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https://www.readbyqxmd.com/read/28533411/bidirectional-regulation-of-a%C3%AE-levels-by-presenilin-1
#1
Victor Bustos, Maria V Pulina, Yildiz Kelahmetoglu, Subhash C Sinha, Fred S Gorelick, Marc Flajolet, Paul Greengard
Alzheimer's disease (AD) is characterized by accumulation of the β-amyloid peptide (Aβ), which is generated through sequential proteolysis of the amyloid precursor protein (APP), first by the action of β-secretase, generating the β-C-terminal fragment (βCTF), and then by the Presenilin 1 (PS1) enzyme in the γ-secretase complex, generating Aβ. γ-Secretase is an intramembranous protein complex composed of Aph1, Pen2, Nicastrin, and Presenilin 1. Although it has a central role in the pathogenesis of AD, knowledge of the mechanisms that regulate PS1 function is limited...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28532787/evolution-of-avian-encephalomyelitis-virus-during-embryo-adaptation
#2
Rüdiger Hauck, C Gabriel Sentíes-Cué, Ying Wang, Colin Kern, H L Shivaprasad, Huaijun Zhou, Rodrigo A Gallardo
Wild-type avian encephalomyelitis virus (AEV) causes neurological signs in young chicks but no disease in pullets after oral or intracutaneous infection. However, if the virus gets embryo-adapted by serial passaging in chicken embryos, it will cause AE after intracutaneous infection in chickens of all ages. Recently, several cases of AE in layer pullets occurring shortly after intracutaneous vaccination were described. The present investigation was initiated to determine if vaccines that had inadvertently been embryo-adapted were responsible for these outbreaks...
May 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28531315/the-interaction-between-cytosine-methylation-and-processes-of-dna-replication-and-repair-shape-the-mutational-landscape-of-cancer-genomes
#3
Rebecca C Poulos, Jake Olivier, Jason W H Wong
Methylated cytosines (5mCs) are frequently mutated in the genome. However, no studies have yet comprehensively analysed mutation-methylation associations across cancer types. Here we analyse 916 cancer genomes, together with tissue type-specific methylation and replication timing data. We describe a strong mutation-methylation association across colorectal cancer subtypes, most interestingly in samples with microsatellite instability (MSI) or Polymerase epsilon (POLE) exonuclease domain mutations. By analysing genomic regions with differential mismatch repair (MMR) efficiency, we suggest a possible role for MMR in the correction of 5mC deamination events, potentially accounting for the high rate of 5mC mutation accumulation in MSI tumours...
May 22, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28529873/white-matter-hyperintensities-are-seen-only-in-grn-mutation-carriers-in-the-genfi-cohort
#4
Carole H Sudre, Martina Bocchetta, David Cash, David L Thomas, Ione Woollacott, Katrina M Dick, John van Swieten, Barbara Borroni, Daniela Galimberti, Mario Masellis, Maria Carmela Tartaglia, James B Rowe, Caroline Graff, Fabrizio Tagliavini, Giovanni Frisoni, Robert Laforce, Elizabeth Finger, Alexandre de Mendonça, Sandro Sorbi, Sébastien Ourselin, M Jorge Cardoso, Jonathan D Rohrer
Genetic frontotemporal dementia is most commonly caused by mutations in the progranulin (GRN), microtubule-associated protein tau (MAPT) and chromosome 9 open reading frame 72 (C9orf72) genes. Previous small studies have reported the presence of cerebral white matter hyperintensities (WMH) in genetic FTD but this has not been systematically studied across the different mutations. In this study WMH were assessed in 180 participants from the Genetic FTD Initiative (GENFI) with 3D T1- and T2-weighed magnetic resonance images: 43 symptomatic (7 GRN, 13 MAPT and 23 C9orf72), 61 presymptomatic mutation carriers (25 GRN, 8 MAPT and 28 C9orf72) and 76 mutation negative non-carrier family members...
2017: NeuroImage: Clinical
https://www.readbyqxmd.com/read/28528135/presymptomatically-applied-ampa-receptor-antagonist-prevents-calcium-increase-in-vulnerable-type-of-motor-axon-terminals-of-mice-modeling-amyotrophic-lateral-sclerosis
#5
Roland Patai, Melinda Paizs, Massimo Tortarolo, Caterina Bendotti, Izabella Obál, József I Engelhardt, László Siklós
Increased intracellular calcium (Ca), which might be the consequence of an excess influx through Ca-permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, plays a crucial role in degeneration of motor neurons. Previously we demonstrated that the presymptomatic application of AMPA receptor antagonist, talampanel, could reduce Ca elevation in spinal motor neurons of mice carrying the G93A mutation of superoxide dismutase 1 (SOD1), modeling amyotrophic lateral sclerosis (ALS). It remained to be examined whether the remote, functionally semi-autonomous motor axon terminals could be rescued from the Ca overload, or if the terminals, where the degeneration possibly starts, already experience intractable changes at early time points...
