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https://www.readbyqxmd.com/read/28928213/cell-cycle-inhibition-to-treat-sleeping-sickness
#1
Conrad L Epting, Brian T Emmer, Nga Y Du, Joann M Taylor, Ming Y Makanji, Cheryl L Olson, David M Engman
African trypanosomiasis is caused by infection with the protozoan parasite Trypanosoma brucei During infection, this pathogen divides rapidly to high density in the bloodstream of its mammalian host in a manner similar to that of leukemia. Like all eukaryotes, T. brucei has a cell cycle involving the de novo synthesis of DNA regulated by ribonucleotide reductase (RNR), which catalyzes the conversion of ribonucleotides into their deoxy form. As an essential enzyme for the cell cycle, RNR is a common target for cancer chemotherapy...
September 19, 2017: MBio
https://www.readbyqxmd.com/read/28923927/mif-and-d-dt-are-potential-disease-severity-modifiers-in-male-ms-subjects
#2
Gil Benedek, Roberto Meza-Romero, Kelley Jordan, Ying Zhang, Ha Nguyen, Gail Kent, Jia Li, Edwin Siu, Jenny Frazer, Marta Piecychna, Xin Du, Antoine Sreih, Lin Leng, Jack Wiedrick, Stacy J Caillier, Halina Offner, Jorge R Oksenberg, Vijayshree Yadav, Dennis Bourdette, Richard Bucala, Arthur A Vandenbark
Little is known about mechanisms that drive the development of progressive multiple sclerosis (MS), although inflammatory factors, such as macrophage migration inhibitory factor (MIF), its homolog D-dopachrome tautomerase (D-DT), and their common receptor CD74 may contribute to disease worsening. Our findings demonstrate elevated MIF and D-DT levels in males with progressive disease compared with relapsing-remitting males (RRMS) and female MS subjects, with increased levels of CD74 in females vs. males with high MS disease severity...
September 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28922373/dynein-light-chain-regulates-adaptive-and-innate-b-cell-development-by-distinctive-genetic-mechanisms
#3
Ashleigh King, Lingli Li, David M Wong, Rui Liu, Rebecca Bamford, Andreas Strasser, David M Tarlinton, Jörg Heierhorst
Mechanistic differences in the development and function of adaptive, high-affinity antibody-producing B-2 cells and innate-like, "natural" antibody-producing B-1a cells remain poorly understood. Here we show that the multi-functional dynein light chain (DYNLL1/LC8) plays important roles in the establishment of B-1a cells in the peritoneal cavity and in the ongoing development of B-2 lymphoid cells in the bone marrow of mice. Epistasis analyses indicate that Dynll1 regulates B-1a and early B-2 cell development in a single, linear pathway with its direct transcriptional activator ASCIZ (ATMIN/ZNF822), and that the two genes also have complementary functions during late B-2 cell development...
September 18, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28921951/a-spring-in-performance-silica-nanosprings-boost-enzyme-immobilization-in-microfluidic-channels
#4
Donya Valikhani, Juan M Bolivar, Martina Viefhues, David Nevil Mcilroy, Elwin Xander Vrouwe, Bernd Nidetzky
Enzyme microreactors are important tools of miniaturized analytics and have promising applications in continuous biomanufacturing. Fundamental problem of their design is that plain microchannels without extensive static internals, or packings, offer limited exposed surface area for immobilizing the enzyme. To boost the immobilization in a manner broadly applicable to enzymes, we coated borosilicate microchannels with silica nanosprings and attached the enzyme, sucrose phosphorylase, via a silica-binding module genetically fused to it...
September 18, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28921694/protease-activated-receptor-2-controls-myelin-development-resiliency-and-repair
#5
Hyesook Yoon, Maja Radulovic, Grant Walters, Alex R Paulsen, Kristen Drucker, Phillip Starski, Jianmin Wu, David P Fairlie, Isobel A Scarisbrick
Oligodendrocytes are essential regulators of axonal energy homeostasis and electrical conduction and emerging target cells for restoration of neurological function. Here we investigate the role of protease activated receptor 2 (PAR2), a unique protease activated G protein-coupled receptor, in myelin development and repair using the spinal cord as a model. Results demonstrate that genetic deletion of PAR2 accelerates myelin production, including higher proteolipid protein (PLP) levels in the spinal cord at birth and higher levels of myelin basic protein and thickened myelin sheaths in adulthood...
