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https://www.readbyqxmd.com/read/28431010/clinical-trial-of-the-anti-pd-l1-antibody-bms-936559-in-hiv-1-infected-participants-on-suppressive-antiretroviral-therapy
#1
Cynthia L Gay, Ronald J Bosch, Justin Ritz, Jason M Hataye, Evgenia Aga, Randall L Tressler, Stephen W Mason, Carey K Hwang, Dennis M Grasela, Neelanjana Ray, Josh C Cyktor, John M Coffin, Edward P Acosta, Richard A Koup, John W Mellors, Joseph J Eron
Background.: Reversing immune exhaustion with an anti-PD-L1 antibody may improve HIV-1-specific immunity and increase clearance of HIV-1 expressing cells. Methods.: Phase I, randomized, double-blind, placebo-controlled dose-escalating study of BMS-936559including HIV-1-infected adults ≥18 to ≤70 years on suppressive antiretroviral therapy with CD4+ counts ≥350 cells/μL and detectable plasma HIV-1 RNA by single copy assay. Data on single infusions of BMS-936559 (0...
April 18, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28426371/optimization-of-preculture-conditions-to-maximize-the-in-vivo-performance-of-cell-seeded-engineered-intervertebral-discs
#2
John T Martin, Sarah E Gullbrand, Bhavana Mohanraj, Beth G Ashinsky, Dong Hwa Kim, Kensuke Ikuta, Dawn M Elliott, Lachlan J Smith, Robert L Mauck, Harvey E Smith
The development of engineered tissues has progressed over the past 20 years from in vitro characterization to in vivo implementation. For musculoskeletal tissue engineering in particular, the emphasis of many of these studies was to select conditions that maximized functional and compositional gains in vitro. However, the transition from the favorable in vitro culture environment to a less favorable in vivo environment has proven difficult, and, in many cases, engineered tissues do not retain their preimplantation phenotype after even short periods in vivo...
April 19, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28425567/effect-of-ngf-from-venom-of-chinese-cobra-naja-atra-on-chondrocytes-proliferation-and-metabolism-in-vitro
#3
Jiachang Tan, Zhenhui Lu, Zhikang Miao, Danqing Lei, Li Zheng, Jinmin Zhao
Autologous chondrocyte implantation (ACI) is promising strategy for cartilage repair. However, chondrocyte phenotype is easily lost when expanded in vitro which defined as "dedifferentiation". To ensure successful therapy, an effective pro-chondrogenic agent is necessary to overcome the obstacle of limited cell numbers in the restoration process, and dedifferentiation is a prerequisite. In the present study, we investigated the chondro-protective effect of NGF from Chinese cobra venom on human chondrocytes by determination of its specific effect on cell viability, proliferation, morphology, GAG production and cartilage specific gene expression...
April 20, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28424334/glycosaminoglycan-based-hydrogels-capture-inflammatory-chemokines-and-rescue-defective-wound-healing-in-mice
#4
Nadine Lohmann, Lucas Schirmer, Passant Atallah, Elke Wandel, Ruben A Ferrer, Carsten Werner, Jan C Simon, Sandra Franz, Uwe Freudenberg
Excessive production of inflammatory chemokines can cause chronic inflammation and thus impair cutaneous wound healing. Capturing chemokine signals using wound dressing materials may offer powerful new treatment modalities for chronic wounds. Here, a modular hydrogel based on end-functionalized star-shaped polyethylene glycol (starPEG) and derivatives of the glycosaminoglycan (GAG) heparin was customized for maximal chemokine sequestration. The material is shown to effectively scavenge the inflammatory chemokines MCP-1 (monocyte chemoattractant protein-1), IL-8 (interleukin-8), and MIP-1α (macrophage inflammatory protein-1α) and MIP-1β (macrophage inflammatory protein-1β) in wound fluids from patients suffering from chronic venous leg ulcers and to reduce the migratory activity of human monocytes and polymorphonuclear neutrophils...
April 19, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28424286/subtype-specific-differences-in-gag-protease-driven-replication-capacity-are-consistent-with-inter-subtype-differences-in-hiv-1-disease-progression
#5
Marion W Kiguoya, Jaclyn K Mann, Denis Chopera, Kamini Gounder, Guinevere Q Lee, Peter W Hunt, Jeffrey N Martin, T Blake Ball, Joshua Kimani, Zabrina L Brumme, Mark A Brockman, Thumbi Ndung'u
There are marked differences in the spread and prevalence of HIV-1 subtypes worldwide, and differences in clinical progression have been reported. However, the biological reasons underlying these differences are unknown. Gag-protease is essential for HIV-1 replication and Gag-protease-driven replication capacity has previously been correlated with disease progression. We show that Gag-protease replication capacity correlates significantly with that of whole isolates (r=0.51; p=0.04), indicating that Gag-protease is a significant contributor to viral replication capacity...
