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Christian Ostalecki, Sebastian Wittki, Jung-Hyun Lee, Miriam M Geist, Nadine Tibroni, Thomas Harrer, Gerold Schuler, Oliver T Fackler, Andreas S Baur
Tumor necrosis factor (TNF) is a key cytokine in HIV replication and pathogenesis. For reasons that are not entirely clear, the cytokine remains upregulated despite anti-retroviral therapy (ART). Here we demonstrate that HIV Nef induces an alternative TNF secretion mechanism that remains active in chronic infection. Ingestion of Nef-containing plasma extracellular vesicles (pEV) from ART patients by primary immune cells, but also Nef expression, induced intracellular proTNF cleavage and secretion of vesicular TNF endosomes...
October 19, 2016: EBioMedicine
Stacey L Kolar, George Y Liu
No abstract text is available yet for this article.
October 17, 2016: EBioMedicine
Ana M Maestre, Ana Fernandez-Sesma
No abstract text is available yet for this article.
October 17, 2016: EBioMedicine
Liqing Wang, Suresh Kumar, Satinder Dahiya, Feng Wang, Jian Wu, Kheng Newick, Rongxiang Han, Arabinda Samanta, Ulf H Beier, Tatiana Akimova, Tricia R Bhatti, Benjamin Nicholson, Mathew P Kodrasov, Saket Agarwal, David E Sterner, Wei Gu, Joseph Weinstock, Tauseef R Butt, Steven M Albelda, Wayne W Hancock
Foxp3+ T-regulatory (Treg) cells are known to suppress protective host immune responses to a wide variety of solid tumors, but their therapeutic targeting is largely restricted to their transient depletion or "secondary" modulation, e.g. using anti-CTLA-4 monoclonal antibody. Our ongoing studies of the post-translational modifications that regulate Foxp3 demonstrated that the histone/protein acetyltransferase, Tip60, plays a dominant role in promoting acetylation, dimerization and function in Treg cells. We now show that the ubiquitin-specific protease, Usp7, controls Treg function largely by stabilizing the expression and promoting the multimerization of Tip60 and Foxp3...
October 15, 2016: EBioMedicine
Lisa M James, Brian E Engdahl, Arthur C Leuthold, Apostolos P Georgopoulos
BACKGROUND: We recently reported that six alleles from class II genes of the Human Leukocyte Antigen (HLA) confer protection from Gulf War Illness (GWI) (Georgopoulos et al., 2015). The most significant effect is exerted on Neurological-Cognitive-Mood (NCM), Pain, and Fatigue symptoms, such that higher number of copies of the protective alleles are associated with lower symptom severity. Here we tested the hypothesis that this effect is exerted by modulating the strength of neural synchronicity...
October 14, 2016: EBioMedicine
Santiago Moreno, Sergio Serrano-Villar
No abstract text is available yet for this article.
October 13, 2016: EBioMedicine
Richard B Kennedy
No abstract text is available yet for this article.
October 13, 2016: EBioMedicine
Colin M Venner, Immaculate Nankya, Fred Kyeyune, Korey Demers, Cynthia Kwok, Pai-Lien Chen, Sandra Rwambuya, Marshall Munjoma, Tsungai Chipato, Josaphat Byamugisha, Barbara Van Der Pol, Peter Mugyenyi, Robert A Salata, Charles S Morrison, Eric J Arts
INTRODUCTION: Long-term natural history cohorts of HIV-1 in the absence of treatment provide the best measure of virulence by different viral subtypes. METHODS: Newly HIV infected Ugandan and Zimbabwean women (N=303) were recruited and monitored for clinical, social, behavioral, immunological and viral parameters for 3 to 9.5years. RESULTS: Ugandan and Zimbabwean women infected with HIV-1 subtype C had 2.5-fold slower rates of CD4 T-cell declines and higher frequencies of long-term non-progression than those infected with subtype A or D (GEE model, P<0...
October 12, 2016: EBioMedicine
Deepta Bhattacharya, Rachel Wong
No abstract text is available yet for this article.
October 11, 2016: EBioMedicine
Nicholas T Funderburg, Grace A McComsey, Manjusha Kulkarni, Tammy Bannerman, Jessica Mantini, Bernadette Thornton, Hui C Liu, Yafeng Zhang, Qinghua Song, Liang Fang, Jason Dinoso, Andrew Cheng, Scott McCallister, Marshall W Fordyce, Moupali Das
BACKGROUND: Initiation of antiretroviral therapy (ART) and subsequent virologic suppression reduces immune activation and systemic inflammation. METHODS: We examined longitudinal changes in biomarkers of monocyte activation (sCD14, sCD163), and systemic (IL-6, hsCRP, sTNFR-I and D-dimer) and vascular (Lp-PLA2) inflammation in a subgroup (N=100 per arm) of participants enrolled in a randomized, placebo-controlled trial comparing elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF; TAF) to E/C/F/tenofovir disoproxil fumarate (E/C/F/TDF; TDF) in treatment-naïve adults...