May 17, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28522916/early-hepatitis-b-viral-dna-clearance-predicts-treatment-response-at-week-96
#6
Xiao-Yu Fu, De-Ming Tan, Cui-Mei Liu, Bin Gu, Li-Hua Hu, Zhong-Tian Peng, Bin Chen, Yuan-Lin Xie, Huan-Yu Gong, Xiao-Xuan Hu, Lian-Hui Yao, Xiao-Ping Xu, Zheng-Yuan Fu, Lang-Qiu He, Si-Hai Li, Yun-Zhu Long, De-Hui Li, Ji-Long Gu, Shi-Fang Peng
AIM: To investigate whether hepatitis viral DNA load at 24 wk of treatment predicts response at 96 wk in patients with chronic hepatitis B. METHODS: A total of 172 hepatitis B envelope antigen (HBeAg)-positive chronic hepatitis B patients who received initial treatment at 16 tertiary hospitals in Hunan Province, China were enrolled in this study. All patients received conventional doses of lamivudine and adefovir dipivoxil, telbivudine, entecavir dispersible tablets, or entecavir tablets for 96 wk...
April 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28521719/virological-suppression-and-patterns-of-resistance-amongst-patients-on-antiretroviral-therapy-at-4-nigerian-military-hospitals
#7
Keshinro Babajide, Ayemoba Ojor, Terfa Kene, Ake Julie, Crowell Trevor A, Adamu Yakubu, Mohammed Tahir, Okoye Ifeanyi, Odeyemi Sunday, Crawford Keith, Hughes Lindsay, Akintunde Ezekiel, Umar Tahir, Hamm Tiffany E, Njoku Ogbonnaya S
BACKGROUND: In resource-constrained settings, plasma HIV-1 RNA quantification has not been routinely available for the monitoring of response to antiretroviral therapy. This study evaluated virological suppression rates amongst patients on first-line ART in four Nigerian military hospitals. METHODS: We conducted a cross-sectional study of 325 randomly selected adult clinic clients (≥18 years old) on first-line ART regimens at four Nigerian military hospitals. Plasma HIV-1 RNA was assayed using a Roche COBAS TaqMan48 with High Pure System...
May 16, 2017: Current HIV Research
https://www.readbyqxmd.com/read/28520979/the-dead-box-helicase-mss116-plays-distinct-roles-in-mitochondrial-ribogenesis-and-mrna-specific-translation
#8
Dasmanthie De Silva, Sarah Poliquin, Rui Zeng, Angelica Zamudio-Ochoa, Natalie Marrero, Xochitl Perez-Martinez, Flavia Fontanesi, Antoni Barrientos
Members of the DEAD-box family are often multifunctional proteins involved in several RNA transactions. Among them, yeast Saccharomyces cerevisiae Mss116 participates in mitochondrial intron splicing and, under cold stress, also in mitochondrial transcription elongation. Here, we show that Mss116 interacts with the mitoribosome assembly factor Mrh4, is required for efficient mitoribosome biogenesis, and consequently, maintenance of the overall mitochondrial protein synthesis rate. Additionally, Mss116 is required for efficient COX1 mRNA translation initiation and elongation...
May 18, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28512298/genetic-load-makes-cancer-cells-more-sensitive-to-common-drugs-evidence-from-cancer-cell-line-encyclopedia
#9
Ana B Pavel, Kirill S Korolev
Genetic alterations initiate tumors and enable the evolution of drug resistance. The pro-cancer view of mutations is however incomplete, and several studies show that mutational load can reduce tumor fitness. Given its negative effect, genetic load should make tumors more sensitive to anticancer drugs. Here, we test this hypothesis across all major types of cancer from the Cancer Cell Line Encyclopedia, which provides genetic and expression data of 496 cell lines together with their response to 24 common anticancer drugs...
May 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28511389/variability-of-iron-load-in-patients-of-sickle-cell-anaemia-hbss-a-study-from-eastern-india
#10
Pranati Mohanty, Rabindra Kumar Jena, Sudha Sethy
INTRODUCTION: Sickle Cell Anaemia (SCA) is one of the commonest haemoglobinopathies due to a point mutation (A→T) of the β-globin gene. Out of five haplotypes, the Arab-Indian haplotype present in India is one of the least severe phenotype and least studied also. It is characterized by lifelong haemolytic anaemia requiring red cell transfusion leading to iron overload. In contrast, there is very high incidence of deficiency of iron, folic acid and vitamin B12. AIM: Our objective was to access the Iron status of SCA patients and to find its correlation with various parameters like red cell transfusion, haemolysis and serum hepcidin...
