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https://www.readbyqxmd.com/read/28337208/natural-killer-cell-development-and-maturation-revisited-possible-implications-of-a-novel-distinct-lin-cd34-dnam-1-bright-cxcr4-cell-progenitor
#1
Federica Bozzano, Francesco Marras, Andrea De Maria
Since the first description of natural killer (NK) cells, the view on their role in innate immunity has evolved considerably. In addition to first-line defense against transformed and pathogen-infected autologous cells, NK cells contribute to modulate adaptive immune responses and in some cases acquire specialized functions, including exhausted, adaptive, and decidual NK cells. NK cells derive from CD34(+) progenitors, in vivo and in vitro; however, it is unclear whether the high phenotype diversity in vivo may be generated from these precursors alone...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28335888/second-and-third-generation-drugs-for-immuno-oncology-treatment-the-more-the-better
#2
REVIEW
Wolfram C M Dempke, Klaus Fenchel, Peter Uciechowski, Stephen P Dale
Recent success in cancer immunotherapy (anti-CTLA-4, anti-PD1/PD-L1) has confirmed the hypothesis that the immune system can control many cancers across various histologies, in some cases producing durable responses in a way not seen with many small-molecule drugs. However, only less than 25% of all patients do respond to immuno-oncology drugs and several resistance mechanisms have been identified (e.g. T-cell exhaustion, overexpression of caspase-8 and β-catenin, PD-1/PD-L1 gene amplification, MHC-I/II mutations)...
March 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28335609/early-and-delayed-antiretroviral-therapy-art-result-in-comparable-reductions-in-cd8-t-cell-exhaustion-marker-expression
#3
Rachel Rutishauser, Wendy Hartogensis, Christian D Deguit, Melissa Krone, Rebecca Hoh, Rick Hecht, Christopher D Pilcher, Peter Bacchetti, Steven G Deeks, Peter W Hunt, Joseph M McCune
In untreated HIV infection, CD8+ T cell exhaustion (i.e., decreased proliferative and effector capacity) is associated with high levels of expression of co-inhibitory receptors, including PD-1, TIGIT, CD160, and 2B4. This is evident for both HIV-specific and non-HIV-specific CD8+ T cells. Antiretroviral therapy (ART) initiated during chronic infection decreases but may not completely normalize the expression of such "exhaustion markers." Compared to initiation of ART later in the course of disease, initiation soon after infection reduces some parameters of chronic inflammation and adaptive immune dysfunction...
March 23, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28334377/lrit3-differentially-affects-connectivity-and-synaptic-transmission-of-cones-to-on-and-off-bipolar-cells
#4
Marion Neuillé, Yan Cao, Romain Caplette, Debbie Guerrero-Given, Connon Thomas, Naomi Kamasawa, José-Alain Sahel, Christian P Hamel, Isabelle Audo, Serge Picaud, Kirill A Martemyanov, Christina Zeitz
Purpose: Mutations in LRIT3 lead to complete congenital stationary night blindness (cCSNB). Using a cCSNB mouse model lacking Lrit3 (nob6), we recently have shown that LRIT3 has a role in the correct localization of TRPM1 (transient receptor potential melastatin 1) to the dendritic tips of ON-bipolar cells (BCs), contacting both rod and cone photoreceptors. Furthermore, postsynaptic clustering of other mGluR6 cascade components is selectively eliminated at the dendritic tips of cone ON-BCs...
March 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28333140/metabolic-and-molecular-insights-into-an-essential-role-of-nicotinamide-phosphoribosyltransferase
#5
Li Q Zhang, Leon Van Haandel, Min Xiong, Peixin Huang, Daniel P Heruth, Charlie Bi, Roger Gaedigk, Xun Jiang, Ding-You Li, Gerald Wyckoff, Dmitry N Grigoryev, Li Gao, Linheng Li, Min Wu, J Steven Leeder, Shui Qing Ye
Nicotinamide phosphoribosyltransferase (NAMPT) is a pleiotropic protein implicated in the pathogenesis of acute respiratory distress syndrome, aging, cancer, coronary heart diseases, diabetes, nonalcoholic fatty liver disease, obesity, rheumatoid arthritis, and sepsis. However, the underlying molecular mechanisms of NAMPT in these physiological and pathological processes are not fully understood. Here, we provide experimental evidence that a Nampt gene homozygous knockout (Nampt(-/-)) resulted in lethality at an early stage of mouse embryonic development and death within 5-10 days in adult mice accompanied by a 25...
