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https://www.readbyqxmd.com/read/28821015/extracting-replicable-associations-across-multiple-studies-empirical-bayes-algorithms-for-controlling-the-false-discovery-rate
#1
David Amar, Ron Shamir, Daniel Yekutieli
In almost every field in genomics, large-scale biomedical datasets are used to report associations. Extracting associations that recur across multiple studies while controlling the false discovery rate is a fundamental challenge. Here, we propose a new method to allow joint analysis of multiple studies. Given a set of p-values obtained from each study, the goal is to identify associations that recur in at least k > 1 studies while controlling the false discovery rate. We propose several new algorithms that differ in how the study dependencies are modeled, and compare them and extant methods under various simulated scenarios...
August 18, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28821013/rictor-positively-regulates-b-cell-receptor-signaling-by-modulating-actin-reorganization-via-ezrin
#2
Lu Huang, Yongjie Zhang, Chenguang Xu, Xiaomei Gu, Linlin Niu, Jinzhi Wang, Xiaoyu Sun, Xiaoming Bai, Xingtian Xuan, Qubei Li, Chunwei Shi, Bing Yu, Heather Miller, Gangyi Yang, Lisa S Westerberg, Wanli Liu, Wenxia Song, Xiaodong Zhao, Chaohong Liu
As the central hub of the metabolism machinery, the mammalian target of rapamycin complex 2 (mTORC2) has been well studied in lymphocytes. As an obligatory component of mTORC2, the role of Rictor in T cells is well established. However, the role of Rictor in B cells still remains elusive. Rictor is involved in B cell development, especially the peripheral development. However, the role of Rictor on B cell receptor (BCR) signaling as well as the underlying cellular and molecular mechanism is still unknown. This study used B cell-specfic Rictor knockout (KO) mice to investigate how Rictor regulates BCR signaling...
August 2017: PLoS Biology
https://www.readbyqxmd.com/read/28820984/identification-of-m-tuberculosis-antigens-in-the-sera-of-tuberculosis-patients-using-biomimetic-affinity-chromatography-in-conjunction-with-esi-cid-ms-ms
#3
Guorong Ma, Jinting Pan, Jincheng Han, Lina Gao, Shulin Zhang, Rongxiu Li
The profiling of abnormally-expressed proteins in host cells using mass spectrometry (MS) analysis is a classical approach for screening disease-associated biomarkers in clinical diagnosis. However, few pathogen-specific antigens can currently be detected in serum using this proteomic approach, since these are very low-abundant proteins that are easily masked by host high-abundant proteins. Identification of pathogen-specific antigens in the sera of tuberculosis patients is crucial for the clinical diagnosis of this infectious disease, especially in immune-compromised patients...
July 31, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28820895/identification-of-leishmania-donovani-antigen-in-circulating-immune-complexes-of-visceral-leishmaniasis-subjects-for-diagnosis
#4
Fauzia Jamal, Pushkar Shivam, Sarita Kumari, Manish Kumar Singh, Abul Hasan Sardar, Pushpanjali, Selvasankar Murugesan, Shyam Narayan, Anil Kumar Gupta, Krishna Pandey, V N R Das, Vahab Ali, Sanjiva Bimal, Pradeep Das, Shubhankar K Singh
The unreliability of most of the existing antibody-based diagnostic kits to discriminate between active and treated VL cases, relapse situation and reinfection are a major hurdle in controlling the cases of Kala-azar in an endemic area. An antigen targeted diagnostic approaches can be an attractive strategy to overcome these problems. Hence, this study was focused on identifying the Leishmania antigens, lies in circulating immune complex (CICs), can be used for diagnostic as well as prognostic purposes. The present study was conducted on peripheral blood samples of 115 human subjects, based on isolation of CICs...
2017: PloS One
https://www.readbyqxmd.com/read/28820387/infectious-polymorphic-toxins-delivered-by-outer-membrane-exchange-discriminate-kin-in-myxobacteria
#5
Christopher N Vassallo, Pengbo Cao, Austin Conklin, Hayley Finkelstein, Christopher S Hayes, Daniel Wall
Myxobacteria are known for complex social behaviors including outer membrane exchange (OME), in which cells exchange large amounts of outer membrane lipids and proteins upon contact. The TraA cell surface receptor selects OME partners based on a variable domain. However, traA polymorphism alone is not sufficient to precisely discriminate kin. Here, we report a novel family of OME-delivered toxins that promote kin discrimination of OME partners. These SitA lipoprotein toxins are polymorphic and widespread in myxobacteria...