October 11, 2016: EBioMedicine
Brett A Morris, Brian Burkel, Suzanne M Ponik, Jing Fan, John S Condeelis, Julio A Aguire-Ghiso, James Castracane, John M Denu, Patricia J Keely
Increased breast density attributed to collagen I deposition is associated with a 4-6 fold increased risk of developing breast cancer. Here, we assessed cellular metabolic reprogramming of mammary carcinoma cells in response to increased collagen matrix density using an in vitro 3D model. Our initial observations demonstrated changes in functional metabolism in both normal mammary epithelial cells and mammary carcinoma cells in response to changes in matrix density. Further, mammary carcinoma cells grown in high density collagen matrices displayed decreased oxygen consumption and glucose metabolism via the tricarboxylic acid (TCA) cycle compared to cells cultured in low density matrices...
October 8, 2016: EBioMedicine
Annie Elong Ngono, Hui-Wen Chen, William W Tang, Yunichel Joo, Kevin King, Daniela Weiskopf, John Sidney, Alessandro Sette, Sujan Shresta
Infection with one of the four dengue virus serotypes (DENV1-4) presumably leads to lifelong immunity against the infecting serotype but not against heterotypic reinfection, resulting in a greater risk of developing Dengue Hemorrhagic Fever/Dengue Shock Syndrome (DHF/DSS) during secondary infection. Both antibodies and T cell responses have been implicated in DHF/DSS pathogenesis. According to the T cell-based hypothesis termed "original antigenic sin," secondary DENV infection is dominated by non-protective, cross-reactive T cells that elicit an aberrant immune response...
October 7, 2016: EBioMedicine
Naoya Matsunaga, Eriko Ikeda, Keisuke Kakimoto, Miyako Watanabe, Naoya Shindo, Akito Tsuruta, Hisako Ikeyama, Kengo Hamamura, Kazuhiro Higashi, Tomohiro Yamashita, Hideaki Kondo, Yuya Yoshida, Masaki Matsuda, Takashi Ogino, Kazutaka Tokushige, Kazufumi Itcho, Yoko Furuichi, Takaharu Nakao, Kaori Yasuda, Atsushi Doi, Toshiaki Amamoto, Hironori Aramaki, Makoto Tsuda, Kazuhide Inoue, Akio Ojida, Satoru Koyanagi, Shigehiro Ohdo
Chronic kidney disease (CKD) is a global health problem, and novel therapies to treat CKD are urgently needed. Here, we show that inhibition of G0/G1 switch 2 (G0s2) ameliorates renal inflammation in a mouse model of CKD. Renal expression of chemokine (C-C motif) ligand 2 (Ccl2) was increased in response to p65 activation in the kidneys of wild-type 5/6 nephrectomy (5/6Nx) mice. Moreover, 5/6Nx Clk/Clk mice, which carry homozygous mutations in the gene encoding circadian locomotor output cycles kaput (CLOCK), did not exhibit aggravation of apoptosis or induction of F4/80-positive cells...
October 6, 2016: EBioMedicine
Andreas Otte, Federico Turkheimer, Ivana Rosenzweig
No abstract text is available yet for this article.
October 6, 2016: EBioMedicine
Jose A Cancelas, Neeta Rugg
No abstract text is available yet for this article.
October 5, 2016: EBioMedicine
Paul A Tooney
No abstract text is available yet for this article.
October 5, 2016: EBioMedicine
Florian S Schoenhoff
No abstract text is available yet for this article.
October 5, 2016: EBioMedicine
Georgios Daniil, Fabio L Fernandes-Rosa, Jean Chemin, Iulia Blesneac, Jacques Beltrand, Michel Polak, Xavier Jeunemaitre, Sheerazed Boulkroun, Laurence Amar, Tim M Strom, Philippe Lory, Maria-Christina Zennaro
Primary aldosteronism (PA) is the most common form of secondary hypertension. Mutations in KCNJ5, ATP1A1, ATP2B3 and CACNA1D are found in aldosterone producing adenoma (APA) and familial hyperaldosteronism (FH). A recurrent mutation in CACNA1H (coding for Cav3.2) was identified in a familial form of early onset PA. Here we performed whole exome sequencing (WES) in patients with different types of PA to identify new susceptibility genes. Four different heterozygous germline CACNA1H variants were identified. A de novo Cav3...
October 4, 2016: EBioMedicine
Colin Thomas, Yingbiao Ji, Niraj Lodhi, Elena Kotova, Aaron Dan Pinnola, Konstantin Golovine, Peter Makhov, Kate Pechenkina, Vladimir Kolenko, Alexei V Tulin
The clinical potential of PARP-1 inhibitors has been recognized >10years ago, prompting intensive research on their pharmacological application in several branches of medicine, particularly in oncology. However, natural or acquired resistance of tumors to known PARP-1 inhibitors poses a serious problem for their clinical implementation. Present study aims to reignite clinical interest to PARP-1 inhibitors by introducing a new method of identifying highly potent inhibitors and presenting the largest known collection of structurally diverse inhibitors...
October 4, 2016: EBioMedicine
Sean E Thatcher
No abstract text is available yet for this article.
October 3, 2016: EBioMedicine
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