957/pyruvate-kinase-m2-activation-may-protect-against-the-progression-of-diabetic-glomerular-pathology-and-mitochondrial-dysfunction
#2
Weier Qi, Hillary A Keenan, Qian Li, Atsushi Ishikado, Aimo Kannt, Thorsten Sadowski, Mark A Yorek, I-Hsien Wu, Samuel Lockhart, Lawrence J Coppey, Anja Pfenninger, Chong Wee Liew, Guifen Qiang, Alison M Burkart, Stephanie Hastings, David Pober, Christopher Cahill, Monika A Niewczas, William J Israelsen, Liane Tinsley, Isaac E Stillman, Peter S Amenta, Edward P Feener, Matthew G Vander Heiden, Robert C Stanton, George L King
Diabetic nephropathy (DN) is a major cause of end-stage renal disease, and therapeutic options for preventing its progression are limited. To identify novel therapeutic strategies, we studied protective factors for DN using proteomics on glomeruli from individuals with extreme duration of diabetes (ł50 years) without DN and those with histologic signs of DN. Enzymes in the glycolytic, sorbitol, methylglyoxal and mitochondrial pathways were elevated in individuals without DN. In particular, pyruvate kinase M2 (PKM2) expression and activity were upregulated...
April 24, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28414330/hiv-persistence-in-tissue-macrophages-of-humanized-myeloid-only-mice-during-antiretroviral-therapy
#3
Jenna B Honeycutt, William O Thayer, Caroline E Baker, Ruy M Ribeiro, Steven M Lada, Youfang Cao, Rachel A Cleary, Michael G Hudgens, Douglas D Richman, J Victor Garcia
Despite years of fully suppressive antiretroviral therapy (ART), HIV persists in its hosts and is never eradicated. One major barrier to eradication is that the virus infects multiple cell types that may individually contribute to HIV persistence. Tissue macrophages are critical contributors to HIV pathogenesis; however, their specific role in HIV persistence during long-term suppressive ART has not been established. Using humanized myeloid-only mice (MoM), we demonstrate that HIV infection of tissue macrophages is rapidly suppressed by ART, as reflected by a rapid drop in plasma viral load and a dramatic decrease in the levels of cell-associated viral RNA and DNA...
April 17, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28414329/alternatively-activated-macrophages-do-not-synthesize-catecholamines-or-contribute-to-adipose-tissue-adaptive-thermogenesis
#4
Katrin Fischer, Henry H Ruiz, Kevin Jhun, Brian Finan, Douglas J Oberlin, Verena van der Heide, Anastasia V Kalinovich, Natasa Petrovic, Yochai Wolf, Christoffer Clemmensen, Andrew C Shin, Senad Divanovic, Frank Brombacher, Elke Glasmacher, Susanne Keipert, Martin Jastroch, Joachim Nagler, Karl-Werner Schramm, Dasa Medrikova, Gustav Collden, Stephen C Woods, Stephan Herzig, Dirk Homann, Steffen Jung, Jan Nedergaard, Barbara Cannon, Matthias H Tschöp, Timo D Müller, Christoph Buettner
Adaptive thermogenesis is the process of heat generation in response to cold stimulation. It is under the control of the sympathetic nervous system, whose chief effector is the catecholamine norepinephrine (NE). NE enhances thermogenesis through β3-adrenergic receptors to activate brown adipose tissue and by 'browning' white adipose tissue. Recent studies have reported that alternative activation of macrophages in response to interleukin (IL)-4 stimulation induces the expression of tyrosine hydroxylase (TH), a key enzyme in the catecholamine synthesis pathway, and that this activation provides an alternative source of locally produced catecholamines during the thermogenic process...
April 17, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28414328/marginal-zone-b-cells-control-the-response-of-follicular-helper-t-cells-to-a-high-cholesterol-diet
#5
Meritxell Nus, Andrew P Sage, Yuning Lu, Leanne Masters, Brian Y H Lam, Stephen Newland, Sandra Weller, Dimitrios Tsiantoulas, Juliette Raffort, Damiënne Marcus, Alison Finigan, Lauren Kitt, Nichola Figg, Reinhold Schirmbeck, Manfred Kneilling, Giles S H Yeo, Christoph J Binder, José Luis de la Pompa, Ziad Mallat
Splenic marginal zone B (MZB) cells, positioned at the interface between circulating blood and lymphoid tissue, detect and respond to blood-borne antigens. Here we show that MZB cells in mice activate a homeostatic program in response to a high-cholesterol diet (HCD) and regulate both the differentiation and accumulation of T follicular helper (TFH) cells. Feeding mice an HCD resulted in upregulated MZB cell surface expression of the immunoregulatory ligand PDL1 in an ATF3-dependent manner and increased the interaction between MZB cells and pre-TFH cells, leading to PDL1-mediated suppression of TFH cell motility, alteration of TFH cell differentiation, reduced TFH abundance and suppression of the proatherogenic TFH response...