August 18, 2017: ELife
https://www.readbyqxmd.com/read/28820071/antibody-fragments-as-potential-biopharmaceuticals-for-cancer-therapy-success-and-limitations
#6
Roman V Kholodenko, Daniel V Kalinovsky, Igor I Doronin, Eugene D Ponomarev, Irina V Kholodenko
Monoclonal antibodies (mAbs) are an important class of therapeutic agents approved for the therapy of many types of malignancies. However, in certain cases applications of conventional mAbs have several limitations in anticancer immunotherapy. These limitations include insufficient efficacy and adverse effects. The antigen-binding fragments of antibodies have a considerable potential to overcome the disadvantages of conventional mAbs, such as poor penetration into solid tumors and Fc-mediated bystander activation of the immune system...
August 17, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28819716/neurological-complications-of-therapeutic-monoclonal-antibodies-trends-from-oncology-to-rheumatology
#7
REVIEW
Chandler Gill, Stasia Rouse, Ryan D Jacobson
PURPOSE OF REVIEW: This review is to describe the scope of neurological complications associated with monoclonal antibody-based therapies, applied across medical specialties, to demonstrate the common and rare neurological syndromes that may be encountered in clinical practice according to the therapeutic agent being receive, and to explain appropriate work-up, diagnosis, and management of drug complications, as supported by the literature. RECENT FINDINGS: The number of commercially available, evidence-based therapeutic monoclonal antibodies continues to expand...
August 17, 2017: Current Neurology and Neuroscience Reports
https://www.readbyqxmd.com/read/28819380/phase-ii-trial-of-adjuvant-immunotherapy-with-autologous-tumor-derived-gp96-vaccination-in-patients-with-gastric-cancer
#8
Kecheng Zhang, Zheng Peng, Xiaohui Huang, Zhi Qiao, Xinxin Wang, Ning Wang, Hongqing Xi, Jianxin Cui, Yunhe Gao, Xijian Huang, Hua Gao, Bo Wei, Lin Chen
Background/Aims: Autologous, tumor-derived, heat shock protein gp96 peptide complexes have antitumor potential. We conducted the first Phase II trial to evaluate the safety and efficacy of gp96 vaccination in adjuvant settings for patients with gastric cancer. Methods: We enrolled 73 consecutive patients from October 2012 to December 2015. Thirty-eight patients received gp96 vaccination plus chemotherapy and 35 received chemotherapy alone. The primary endpoints were disease-free survival (DFS) and toxicity...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28819237/disruption-of-the-plant-specific-cfs1-gene-impairs-autophagosome-turnover-and-triggers-eds1-dependent-cell-death
#9
Arpaporn Sutipatanasomboon, Stefanie Herberth, Ellen G Alwood, Heidrun Häweker, Britta Müller, Mojgan Shahriari, Anke Y Zienert, Birger Marin, Silke Robatzek, Gerrit J K Praefcke, Kathryn R Ayscough, Martin Hülskamp, Swen Schellmann
Cell death, autophagy and endosomal sorting contribute to many physiological, developmental and immunological processes in plants. They are mechanistically interconnected and interdependent, but the molecular basis of their mutual regulation has only begun to emerge in plants. Here, we describe the identification and molecular characterization of CELL DEATH RELATED ENDOSOMAL FYVE/SYLF PROTEIN 1 (CFS1). The CFS1 protein interacts with the ENDOSOMAL SORTING COMPLEX REQUIRED FOR TRANSPORT I (ESCRT-I) component ELCH (ELC) and is localized at ESCRT-I-positive late endosomes likely through its PI3P and actin binding SH3YL1 Ysc84/Lsb4p Lsb3p plant FYVE (SYLF) domain...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819133/combined-transcriptome-and-metabolome-analyses-of-metformin-effects-reveal-novel-links-between-metabolic-networks-in-steroidogenic-systems
#10
Sameer S Udhane, Balazs Legeza, Nesa Marti, Damian Hertig, Gaëlle Diserens, Jean-Marc Nuoffer, Peter Vermathen, Christa E Flück
Metformin is an antidiabetic drug, which inhibits mitochondrial respiratory-chain-complex I and thereby seems to affect the cellular metabolism in many ways. It is also used for the treatment of the polycystic ovary syndrome (PCOS), the most common endocrine disorder in women. In addition, metformin possesses antineoplastic properties. Although metformin promotes insulin-sensitivity and ameliorates reproductive abnormalities in PCOS, its exact mechanisms of action remain elusive. Therefore, we studied the transcriptome and the metabolome of metformin in human adrenal H295R cells...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28818454/the-anti-tumor-effect-of-intravesical-administration-of-normal-urothelial-cells-on-bladder-cancer
#11
Chi-Ping Huang, Chi-Cheng Chen, Chih-Rong Shyr
BACKGROUND AIMS: Urothelial bladder cancer (UBC) is the second most common cancer of the genitourinary tract and for advanced forms of the disease it has a high mortality rate. There are no approved new molecularly targeted agents or chemotherapeutics for advanced UBC beyond cisplatin-based chemotherapy except the recently approved anti-programmed death ligand 1 (anti-PD-1/PD-L1) antibody. With complex genetic and epigenetic alterations in tumors, despite several druggable targets identified, to cure UBC is still a challenging unmet medical need...