March 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28331002/personalized-in-vitro-and-in-vivo-cancer-models-to-guide-precision-medicine
#6
Chantal Pauli, Benjamin D Hopkins, Davide Prandi, Reid Shaw, Tarcisio Fedrizzi, Andrea Sboner, Verena Sailer, Michael Augello, Loredana Puca, Rachele Rosati, Terra J McNary, Yelena Churakova, Cynthia Cheung, Joanna Triscott, David Pisapia, Rema Rao, Juan Miguel Mosquera, Brian Robinson, Bishoy M Faltas, Brooke E Emerling, Vijayakrishna K Gadi, Brady Bernard, Olivier Elemento, Himisha Beltran, Francesca Demichelis, Christopher J Kemp, Carla Grandori, Lewis C Cantley, Mark A Rubin
Precision medicine is an approach that takes into account the influence of individuals' genes, environment, and lifestyle exposures to tailor interventions. Here, we describe the development of a robust precision cancer care platform that integrates whole-exome sequencing with a living biobank that enables high-throughput drug screens on patient-derived tumor organoids. To date, 56 tumor-derived organoid cultures and 19 patient-derived xenograft (PDX) models have been established from the 769 patients enrolled in an Institutional Review Board-approved clinical trial...
March 22, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28329725/ammonium-assimilation-an-important-accessory-during-aerobic-denitrification-of-pseudomonas-stutzeri-t13
#7
Yilu Sun, Liang Feng, Ang Li, Xuening Zhang, Jixian Yang, Fang Ma
The present study investigated effect of ammonium utilization on aerobic denitrification by Pseudomonas stutzeri T13. Per nitrogen balance calculation, all consumed ammonium was utilized as nitrogen source for cell propagation by assimilation rather than heterotrophic nitrification. Total organic carbon (TOC) and ammonium were necessary substrates to sustain heterotrophic propagation of P. stutzeri T13 at optimum proportion equal to seven. Under aerobic condition, nitrate was utilized as substitute nitrogen source when ammonium was completely exhausted...
March 12, 2017: Bioresource Technology
https://www.readbyqxmd.com/read/28328794/hcv-drives-increased-type-i-ifn-associated-impairments-associated-to-fibrosis-severity-in-art-treated-hiv-1-hcv-coinfected-individuals
#8
Morgane Griesbeck, Marc-Antoine Valantin, Karine Lacombe, Assia Samri-Hassimi, Julie Bottero, Catherine Blanc, Zineb Sbihi, Rima Zoorob, Christine Katlama, Marguerite Guiguet, Marcus Altfeld, Brigitte Autran
BACKGROUND: Viral coinfections might contribute to the increased immune activation and inflammation that persist in ART-treated HIV-1 patients. We investigated whether the HCV co-infection contributes to such alterations by impairing the pDC IFNα/TLR7 pathway in a highly homogeneous group of ART-treated HIV-1-HCV co-infected patients. METHODS: Twenty nine HIV-1-infected patients with fully suppressive ART were included, fifteen of whom being HCV co-infected with mild to moderate fibrosis and matched for their HIV-1 disease, and thirteen control healthy donors...
March 21, 2017: AIDS
https://www.readbyqxmd.com/read/28325871/progression-of-type-1-diabetes-from-the-prediabetic-stage-is-controlled-by-interferon-%C3%AE-signaling
#9
Brett S Marro, Brian C Ware, Jaroslav Zak, Juan Carlos de la Torre, Hugh Rosen, Michael B A Oldstone
Blockade of IFN-α but not IFN-β signaling using either an antibody or a selective S1PR1 agonist, CYM-5442, prevented type 1 diabetes (T1D) in the mouse Rip-LCMV T1D model. First, treatment with antibody or CYM-5442 limited the migration of autoimmune "antiself" T cells to the external boundaries around the islets and prevented their entry into the islets so they could not be positioned to engage, kill, and thus remove insulin-producing β cells. Second, CYM-5442 induced an exhaustion signature in antiself T cells by up-regulating the negative immune regulator receptor genes Pdcd1, Lag3, Ctla4, Tigit, and Btla, thereby limiting their killing ability...
March 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28324831/primary-and-acquired-resistance-to-pd-1-pd-l1-blockade-in-cancer-treatment
#10
REVIEW
Qiaohong Wang, Xia Wu
PD-1/PD-L1 blockade appears to be a very promising immunotherapy with significant clinical benefits and durable responses in multiple tumor types. However, the effectual clinical benefits of PD-1/PD-L1 blockade are hampered by a high rate of primary resistance, where patients do not respond to PD-1/PD-L1 blockade initially. And more distressingly, most patients eventually develop acquired resistance after an initial response to PD-1/PD-L1 blockade. The mechanisms underlying primary and acquired resistance to PD-1/PD-L1 blockade have remained ambiguous...
