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Yifan Liu, Ming Han, Xiaoshuang Li, Hui Wang, Minyue Ma, Shihui Zhang, Yifan Guo, Shuling Wang, Yuanfen Wang, N Duan, Bing Xu, Jingwen Yin, Yuanqing Yao
STUDY QUESTION: What changes in the mitochondria of human mural granulosa cells (mGCs) with maternal aging? SUMMARY ANSWER: The mitochondrial membrane potential (MMP) and the ability of oxidative phosphorylation (OXPHOS) of mGCs declines with reproductive aging, accompanied with more abnormal mitochondria. WHAT IS KNOWN ALREADY: Mitochondria play an important role in the dialogue between the mGCs and oocytes. However, the underlying mechanism of mitochondrial dysfunction in mGCs in aging is still poorly understood...
October 17, 2017: Human Reproduction
Medhanie E Kidane, Boden H Vanderloop, Wenxu Zhou, Crista D Thomas, Emilio Ramos, Ujjal Singha, Minu Chaudhuri, W David Nes
Ergosterol biosynthesis pathways essential to pathogenic protozoa growth (Haubrich, B. A. et al. 2015. J. Lipid Res. 56: 331-341) and absent from the human host offer new chokepoint targets. Here, we present characterization and cell-based interference of Acanthamoeba spp sterol 24/28methylases (SMT) that catalyze the committed step in C28- and C29-sterol synthesis. Intriguingly, our kinetic analyses suggest 24SMT prefers plant cycloartenol while 28SMT prefers 24(28)methylene lophenol in similar fashion to the substrate preferences of land plant SMT1 and SMT2...
October 17, 2017: Journal of Lipid Research
Vanesa Viana-Huete, Carlos Guillén, Gema García, Silvia Fernández, Ana García-Aguilar, C R Kahn, Manuel Benito
It is unknown how the lack of IR (insulin receptor)/ IGFIR (insulin like growth factor receptor) in a tissue-specific manner does affect brown fat development and mitochondrial integrity and function and its impact on the redistribution of the adipose organ and the metabolic status. To address this important issue, we have developed the IR/IGFIR double knockout in brown adipose tissue-specific manner (DKO). Lack of those receptors caused a severe brown fat atrophy, an enhanced beige cell clusters in inguinal fat, loss of mitochondrial mass, mitochondrial damage related to cristae disruption, and the loss of proteins involved in autophagosome formation, mitophagy, mitochondrial quality control and dynamics and thermogenesis...
October 10, 2017: Endocrinology
Shiran Abadi, Winston X Yan, David Amar, Itay Mayrose
The adaptation of the CRISPR-Cas9 system as a genome editing technique has generated much excitement in recent years owing to its ability to manipulate targeted genes and genomic regions that are complementary to a programmed single guide RNA (sgRNA). However, the efficacy of a specific sgRNA is not uniquely defined by exact sequence homology to the target site, thus unintended off-targets might additionally be cleaved. Current methods for sgRNA design are mainly concerned with predicting off-targets for a given sgRNA using basic sequence features and employ elementary rules for ranking possible sgRNAs...
October 16, 2017: PLoS Computational Biology
Jasmine Abdulcadir, Omar Abdulcadir, Martin Caillet, Lucrezia Catania, Béatrice Cuzin, Birgitta Essén, Pierre Foldès, Sara Johnsdotter, Crista Johnson-Agbakwu, Nawal Nour, Charlemagne Ouedraogo, Nicole Warren, Sophie Wylomanski
No abstract text is available yet for this article.
