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Factor deficiencies

Corinna Schmitz, Heidi Noels, Omar El Bounkari, Eva Straussfeld, Remco T A Megens, Marieke Sternkopf, Setareh Alampour-Rajabi, Christine Krammer, Pathricia V Tilstam, Norbert Gerdes, Christina Bürger, Aphrodite Kapurniotu, Richard Bucala, Joachim Jankowski, Christian Weber, Jürgen Bernhagen
The inflammatory cytokine macrophage migration-inhibitory factor (MIF) promotes atherosclerosis via lesional monocyte and T-cell recruitment. B cells have emerged as important components in atherogenesis, but the interaction between MIF and B cells in atherogenesis is unknown. Here, we investigated the atherosclerotic phenotype of Mif-gene deletion in Apoe-/- mice. Apoe-/- Mif-/- mice on a Western-diet exhibited strongly reduced atherosclerotic lesions in brachiocephalic artery (BC) and abdominal aorta compared with controls...
March 15, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Wen-Yi Zhou, Shan-Shan Li, Jieyao Song, Min Jiang, Tian-Jia Jiang, Jinyun Liu, Jinhuai Liu, Xing-Jiu Huang
Mutual interference is a severe issue that occurs during the electrochemical detection of heavy metal ions. This limitation presents a notable drawback for its high sensitivity to specific targets. Here, we present a high electrochemical sensitivity of ~237.1 μA cm-2 μM-1 toward copper(II) [Cu(II)] based on oxygen-deficient titanium dioxide (TiO2-x) nanosheets. We fully demonstrated an atomic-level relationship between electrochemical behaviors and the key factors, including the high-energy (001) facet percentage, oxygen vacancy concentration, surface -OH content, and charge carrier density, is fully demonstrated...
March 15, 2018: Analytical Chemistry
Eiki Yoshida, Takafumi Suzuki, Masanobu Morita, Keiko Taguchi, Kohei Tsuchida, Hozumi Motohashi, Minoru Doita, Masayuki Yamamoto
Keap1 is a negative regulator of Nrf2, a master transcription factor that regulates cytoprotection against oxidative and electrophilic stresses. Although several studies have suggested that the Keap1-Nrf2 system contributes to bone formation besides the maintenance of redox homeostasis, how Nrf2 hyperactivation by Keap1 deficiency affects the bone formation remains to be explored, as the Keap1-null mice are juvenile lethal. To overcome this problem, we used viable Keap1-deficient mice that we have generated by deleting the esophageal Nrf2 in Keap1-null mice (NEKO mice)...
March 15, 2018: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
Helen V Wilmot, Jason Hockley, Peter Rigsby, Elaine Gray
Until recently, the role of factor XII (FXII) in hemostasis was not considered to be important since patients with FXII deficiency do not present with bleeding. The activation of FXII by agents including mast cells and platelet polyphosphates suggests that it may have a role in thrombogenesis. The inhibition of FXII therefore presents an option for antithrombotic therapy, and antibodies and inhibitors are already in development. Assays for FXII will be required to support these technologies, and an international standard (IS) for FXII would be useful for the development of these methods and for the clinical monitoring of patients...
2018: Frontiers in Medicine
Antonella Mancusi, Sara Piccinelli, Andrea Velardi, Antonio Pierini
FoxP3+ regulatory T cells (Tregs) are a subset of CD4+ T cells that can suppress proliferation and effector functions of T cells, B cells, NK cells, and antigen-presenting cells. Treg deficiency causes dramatic immunologic disease in both animal models and humans. As they are capable to suppress the function and the proliferation of conventional CD4+ and CD8+ T cells, Treg-based cell therapies are under evaluation for the treatment of various autoimmune diseases and are currently employed to prevent graft-versus-host disease (GvHD) in clinical trials of hematopoietic stem cell transplantation...
