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https://www.readbyqxmd.com/read/29458168/apoptosis-of-enterocytes-and-nitration-of-junctional-complex-proteins-promote-alcohol-induced-gut-leakiness-and-liver-injury
#1
Young-Eun Cho, Li-Rong Yu, Mohamed A Abdelmegeed, Seong-Ho Yoo, Byoung-Joon Song
BACKGROUND & AIMS: Binge alcohol causes gut leakiness, contributing to increased endotoxemia and inflammatory liver injury, although the molecular mechanisms are still elusive. This study was aimed at investigating the roles of apoptosis of enterocytes and nitration followed by degradation of intestinal tight junction (TJ) and adherent junction (AJ) proteins in binge alcohol-induced gut leakiness. METHODS: The levels of intestinal (ileum) junctional complex proteins, oxidative stress markers and apoptosis-related proteins in rodents, T84 colonic cells and autopsied human ileums were determined by immunoblot, immunoprecipitation, immunofluorescence, and mass-spectral analyses...
February 16, 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/29458012/klf10-gene-expression-modulates-fibrosis-in-dystrophic-skeletal-muscle
#2
Joseph X DiMario
Dystrophic skeletal muscle is characterized by fibrotic accumulation of extracellular matrix components that compromise muscle structure, function, and capacity for regeneration. Tissue fibrosis is often initiated and sustained through transforming growth factor β (TGFβ) signaling, and KLF10 is an immediate early gene that is transcriptionally activated in response to TGFβ signaling. It encodes a transcriptional regulator that mediates the effects of TGFβ signaling in a variety of cell types. This report presents results of investigation of the effects of loss of KLF10 gene expression in wild-type and dystrophic (mdx) skeletal muscle...
February 16, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29456763/causal-effect-of-smoking-on-dna-methylation-in-peripheral-blood-a-twin-and-family-study
#3
Shuai Li, Ee Ming Wong, Minh Bui, Tuong L Nguyen, Ji-Hoon Eric Joo, Jennifer Stone, Gillian S Dite, Graham G Giles, Richard Saffery, Melissa C Southey, John L Hopper
Background: Smoking has been reported to be associated with peripheral blood DNA methylation, but the causal aspects of the association have rarely been investigated. We aimed to investigate the association and underlying causation between smoking and blood methylation. Methods: The methylation profile of DNA from the peripheral blood, collected as dried blood spots stored on Guthrie cards, was measured for 479 Australian women including 66 monozygotic twin pairs, 66 dizygotic twin pairs, and 215 sisters of twins from 130 twin families using the Infinium HumanMethylation450K BeadChip array...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29456407/analysis-of-hepatitis-b-virus-pres1-variability-and-prevalence-of-the-rs2296651-polymorphism-in-a-spanish-population
#4
Rosario Casillas, David Tabernero, Josep Gregori, Irene Belmonte, Maria Francesca Cortese, Carolina González, Mar Riveiro-Barciela, Rosa Maria López, Josep Quer, Rafael Esteban, Maria Buti, Francisco Rodríguez-Frías
AIM: To determine the variability/conservation of the domain of hepatitis B virus (HBV) preS1 region that interacts with sodium-taurocholate cotransporting polypeptide (hereafter, NTCP-interacting domain) and the prevalence of the rs2296651 polymorphism (S267F, NTCP variant) in a Spanish population. METHODS: Serum samples from 246 individuals were included and divided into 3 groups: patients with chronic HBV infection (CHB) ( n = 41, 73% Caucasians), patients with resolved HBV infection ( n = 100, 100% Caucasians) and an HBV-uninfected control group ( n = 105, 100% Caucasians)...
February 14, 2018: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29456190/pink1-phosphorylates-mic60-mitofilin-to-control-structural-plasticity-of-mitochondrial-crista-junctions
#5
Pei-I Tsai, Chin-Hsien Lin, Chung-Han Hsieh, Amanda M Papakyrikos, Min Joo Kim, Valerio Napolioni, Carmen Schoor, Julien Couthouis, Ruey-Meei Wu, Zbigniew K Wszolek, Dominic Winter, Michael D Greicius, Owen A Ross, Xinnan Wang
Mitochondrial crista structure partitions vital cellular reactions and is precisely regulated by diverse cellular signals. Here, we show that, in Drosophila, mitochondrial cristae undergo dynamic remodeling among distinct subcellular regions and the Parkinson's disease (PD)-linked Ser/Thr kinase PINK1 participates in their regulation. Mitochondria increase crista junctions and numbers in selective subcellular areas, and this remodeling requires PINK1 to phosphorylate the inner mitochondrial membrane protein MIC60/mitofilin, which stabilizes MIC60 oligomerization...
