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protein S deficiency

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https://www.readbyqxmd.com/read/28640740/differential-effects-of-isc-operon-mutations-on-the-biosynthesis-and-activity-of-key-anaerobic-metalloenzymes-in-escherichia-coli
#1
Monique Jaroschinsky, Constanze Pinske, R Gary Sawers
Escherichia coli has two machineries for the synthesis of FeS clusters, namely Isc (iron-sulfur cluster) and Suf (sulfur formation). The Isc machinery, encoded by the iscRSUA-hscBA-fdx-iscXoperon, plays a crucial role in the biogenesis of FeS clusters for the oxidoreductases of aerobic metabolism. Less is known, however, about the role of ISC in the maturation of key multi-subunit metalloenzymes of anaerobic metabolism. Here, we determined the contribution of each iscoperon gene product towards the functionality of the major anaerobic oxidoreductases in E...
June 22, 2017: Microbiology
https://www.readbyqxmd.com/read/28634538/prevalence-and-clinical-impact-of-vitamin-d-deficiency-on-abdominal-tuberculosis
#2
Vishal Sharma, Harshal S Mandavdhare, Amit Kumar, Ravi Sharma, Naresh Sachdeva, Kaushal K Prasad, Surinder S Rana
BACKGROUND: Vitamin D is recognised to have multiple actions, including role in immune modulation. The prevalence and impact of vitamin D deficiency (VDD) in abdominal tuberculosis is unknown. METHODS: We report the prevalence and clinical impact of VDD in patients with abdominal tuberculosis. The patients were divided into two groups: VDD (<20 ng/ml) or vitamin D sufficient (VDS) (⩾20 ng/ml). Groups were compared for extent (abdominal alone or extra-abdominal also) of disease and pattern of involvement (intestinal, peritoneal or both) and inflammatory response [serum C-reactive protein (CRP)]...
May 2017: Therapeutic Advances in Infectious Disease
https://www.readbyqxmd.com/read/28630339/ucp1-deficiency-causes-brown-fat-respiratory-chain-depletion-and-sensitizes-mitochondria-to-calcium-overload-induced-dysfunction
#3
Lawrence Kazak, Edward T Chouchani, Irina G Stavrovskaya, Gina Z Lu, Mark P Jedrychowski, Daniel F Egan, Manju Kumari, Xingxing Kong, Brian K Erickson, John Szpyt, Evan D Rosen, Michael P Murphy, Bruce S Kristal, Steven P Gygi, Bruce M Spiegelman
Brown adipose tissue (BAT) mitochondria exhibit high oxidative capacity and abundant expression of both electron transport chain components and uncoupling protein 1 (UCP1). UCP1 dissipates the mitochondrial proton motive force (Δp) generated by the respiratory chain and increases thermogenesis. Here we find that in mice genetically lacking UCP1, cold-induced activation of metabolism triggers innate immune signaling and markers of cell death in BAT. Moreover, global proteomic analysis reveals that this cascade induced by UCP1 deletion is associated with a dramatic reduction in electron transport chain abundance...
June 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28630280/ki-67-contributes-to-normal-cell-cycle-progression-and-inactive-x-heterochromatin-in-p21-checkpoint-proficient-human-cells
#4
Xiaoming Sun, Aizhan Bizhanova, Timothy D Matheson, Jun Yu, Julie L Zhu, Paul D Kaufman
Ki-67 protein is widely used as a tumor proliferation marker. However, whether Ki-67 affects cell cycle progression has been controversial. Here, we demonstrate that depletion of Ki-67 in human hTERT-RPE1, WI-38, IMR90, hTERT-BJ cell lines and primary fibroblast cells slowed entry into S phase and coordinately downregulated genes related to DNA replication. Some gene expression changes were partially relieved in Ki-67-depleted hTERT-RPE1 cells by co-depletion of the Rb checkpoint protein, but more thorough suppression of the transcriptional and cell cycle defects was observed upon depletion of cell cycle inhibitor p21...
June 19, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28630137/structure-and-function-of-dhhc-protein-s-acyltransferases
#5
REVIEW
Colin D Gottlieb, Maurine E Linder
It has been estimated that 10% of the human genome encodes proteins that are fatty acylated at cysteine residues. The vast majority of these proteins are modified by members of the DHHC protein family, which carry out their enzymatic function on the cytoplasmic face of cell membranes. The biomedical importance of DHHC proteins is underscored by their association with human disease; unique and essential roles for DHHC proteins have been uncovered using DHHC-deficient mouse models. Accordingly, there is great interest in elucidating the molecular mechanisms that underlie DHHC protein function...
