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Nature Medicine

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https://www.readbyqxmd.com/read/28628112/gut-microbiome-and-serum-metabolome-alterations-in-obesity-and-after-weight-loss-intervention
#1
Ruixin Liu, Jie Hong, Xiaoqiang Xu, Qiang Feng, Dongya Zhang, Yanyun Gu, Juan Shi, Shaoqian Zhao, Wen Liu, Xiaokai Wang, Huihua Xia, Zhipeng Liu, Bin Cui, Peiwen Liang, Liuqing Xi, Jiabin Jin, Xiayang Ying, Xiaolin Wang, Xinjie Zhao, Wanyu Li, Huijue Jia, Zhou Lan, Fengyu Li, Rui Wang, Yingkai Sun, Minglan Yang, Yuxin Shen, Zhuye Jie, Junhua Li, Xiaomin Chen, Huanzi Zhong, Hailiang Xie, Yifei Zhang, Weiqiong Gu, Xiaxing Deng, Baiyong Shen, Xun Xu, Huanming Yang, Guowang Xu, Yufang Bi, Shenghan Lai, Jian Wang, Lu Qi, Lise Madsen, Jiqiu Wang, Guang Ning, Karsten Kristiansen, Weiqing Wang
Emerging evidence has linked the gut microbiome to human obesity. We performed a metagenome-wide association study and serum metabolomics profiling in a cohort of lean and obese, young, Chinese individuals. We identified obesity-associated gut microbial species linked to changes in circulating metabolites. The abundance of Bacteroides thetaiotaomicron, a glutamate-fermenting commensal, was markedly decreased in obese individuals and was inversely correlated with serum glutamate concentration. Consistently, gavage with B...
June 19, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28628111/interaction-of-reactive-astrocytes-with-type-i-collagen-induces-astrocytic-scar-formation-through-the-integrin-n-cadherin-pathway-after-spinal-cord-injury
#2
Masamitsu Hara, Kazu Kobayakawa, Yasuyuki Ohkawa, Hiromi Kumamaru, Kazuya Yokota, Takeyuki Saito, Ken Kijima, Shingo Yoshizaki, Katsumi Harimaya, Yasuharu Nakashima, Seiji Okada
Central nervous system (CNS) injury transforms naive astrocytes into reactive astrocytes, which eventually become scar-forming astrocytes that can impair axonal regeneration and functional recovery. This sequential phenotypic change, known as reactive astrogliosis, has long been considered unidirectional and irreversible. However, we report here that reactive astrocytes isolated from injured spinal cord reverted in retrograde to naive astrocytes when transplanted into a naive spinal cord, whereas they formed astrocytic scars when transplanted into injured spinal cord, indicating the environment-dependent plasticity of reactive astrogliosis...
June 19, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28628110/colonic-organoids-derived-from-human-induced-pluripotent-stem-cells-for-modeling-colorectal-cancer-and-drug-testing
#3
Miguel Crespo, Eduardo Vilar, Su-Yi Tsai, Kyle Chang, Sadaf Amin, Tara Srinivasan, Tuo Zhang, Nina H Pipalia, Huanhuan Joyce Chen, Mavee Witherspoon, Miriam Gordillo, Jenny Zhaoying Xiang, Frederick R Maxfield, Steven Lipkin, Todd Evans, Shuibing Chen
With the goal of modeling human disease of the large intestine, we sought to develop an effective protocol for deriving colonic organoids (COs) from differentiated human embryonic stem cells (hESCs) or induced pluripotent stem cells (iPSCs). Extensive gene and immunohistochemical profiling confirmed that the derived COs represent colon rather than small intestine, containing stem cells, transit-amplifying cells, and the expected spectrum of differentiated cells, including goblet and endocrine cells. We applied this strategy to iPSCs derived from patients with familial adenomatous polyposis (FAP-iPSCs) harboring germline mutations in the WNT-signaling-pathway-regulator gene encoding APC, and we generated COs that exhibit enhanced WNT activity and increased epithelial cell proliferation, which we used as a platform for drug testing...