April 17, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28394333/a-heart-brain-kidney-network-controls-adaptation-to-cardiac-stress-through-tissue-macrophage-activation
#6
Katsuhito Fujiu, Munehiko Shibata, Yukiteru Nakayama, Fusa Ogata, Sahohime Matsumoto, Koji Noshita, Shingo Iwami, Susumu Nakae, Issei Komuro, Ryozo Nagai, Ichiro Manabe
Heart failure is a complex clinical syndrome characterized by insufficient cardiac function. In addition to abnormalities intrinsic to the heart, dysfunction of other organs and dysregulation of systemic factors greatly affect the development and consequences of heart failure. Here we show that the heart and kidneys function cooperatively in generating an adaptive response to cardiac pressure overload. In mice subjected to pressure overload in the heart, sympathetic nerve activation led to activation of renal collecting-duct (CD) epithelial cells...
April 10, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28394332/mafb-prevents-excess-inflammation-after-ischemic-stroke-by-accelerating-clearance-of-damage-signals-through-msr1
#7
Takashi Shichita, Minako Ito, Rimpei Morita, Kyoko Komai, Yoshiko Noguchi, Hiroaki Ooboshi, Ryusuke Koshida, Satoru Takahashi, Tatsuhiko Kodama, Akihiko Yoshimura
Damage-associated molecular patterns (DAMPs) trigger sterile inflammation after tissue injury, but the mechanisms underlying the resolution of inflammation remain unclear. In this study, we demonstrate that common DAMPs, such as high-mobility-group box 1 (HMGB1), peroxiredoxins (PRXs), and S100A8 and S100A9, were internalized through the class A scavenger receptors MSR1 and MARCO in vitro. In ischemic murine brain, DAMP internalization was largely mediated by MSR1. An elevation of MSR1 levels in infiltrating myeloid cells observed 3 d after experimental stroke was dependent on the transcription factor Mafb...
April 10, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28394331/dectin-1-activation-on-macrophages-by-galectin-9-promotes-pancreatic-carcinoma-and-peritumoral-immune-tolerance
#8
Donnele Daley, Vishnu R Mani, Navyatha Mohan, Neha Akkad, Atsuo Ochi, Daniel W Heindel, Ki Buom Lee, Constantinos P Zambirinis, Gautam Sd Balasubramania Pandian, Shivraj Savadkar, Alejandro Torres-Hernandez, Shruti Nayak, Ding Wang, Mautin Hundeyin, Brian Diskin, Berk Aykut, Gregor Werba, Rocky M Barilla, Robert Rodriguez, Steven Chang, Lawrence Gardner, Lara K Mahal, Beatrix Ueberheide, George Miller
The progression of pancreatic oncogenesis requires immune-suppressive inflammation in cooperation with oncogenic mutations. However, the drivers of intratumoral immune tolerance are uncertain. Dectin 1 is an innate immune receptor crucial for anti-fungal immunity, but its role in sterile inflammation and oncogenesis has not been well defined. Furthermore, non-pathogen-derived ligands for dectin 1 have not been characterized. We found that dectin 1 is highly expressed on macrophages in pancreatic ductal adenocarcinoma (PDA)...
April 10, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28394330/thymosin-%C3%AE-1-represents-a-potential-potent-single-molecule-based-therapy-for-cystic-fibrosis
#9
Luigina Romani, Vasilis Oikonomou, Silvia Moretti, Rossana G Iannitti, Maria Cristina D'Adamo, Valeria R Villella, Marilena Pariano, Luigi Sforna, Monica Borghi, Marina M Bellet, Francesca Fallarino, Maria Teresa Pallotta, Giuseppe Servillo, Eleonora Ferrari, Paolo Puccetti, Guido Kroemer, Mauro Pessia, Luigi Maiuri, Allan L Goldstein, Enrico Garaci
Cystic fibrosis (CF) is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) that compromise its chloride channel activity. The most common mutation, p.Phe508del, results in the production of a misfolded CFTR protein, which has residual channel activity but is prematurely degraded. Because of the inherent complexity of the pathogenetic mechanisms involved in CF, which include impaired chloride permeability and persistent lung inflammation, a multidrug approach is required for efficacious CF therapy...