March 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28508967/a-case-of-xanthinuria-type-i-with-a-novel-mutation-in-xanthine-dehydrogenase
#11
Akira Iguchi, Takaaki Sato, Mihoko Yamazaki, Kazuyuki Tasaki, Yasushi Suzuki, Noriaki Iino, Hiroshi Hasegawa, Kimiyoshi Ichida, Ichiei Narita
Hereditary hypouricemia is generally caused by renal hypouricemia, an autosomal recessive disorder that is characterized by impaired renal tubular uric acid transport, or by xanthinuria, a rare autosomal recessive disorder caused by a deficiency of xanthine dehydrogenase (XDH; xanthinuria type I) or by a deficiency of both XDH and aldehyde oxidase (xanthinuria type II). In contrast to renal hypouricemia, which sometimes leads to exercise-induced acute kidney injury (EIAKI), xanthinuria has not been associated with this disorder...
November 2016: CEN Case Reports
https://www.readbyqxmd.com/read/28507934/the-challenges-of-recombinant-endostatin-in-clinical-application-focus-on-the-different-expression-systems-and-molecular-bioengineering
#12
REVIEW
Abbas Mohajeri, Sarvin Sanaei, Farhad Kiafar, Amir Fattahi, Majid Khalili, Nosratollah Zarghami
Angiogenesis plays an essential role in rapid growing and metastasis of the tumors. Inhibition of angiogenesis is a putative strategy for cancer therapy. Endostatin (Es) is an attractive anti-angiogenesis protein with some clinical application challenges including; short half-life, instability in serum and requirement to high dosage. Therefore, production of recombinant endostatin (rEs) is necessary in large scale. The production of rEs is difficult because of its structural properties and is high-cost. Therefore, this review focused on the different expression systems that involved in rEs production including; mammalian, baculovirus, yeast, and Escherichia coli (E...
April 2017: Advanced Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28501451/habitual-exercise-levels-are-associated-with-cerebral-amyloid-load-in-presymptomatic-autosomal-dominant-alzheimer-s-disease
#13
Belinda M Brown, Hamid R Sohrabi, Kevin Taddei, Samantha L Gardener, Stephanie R Rainey-Smith, Jeremiah J Peiffer, Chengjie Xiong, Anne M Fagan, Tammie Benzinger, Virginia Buckles, Kirk I Erickson, Roger Clarnette, Tejal Shah, Colin L Masters, Michael Weiner, Nigel Cairns, Martin Rossor, Neill R Graff-Radford, Stephen Salloway, Jonathan Vöglein, Christoph Laske, James Noble, Peter R Schofield, Randall J Bateman, John C Morris, Ralph N Martins
INTRODUCTION: The objective of this study was to evaluate the relationship between self-reported exercise levels and Alzheimer's disease (AD) biomarkers, in a cohort of autosomal dominant AD mutation carriers. METHODS: In 139 presymptomatic mutation carriers from the Dominantly Inherited Alzheimer Network, the relationship between self-reported exercise levels and brain amyloid load, cerebrospinal fluid (CSF) Aβ42, and CSF tau levels was evaluated using linear regression...
May 11, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28500754/mutational-phospho-mimicry-reveals-a-regulatory-role-for-the-xrcc4-and-xlf-c-terminal-tails-in-modulating-dna-bridging-during-classical-non-homologous-end-joining
#14
Davide Normanno, Aurélie Négrel, Abinadabe J de Melo, Stéphane Betzi, Katheryn Meek, Mauro Modesti
XRCC4 and DNA Ligase 4 (LIG4) form a tight complex that provides DNA ligase activity for classical non-homologous end joining (the predominant DNA double-strand break repair pathway in higher eukaryotes) and is stimulated by XLF. Independently of LIG4, XLF also associates with XRCC4 to form filaments that bridge DNA. These XRCC4/XLF complexes rapidly load and connect broken DNA, thereby stimulating intermolecular ligation. XRCC4 and XLF both include disordered C-terminal tails that are functionally dispensable in isolation but are phosphorylated in response to DNA damage by DNA-PK and/or ATM...
May 13, 2017: ELife
https://www.readbyqxmd.com/read/28500398/comparative-clinical-utility-of-tumor-genomic-testing-and-cell-free-dna-in-metastatic-breast-cancer
#15
Kara N Maxwell, Danielle Soucier-Ernst, Emin Tahirovic, Andrea B Troxel, Candace Clark, Michael Feldman, Christopher Colameco, Bijal Kakrecha, Melissa Langer, David Lieberman, Jennifer J D Morrissette, Matt R Paul, Tien-Chi Pan, Stephanie Yee, Natalie Shih, Erica Carpenter, Lewis A Chodosh, Angela DeMichele
PURPOSE: Breast cancer metastases differ biologically from primary disease; therefore, metastatic biopsies may assist in treatment decision making. Commercial genomic testing of both tumor and circulating tumor DNA have become available clinically, but utility of these tests in breast cancer management remains unclear. METHODS: Patients undergoing a clinically indicated metastatic tumor biopsy were consented to the ongoing METAMORPH registry. Tumor and blood were collected at the time of disease progression before subsequent therapy, and patients were followed for response on subsequent treatment...