June 19, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28630090/t-cell-transcriptomes-from-paroxysmal-nocturnal-hemoglobinuria-patients-reveal-novel-signaling-pathways
#6
Kohei Hosokawa, Sachiko Kajigaya, Keyvan Keyvanfar, Wangmin Qiao, Yanling Xie, Danielle M Townsley, Xingmin Feng, Neal S Young
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired disorder originating from hematopoietic stem cells and is a life-threating disease characterized by intravascular hemolysis, bone marrow (BM) failure, and venous thrombosis. The etiology of PNH is a somatic mutation in the phosphatidylinositol glycan class A gene (PIG-A) on the X chromosome, which blocks synthesis of the glycolipid moiety and causes deficiency in GPI-anchored proteins. PNH is closely related to aplastic anemia, in which T cells mediate destruction of BM...
June 19, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28627412/macrophages-regulate-unilateral-ureteral-obstruction-induced-renal-lymphangiogenesis-through-c-c-motif-chemokine-receptor-2-dependent-phosphatidylinositol-3-kinase-akt-mechanistic-target-of%C3%A2-rapamycin-signaling-and-hypoxia-inducible-factor-1%C3%AE-vascular-endothelial
#7
Yan-Chao Guo, Meng Zhang, Fa-Xi Wang, Guang-Chang Pei, Fei Sun, Ying Zhang, Xiaoyu He, Yi Wang, Jia Song, Feng-Ming Zhu, Nuruliarizki S Pandupuspitasari, Jing Liu, Kun Huang, Ping Yang, Fei Xiong, Shu Zhang, Qilin Yu, Ying Yao, Cong-Yi Wang
Lymphangiogenesis occurs during renal fibrosis in patients with chronic kidney diseases and vascular endothelial growth factor (VEGF)-C is required for the formation of lymphatic vessels; however, the underlying mechanisms remain unclear. We demonstrate that macrophages can regulate unilateral ureteral obstruction (UUO)-induced renal lymphangiogenesis by expressing high levels of VEGF-C by C-C motif chemokine receptor 2 (CCR2)-mediated signaling. Mice deficient in Ccr2 manifested repressed lymphangiogenesis along with attenuated renal injury and fibrosis after UUO induction...
June 13, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28627093/characterization-of-thrombosis-in-patients-with-proteus-syndrome
#8
Kim M Keppler-Noreuil, Jay N Lozier, Julie C Sapp, Leslie G Biesecker
Patients with overgrowth and complex vascular malformation syndromes, including Proteus syndrome have an increased risk of thromboembolism. Proteus syndrome is a mosaic, progressive overgrowth disorder involving vasculature, skin, and skeleton, and caused by a somatic activating mutation in AKT1. We conducted a comprehensive review of the medical histories and hematologic evaluations of 57 patients with Proteus syndrome to identify potential risk factors for thrombosis. We found that six of ten patients, who were deceased, died secondary to deep venous thrombosis and/or pulmonary embolism...
June 19, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28623080/increased-constitutive-nitric-oxide-production-by-whole-body-periodic-acceleration-ameliorates-alterations-in-cardiomyocytes-associated-with-utrophin-dystrophin-deficiency
#9
Jose R Lopez, Juan Kolster, Rui Zhang, Jose Adams
Duchenne Muscular Dystrophy (DMD) cardiomyopathy is a progressive lethal disease caused by the lack of the dystrophin protein in the heart. The most widely used animal model of DMD is the dystrophin-deficient mdx mouse; however, these mice exhibit a mild dystrophic phenotype with heart failure only late in life. In contrast, mice deficient for both dystrophin and utrophin (mdx/utrn(-/-), or dKO) can be used to model severe DMD cardiomyopathy where pathophysiological indicators of heart failure are detectable by 8-10weeks of age...
June 13, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28621910/allospecific-memory-b-cell-responses-are-dependent-on-autophagy
#10
Miguel Fribourg, Jie Ni, F Nina Papavasiliou, Zhenyu Yue, Peter S Heeger, Jeremy S Leventhal
Long-lived, donor-reactive memory B cells (Bmem) can produce alloantibodies that mediate transplant injury. Autophagy, an intrinsic mechanism of cell organelle/component recycling, is required for Bmem survival in infectious and model antigen systems but whether autophagy impacts alloreactive Bmem is unknown. We studied mice with an inducible yellow fluorescent protein (YFP) reporter expressed under the Activation-Induced Cytidine Deaminase (AID) promoter active in B cells undergoing germinal center reactions...
June 16, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28619052/heterologous-expression-of-an-%C3%AE-amylase-inhibitor-from-common-bean-phaseolus-vulgaris-in-kluyveromyces-lactis-and-saccharomyces-cerevisiae
#11
Stephanie Brain-Isasi, Alejandro Álvarez-Lueje, Thomas Joseph V Higgins
BACKGROUND: Phaseolamin or α-amylase inhibitor 1 (αAI) is a glycoprotein from common beans (Phaseolus vulgaris L.) that inhibits some insect and mammalian α-amylases. Several clinical studies support the beneficial use of bean αAI for control of diabetes and obesity. Commercial extracts of P. vulgaris are available but their efficacy is still under question, mainly because some of these extracts contain antinutritional impurities naturally present in bean seeds and also exhibit a lower specific activity αAI...