February 14, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29456189/programmable-rna-cleavage-and-recognition-by-a-natural-crispr-cas9-system-from-neisseria-meningitidis
#6
Beth A Rousseau, Zhonggang Hou, Max J Gramelspacher, Yan Zhang
The microbial CRISPR systems enable adaptive defense against mobile elements and also provide formidable tools for genome engineering. The Cas9 proteins are type II CRISPR-associated, RNA-guided DNA endonucleases that identify double-stranded DNA targets by sequence complementarity and protospacer adjacent motif (PAM) recognition. Here we report that the type II-C CRISPR-Cas9 from Neisseria meningitidis (Nme) is capable of programmable, RNA-guided, site-specific cleavage and recognition of single-stranded RNA targets and that this ribonuclease activity is independent of the PAM sequence...
February 14, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29455626/diagnosis-of-anaplastic-large-cell-lymphoma-in-a-dog-using-cd30-immunohistochemistry
#7
Rachel Pittaway, Ying Wu, Balazs Szladovits, Alejandro Suárez-Bonnet, Emma J Scurrell, Oliver A Garden, Gerry Polton, Simon L Priestnall
Anaplastic large-cell lymphoma or null-cell lymphoma is a clinical entity reported in people, classified according to the unique appearance of large pleomorphic cells that express CD30. Null-cell lymphoma has also been described in dogs when neither CD3 nor CD79α is expressed by the tumor. We describe a case of lymphoma in the dog in which neoplastic cells did not express routine B- or T-lymphocyte markers on flow cytometry or immunohistochemistry; however, cells immunohistochemically labeled for CD30. The dog in our case died 5 mo after initial presentation, confirming a poor prognosis...
February 1, 2018: Journal of Veterinary Diagnostic Investigation
https://www.readbyqxmd.com/read/29455446/big2-arf1-rhoa-mdia1-signaling-regulates-dendritic-golgi-polarization-in-hippocampal-neurons
#8
Eun-Hye Hong, Ji-Ye Kim, Jeong-Hoon Kim, Dae-Sik Lim, Minkyu Kim, Jeong-Yoon Kim
Proper dendrite development is essential for establishing neural circuitry, and Rho GTPases play key regulatory roles in this process. From mouse brain lysates, we identified Brefeldin A-inhibited guanine exchange factor 2 (BIG2) as a novel Rho GTPase regulatory protein involved in dendrite growth and maintenance. BIG2 was highly expressed during early development, and knockdown of the ARFGEF2 gene encoding BIG2 significantly reduced total dendrite length and the number of branches. Expression of the constitutively active ADP-ribosylation factor 1 ARF1 Q71L rescued the defective dendrite morphogenesis of ARFGEF2-null neurons, indicating that BIG2 controls dendrite growth and maintenance by activating ARF1...
February 17, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29454706/gata6-phosphorylation-by-erk1-2-propels-exit-from-pluripotency-and-commitment-to-primitive-endoderm
#9
Yue Meng, Robert Moore, Wensi Tao, Elizabeth R Smith, Jeffrey D Tse, Corrado Caslini, Xiang-Xi Xu
The transcription factor GATA6 and the Fgf/Ras/MAPK signaling pathway are essential for the development of the primitive endoderm (PrE), one of the two lineages derived from the pluripotent inner cell mass (ICM) of mammalian blastocysts. A mutant mouse line in which Gata6-coding exons are replaced with H2BGFP (histone H2B Green Fluorescence Protein fusion protein) was developed to monitor Gata6 promoter activity. In the Gata6-H2BGFP heterozygous blastocysts, the ICM cells that initially had uniform GFP fluorescence signal at E3...
February 15, 2018: Developmental Biology
https://www.readbyqxmd.com/read/29454255/effects-of-adjunctive-eslicarbazepine-acetate-on-neurocognitive-functioning-in-children-with-refractory-focal-onset-seizures
#10
Sergiusz Jóźwiak, P Veggiotti, J Moreira, H Gama, F Rocha, P Soares-da-Silva
PURPOSE: This was a phase-II, randomized, double-blind (DB), placebo-controlled study aimed to evaluate neurocognitive effects of eslicarbazepine acetate (ESL) as adjunctive therapy in pediatric patients with refractory focal-onset seizures (FOS). METHODS: Children (6-16years old) with FOS were randomized (2:1) to ESL or placebo. Treatment started at 10mg/kg/day, was up-titrated up to 30mg/kg/day (target dose), and maintained for 8weeks, followed by one-year open-label follow-up...