April 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28424281/distinct-roles-of-vaccinia-virus-nf-kb-inhibitor-proteins-a52-b15-and-k7-in-the-immune-response
#6
Mauro Di Pilato, Ernesto Mejías-Pérez, Carlos Oscar S Sorzano, Mariano Esteban
Poxviruses use a complex strategy to escape immune control, by expressing immunomodulatory proteins that could limit their use as vaccine vectors. To test the role of poxvirus NF-κB pathway inhibitors A52, B15 and K7 in immunity, we deleted their genes in a NYVAC vaccinia virus strain that expresses HIV-1 clade C antigens. After infection of mice, ablation of A52R, B15R and K7R increased dendritic cell, natural killer cell and neutrophil migration as well as chemokine/cytokine expression. Revertant viruses for these genes confirmed their role in inhibiting the innate immune system...
April 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28422791/intrastructural-help-improving-the-hiv-1-envelope-antibody-response-induced-by-virus-like-particle-vaccines
#7
Vladimir Temchura, Klaus Überla
PURPOSE OF REVIEW: The importance of IgG Fc-effector functions for the efficacy of HIV vaccines is increasingly recognized. Although different types of vaccines were shown to induce antibodies with different Fc-activities, there is no clear strategy how to raise antibody responses with a desired pattern of Fc-effector functions. Given the central role of T-helper cells in regulating the germinal center reaction and the differentiation of B cells in an antigen-specific manner, the review will discuss whether T-helper cells directed against non-HIV envelope (Env) antigens could be harnessed to improve the HIV-Env antibody response...
May 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28420127/glycosaminoglycan-binding-and-non-endocytic-membrane-translocation-of-cell-permeable-octaarginine-monitored-by-real-time-in-cell-nmr-spectroscopy
#8
Yuki Takechi-Haraya, Kenzo Aki, Yumi Tohyama, Yuichi Harano, Toru Kawakami, Hiroyuki Saito, Emiko Okamura
Glycosaminoglycans (GAGs), which are covalently-linked membrane proteins at the cell surface have recently been suggested to involve in not only endocytic cellular uptake but also non-endocytic direct cell membrane translocation of arginine-rich cell-penetrating peptides (CPPs). However, in-situ comprehensive observation and the quantitative analysis of the direct membrane translocation processes are challenging, and the mechanism therefore remains still unresolved. In this work, real-time in-cell NMR spectroscopy was applied to investigate the direct membrane translocation of octaarginine (R8) into living cells...
April 15, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28420082/can-early-rehabilitation-prevent-posttraumatic-osteoarthritis-in-the-patellofemoral-joint-after-anterior-cruciate-ligament-rupture-understanding-the-pathological-features
#9
Nai-Jen Chang, Ming-You Shie, Kuan-Wei Lee, Pei-Hsi Chou, Chih-Chan Lin, Chih-Jou Chu
Knee instability resulting from anterior cruciate ligament (ACL) rupture is a high-risk factor for posttraumatic osteoarthritis (PTOA) in the patellofemoral joint (PFJ). However, whether non-weight-bearing and weight-bearing treatments have chondroprotective effects remains unclear. Twenty-four adult New Zealand White male rabbits were employed in this study. All animals received ACL transection in the right knee and sham surgery in the left knee. The rabbits were randomly assigned to the following groups: (I) In the sedentary (SED) group, the rabbits (n = 6) were simply kept in their cage; (II) In the continuous passive motion (CPM) group, the rabbits (n = 6) performed CPM exercise for 7 days, starting from the first postoperative day; (III) In the active treadmill exercise (TRE) group, the rabbits (n = 6) performed TRE for 2 weeks; (IV) In the CPM + TRE group, the rabbits (n = 6) executed CPM exercise, followed by TRE...