June 15, 2017: Microbial Cell Factories
https://www.readbyqxmd.com/read/28617419/utilization-of-genomic-sequencing-for-population-screening-of-immunodeficiencies-in-the-newborn
#12
Ashleigh R Pavey, Dale L Bodian, Thierry Vilboux, Alina Khromykh, Natalie S Hauser, Kathi Huddleston, Elisabeth Klein, Aaron Black, Megan S Kane, Ramaswamy K Iyer, John E Niederhuber, Benjamin D Solomon
PurposeImmunodeficiency screening has been added to many state-directed newborn screening programs. The current methodology is limited to screening for severe T-cell lymphopenia disorders. We evaluated the potential of genomic sequencing to augment current newborn screening for immunodeficiency, including identification of non-T cell disorders.MethodsWe analyzed whole-genome sequencing (WGS) and clinical data from a cohort of 1,349 newborn-parent trios by genotype-first and phenotype-first approaches. For the genotype-first approach, we analyzed predicted protein-impacting variants in 329 immunodeficiency-related genes in the WGS data...
June 15, 2017: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/28615259/adjusting-ferritin-concentrations-for-inflammation-biomarkers-reflecting-inflammation-and-nutritional-determinants-of-anemia-brinda-project
#13
REVIEW
Sorrel Ml Namaste, Fabian Rohner, Jin Huang, Nivedita L Bhushan, Rafael Flores-Ayala, Roland Kupka, Zuguo Mei, Rahul Rawat, Anne M Williams, Daniel J Raiten, Christine A Northrop-Clewes, Parminder S Suchdev
Background: The accurate estimation of iron deficiency is important in planning and implementing interventions. Ferritin is recommended as the primary measure of iron status, but interpretability is challenging in settings with infection and inflammation.Objective: We assessed the relation between ferritin concentrations and inflammation and malaria in preschool children (PSC) (age range: 6-59 mo) and women of reproductive age (WRA) (age range: 15-49 y) and investigated adjustment algorithms to account for these effects...
June 14, 2017: American Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28615256/adjusting-soluble-transferrin-receptor-concentrations-for-inflammation-biomarkers-reflecting-inflammation-and-nutritional-determinants-of-anemia-brinda-project
#14
REVIEW
Fabian Rohner, Sorrel Ml Namaste, Leila M Larson, O Yaw Addo, Zuguo Mei, Parminder S Suchdev, Anne M Williams, Fayrouz A Sakr Ashour, Rahul Rawat, Daniel J Raiten, Christine A Northrop-Clewes
Background: Iron deficiency is thought to be one of the most prevalent micronutrient deficiencies globally, but an accurate assessment in populations who are frequently exposed to infections is impeded by the inflammatory response, which causes iron-biomarker alterations.Objectives: We assessed the relation between soluble transferrin receptor (sTfR) concentrations and inflammation and malaria in preschool children (PSC) (age range: 6-59 mo) and women of reproductive age (WRA) (age range: 15-49 y) and investigated adjustment algorithms to account for these effects...
June 14, 2017: American Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28615255/adjusting-total-body-iron-for-inflammation-biomarkers-reflecting-inflammation-and-nutritional-determinants-of-anemia-brinda-project
#15
REVIEW
Zuguo Mei, Sorrel Ml Namaste, Mary Serdula, Parminder S Suchdev, Fabian Rohner, Rafael Flores-Ayala, O Yaw Addo, Daniel J Raiten
Background: Total body iron (TBI) that is calculated from ferritin and soluble transferrin receptor (sTfR) allows for the evaluation of the full range of iron status from deficiency to excess. However, both ferritin and sTfR are affected by inflammation and malaria, which may require a statistical adjustment. TBI has been used to assess iron status in the United States, but its use worldwide and in settings with inflammation has been limited.Objective: We examine whether inflammation-adjusted ferritin and sTfR concentrations affect TBI values and the prevalence of low TBI (<0 mg/kg) in preschool children (PSC) (age range: 6-59 mo) and women of reproductive age (WRA) (age range: 15-49 y)...
June 14, 2017: American Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28615254/methodologic-approach-for-the-biomarkers-reflecting-inflammation-and-nutritional-determinants-of-anemia-brinda-project
#16
REVIEW
Sorrel Ml Namaste, Grant J Aaron, Ravi Varadhan, Janet M Peerson, Parminder S Suchdev
Background: The Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project is a multiagency and multicountry collaboration that was formed to improve micronutrient assessment and to better characterize anemia.Objectives: The aims of the project were to 1) identify factors associated with inflammation, 2) assess the relations between inflammation, malaria infection, and biomarkers of iron and vitamin A status and compare adjustment approaches, and 3) assess risk factors for anemia in preschool children (PSC) and women of reproductive age (WRA)...