August 14, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28818081/what-makes-gouty-inflammation-so-variable
#12
REVIEW
Robert Terkeltaub
Acute gout arthritis flares contribute dominantly to gout-specific impaired health-related quality of life, representing a progressively increasing public health problem. Flares can be complex and expensive to treat, partly due to the frequent comorbidities. Unmet needs in gout management are more pressing given the markedly increasing gout flare hospital admission rates. In addition, chronic gouty arthritis can cause joint damage and functional impairment. This review addresses new knowledge on the basis for the marked, inherent variability of responses to deposited urate crystals, including the unpredictable and self-limited aspects of many gout flares...
August 18, 2017: BMC Medicine
https://www.readbyqxmd.com/read/28817603/expression-of-the-mhc-class-ii-in-triple-negative-breast-cancer-is-associated-with-tumor-infiltrating-lymphocytes-and-interferon-signaling
#13
In Ah Park, Seong-Hye Hwang, In Hye Song, Sun-Hee Heo, Young-Ae Kim, Won Seon Bang, Hye Seon Park, Miseon Lee, Gyungyub Gong, Hee Jin Lee
Tumor-infiltrating lymphocytes (TILs) have been known for their strong prognostic and predictive significance in triple-negative breast cancer (TNBC). Several mechanisms for TIL influx in TNBC have been elucidated. Major histocompatibility complex class II (MHC-II) is an essential component of the adaptive immune system and is generally restricted to the surface of antigen-presenting cells. However, it has been reported that interferon-gamma signaling may induce MHC-II in almost all cell types, including those derived from cancer...
2017: PloS One
https://www.readbyqxmd.com/read/28817177/the-n-terminal-ubiquitin-associated-domain-of-cezanne-is-crucial-for-its-function-to-suppress-nf-%C3%AE%C2%BAb-pathway
#14
Yanxi Ji, Liu Cao, Lanyi Zeng, Zhen Zhang, Qiaoqiao Xiao, Penglin Guan, Shiyou Chen, Yu Chen, Min Wang, Deyin Guo
Cezanne, a deubiquitinating cysteine protease (DUB) belonging to A20 subgroup of ovarian tumor (OTU) protein superfamily, functions as a negative regulator of NF-κB to attenuate NF-κB activation and to restrain pro-inflammatory transcription in response to TNF receptor (TNFR) signaling. It is the first documented OTU DUB that preferably disassembles Lys11-linked polyubiquitin chains and has been shown to regulate multiple cellular events including immune signaling, cell survival and tumor progression. Previous studies showed that in response to TNF stimulation, Cezanne is recruited to the activated TNFR complex to suppress the build-up of polyubiquitinated RIP1 signal by removing Lys63 polyubiquitin from RIP1...
August 17, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28817095/human-milk-and-allergic-diseases-an-unsolved-puzzle
#15
REVIEW
Daniel Munblit, Diego G Peroni, Alba Boix-Amorós, Peter S Hsu, Belinda Van't Land, Melvin C L Gay, Anastasia Kolotilina, Chrysanthi Skevaki, Robert J Boyle, Maria Carmen Collado, Johan Garssen, Donna T Geddes, Ralph Nanan, Carolyn Slupsky, Ganesa Wegienka, Anita L Kozyrskyj, John O Warner
There is conflicting evidence on the protective role of breastfeeding in relation to the development of allergic sensitisation and allergic disease. Studies vary in methodology and definition of outcomes, which lead to considerable heterogeneity. Human milk composition varies both within and between individuals, which may partially explain conflicting data. It is known that human milk composition is very complex and contains variable levels of immune active molecules, oligosaccharides, metabolites, vitamins and other nutrients and microbial content...