September 18, 2017: Glia
https://www.readbyqxmd.com/read/28920489/primer-in-genetics-and-genomics-article-5-further-defining-the-concepts-of-genotype-and-phenotype-and-exploring-genotype-phenotype-associations
#6
Fay Wright, Kristen Fessele
As nurses begin to incorporate genetic and genomic sciences into clinical practice, education, and research, it is essential that they have a working knowledge of the terms foundational to the science. The first article in this primer series provided brief definitions of the basic terms (e.g., genetics and genomics) and introduced the concept of phenotype during the discussion of Mendelian inheritance. These terms, however, are inconsistently used in publications and conversations, and the linkage between genotype and phenotype requires clarification...
October 2017: Biological Research for Nursing
https://www.readbyqxmd.com/read/28918952/a-dual-function-for-prickle-in-regulating-frizzled-stability-during-feedback-dependent-amplification-of-planar-polarity
#7
Samantha J Warrington, Helen Strutt, Katherine H Fisher, David Strutt
The core planar polarity pathway coordinates epithelial cell polarity during animal development, and loss of its activity gives rise to a range of defects, from aberrant morphogenetic cell movements to failure to correctly orient structures, such as hairs and cilia. The core pathway functions via a mechanism involving segregation of its protein components to opposite cells ends, where they form asymmetric intracellular complexes that couple cell-cell polarity. This segregation is a self-organizing process driven by feedback interactions between the core proteins themselves...
September 7, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28916184/role-of-the-il-12-il-35-balance-in-sj%C3%A3-gren-s-syndrome
#8
Olivier Fogel, Elodie Rivière, Raphaèle Seror, Gaetane Nocturne, Saida Boudaoud, Bineta Ly, Jacques-Eric Gottenberg, Véronique Le Guern, Jean-Jacques Dubost, Joanne Nititham, Kimberly E Taylor, Philippe Chanson, Philippe Dieudé, Lindsey A Criswell, Bernd Jagla, Alice Thai, Michael Mingueneau, Xavier Mariette, Corinne Miceli-Richard
BACKGROUND: An interferon (IFN) signature is involved in the pathogenesis of primary Sjögren's syndrome (pSS), but whether the signature is type 1 or 2 remains controversial. Mouse models and genetic studies suggested the involvement of T helper 1 and type 2 IFN pathways. Likewise, polymorphisms of interleukin 12A gene (IL-12A), which encodes for IL-12p35, have been associated with pSS. IL-12p35 subunit is shared by 2 heterodimers, IL-12 and IL-35. OBJECTIVE: To confirm the genetic association of IL-12A polymorphism and pSS and elucidate the involvement of the IL-12/IL-35 balance in pSS by functional studies...
September 12, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28915575/hexokinase-2-promotes-tumor-growth-and-metastasis-by-regulating-lactate-production-in-pancreatic-cancer
#9
Marybeth Anderson, Raoud Marayati, Richard Moffitt, Jen Jen Yeh
Pancreatic ductal adenocarcinoma (PDAC) is a KRAS-driven cancer with a high incidence of metastasis and an overall poor prognosis. Previous work in a genetically engineered mouse model of PDAC showed glucose metabolism to be important for maintaining tumor growth. Multiple glycolytic enzymes, including hexokinase 2 (HK2), were upregulated in primary PDAC patient tumors, supporting a role for glycolysis in promoting human disease. HK2 was most highly expressed in PDAC metastases, suggesting a link between HK2 and aggressive tumor biology...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28914344/influence-of-genetic-co-factors-on-the-population-pharmacokinetic-model-for-clopidogrel-and-its-active-thiol-metabolite
#10
Dorota Danielak, Marta Karaźniewicz-Łada, Anna Komosa, Paweł Burchardt, Maciej Lesiak, Łukasz Kruszyna, Agnieszka Graczyk-Szuster, Franciszek Główka
PURPOSE: A high interindividual variability is observed in the pharmacokinetics of clopidogrel, a widely used antiplatelet drug. In the present study, a joint parent-metabolite population pharmacokinetic model was developed to adequately describe observed concentrations of clopidogrel and its active thiol metabolite (H4). METHODS: The study included 63 patients undergoing elective coronarography or percutaneous coronary intervention. The population pharmacokinetic model was developed in the NONMEM 7...