2018: Frontiers in Immunology
Girak Kim, Min Jeong Gu, Soo Ji Kim, Kwang Hyun Ko, Yoon-Chul Kye, Cheol Gyun Kim, Jae-Ho Cho, Woon-Kyu Lee, Ki-Duk Song, Hyuk Chu, Yeong-Min Park, Seung Hyun Han, Cheol-Heui Yun
γδ T cells, known to be an important source of innate IL-17 in mice, provide critical contributions to host immune responses. Development and function of γδ T cells are directed by networks of diverse transcription factors (TFs). Here, we examine the role of the zinc finger TFs, Kruppel-like factor 10 (KLF10), in the regulation of IL-17-committed CD27- γδ T (γδ27- -17) cells. We found selective augmentation of Vγ4+ γδ27- cells with higher IL-17 production in KLF10-deficient mice. Surprisingly, KLF10-deficient CD127hi Vγ4+ γδ27- -17 cells expressed higher levels of CD5 than their wild-type counterparts, with hyper-responsiveness to cytokine, but not T-cell receptor, stimuli...
2018: Frontiers in Immunology
Gabriela Nestal de Moraes, Zongling Ji, Lavender Y-N Fan, Shang Yao, Stefania Zona, Andrew D Sharrocks, Eric W-F Lam
The forkhead transcription factor FOXK2 plays a critical role in suppressing tumorigenesis and mediating cytotoxic drug action in breast cancer. However, the mechanism by which the biological function of FOXK2 is regulated remains poorly understood. Here, we investigated the role of SUMOylation in modulating FOXK2-mediated drug sensitivity. We identified SUMOylation consensus motifs within the FOXK2 sequence and constructed two SUMOylation-defective double mutants by converting lysine 527 and 633 to arginines and glutamic acid 529 and 635 to alanines, respectively...
March 13, 2018: Oncogenesis
Yuichi Miura, Mizuho Morooka, Nicolas Sax, Rahul Roychoudhuri, Ari Itoh-Nakadai, Andrey Brydun, Ryo Funayama, Keiko Nakayama, Susumu Satomi, Mitsuyo Matsumoto, Kazuhiko Igarashi, Akihiko Muto
BTB and CNC homology 2 (Bach2) is a transcriptional repressor that is required for the formation of the germinal center (GC) and reactions, including class switch recombination and somatic hypermutation of Ig genes in B cells, within the GC. Although BCR-induced proliferation is essential for GC reactions, the function of Bach2 in regulating B cell proliferation has not been elucidated. In this study, we demonstrate that Bach2 is required to sustain high levels of B cell proliferation in response to BCR signaling...
March 14, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Valeryi K Lishko, Valentin P Yakubenko, Tatiana P Ugarova, Nataly P Podolnikova
Platelet Factor 4 (PF4) is one of the most abundant cationic proteins secreted from α-granules of activated platelets. Based on its structure, PF4 was assigned to the CXC family of chemokines and has been shown to have numerous effects on myeloid leukocytes. However, the receptor for PF4 remains unknown. Here, we demonstrate that PF4 induces leukocyte responses through the integrin Mac-1 (αM β2 , CD11b/CD18). Human neutrophils, monocytes, U937 monocytic and HEK293 cells expressing Mac-1 strongly adhered to immobilized PF4 in a concentration-dependent manner...
March 14, 2018: Journal of Biological Chemistry
Ronald J Maughan, Louise M Burke, Jiri Dvorak, D Enette Larson-Meyer, Peter Peeling, Stuart M Phillips, Eric S Rawson, Neil P Walsh, Ina Garthe, Hans Geyer, Romain Meeusen, Lucas J C van Loon, Susan M Shirreffs, Lawrence L Spriet, Mark Stuart, Alan Vernec, Kevin Currell, Vidya M Ali, Richard Gm Budgett, Arne Ljungqvist, Margo Mountjoy, Yannis P Pitsiladis, Torbjørn Soligard, Uğur Erdener, Lars Engebretsen
Nutrition usually makes a small but potentially valuable contribution to successful performance in elite athletes, and dietary supplements can make a minor contribution to this nutrition programme. Nonetheless, supplement use is widespread at all levels of sport. Products described as supplements target different issues, including (1) the management of micronutrient deficiencies, (2) supply of convenient forms of energy and macronutrients, and (3) provision of direct benefits to performance or (4) indirect benefits such as supporting intense training regimens...