October 1, 2017: Aesthetic Surgery Journal
Zilong Sun, Sujuan Li, Zhenzhen Guo, Rui Li, Jixiang Wang, Ruiyan Niu, Jundong Wang
Oxidative damage has been implicated to be one of main mechanisms by which fluoride (F) induces toxic effects. Previous studies reported that F destroyed the epididymal structure of mouse and rabbit. Epididymis is the important place for sperm maturation. However, little is known about the effect of F on the oxidative stress status of epididymis. Therefore, the aim of the present study was to explore the changes in the activities and transcriptional levels of CuZn superoxide dismutase (CuZn-SOD, SOD1) and catalase (CAT), as well as the ultrastructure, in testis and epididymis of mice administrated with F...
October 8, 2017: Biological Trace Element Research
Mini Chandra, Diana Escalante-Alcalde, Md Shenuarin Bhuiyan, Anthony Wayne Orr, Christopher Kevil, Andrew J Morris, Hyung Nam, Paari Dominic, Kevin J McCarthy, Sumitra Miriyala, Manikandan Panchatcharam
Lipid Phosphate phosphatase 3 (LPP3), encoded by the Plpp3 gene, is an enzyme that dephosphorylates the bioactive lipid mediator lysophosphatidic acid (LPA). To study the role of LPP3 in the myocardium, we generated a cardiac specific Plpp3 deficient mouse strain. Although these mice were viable at birth in contrast to global Plpp3 knockout mice, they showed increased mortality ~ 8 months. LPP3 deficient mice had enlarged hearts with reduced left ventricular performance as seen by echocardiography. Cardiac specific Plpp3 deficient mice had longer ventricular effective refractory periods compared to their Plpp3 littermates...
September 28, 2017: Redox Biology
G Yu Tsarapkin, A S Tovmasyan, К M Fedotkina, E V Gorovaya, S G Arzamazov, S A Panasov
The objective of the present work was to develop a technique for the endonasal surgical access to the maxillary sinus through crista conchalis of the maxillary bone and to evaluate the effectiveness and safety of the surgical treatment by this method. A total of 210 patients underwent the CT-assisted examination of the paranasal sinuses. The data obtained made it possible to characterize the detailed anatomical structure of crista conchalis of a maxillary bone that forms the anterior part of the medial wall of the maxillary sinus...
2017: Vestnik Otorinolaringologii
G Yu Tsarapkin, A Yu Ivoylov, P L Chumakov, К M Fedotkina, E V Gorovaya, A V Artemieva-Karelova, E G Lapenko
The objective of the present work was to study syntopy of the distal end of the nasolacrimal duct based on the results of the vector analysis of the CT-identified anatomical features of the nasal cavity and the paranasal sinuses in 102 patients (204 nasolacrimal channels). The main criterion for inclusion in the study was the absence of traumatic injuries and inflammatory changes in the nasal cavity and the paranasal sinuses. X-ray studies of the distal end of the nasolacrimal duct (NLD), turbinate crest (crista conchalis), the edge of the nasal aperture, and the floor of the nasal cavity were carried out...
2017: Vestnik Otorinolaringologii
Salvatore Raffa, Cristina Scrofani, Sabatino Valente, Andrea Micaloni, Forte Maurizio, Franca Bianchi, Roberta Coluccia, Aron M Geurts, Sebastiano Sciarretta, Massimo Volpe, Maria Rosaria Torrisi, Speranza Rubattu
Ndufc2, a subunit of the NADH:ubiquinone oxidoreductase, plays a key role in the assembly and activity of complex I within the mitochondrial OXPHOS chain. Its deficiency has been shown to be involved in diabetes, cancer and stroke. To improve our knowledge on the mechanisms underlying the increased disease risk due to Ndufc2 reduction, we performed the present in vitro study aimed at the fine characterization of the derangements in mitochondrial structure and function consequent to Ndufc2 deficiency. We found that both fibroblasts obtained from skin of heterozygous Ndufc2 knock-out rat model showed marked mitochondrial dysfunction and PBMC obtained from subjects homozygous for the TT genotype of the rs11237379/NDUFC2 variant, previously shown to associate with reduced gene expression, demonstrated increased generation of reactive oxygen species and mitochondrial damage...