September 15, 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28912445/cofilin-mediated-neuronal-apoptosis-via-p53-translocation-and-pld1-regulation
#11
Tian Liu, Fang Wang, Patrick LePochat, Jung-A A Woo, Mohammed Zaheen Bukhari, Kyung Woo Hong, Courtney Trotter, David E Kang
Amyloid β (Aβ) accumulation is an early event in the pathogenesis of Alzheimer's disease (AD), leading to mitochondrial and synaptic dysfunction, tau accumulation, and eventual neuronal death. While the p53 apoptotic pathway has clearly been associated with Aβ deposits and neuronal apoptosis, the critical upstream factors contributing to p53 activation in AD are not well understood. We have previously shown that cofilin activation plays a pivotal role in Aβ-induced mitochondrial and synaptic dysfunction...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28911789/a-retrospective-study-of-pregnancy-associated-atypical-hemolytic-uremic-syndrome
#12
Ana Huerta, Emilia Arjona, Jose Portoles, Paula Lopez-Sanchez, Cristina Rabasco, Mario Espinosa, Teresa Cavero, Miquel Blasco, Mercedes Cao, Joaquin Manrique, Virginia Cabello-Chavez, Marta Suñer, Manuel Heras, Xavier Fulladosa, Lara Belmar, Amparo Sempere, Carmen Peralta, Lorena Castillo, Alvaro Arnau, Manuel Praga, Santiago Rodriguez de Cordoba
Pregnancy-associated atypical hemolytic uremic syndrome (aHUS) refers to the thrombotic microangiopathy resulting from uncontrolled complement activation during pregnancy or the postpartum period. Pregnancy-associated aHUS is a devastating disease for which there is a limited clinical understanding and treatment experience. Here we report a retrospective study to analyze the clinical and prognostic data of 22 cases of pregnancy-associated aHUS from the Spanish aHUS Registry under different treatments. Sixteen patients presented during the first pregnancy and as many as nine patients required hemodialysis at diagnosis...
September 11, 2017: Kidney International
https://www.readbyqxmd.com/read/28910986/elimination-of-the-last-reactions-in-ergosterol-biosynthesis-alters-the-resistance-of-saccharomyces-cerevisiae-to-multiple-stresses
#13
Guodong Liu, Yun Chen, Nils J Færgeman, Jens Nielsen
The sterol composition of membranes is known to influence many phenotypes of yeast. However, a systematic study of the relationship between sterol composition and stress resistances has not been conducted. Here, we therefore constructed single or double gene deletion mutants of the last four enzymes in ergosterol biosynthesis in a prototrophic genetic background of Saccharomyces cerevisiae. Identification of the sterol composition of these mutants revealed a high flexibility of the sterol-processing steps instead of the previously proposed sequential conversion...
September 1, 2017: FEMS Yeast Research
https://www.readbyqxmd.com/read/28904214/after-nerve-injury-lineage-tracing-shows-that-myelin-and-remak-schwann-cells-elongate-extensively-and-branch-to-form-repair-schwann-cells-which-shorten-radically-on-remyelination
#14
Jose A Gomez-Sanchez, Kjara S Pilch, Milou van der Lans, Shaline V Fazal, Cristina Benito, Laura J Wagstaff, Rhona Mirsky, Kristjan R Jessen
There is consensus that, distal to peripheral nerve injury, myelin and Remak cells reorganize to form cellular columns, Bungner's bands, which are indispensable for regeneration. However, knowledge of the structure of these regeneration tracks has not advanced for decades and the structure of the cells that form them, denervated or repair Schwann cells, remains obscure. Furthermore, the origin of these cells from myelin and Remak cells and their ability to give rise to myelin cells after regeneration has not been demonstrated directly, although these conversions are believed to be central to nerve repair...
September 13, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28904201/heterogeneity-of-the-epstein-barr-virus-major-internal-repeat-reveals-evolutionary-mechanisms-of-ebv-and-a-functional-defect-in-the-prototype-ebv-strain-b95-8
#15
Mohammed Ba Abdullah, Richard Palermo, Anne Palser, Nicholas E Grayson, Paul Kellam, Samantha Correia, Agnieszka Szymula, Rob White
Epstein-Barr virus (EBV) is a ubiquitous pathogen of humans that can cause several types of lymphoma and carcinoma. Like other herpesviruses, EBV has diversified both through co-evolution with its host, and genetic exchange between virus strains. Sequence analysis of the EBV genome is unusually challenging, because of the large number and length of repeat regions within the virus. Here we describe the sequence assembly and analysis of the large internal repeat of EBV (IR1 or BamW repeats) from over 70 strains...