June 14, 2017: American Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28615251/adjusting-retinol-binding-protein-concentrations-for-inflammation-biomarkers-reflecting-inflammation-and-nutritional-determinants-of-anemia-brinda-project
#17
REVIEW
Leila M Larson, Sorrel Ml Namaste, Anne M Williams, Reina Engle-Stone, O Yaw Addo, Parminder S Suchdev, James P Wirth, Victor Temple, Mary Serdula, Christine A Northrop-Clewes
Background: The accurate estimation of the prevalence of vitamin A deficiency (VAD) is important in planning and implementing interventions. Retinol-binding protein (RBP) is often used in population surveys to measure vitamin A status, but its interpretation is challenging in settings where inflammation is common because RBP concentrations decrease during the acute-phase response.Objectives: We aimed to assess the relation between RBP concentrations and inflammation and malaria in preschool children (PSC) (age range: 6-59 mo) and women of reproductive age (WRA) (age range: 15-49 y) and to investigate adjustment algorithms to account for these effects...
June 14, 2017: American Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28615047/sensitivity-to-sevoflurane-anesthesia-is-decreased-in-mice-with-a-congenital-deletion-of-guanylyl-cyclase-1-alpha
#18
Yasuko Nagasaka, Martin Wepler, Robrecht Thoonen, Patrick Y Sips, Kaitlin Allen, Jan A Graw, Vincent Yao, Sara M Burns, Stefan Muenster, Peter Brouckaert, Keith Miller, Ken Solt, Emmanuel S Buys, Fumito Ichinose, Warren M Zapol
BACKGROUND: Volatile anesthetics increase levels of the neurotransmitter nitric oxide (NO) and the secondary messenger molecule cyclic guanosine monophosphate (cGMP) in the brain. NO activates the enzyme guanylyl cyclase (GC) to produce cGMP. We hypothesized that the NO-GC-cGMP pathway contributes to anesthesia-induced unconsciousness. METHODS: Sevoflurane-induced loss and return of righting reflex (LORR and RORR, respectively) were studied in wild-type mice (WT) and in mice congenitally deficient in the GC-1α subunit (GC-1(-/-) mice)...
June 14, 2017: BMC Anesthesiology
https://www.readbyqxmd.com/read/28614791/human-vaccination-against-plasmodium-vivax-duffy-binding-protein-induces-strain-transcending-antibodies
#19
Ruth O Payne, Sarah E Silk, Sean C Elias, Kathryn H Milne, Thomas A Rawlinson, David Llewellyn, A Rushdi Shakri, Jing Jin, Geneviève M Labbé, Nick J Edwards, Ian D Poulton, Rachel Roberts, Ryan Farid, Thomas Jørgensen, Daniel Gw Alanine, Simone C de Cassan, Matthew K Higgins, Thomas D Otto, James S McCarthy, Willem A de Jongh, Alfredo Nicosia, Sarah Moyle, Adrian Vs Hill, Eleanor Berrie, Chetan E Chitnis, Alison M Lawrie, Simon J Draper
BACKGROUND: Plasmodium vivax is the most widespread human malaria geographically; however, no effective vaccine exists. Red blood cell invasion by the P. vivax merozoite depends on an interaction between the Duffy antigen receptor for chemokines (DARC) and region II of the parasite's Duffy-binding protein (PvDBP_RII). Naturally acquired binding-inhibitory antibodies against this interaction associate with clinical immunity, but it is unknown whether these responses can be induced by human vaccination...
June 15, 2017: JCI Insight
https://www.readbyqxmd.com/read/28613987/methyl-%C3%AE-cyclodextrin-restores-impaired-autophagy-flux-in-niemann-pick-c1-deficient-cells-through-activation-of-ampk
#20
Sheng Dai, Andrés E Dulcey, Xin Hu, Christopher A Wassif, Forbes D Porter, Christopher P Austin, Daniel S Ory, Juan Marugan, Wei Zheng
The drug 2-hydroxypropyl-β-cyclodextrin (HPβCD) reduces lysosomal cholesterol accumulation in Niemann-Pick disease, type C (NPC) and has been advanced to human clinical trials. However, its mechanism of action for reducing cholesterol accumulation in NPC cells is uncertain and its molecular target is unknown. We found that methyl-β-cyclodextrin (MβCD), a potent analog of HPβCD, restored impaired macroautophagy/autophagy flux in Niemann-Pick disease, type C1 (NPC1) cells. This effect was mediated by a direct activation of AMP-activated protein kinase (AMPK), an upstream kinase in the autophagy pathway, through MβCD binding to its β-subunits...
June 14, 2017: Autophagy
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