June 19, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28604704/thermoneutral-housing-exacerbates-nonalcoholic-fatty-liver-disease-in-mice-and-allows-for-sex-independent-disease-modeling
#4
Daniel A Giles, Maria E Moreno-Fernandez, Traci E Stankiewicz, Simon Graspeuntner, Monica Cappelletti, David Wu, Rajib Mukherjee, Calvin C Chan, Matthew J Lawson, Jared Klarquist, Annika Sünderhauf, Samir Softic, C Ronald Kahn, Kerstin Stemmer, Yoichiro Iwakura, Bruce J Aronow, Rebekah Karns, Kris A Steinbrecher, Christopher L Karp, Rachel Sheridan, Shiva K Shanmukhappa, Damien Reynaud, David B Haslam, Christian Sina, Jan Rupp, Simon P Hogan, Senad Divanovic
Nonalcoholic fatty liver disease (NAFLD), a common prelude to cirrhosis and hepatocellular carcinoma, is the most common chronic liver disease worldwide. Defining the molecular mechanisms underlying the pathogenesis of NAFLD has been hampered by a lack of animal models that closely recapitulate the severe end of the disease spectrum in humans, including bridging hepatic fibrosis. Here we demonstrate that a novel experimental model employing thermoneutral housing, as opposed to standard housing, resulted in lower stress-driven production of corticosterone, augmented mouse proinflammatory immune responses and markedly exacerbated high-fat diet (HFD)-induced NAFLD pathogenesis...
June 12, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28604703/cold-induced-conversion-of-cholesterol-to-bile-acids-in-mice-shapes-the-gut-microbiome-and-promotes-adaptive-thermogenesis
#5
Anna Worthmann, Clara John, Malte C Rühlemann, Miriam Baguhl, Femke-Anouska Heinsen, Nicola Schaltenberg, Markus Heine, Christian Schlein, Ioannis Evangelakos, Chieko Mineo, Markus Fischer, Maura Dandri, Claus Kremoser, Ludger Scheja, Andre Franke, Philip W Shaul, Joerg Heeren
Adaptive thermogenesis is an energy-demanding process that is mediated by cold-activated beige and brown adipocytes, and it entails increased uptake of carbohydrates, as well as lipoprotein-derived triglycerides and cholesterol, into these thermogenic cells. Here we report that cold exposure in mice triggers a metabolic program that orchestrates lipoprotein processing in brown adipose tissue (BAT) and hepatic conversion of cholesterol to bile acids via the alternative synthesis pathway. This process is dependent on hepatic induction of cytochrome P450, family 7, subfamily b, polypeptide 1 (CYP7B1) and results in increased plasma levels, as well as fecal excretion, of bile acids that is accompanied by distinct changes in gut microbiota and increased heat production...
June 12, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28604702/isdot-in-situ-decellularization-of-tissues-for-high-resolution-imaging-and-proteomic-analysis-of-native-extracellular-matrix
#6
Alejandro E Mayorca-Guiliani, Chris D Madsen, Thomas R Cox, Edward R Horton, Freja A Venning, Janine T Erler
The extracellular matrix (ECM) is a master regulator of cellular phenotype and behavior. It has a crucial role in both normal tissue homeostasis and disease pathology. Here we present a fast and efficient approach to enhance the study of ECM composition and structure. Termed in situ decellularization of tissues (ISDoT), it allows whole organs to be decellularized, leaving native ECM architecture intact. These three-dimensional decellularized tissues can be studied using high-resolution fluorescence and second harmonic imaging, and can be used for quantitative proteomic interrogation of the ECM...