September 13, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28902217/a-bifunctional-old-yellow-enzyme-from-penicillium-roqueforti-is-involved-in-ergot-alkaloid-biosynthesis
#16
Nina Gerhards, Shu-Ming Li
The blue cheese-making fungus Penicillium roqueforti produces isofumigaclavine A as the main ergot alkaloid. Recently, genome mining revealed the presence of two DNA loci bearing the genetic potential for its biosynthesis. In this study, a short-chain dehydrogenase/reductase (SDR) from one of the loci was proved to be responsible for the conversion of chanoclavine-I to its aldehyde. Furthermore, a putative gene coding for an enzyme with high homology to Old Yellow Enzymes (OYEs) involved in the ergot alkaloid biosynthesis was found outside the two clusters...
September 13, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28900693/complete-genome-sequence-of-geobacillus-thermodenitrificans-t12-a-potential-host-for-biotechnological-applications
#17
Martinus J A Daas, Bastienne Vriesendorp, Antonius H P van de Weijer, John van der Oost, Richard van Kranenburg
In attempt to obtain a thermophilic host for the conversion of lignocellulose derived substrates into lactic acid, Geobacillus thermodenitrificans T12 was isolated from a compost heap. It was selected from over 500 isolates as a genetically tractable hemicellulolytic lactic acid producer, requiring little nutrients. The strain is able to ferment glucose and xylose simultaneously and can produce lactic acid from xylan, making it a potential host for biotechnological applications. The genome of strain T12 consists of a 3...
September 12, 2017: Current Microbiology
https://www.readbyqxmd.com/read/28894301/lateral-hypothalamic-glp-1-receptors-are-critical-for-the-control-of-food-reinforcement-ingestive-behavior-and-body-weight
#18
L López-Ferreras, J E Richard, E E Noble, K Eerola, R H Anderberg, K Olandersson, L Taing, S E Kanoski, M R Hayes, K P Skibicka
Increased motivation for highly rewarding food is a major contributing factor to obesity. Most of the literature focuses on the mesolimbic nuclei as the core of reward behavior regulation. However, the lateral hypothalamus (LH) is also a key reward-control locus in the brain. Here we hypothesize that manipulating glucagon-like peptide-1 receptor (GLP-1R) activity selectively in the LH can profoundly affect food reward behavior, ultimately leading to obesity. Progressive ratio operant responding for sucrose was examined in male and female rats, following GLP-1R activation and pharmacological or genetic GLP-1R blockade in the LH...
September 12, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28887496/differential-gene-expression-profiling-linked-to-tumor-progression-of-splenic-marginal-zone-lymphoma
#19
Tomonori Higuchi, Yumiko Hashida, Ayuko Taniguchi, Mikio Kamioka, Masanori Daibata
The genetic events that lead to aggressive transformation of cases of splenic marginal zone lymphoma (SMZL) after the chronic clinical stage have not been well understood. We aimed to find candidate genes associated with aggressive features of SMZL. We have successfully established two SMZL cell lines, designated SL-15 and SL-22, derived from the same patient's tumor clone in chronic and aggressive phases, respectively. Microarray analysis identified cell cycle-associated genes-specifically PLK1-as the most significantly upregulated in primary aggressive SMZL cells compared with cells from chronic phase...
September 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28887417/high-substrate-uptake-rates-empower-vibrio-natriegens-as-production-host-for-industrial-biotechnology
#20
Eugenia Hoffart, Sebastian Grenz, Julian Lange, Robert Nitschel, Felix Müller, Andreas Schwentner, André Feith, Mira Lenfers-Lücker, Ralf Takors, Bastian Blombach
The productivity of industrial fermentation processes is essentially limited by the biomass specific substrate consumption rate (qS) of the applied microbial production system. Since qS depends on the growth rate (μ), we highlight the potential of the fastest growing non-pathogenic bacterium, Vibrio natriegens, as novel candidate for future biotechnological processes. V. natriegens grows rapidly in BHIN complex medium with a μ of up to 4.43 h(-1) (doubling time of 9.4 min) as well as in minimal medium supplemented with various industrially relevant substrates...
September 8, 2017: Applied and Environmental Microbiology
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