March 18, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28323897/hcv-coinfection-contributes-to-hiv-pathogenesis-by-increasing-immune-exhaustion-in-cd8-t-cells
#11
Norma Rallón, Marcial García, Javier García-Samaniego, Noelia Rodríguez, Alfonso Cabello, Clara Restrepo, Beatriz Álvarez, Rosa García, Miguel Górgolas, José M Benito
BACKGROUND: There are several contributors to HIV-pathogenesis or insufficient control of the infection. However, whether HIV/HCV-coinfected population exhibits worst evolution of HIV-pathogenesis remains unclear. Recently, some markers of immune exhaustion have been proposed as preferentially upregulated on T-cells during HIV-infection. Herein, we have analyzed T-cell exhaustion together with several other contributors to HIV-pathogenesis that could be affected by HCV-coinfection. PATIENTS AND METHODS: Ninety-six patients with chronic HIV-infection (60 HIV-monoinfected and 36 HIV/HCV-coinfected), and 20 healthy controls were included in the study...
2017: PloS One
https://www.readbyqxmd.com/read/28323492/regulatory-and-exhausted-t-cell-responses-to-aav-capsid
#12
Gwladys Gernoux, James M Wilson, Christian Mueller
Recombinant adeno-associated viruses are quickly becoming the preferred viral vector for viral gene delivery for the treatment of a wide variety of genetic disorders. However, since their use in a clinical trial targeting Hemophilia B patients 10 years ago, immune responses to AAV capsid appear to have hampered some of the early clinical gene transfer efficacy. Indeed, AAV-based gene transfer has been shown to reactivate capsid-specific memory T cells which have correlated with a decline in AAV transduced tissue in some patients...
March 21, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28319732/an-antigen-to-remember-regulation-of-b-cell-memory-in-health-and-disease
#13
REVIEW
Aleta Pupovac, Kim L Good-Jacobson
Vaccine success relies on the formation of immunity. Humoral immunity is critical and is mediated by long-lived antibody-secreting cells and memory B cells (MBCs). Chronic infectious diseases cause a significant global burden of disease; pathogens that evade the immune system can cause phenotypical and functional changes to immune memory populations. Thus, recent studies have focused on MBC subset function. IgM(+) MBCs have emerged as important early responders in malaria. Atypical MBCs have functional qualities associated with exhaustion in chronic infectious diseases, but the requirements for their formation and where they localize remains unknown...
March 16, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28315692/role-of-epithelial-mesenchymal-transition-emt-and-fibroblast-function-in-cerium-oxide-nanoparticles-induced-lung-fibrosis
#14
Jane Ma, Bridget Bishoff, R R Mercer, Mark Barger, Diane Schwegler-Berry, Vincent Castranova
The emission of cerium oxide nanoparticles (CeO2) from diesel engines, using cerium compounds as a catalyst to lower the diesel exhaust particles, is a health concern. We have previously shown that CeO2 induced pulmonary inflammation and lung fibrosis. The objective of the present study was to investigate the modification of fibroblast function and the role of epithelial-mesenchymal transition (EMT) in CeO2-induced fibrosis. Male Sprague-Dawley rats were exposed to CeO2 (0.15 to 7mg/kg) by a single intratracheal instillation and sacrificed at various times post-exposure...
March 16, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28315615/mir155-regulation-of-ubiquilin1-and-ubiquilin2-implications-in-cellular-protection-and-tumorigenesis
#15
Sanjay Yadav, Nishant Singh, Parag P Shah, David A Rowbotham, Danial Malik, Ankita Srivastav, Jai Shankar, Wan L Lam, William W Lockwood, Levi J Beverly
Ubiquilin (UBQLN) proteins are adaptors thought to link ubiquitinated proteins to the proteasome. However, our lab has recently reported a previously unappreciated role for loss of UBQLN in lung cancer progression. In fact, UBQLN genes are lost in over 50% of lung cancer samples examined. However, a reason for the loss of UBQLN has not been proposed, nor has a selective pressure that could lead to deletion of UBQLN been reported. Diesel Exhaust Particles (DEP) are a major concern in the large cities of developing nations and DEP exposed populations are at an increased risk of developing a number of illnesses, including lung cancer...