June 12, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28604701/elimination-of-large-tumors-in-mice-by-mrna-encoded-bispecific-antibodies
#7
Christiane R Stadler, Hayat Bähr-Mahmud, Leyla Celik, Bernhard Hebich, Alexandra S Roth, René P Roth, Katalin Karikó, Özlem Türeci, Ugur Sahin
The potential of bispecific T cell-engaging antibodies is hindered by manufacturing challenges and short serum half-life. We circumvented these limitations by treating mice with in vitro-transcribed pharmacologically optimized, nucleoside-modified mRNA encoding the antibody. We achieved sustained endogenous synthesis of the antibody, which eliminated advanced tumors as effectively as the corresponding purified bispecific antibody. Because manufacturing of pharmaceutical mRNA is fast, this approach could accelerate the clinical development of novel bispecific antibodies...
June 12, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28553933/novel-assay-reveals-a-large-inducible-replication-competent-hiv-1-reservoir-in-resting-cd4-t-cells
#8
Anwesha Sanyal, Robbie B Mailliard, Charles R Rinaldo, Deena Ratner, Ming Ding, Yue Chen, Jennifer M Zerbato, Nicholas S Giacobbi, Narasimhan J Venkatachari, Bruce K Patterson, Amanda Chargin, Nicolas Sluis-Cremer, Phalguni Gupta
Although antiretroviral therapy can suppress HIV-1 infection to undetectable levels of plasma viremia, integrated latent HIV-1 genomes that encode replication-competent virus persist in resting CD4(+) T cells. This latent HIV-1 reservoir represents a major barrier to a cure. Currently, there are substantial efforts to identify therapeutic approaches that will eliminate or reduce the size of this latent HIV-1 reservoir. In this regard, a sensitive assay that can accurately and rapidly quantify inducible, replication-competent latent HIV-1 from resting CD4(+) T cells is essential for HIV-1 eradication studies...
May 29, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28553932/combined-mutation-in-vhl-trp53-and-rb1-causes-clear-cell-renal-cell-carcinoma-in-mice
#9
Sabine Harlander, Désirée Schönenberger, Nora C Toussaint, Michael Prummer, Antonella Catalano, Laura Brandt, Holger Moch, Peter J Wild, Ian J Frew
Clear cell renal cell carcinomas (ccRCCs) frequently exhibit inactivation of the von Hippel-Lindau tumor-suppressor gene, VHL, and often harbor multiple copy-number alterations in genes that regulate cell cycle progression. We show here that modeling these genetic alterations by combined deletion of Vhl, Trp53 and Rb1 specifically in renal epithelial cells in mice caused ccRCC. These tumors arose from proximal tubule epithelial cells and shared molecular markers and mRNA expression profiles with human ccRCC...
May 29, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28530702/metformin-alters-the-gut-microbiome-of-individuals-with-treatment-naive-type-2-diabetes-contributing-to-the-therapeutic-effects-of-the-drug
#10
Hao Wu, Eduardo Esteve, Valentina Tremaroli, Muhammad Tanweer Khan, Robert Caesar, Louise Mannerås-Holm, Marcus Ståhlman, Lisa M Olsson, Matteo Serino, Mercè Planas-Fèlix, Gemma Xifra, Josep M Mercader, David Torrents, Rémy Burcelin, Wifredo Ricart, Rosie Perkins, José Manuel Fernàndez-Real, Fredrik Bäckhed
Metformin is widely used in the treatment of type 2 diabetes (T2D), but its mechanism of action is poorly defined. Recent evidence implicates the gut microbiota as a site of metformin action. In a double-blind study, we randomized individuals with treatment-naive T2D to placebo or metformin for 4 months and showed that metformin had strong effects on the gut microbiome. These results were verified in a subset of the placebo group that switched to metformin 6 months after the start of the trial. Transfer of fecal samples (obtained before and 4 months after treatment) from metformin-treated donors to germ-free mice showed that glucose tolerance was improved in mice that received metformin-altered microbiota...
May 22, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28586342/a-role-for-neutrophils-in-asthma-exacerbations
#11
William W Busse
No abstract text is available yet for this article.
June 6, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28586341/erratum-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
No abstract text is available yet for this article.