May 12, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28499009/a-viral-suppressor-of-rna-silencing-inhibits-argonaute-1-function-by-precluding-target-rna-binding-to-pre-assembled-risc
#16
Erzsébet Kenesi, Alberto Carbonell, Rita Lózsa, Beáta Vértessy, Lóránt Lakatos
In most eukaryotes, RNA silencing is an adaptive immune system regulating key biological processes including antiviral defense. To evade this response, viruses of plants, worms and insects have evolved viral suppressors of RNA silencing proteins (VSRs). Various VSRs, such as P1 from Sweet potato mild mottle virus (SPMMV), inhibit the activity of RNA-induced silencing complexes (RISCs) including an ARGONAUTE (AGO) protein loaded with a small RNA. However, the specific mechanisms explaining this class of inhibition are unknown...
May 12, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28494793/real-time-pcr-assays-for-hepatitis-b-virus-dna-quantification-may-require-two-different-targets
#17
Chao Liu, Le Chang, Tingting Jia, Fei Guo, Lu Zhang, Huimin Ji, Junpeng Zhao, Lunan Wang
BACKGROUND: Quantification Hepatitis B virus (HBV) DNA plays a critical role in the management of chronic HBV infections. However, HBV is a DNA virus with high levels of genetic variation, and drug-resistant mutations have emerged with the use of antiviral drugs. If a mutation caused a sequence mismatched in the primer or probe of a commercial DNA quantification kit, this would lead to an underestimation of the viral load of the sample. The aim of this study was to determine whether commercial kits, which use only one pair of primers and a single probe, accurately quantify the HBV DNA levels and to develop an improved duplex real-time PCR assay...
May 12, 2017: Virology Journal
https://www.readbyqxmd.com/read/28494446/mutation-load-of-multiple-ion-channel-gene-mutations-in-brugada-syndrome
#18
Francesca Gualandi, Fatima Zaraket, Michele Malagù, Giulia Parmeggiani, Cecilia Trabanelli, Sergio Fini, Xiao Dang, Xiaoming Wei, Mingyan Fang, Matteo Bertini, Roberto Ferrari, Alessandra Ferlini
Brugada syndrome is a primary arrhythmic syndrome that accounts for 20% of all sudden cardiac death cases in individuals with a structurally normal heart. Pathogenic variants associated with Brugada syndrome have been identified in over 19 genes, with SCN5A as a pivotal gene accounting for nearly 30% of cases. In contrast to other arrhythmogenic channelopathies (such as long QT syndrome), digenic inheritance has never been reported in Brugada syndrome. Exploring 66 cardiac genes using a new custom next-generation sequencing panel, we identified a double heterozygosity for pathogenic mutations in SCN5A and TRPM4 in a Brugada syndrome patient...
May 12, 2017: Cardiology
https://www.readbyqxmd.com/read/28493171/immunotherapy-in-urothelial-cancer-recent-results-and-future-perspectives
#19
REVIEW
Matthew S Farina, Kevin T Lundgren, Joaquim Bellmunt
Cytotoxic chemotherapy has been the only systemic treatment of locally advanced and metastatic urothelial carcinoma for decades. Long-term survival remains stagnant around 12-14 months for patients with advanced disease who have progressed on or recurred after receiving first-line platinum-based chemotherapy. Improving clinical outcomes for patients with urothelial carcinoma in all disease settings requires the development of novel treatments, especially for patients who failed on first-line chemotherapy. Since the discovery of intravesical Bacillus-Calmette Guerin (BCG) in the 1970s for non-muscle invasive disease, there have not been any major breakthrough drugs that exploit the immune-sensitivity of bladder cancer until recently...
May 11, 2017: Drugs
https://www.readbyqxmd.com/read/28491135/highlights-from-the-15th-st-gallen-international-breast-cancer-conference-15-18-march-2017-vienna-tailored-treatments-for-patients-with-early-breast-cancer
#20
Consuelo Morigi
The 15th St Gallen International Breast Cancer Conference was held in Vienna for the second time, from 15th-18th March 2017. 4000 people from 105 countries all over the world were invited to take part in the event. The real highlight of the conference was the last day with the International Consensus Session which was chaired by around 50 experts on breast cancer worldwide. With reference to data from scientific research, the consensus panel tried to offer guidelines for the management of breast cancer with the aim of providing patients with optimal treatment...
2017: Ecancermedicalscience
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