August 30, 2017: Human Molecular Genetics
Giulia Vecchione, Elena Grasselli, Federica Cioffi, Francesca Baldini, Paulo J Oliveira, Vilma A Sardão, Katia Cortese, Antonia Lanni, Adriana Voci, Piero Portincasa, Laura Vergani
Non-alcoholic fatty liver disease (NAFLD) is a major cause of liver-related morbidity and mortality. Oxidative stress and release of pro-inflammatory cytokines, such as tumor necrosis factor α (TNFα), are major consequences of hepatic lipid overload, which can contribute to progression of NAFLD to non-alcoholic steatohepatitis (NASH). Also, mitochondria are involved in the NAFLD pathogenesis for their role in hepatic lipid metabolism. Definitive treatments for NAFLD/NASH are lacking so far. Silybin, the extract of the milk thistle seeds, has previously shown beneficial effects in NAFLD...
2017: Frontiers in Nutrition
Diego C Musial, Guilherme H Bomfim, Juan A Arranz-Tagarro, Iago Méndez-López, Regiane Miranda-Ferreira, Aron Jurkiewicz, Neide H Jurkiewicz, Antonio G García, Juan F Padín
Comorbidity of diabetes and hypertension is frequent. Here, we have performed a comparative study in three animal models namely, normotensive Wistar Kyoto (WKY) rats, streptozotocin-induced diabetic rats (STZ), and spontaneously hypertensive rats (SHR). With respect WKY rats, we have found the following alterations in adrenal chromaffin cells from STZ and SHR rats: (1) diminished Ca(2+) currents; (2) augmented [Ca(2+])c elevations and catecholamine release in cells stimulated with angiotensin II or high K(+); (3) unchanged expression of angiotensin II receptors AT1 and AT2; (4) higher density of secretory vesicles at subplasmalemmal sites; (5) mitochondria with lower cristae density that were partially depolarized; and (6) lower whole cell ATP content...
September 30, 2017: European Journal of Pharmacology
Sylvie Gerber, Majida Charif, Arnaud Chevrollier, Tanguy Chaumette, Claire Angebault, Mariame Selma Kane, Aurélien Paris, Jennifer Alban, Mélanie Quiles, Cécile Delettre, Dominique Bonneau, Vincent Procaccio, Patrizia Amati-Bonneau, Pascal Reynier, Stéphanie Leruez, Raphael Calmon, Nathalie Boddaert, Benoit Funalot, Marlène Rio, Didier Bouccara, Isabelle Meunier, Hiromi Sesaki, Josseline Kaplan, Christian P Hamel, Jean-Michel Rozet, Guy Lenaers
Dominant optic atrophy is a blinding disease due to the degeneration of the retinal ganglion cells, the axons of which form the optic nerves. In most cases, the disease is caused by mutations in OPA1, a gene encoding a mitochondrial large GTPase involved in cristae structure and mitochondrial network fusion. Using exome sequencing, we identified dominant mutations in DNM1L on chromosome 12p11.21 in three large families with isolated optic atrophy, including the two families that defined the OPA5 locus on chromosome 19q12...
October 1, 2017: Brain: a Journal of Neurology
Jin Woo Choi, Jung Hun Ohn, Hye Seung Jung, Young Joo Park, Hak Chul Jang, Sung Soo Chung, Kyong Soo Park
OBJECTIVE: Autophagy is suppressed in skeletal muscle and the liver with insulin resistance induced by a high-fat diet. Autophagy is essential for maintaining mitochondrial function, and dysfunctional mitochondria are associated with insulin resistance. As carnitine treatment is well known to improve insulin resistance by promoting mitochondrial function, we investigated if carnitine affects autophagy in the skeletal muscle of a high-fat diet-induced rodent model of obesity. RESULTS: After 6 weeks on a high-fat diet (48 kcal% fat), mice developed glucose intolerance, and the gastrocnemius muscle showed a decrease in insulin signaling and mitochondrial function, which was reversed after carnitine (100 mg/kg/day) treatment by oral gavage for 2 weeks...