April 14, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28418595/validation-of-page-b-model-in-asian-chronic-hepatitis-b-patients-receiving-entecavir-or-tenofovir
#10
Mi Na Kim, Seong Gyu Hwang, Kyu Sung Rim, Beom Kyung Kim, Jun Yong Park, Do Young Kim, Sang Hoon Ahn, Kwang-Hyub Han, Seung Up Kim
BACKGROUND & AIMS: A new hepatocellular carcinoma (HCC) risk prediction model, PAGE-B, which includes age, gender, and platelet count as constituent variables, has recently been proposed in Caucasian chronic hepatitis B (CHB) patients. We validated PAGE-B model and compared its accuracy with that of conventional risk prediction models in Asian CHB patients. METHODS: CHB patients treated with entecavir or tenofovir were consecutively recruited. The performance of PAGE-B and three conventional risk prediction models (CU-HCC, GAG-HCC, and REACH-B) were analyzed...
April 18, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28416438/nsaid-use-in-intervertebral-disc-degeneration-what-are-the-effects-on-matrix-homeostasis-in-vivo
#11
Nicholas Vaudreuil, Tiffany Kadow, Takashi Yurube, Robert Hartman, Kevin Ngo, Qing Dong, Pedro Pohl, J Paulo Coelho, James Kang, Nam Vo, Gwendolyn Sowa
BACKGROUND CONTEXT: Non-steroidal anti-inflammatory (NSAID) agents are a widely utilized treatment for low back pain (LBP). Literature on NSAID use in articular cartilage has shown detrimental effects; however, minimal data exist to detail the effects of NSAIDs in intervertebral disc degeneration (IDD). As IDD is a major cause of LBP, we explored the effects of indomethacin, a commonly used NSAID, on disc matrix homeostasis in an animal model of IDD. PURPOSE: To determine the effects of oral indomethacin administration on IDD in an in vivo rabbit model...
April 14, 2017: Spine Journal: Official Journal of the North American Spine Society
https://www.readbyqxmd.com/read/28415472/supercritical-carbon-dioxide-extracted-extracellular-matrix-material-from-adipose-tissue
#12
Jun Kit Wang, Baiwen Luo, Vipra Guneta, Liang Li, Selin Ee Min Foo, Yun Dai, Timothy Thatt Yang Tan, Nguan Soon Tan, Cleo Choong, Marcus Thien Chong Wong
Adipose tissue is a rich source of extracellular matrix (ECM) material that can be isolated by delipidating and decellularizing the tissue. However, the current delipidation and decellularization methods either involve tedious and lengthy processes or require toxic chemicals, which may result in the elimination of vital proteins and growth factors found in the ECM. Hence, an alternative delipidation and decellularization method for adipose tissue was developed using supercritical carbon dioxide (SC-CO2) that eliminates the need of any harsh chemicals and also reduces the amount of processing time required...
June 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28402707/physicians-firearms-and-free-speech-overturning-florida-s-firearm-safety-gag-rule
#13
Wendy E Parmet, Jason A Smith, Matthew Miller
In February, the full U.S. Court of Appeals for the Eleventh Circuit issued its long-awaited ruling in Wollschlaeger v. Governor, State of Florida, invalidating parts of Florida’s Firearm Owners’ Privacy Act (FOPA) and affirming that the First Amendment applies to the speech between physicians and..
April 12, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28401373/sulfated-glycosaminoglycans-in-protein-aggregation-diseases
#14
REVIEW
Kazuchika Nishitsuji, Kenji Uchimura
Protein aggregation diseases are characterized by intracellular or extracellular deposition of misfolded and aggregated proteins. These aggregated deposits contain multiple proteinaceous and non-protein components that are thought to play critical roles in the etiology and pathogenesis of protein aggregation diseases in vivo. One of these components, the sulfated glycosaminoglycans (GAGs), includes heparan sulfate, chondroitin sulfate, and keratan sulfate. The sulfated GAGs are negatively charged heteropolysaccharides expressed in all mammalian tissues...
April 11, 2017: Glycoconjugate Journal
https://www.readbyqxmd.com/read/28398343/large-scale-interaction-effects-reveal-missing-heritability-in-schizophrenia-bipolar-disorder-and-posttraumatic-stress-disorder
#15
H J Woo, C Yu, K Kumar, J Reifman
Genetic susceptibility factors behind psychiatric disorders typically contribute small effects individually. A possible explanation for the missing heritability is that the effects of common variants are not only polygenic but also non-additive, appearing only when interactions within large groups are taken into account. Here, we tested this hypothesis for schizophrenia (SZ) and bipolar disorder (BP) disease risks, and identified genetic factors shared with posttraumatic stress disorder (PTSD). When considered independently, few single-nucleotide polymorphisms (SNPs) reached genome-wide significance...