February 13, 2018: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/29454124/brainstem-dose-constraints-in-non-isometric-radiosurgical-treatment-planning-of-trigeminal-neuralgia-a-single-institution-experience
#11
Michael Zhang, Layton A Lamsam, Matthew K Schoen, Swapnil S Mehta, Geoffrey Appelboom, John K Adler, Scott G Soltys, Steven D Chang
INTRODUCTION: CyberKnife stereotactic radiosurgery (SRS) for trigeminal neuralgia (TGN) administers non-isometric, conformational high-dose radiation to the trigeminal nerve with risk of subsequent hypoesthesia. METHODS: We performed a retrospective, single-institution review of 66 TGN patients, treated by CyberKnife, to compare outcomes from two distinct treatment periods (standard dosing, N = 38 and reduced dosing, N = 28). Standard and reduced dosing permitted a maximum brainstem dose of 45 Gy and 25 Gy, respectively, each with a prescription dose of 60 Gy...
February 14, 2018: World Neurosurgery
https://www.readbyqxmd.com/read/29453401/endothelial-smoothened-dependent-hedgehog-signaling-is-not-required-for-sonic-hedgehog-induced-angiogenesis-or-ischemic-tissue-repair
#12
Rajesh Gupta, Alexander R Mackie, Sol Misener, Lijun Liu, Douglas W Losordo, Raj Kishore
Sonic Hedgehog (Shh) signaling induces neovascularization and angiogenesis. It is not known whether the hedgehog signaling pathway in endothelial cells is essential to angiogenesis. Smoothened (Smo) transduces hedgehog signaling across the cell membrane. This study assessed whether endothelial Smoothened-dependent Shh signaling is required for Shh-mediated angiogenesis and ischemic tissue repair. Endothelial-specific smoothened knockout mice, eSmo Null were created using Cre-lox recombination system. eSmo Null mice had no observable phenotype at baseline and showed normal cardiac function...
February 16, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29453277/editing-out-five-serpina1-paralogs-to-create-a-mouse-model-of-genetic-emphysema
#13
Florie Borel, Huaming Sun, Marina Zieger, Andrew Cox, Brynn Cardozo, Weiying Li, Gabriella Oliveira, Airiel Davis, Alisha Gruntman, Terence R Flotte, Michael H Brodsky, Andrew M Hoffman, Mai K Elmallah, Christian Mueller
Chronic obstructive pulmonary disease affects 10% of the worldwide population, and the leading genetic cause is α-1 antitrypsin (AAT) deficiency. Due to the complexity of the murine locus, which includes up to six Serpina1 paralogs, no genetic animal model of the disease has been successfully generated until now. Here we create a quintuple Serpina1a-e knockout using CRISPR/Cas9-mediated genome editing. The phenotype recapitulates the human disease phenotype, i.e., absence of hepatic and circulating AAT translates functionally to a reduced capacity to inhibit neutrophil elastase...
February 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29452748/knockout-of-human-muscle-genes-revealed-by-large-scale-whole-exome-studies
#14
Stefano Schiaffino
Large scale whole-exome sequence studies have revealed that a number of individuals from different populations have predicted loss-of-function of different genes due to nonsense, frameshift, or canonical splice-site mutations. Surprisingly, many of these mutations do not apparently show the deleterious phenotypic consequences expected from gene knockout. These homozygous null mutations, when confirmed, can provide insight into human gene function and suggest novel approaches to correct gene dysfunction, as the lack of the expected disease phenotype may reflect the existence of modifier genes that reveal potential therapeutic targets...
February 10, 2018: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/29452640/serine-catabolism-by-shmt2-is-required-for-proper-mitochondrial-translation-initiation-and-maintenance-of-formylmethionyl-trnas
#15
Denise R Minton, Minwoo Nam, Daniel J McLaughlin, Jong Shin, Erol C Bayraktar, Samantha W Alvarez, Vladislav O Sviderskiy, Thales Papagiannakopoulos, David M Sabatini, Kıvanç Birsoy, Richard Possemato
Upon glucose restriction, eukaryotic cells upregulate oxidative metabolism to maintain homeostasis. Using genetic screens, we find that the mitochondrial serine hydroxymethyltransferase (SHMT2) is required for robust mitochondrial oxygen consumption and low glucose proliferation. SHMT2 catalyzes the first step in mitochondrial one-carbon metabolism, which, particularly in proliferating cells, produces tetrahydrofolate (THF)-conjugated one-carbon units used in cytoplasmic reactions despite the presence of a parallel cytoplasmic pathway...