June 6, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28586340/patrolling-monocytes-sense-peripheral-infection-and-induce-cytokine-mediated-neuronal-dysfunction
#13
Josef Priller, Chotima Böttcher
No abstract text is available yet for this article.
June 6, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28586339/erratum-blocking-microglial-pannexin-1-channels-alleviates-morphine-withdrawal-in-rodents
#14
Nicole E Burma, Robert P Bonin, Heather Leduc-Pessah, Corey Baimel, Zoe F Cairncross, Michael Mousseau, Jhenkruthi Vijaya Shankara, Patrick L Stemkowski, Dinara Baimoukhametova, Jaideep S Bains, Michael C Antle, Gerald W Zamponi, Catherine M Cahill, Stephanie L Borgland, Yves DeKoninck, Tuan Trang
No abstract text is available yet for this article.
June 6, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28586338/understanding-cancer-from-the-stem-cells-up
#15
Christopher A Eide, Brian J Druker
No abstract text is available yet for this article.
June 6, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28586337/corrigendum-samhd1-is-a-biomarker-for-cytarabine-response-and-a-therapeutic-target-in-acute-myeloid-leukemia
#16
Constanze Schneider, Thomas Oellerich, Hanna-Mari Baldauf, Sarah-Marie Schwarz, Dominique Thomas, Robert Flick, Hanibal Bohnenberger, Lars Kaderali, Lena Stegmann, Anjali Cremer, Margarethe Martin, Julian Lohmeyer, Martin Michaelis, Veit Hornung, Christoph Schliemann, Wolfgang E Berdel, Wolfgang Hartmann, Eva Wardelmann, Federico Comoglio, Martin-Leo Hansmann, Alexander F Yakunin, Gerd Geisslinger, Philipp Ströbel, Nerea Ferreirós, Hubert Serve, Oliver T Keppler, Jindrich Cinatl
No abstract text is available yet for this article.
June 6, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28586336/erratum-pim1-kinase-regulates-cell-death-tumor-growth-and-chemotherapy-response-in-triple-negative-breast-cancer
#17
Fara Brasó-Maristany, Simone Filosto, Steven Catchpole, Rebecca Marlow, Jelmar Quist, Erika Francesch-Domenech, Darren A Plumb, Leila Zakka, Patrycja Gazinska, Gianmaria Liccardi, Pascal Meier, Albert Gris-Oliver, Maggie Chon U Cheang, Anna Perdrix-Rosell, Manar Shafat, Elodie Noël, Nirmesh Patel, Kristen McEachern, Maurizio Scaltriti, Pau Castel, Farzana Noor, Richard Buus, Sumi Mathew, Johnathan Watkins, Violeta Serra, Pierfrancesco Marra, Anita Grigoriadis, Andrew N Tutt
No abstract text is available yet for this article.
June 6, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28586335/biology-and-evolution-of-poorly-differentiated-neuroendocrine-tumors
#18
David S Rickman, Himisha Beltran, Francesca Demichelis, Mark A Rubin
Neuroendocrine (NE) cancers are a diverse group of neoplasms typically diagnosed and treated on the basis of their site of origin. This Perspective focuses on advances in our understanding of the tumorigenesis and treatment of poorly differentiated neuroendocrine tumors. Recent evidence from sequencing indicates that, although neuroendocrine tumors can arise de novo, they can also develop as a result of lineage plasticity in response to pressure from targeted therapies. We discuss the shared genomic alterations of these tumors independently of their site of origin, and we explore potential therapeutic strategies on the basis of recent biological findings...
June 6, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28586334/biased-for-benefit-stimulating-the-world-s-most-popular-drug-targets-with-more-nuance
#19
Dyani Lewis
No abstract text is available yet for this article.
June 6, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28586333/the-cannabis-paradox-when-age-matters
#20
Andrés Ozaita, Ester Aso
No abstract text is available yet for this article.
June 6, 2017: Nature Medicine
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