April 10, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28394329/a-stemness-related-zeb1-msrb3-axis-governs-cellular-pliancy-and-breast-cancer-genome-stability
#10
Anne-Pierre Morel, Christophe Ginestier, Roxane M Pommier, Olivier Cabaud, Emmanuelle Ruiz, Julien Wicinski, Mojgan Devouassoux-Shisheboran, Valérie Combaret, Pascal Finetti, Christelle Chassot, Christiane Pinatel, Frédérique Fauvet, Pierre Saintigny, Emilie Thomas, Caroline Moyret-Lalle, Joël Lachuer, Emmanuelle Despras, Jean-Luc Jauffret, François Bertucci, Jérôme Guitton, Anne Wierinckx, Qing Wang, Nina Radosevic-Robin, Frédérique Penault-Llorca, David G Cox, Frédéric Hollande, Stéphane Ansieau, Julie Caramel, Daniel Birnbaum, Arnaud M Vigneron, Agnès Tissier, Emmanuelle Charafe-Jauffret, Alain Puisieux
Chromosomal instability (CIN), a feature of most adult neoplasms from their early stages onward, is a driver of tumorigenesis. However, several malignancy subtypes, including some triple-negative breast cancers, display a paucity of genomic aberrations, thus suggesting that tumor development may occur in the absence of CIN. Here we show that the differentiation status of normal human mammary epithelial cells dictates cell behavior after an oncogenic event and predetermines the genetic routes toward malignancy...
April 10, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28394328/a-live-attenuated-zika-virus-vaccine-candidate-induces-sterilizing-immunity-in-mouse-models
#11
Chao Shan, Antonio E Muruato, Bruno T D Nunes, Huanle Luo, Xuping Xie, Daniele B A Medeiros, Maki Wakamiya, Robert B Tesh, Alan D Barrett, Tian Wang, Scott C Weaver, Pedro F C Vasconcelos, Shannan L Rossi, Pei-Yong Shi
Zika virus (ZIKV) infection of pregnant women can cause a wide range of congenital abnormalities, including microcephaly, in the infant, a condition now collectively known as congenital ZIKV syndrome. A vaccine to prevent or significantly attenuate viremia in pregnant women who are residents of or travelers to epidemic or endemic regions is needed to avert congenital ZIKV syndrome, and might also help to suppress epidemic transmission. Here we report on a live-attenuated vaccine candidate that contains a 10-nucleotide deletion in the 3' untranslated region of the ZIKV genome (10-del ZIKV)...
April 10, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28368383/oncostatin-m-drives-intestinal-inflammation-and-predicts-response-to-tumor-necrosis-factor-neutralizing-therapy-in-patients-with-inflammatory-bowel-disease
#12
Nathaniel R West, Ahmed N Hegazy, Benjamin M J Owens, Samuel J Bullers, Bryan Linggi, Sofia Buonocore, Margherita Coccia, Dieter Görtz, Sébastien This, Krista Stockenhuber, Johanna Pott, Matthias Friedrich, Grigory Ryzhakov, Frédéric Baribaud, Carrie Brodmerkel, Constanze Cieluch, Nahid Rahman, Gerhard Müller-Newen, Raymond J Owens, Anja A Kühl, Kevin J Maloy, Scott E Plevy, Satish Keshav, Simon P L Travis, Fiona Powrie
Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are complex chronic inflammatory conditions of the gastrointestinal tract that are driven by perturbed cytokine pathways. Anti-tumor necrosis factor-α (TNF) antibodies are mainstay therapies for IBD. However, up to 40% of patients are nonresponsive to anti-TNF agents, which makes the identification of alternative therapeutic targets a priority. Here we show that, relative to healthy controls, inflamed intestinal tissues from patients with IBD express high amounts of the cytokine oncostatin M (OSM) and its receptor (OSMR), which correlate closely with histopathological disease severity...