March 15, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28306177/frequency-and-functional-characterization-of-exhausted-cd8-t-cells-in-chronic-lymphocytic-leukemia
#16
Saeid Taghiloo, Esmaeil Allahmoradi, Mohsen Tehrani, Hadi Hossein-Nataj, Ramin Shekarriz, Ghasem Janbabaei, Saeid Abediankenari, Hossein Asgarian-Omran
OBJECTIVES: The phenotypic and functional properties of Tim-3+/PD-1+/CD8+ cells as exhausted T-cells were investigated in chronic lymphocytic leukemia (CLL). METHODS: Frequency of CD8+/Tim-3+/PD-1+ exhausted cells was determined by flow cytometry. For functional analysis, magnetic beads isolated CD8+ T-cells were stimulated with PHA and PMA/ionocymin to assess their proliferative responses and cytokine production by MTT and ELISA, respectively. Cytotoxic activity of isolated CD8+ T-cells was determined using CD107a degranulation assay...
March 17, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28302043/cul5-and-apobec3g-polymorphisms-are-partially-implicated-in-hiv-1-infection-and-antiretroviral-therapy-in-a-brazilian-population
#17
Ronaldo Celerino da Silva, Antonio Victor Campos Coelho, Ronald Rodrigues Moura, Luiz Cláudio Arraes, Lucas André Cavalcanti Brandão, Rafael Lima Guimarães, Sérgio Crovella
BACKGROUND: Host restriction factors are cellular proteins able to diminish or block viral replication in a cell-specific way. Objetive and Method: We evaluated the distribution of selected SNPs in APOBEC3G (rs3736685, rs2294367) and CUL5 (rs7117111, rs7103534, rs11212495) genes, among 264 HIV-1 infected (HIV-1+) and 259 unexposed uninfected individuals from Northeast Brazil, looking for a possible association with susceptibility to HIV-1 infection, viral load, CD4+ T cell count and success of antiretroviral therapy...
March 15, 2017: Current HIV Research
https://www.readbyqxmd.com/read/28296653/involvement-of-hypothalamic-nitric-oxide-signaling-in-the-modulation-of-a-rat-s-exercise-capacity
#18
Hongyu Liu, Jinjuan Xue
PURPOSE: The aim of this study was to explore the effect of nitric oxide (NO) in some regions of the hypothalamus on exercise capacity. MATERIALS AND METHODS: To assess the role of central NO in exercise capacity, L-arginine (L-Arg, a precursor of NO synthesis), NG-nitro-L-arginine methyl ester (L-NAME, a NO synthase inhibitor), or placebo saline was injected into the lateral cerebral ventricle of rats once a day for 4 consecutive days. Thereafter, an one-time exhaustive treadmill exercise was performed, and the levels of nitrate/nitrite, as a marker of NO production, in blood plasma and hypothalamus were assayed...
March 14, 2017: Neuroreport
https://www.readbyqxmd.com/read/28295401/staging-cutaneous-squamous-cell-carcinoma-metastases-to-the-parotid-gland
#19
Lukasz Czerwonka, Robert J De Santis, Gilad Horowitz, Michael Hong, Mario Orsini, Danny Enepekides, David P Goldstein, Joe Dort, Kevin Higgins
OBJECTIVE: The staging of cutaneous squamous cell cancers (cSCC) was revised by the American Joint Committee on Cancer in 2010 to incorporate known prognostic factors and expand the N (node) category. The purpose of this study was to validate this staging system using a North American cohort, and to compare it to the O'Brien P (Parotid) and N staging system. METHODS: An exhaustive collaborative database search was performed for all patients with cSCC metastasis to the parotid gland treated at three major Canadian tertiary referral centers from December 1999 to March 2015...
March 14, 2017: Laryngoscope
https://www.readbyqxmd.com/read/28294504/dynamics-of-o2-chemisorption-on-a-flat-platinum-surface-probed-by-an-alignment-controlled-o2-beam
#20
Hirokazu Ueta, Mitsunori Kurahashi
O2 adsorption on Pt surfaces is of great technological importance owing to its relevance to reactions for the purification of car exhaust gas and the oxygen reduction on fuel-cell electrodes. Although the O2 /Pt(111) system has been investigated intensively, questions still remain concerning the origin of the low O2 sticking probability and its unusual energy dependence. We herein clarify the alignment dependence of the initial sticking probability (S0 ) using the single spin-rotational state-selected [(J,M)=(2,2)] O2 beam...
March 15, 2017: Angewandte Chemie
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