March 14, 2018: British Journal of Sports Medicine
Sirithip Chuaijit, Worawit Boonyatistan, Pichsinee Boonchuay, Chanatip Metheetrairut, Wichit Suthammarak
Assembly of complex I of the mitochondrial respiratory chain (MRC) requires not only structural subunits for electron transport, but also assembly factors. In the nematode Caenorhabditis elegans, NUAF-1 and NUAF-3 are the only two assembly factors that have been characterized. In this study, we identify ACDH-12 as an assembly factor of the respiratory complex I. We demonstrate for the first time that a deficiency of ACDH-12 affects the formation and function of complex I. RNAi knockdown of acdh-12 also shortens lifespan and decreases fecundity...
March 11, 2018: Mitochondrion
Maria Rosaria Marchili, Elisa Santoro, Alessandra Marchesi, Simona Bianchi, Lelia Rotondi Aufiero, Alberto Villani
BACKGROUND: Vitamin K, a fat soluble vitamin, is a necessary cofactor for the activation of coagulation factors II, VII, IX, X, and protein C and S. In neonatal period, vitamin K deficiency may lead to Vitamin K Deficiency Bleeding (VKDB). CASE PRESENTATION: We present the case of a 2 months and 20 days Caucasian male, presented for bleeding from the injections sites of vaccines. At birth oral vitamin K prophylaxis was administered. Neonatal period was normal...
March 14, 2018: Italian Journal of Pediatrics
Adélaïde Compaoré, Sabine Gies, Bernard Brabin, Halidou Tinto, Loretta Brabin
BACKGROUND: Iron deficiency remains a prevalent adolescent health problem in low income countries. Iron supplementation is recommended but improvement of iron status requires good adherence. OBJECTIVES: We explored factors affecting adolescent adherence to weekly iron and/or folic acid supplements in a setting of low secondary school attendance. METHODS: Taped in-depth interviews were conducted with participants in a randomised, controlled, periconceptional iron supplementation trial for young nulliparous women living in a rural, malaria endemic region of Burkina Faso...
March 14, 2018: Reproductive Health
Margareta Heby, Sebastian Lundgren, Björn Nodin, Jacob Elebro, Jakob Eberhard, Karin Jirström
BACKGROUND: Periampullary adenocarcinomas, including pancreatic cancer, are a heterogeneous group of tumors with poor prognosis, where classification into intestinal type (I-type) or pancreatobiliary type (PB-type) is a relevant prognostic factor. The clinical significance of deficient mismatch repair (dMMR) in periampullary adenocarcinoma is comparatively unexplored. Herein, we examined the associations of MMR immunophenotype with long-term survival in patients with resected periampullary adenocarcinoma, with particular reference to morphology and adjuvant treatment response...
March 14, 2018: Journal of Translational Medicine
Hiroto Kambara, Fei Liu, Xiaoyu Zhang, Peng Liu, Besnik Bajrami, Yan Teng, Li Zhao, Shiyi Zhou, Hongbo Yu, Weidong Zhou, Leslie E Silberstein, Tao Cheng, Mingzhe Han, Yuanfu Xu, Hongbo R Luo
Gasdermin D (GSDMD) is considered a proinflammatory factor that mediates pyroptosis in macrophages to protect hosts from intracellular bacteria. Here, we reveal that GSDMD deficiency paradoxically augmented host responses to extracellular Escherichia coli, mainly by delaying neutrophil death, which established GSDMD as a negative regulator of innate immunity. In contrast to its activation in macrophages, in which activated inflammatory caspases cleave GSDMD to produce an N-terminal fragment (GSDMD-cNT) to trigger pyroptosis, GSDMD cleavage and activation in neutrophils was caspase independent...
March 13, 2018: Cell Reports
K Hari Krishna, Muthuvel Suresh Kumar
Eukaryotic translation initiation factor 2-alpha kinase (EIF2AK) proteins inhibit protein synthesis at translation initiation level, in response to various stress conditions, including oxidative stress, heme deficiency, osmotic shock, and heat shock. Origin and functional diversification of EIF2AK sequences remain ambiguous. Here we determine the origin and molecular evolution of EIF2AK proteins in lower eukaryotes and studied the molecular basis of divergence among sub-family sequences. Present work emphasized primitive origin of EIF2AK4 sub-family gene in lower eukaryotes of protozoan lineage...