August 17, 2017: Nutrients
https://www.readbyqxmd.com/read/28816360/c-c-motif-chemokine-ligand-2-regulates-lps-induced-inflammation-and-er-stress-to-enhance-proliferation-of-bovine-endometrial-epithelial-cells
#16
Whasun Lim, Hyocheol Bae, Fuller W Bazer, Sung-Man Kim, Gwonhwa Song
Chemokines play an important role in regulating the complex immune system at the maternal-fetal interface during pregnancy. Among various chemokines, C-C motif chemokine ligand 2 (CCL2) plays a role in the recruitment of immune regulatory cells to implantation sites within the endometrium. In cattle, CCL2 is abundantly expressed in the uterine endometrium. However, its intracellular signaling has not been identified. In this study, we examined the effects of CCL2 on bovine endometrial (BEND) cell proliferation...
August 17, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28815730/loss-of-bmi-1-dampens-migration-and-emt-of-colorectal-cancer-in-inflammatory-microenvironment-through-tlr4-md-2-myd88-mediated-nf-%C3%AE%C2%BAb-signaling
#17
Kai Ye, Qi-Wei Chen, Ya-Feng Sun, Jian-An Lin, Jian-Hua Xu
Increasing evidence from various clinical and experimental studies has demonstrated that the inflammatory microenvironment created by immune cells facilitates tumor migration. Epithelial-mesenchymal transition (EMT) is involved in the progression of cancer invasion and metastasis in an inflammatory microenvironment. B-lymphoma Moloney murine leukemia virus insertion region 1 (BMI-1) acts as an oncogene in various tumors. Ectopic expression of Bmi-1 have an effect on EMT and invasiveness. The purpose of this study was to investigate the efficacy of BMI-1 on inflammation-induced tumor migration and EMT and the underlying mechanism...
August 16, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28815531/mitochondria-endoplasmic-reticulum-contact-sites-mediate-innate-immune-responses
#18
Takuma Misawa, Michihiro Takahama, Tatsuya Saitoh
Mitochondria and the endoplasmic reticulum (ER) are fundamental organelles that coordinate high-order cell functions. Mitochondria are centers of energy production, whereas the ER is responsible for folding, transport, and degradation of proteins. In addition to their specific functions, mitochondria and ER actively communicate with each other to promote a variety of cellular events, such as material transfer and signal transduction. Recent studies have shown the critical involvement of these organelles in regulation of the innate immune system, which functions in host defense...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28815458/backbone-and-side-chain-resonance-assignments-of-ca-2-4-calmodulin-bound-to-beta-calcineurin-a-cambd-peptide
#19
C Andrew Fowler, Maria F Núñez Hernandez, Susan E O'Donnell, Liping Yu, Madeline A Shea
Calcineurin (CaN) is a heterodimeric and highly conserved serine/threonine phosphatase (PP2B) that plays a critical role in coupling calcium signals to physiological processes including embryonic cardiac development, NF-AT-regulated gene expression in immune responses, and apoptosis. The catalytic subunit (CaNA) has three isoforms (α, β, and γ,) in humans and seven isoforms in Paramecium. In all eukaryotes, the EF-hand protein calmodulin (CaM) regulates CaN activity in a calcium-dependent manner. The N- and C-domains of CaM (CaMN and CaMC) recognize a CaM-binding domain (CaMBD) within an intrinsically disordered region of CaNA that precedes the auto-inhibitory domain (AID) of CaNA...
August 16, 2017: Biomolecular NMR Assignments
https://www.readbyqxmd.com/read/28815216/epistatic-interactions-within-the-influenza-a-virus-polymerase-complex-mediate-mutagen-resistance-and-replication-fidelity
#20
Matthew D Pauly, Daniel M Lyons, William J Fitzsimmons, Adam S Lauring
Lethal mutagenesis is a broad-spectrum antiviral strategy that employs mutagenic nucleoside analogs to exploit the high mutation rate and low mutational tolerance of many RNA viruses. Studies of mutagen-resistant viruses have identified determinants of replicative fidelity and the importance of mutation rate to viral population dynamics. We have previously demonstrated the effective lethal mutagenesis of influenza A virus using three nucleoside analogs as well as the virus's high genetic barrier to mutagen resistance...
July 2017: MSphere
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