April 3, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28346412/vista-is-an-inhibitory-immune-checkpoint-that-is-increased-after-ipilimumab-therapy-in-patients-with-prostate-cancer
#13
Jianjun Gao, John F Ward, Curtis A Pettaway, Lewis Z Shi, Sumit K Subudhi, Luis M Vence, Hao Zhao, Jianfeng Chen, Hong Chen, Eleni Efstathiou, Patricia Troncoso, James P Allison, Christopher J Logothetis, Ignacio I Wistuba, Manuel A Sepulveda, Jingjing Sun, Jennifer Wargo, Jorge Blando, Padmanee Sharma
To date, anti-CTLA-4 (ipilimumab) or anti-PD-1 (nivolumab) monotherapy has not been demonstrated to be of substantial clinical benefit in patients with prostate cancer. To identify additional immune-inhibitory pathways in the prostate-tumor microenvironment, we evaluated untreated and ipilimumab-treated tumors from patients in a presurgical clinical trial. Levels of the PD-L1 and VISTA inhibitory molecules increased on independent subsets of macrophages in treated tumors. Our data suggest that VISTA represents another compensatory inhibitory pathway in prostate tumors after ipilimumab therapy...
March 27, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28346411/the-cold-induced-lipokine-12-13-dihome-promotes-fatty-acid-transport-into-brown-adipose-tissue
#14
Matthew D Lynes, Luiz O Leiria, Morten Lundh, Alexander Bartelt, Farnaz Shamsi, Tian Lian Huang, Hirokazu Takahashi, Michael F Hirshman, Christian Schlein, Alexandra Lee, Lisa A Baer, Francis J May, Fei Gao, Niven R Narain, Emily Y Chen, Michael A Kiebish, Aaron M Cypess, Matthias Blüher, Laurie J Goodyear, Gökhan S Hotamisligil, Kristin I Stanford, Yu-Hua Tseng
Brown adipose tissue (BAT) and beige adipose tissue combust fuels for heat production in adult humans, and so constitute an appealing target for the treatment of metabolic disorders such as obesity, diabetes and hyperlipidemia. Cold exposure can enhance energy expenditure by activating BAT, and it has been shown to improve nutrient metabolism. These therapies, however, are time consuming and uncomfortable, demonstrating the need for pharmacological interventions. Recently, lipids have been identified that are released from tissues and act locally or systemically to promote insulin sensitivity and glucose tolerance; as a class, these lipids are referred to as 'lipokines'...
March 27, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28263312/diagnosis-of-zika-virus-infection-on-a-nanotechnology-platform
#15
Bo Zhang, Benjamin A Pinsky, Jeyarama S Ananta, Su Zhao, Shylaja Arulkumar, Hao Wan, Malaya K Sahoo, Janaki Abeynayake, Jesse J Waggoner, Clay Hopes, Meijie Tang, Hongjie Dai
We developed a multiplexed assay on a plasmonic-gold platform for measuring IgG and IgA antibodies and IgG avidity against both Zika virus (ZIKV) and dengue virus (DENV) infections. In contrast to IgM cross-reactivity, IgG and IgA antibodies against ZIKV nonstructural protein 1 (NS1) antigen were specific to ZIKV infection, and IgG avidity revealed recent ZIKV infection and past DENV-2 infection in patients in dengue-endemic regions. This assay could enable specific diagnosis of ZIKV infection over other flaviviral infections...
March 6, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28388614/correction
#16
(no author information available yet)
No abstract text is available yet for this article.
April 7, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28388613/erratum-reply-to-neutrophils-are-not-required-for-resolution-of-acute-gouty-arthritis-in-mice
#17
Christiane Reinwald, Christine Schauer, Janka Zsófia Csepregi, Deborah Kienhöfer, Daniela Weidner, Marie Malissen, Attila Mocsai, Georg Schett, Martin Herrmann, Markus Hoffmann
No abstract text is available yet for this article.
April 7, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28388612/the-drug-repurposing-hub-a-next-generation-drug-library-and-information-resource
#18
Steven M Corsello, Joshua A Bittker, Zihan Liu, Joshua Gould, Patrick McCarren, Jodi E Hirschman, Stephen E Johnston, Anita Vrcic, Bang Wong, Mariya Khan, Jacob Asiedu, Rajiv Narayan, Christopher C Mader, Aravind Subramanian, Todd R Golub
No abstract text is available yet for this article.
April 7, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28388611/science-over-speed
#19
EDITORIAL
(no author information available yet)
No abstract text is available yet for this article.
April 7, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28388610/untangling-the-role-of-mutant-histone-h3-in-diffuse-intrinsic-pontine-glioma
#20
Caretha L Creasy
No abstract text is available yet for this article.
April 7, 2017: Nature Medicine
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