February 15, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29452300/therapeutic-strategy-for-rheumatoid-arthritis-patients-who-have-achieved-remission
#16
Bruno Fautrel
Once remission or low disease activity (LDA) is attained in established rheumatoid arthritis (RA) patients, attempting disease-modifying anti-rheumatic drug (DMARD) tapering appears to be a viable option to avoid patient overtreatment. Potential benefits include reduction in the treatment burden and the risk of adverse events, although the latter has not been demonstrated convincingly.The feasibility of DMARD discontinuation has been tested in numerous studies or trials. All have revealed a high risk of relapse, ranging from 56% to 87% at one year...
February 13, 2018: Joint, Bone, Spine: Revue du Rhumatisme
https://www.readbyqxmd.com/read/29452137/aryl-hydrocarbon-receptor-ahr-mediated-short-term-effects-of-2-3-7-8-tetrachlorodibenzo-p-dioxin-tcdd-on-bile-acid-homeostasis-in-wild-type-and-ahr-null-mice
#17
Iván L Csanaky, Andrew J Lickteig, Curtis D Klaassen
The effects of the most potent aryl hydrocarbon receptor (AhR) agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on bile acid (BA) homeostasis was examined in male and female wild-type and AhR-null mice shortly after 4-day exposure, rather than at a later time when secondary non-AhR dependent effects are more likely to occur. TCDD had similar effects on BA homeostasis in male and female mice. TCDD decreased the concentration of total-(Σ) BAs in liver by approximately 50% (all major BA categories except for the non-6,12-OH BAs), without decreasing the expression of the rate limiting BA synthetic enzyme (Cyp7a1) or altering the major BA regulatory pathways (FXR) in liver and intestine...
February 13, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29452107/trabecular-meshwork-morphogenesis-a-comparative-analysis-of-wildtype-and-anterior-segment-dysgenesis-mouse-models
#18
Rebecca L Rausch, Richard T Libby, Amy E Kiernan
The trabecular meshwork (TM), a tissue residing in the iridocorneal angle of the eye, is the primary site of aqueous humor outflow and often develops abnormally in children with anterior segment dysgenesis (ASD). However, the cellular mechanisms underlying both normal and pathophysiological TM formation are poorly understood. Here, we improve the characterization of TM development via morphological and molecular analyses. We first assessed the TM of wild-type C57BL/6J mice at multiple time points throughout development (E15...
February 13, 2018: Experimental Eye Research
https://www.readbyqxmd.com/read/29450895/a-test-of-multi-session-automatic-action-tendency-retraining-to-reduce-alcohol-consumption-among-young-adults-in-the-context-of-a-human-laboratory-paradigm
#19
Robert F Leeman, Christine Nogueira, Reinout W Wiers, Janna Cousijn, Kelly Serafini, Kelly S DeMartini, John A Bargh, Stephanie S O'Malley
BACKGROUND: Young adult heavy drinking is an important public health concern. Current interventions have efficacy but with only modest effects, thus novel interventions are needed. In prior studies, heavy drinkers, including young adults, have demonstrated stronger automatically triggered approach tendencies to alcohol-related stimuli than lighter drinkers. Automatic action tendency retraining has been developed to correct this tendency and consequently reduce alcohol consumption. The current study is the first to test multiple iterations of automatic action tendency retraining, followed by laboratory alcohol self-administration...
February 16, 2018: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/29450776/modulatory-role-of-gstt1-and-gstm1-in-punjabi-agricultural-workers-exposed-to-pesticides
#20
Meenakshi Ahluwalia, Anupam Kaur
Glutathione S-transferases are important detoxification enzymes involved in the metabolism of endogenous as well as exogenous compounds. Individuals differ in metabolic capacity due to inherited genetic variations. Due to the polymorphism exhibited by GSTT1 and GSTM1 that results in the complete loss of function, the present study was aimed towards the determination of the frequency distribution of GSTT1 and GSTM1 in agricultural workers in Punjab, India. The study aimed to investigate their contribution in susceptibility to increased disease risk...
February 15, 2018: Environmental Science and Pollution Research International
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