2018: PloS One
Marjolein Drent, Petal Wijnen, Aalt Bast
PURPOSE OF REVIEW: Fibrosing interstitial pneumonias are associated with various stages of fibrosis. The cause of this group of syndromes remains largely unknown. For most of these diseases, a genetic basis, environmental factors and certain triggers have been suggested as possible risk factors. Various studies have found an association between genetic polymorphisms, or the presence of certain variant alleles, and the occurrence and/or progression of interstitial pneumonias of unknown origin...
March 13, 2018: Current Opinion in Pulmonary Medicine
Kankan Su, Xiaoxiao Cai, Wenli Xia, Yanhui Jin, Lihong Yang, Mingshan Wang
: The objective is to study a gene mutation (Tyr503Cys) found in a Chinese consanguineous marriage family with inherited factor XI (FXI) deficiency (cross-reacting material positive, type II). The FXI activity and FXI antigen were tested with clotting assay and ELISA, respectively. The FXI gene was amplified by PCR with direct sequencing. ClustalX-2.1-win and three online bioinformatics softwares were used to study the conservatism and harm of the mutation. The proband had reduced FXI: activity at 13%; three members had decreased to about 35%, all of whom had nomal FXI: antigen...
March 13, 2018: Blood Coagulation & Fibrinolysis: An International Journal in Haemostasis and Thrombosis
Antoine Guérin, Gaspard Kerner, Nico Marr, Janet G Markle, Florence Fenollar, Natalie Wong, Sabri Boughorbel, Danielle T Avery, Cindy S Ma, Salim Bougarn, Matthieu Bouaziz, Vivien Beziat, Erika Della Mina, Carmen Oleaga-Quintas, Tomi Lazarovt, Lisa Worley, Tina Nguyen, Etienne Patin, Caroline Deswarte, Rubén Martinez-Barricarte, Soraya Boucherit, Xavier Ayral, Sophie Edouard, Stéphanie Boisson-Dupuis, Vimel Rattina, Benedetta Bigio, Guillaume Vogt, Frédéric Geissmann, Lluis Quintana-Murci, Damien Chaussabel, Stuart G Tangye, Didier Raoult, Laurent Abel, Jacinta Bustamante, Jean-Laurent Casanova
Most humans are exposed to Tropheryma whipplei (Tw). Whipple's disease (WD) strikes only a small minority of individuals infected with Tw (<0.01%), whereas asymptomatic chronic carriage is more common (<25%). We studied a multiplex kindred, containing four WD patients and five healthy Tw chronic carriers. We hypothesized that WD displays autosomal dominant (AD) inheritance, with age-dependent incomplete penetrance. We identified a single very rare non-synonymous mutation in the four patients: the private R98W variant of IRF4, a transcription factor involved in immunity...
March 14, 2018: ELife
V Rochira, G Mossetto, N Jia, S Cannavo, P Beck-Peccoz, G Aimaretti, M R Ambrosio, C Di Somma, M Losa, D Ferone, C Lubrano, C Scaroni, A Giampietro, S M Corsello, M Poggi
PURPOSE: To examine differences in effects according to growth hormone (GH) treatment duration in adult GH-deficient patients. METHODS: In the Italian cohort of the observational Hypopituitary Control and Complications Study, GH-treated adults with GH deficiency (GHD) were grouped by duration of treatment; ≤ 2 years (n = 451), > 2 to ≤ 6 years (n = 387) and > 6 years (n = 395). Between-group differences in demographics, medical history, physical characteristics, insulin-like growth factor-I standard deviation score (IGF-I SDS) and lipid profile at baseline, last study visit and changes from baseline to last study visit were assessed overall, for adult- and childhood-onset GHD and by gender using ANOVA for continuous variables and Chi-squared test for categorical variables...
March 13, 2018: Journal of Endocrinological Investigation
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