April 11, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28398238/ltr-retrotransposons-from-bdelloid-rotifers-capture-additional-orfs-shared-between-highly-diverse-retroelement-types
#16
Fernando Rodriguez, Aubrey W Kenefick, Irina R Arkhipova
Rotifers of the class Bdelloidea, microscopic freshwater invertebrates, possess a highlydiversified repertoire of transposon families, which, however, occupy less than 4% of genomic DNA in the sequenced representative Adineta vaga. We performed a comprehensive analysis of A. vaga retroelements, and found that bdelloid long terminal repeat (LTR)retrotransposons, in addition to conserved open reading frame (ORF) 1 and ORF2 corresponding to gag and pol genes, code for an unusually high variety of ORF3 sequences...
April 11, 2017: Viruses
https://www.readbyqxmd.com/read/28396681/evolution-of-nucleotide-punctuation-marks-from-structural-to-linear-signals
#17
Nawal El Houmami, Hervé Seligmann
We present an evolutionary hypothesis assuming that signals marking nucleotide synthesis (DNA replication and RNA transcription) evolved from multi- to unidimensional structures, and were carried over from transcription to translation. This evolutionary scenario presumes that signals combining secondary and primary nucleotide structures are evolutionary transitions. Mitochondrial replication initiation fits this scenario. Some observations reported in the literature corroborate that several signals for nucleotide synthesis function in translation, and vice versa...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28396578/comparative-characterization-of-decellularized-renal-scaffolds-for-tissue-engineering
#18
Iris Fischer, Michael Westphal, Bella Rossbach, Nicole Bethke, Krithika Hariharan, Imran Ullah, Petra Reinke, Andreas Kurtz, Harald Stachelscheid
Native extracellular matrix (ECM) provides scaffolds for tissue engineering with natural architecture and biochemical composition. Maintaining the native ECM in decellularized tissues provides cues for cells, which promote their tissue specific arrangement and function. Several approaches have been used to decellularize ECM from the kidney in order to reestablish renal tissue but their comparability is hampered because methods for decellularization and assessment of ECM vary widely. Therefore, we applied a standardized immersion protocol to decellularize porcine kidney tissue with three detergents Triton X-100, sodium dodecyl sulfate (SDS) and sodium deoxycholate (SDC) at variable temperatures...
April 11, 2017: Biomedical Materials
https://www.readbyqxmd.com/read/28394277/structure-of-ty1-internally-initiated-rna-influences-restriction-factor-expression
#19
Leszek Błaszczyk, Marcin Biesiada, Agniva Saha, David J Garfinkel, Katarzyna J Purzycka
The long-terminal repeat retrotransposon Ty1 is the most abundant mobile genetic element in many Saccharomyces cerevisiae isolates. Ty1 retrotransposons contribute to the genetic diversity of host cells, but they can also act as an insertional mutagen and cause genetic instability. Interestingly, retrotransposition occurs at a low level despite a high level of Ty1 RNA, even though S. cerevisiae lacks the intrinsic defense mechanisms that other eukaryotes use to prevent transposon movement. p22 is a recently discovered Ty1 protein that inhibits retrotransposition in a dose-dependent manner...
April 10, 2017: Viruses
https://www.readbyqxmd.com/read/28388673/proteolysis-of-mature-hiv-1-p6-gag-protein-by-the-insulin-degrading-enzyme-ide-regulates-virus-replication-in-an-env-dependent-manner
#20
Friedrich Hahn, Adrian Schmalen, Christian Setz, Melanie Friedrich, Stefan Schlößer, Julia Kölle, Robert Spranger, Pia Rauch, Kirsten Fraedrich, Tatjana Reif, Julia Karius-Fischer, Ashok Balasubramanyam, Petra Henklein, Torgils Fossen, Ulrich Schubert
There is a significantly higher risk for type II diabetes in HIV-1 carriers, albeit the molecular mechanism for this HIV-related pathology remains enigmatic. The 52 amino acid HIV-1 p6 Gag protein is synthesized as the C-terminal part of the Gag polyprotein Pr55. In this context, p6 promotes virus release by its two late (L-) domains, and facilitates the incorporation of the viral accessory protein Vpr. However, the function of p6 in its mature form, after proteolytic release from Gag, has not been investigated yet...
2017: PloS One
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