September 28, 2017: Metabolism: Clinical and Experimental
Lubna Mobin, Syed Asad Saeed, Rashida Ali, Syed Ghufran Saeed, Rahil Ahmed
Crude seed coat extracts from Abrus precatorius and Caesalpinia crista were purified into four different fractions namely phenolic acids, flavonols, flavanols and anthocyanin which were then examined for their polyphenol contents and antimicrobial potentials. The fractions derived from seed coat of A. precatorius were found more potent with high phenolic and flavonoid contents as compared to C. crista fractions. The significant antibacterial activity was observed against all strain tested by the fractions of both samples apart from anthocyanin fraction...
September 26, 2017: Natural Product Research
Sang Jun Han, Hong Seok Choi, Jee In Kim, Jeen-Woo Park, Kwon Moo Park
Mitochondrial NADP(+)-dependent isocitrate dehydrogenase 2 (IDH2) is a major producer of mitochondrial NADPH, required for glutathione (GSH)-associated mitochondrial antioxidant systems including glutathione peroxidase (GPx) and glutathione reductase (GR). Here, we investigated the role of IDH2 in hepatic ischemia-reperfusion (HIR)-associated mitochondrial injury using Idh2-knockout (Idh2(-/-)) mice and wild-type (Idh2(+/+)) littermates. Mice were subjected to either 60min of partial liver ischemia or sham-operation...
September 8, 2017: Redox Biology
Rita Gorgulho, Raquel Jacinto, Susana S Lopes, Sofia A Pereira, Erin M Tranfield, Gabriel G Martins, Emilio J Gualda, Rico J E Derks, Ana C Correia, Evelyne Steenvoorden, Petra Pintado, Oleg A Mayboroda, Emilia C Monteiro, Judit Morello
Prediction and management of drug-induced renal injury (DIRI) rely on the knowledge of the mechanisms of drug insult and on the availability of appropriate animal models to explore it. Zebrafish (Danio rerio) offers unique advantages for assessing DIRI because the larval pronephric kidney has a high homology with its human counterpart and it is fully mature at 3.5 days post-fertilization. Herein, we aimed to evaluate the usefulness of zebrafish larvae as a model of renal tubular toxicity through a comprehensive analysis of the renal alterations induced by the lethal concentrations for 10% of the larvae for gentamicin, paracetamol and tenofovir...
September 20, 2017: Archives of Toxicology
Qing-Wei Tan, Jian-Cheng Ni, Pei-Hua Fang, Qi-Jian Chen
A new Erythrina alkaloid glycoside, named erythraline-11β-O-glucopyranoside, was isolated from the seeds of Erythrina crista-galli L., together with five known Erythrina alkaloids and an indole alkaloid. The structure of the new alkaloid glycoside was elucidated by spectroscopic methods, and all of the compounds were evaluated for their antiviral activity against tobacco mosaic virus.
September 16, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Stefan Schorr, Martin van der Laan
Mitochondria are complex double-membrane-bound organelles of eukaryotic cells that function as energy-converting powerhouses, metabolic factories and signaling centers. The outer membrane controls the exchange of material and information with other cellular compartments. The inner membrane provides an extended, highly folded surface for selective transport and energy-coupling reactions. It can be divided into an inner boundary membrane and tubular or lamellar cristae membranes that accommodate the oxidative phosphorylation units...
September 28, 2017: Seminars in Cell & Developmental Biology
Ramon I Klein Geltink, David O'Sullivan, Mauro Corrado, Anna Bremser, Michael D Buck, Joerg M Buescher, Elke Firat, Xuekai Zhu, Gabriele Niedermann, George Caputa, Beth Kelly, Ursula Warthorst, Anne Rensing-Ehl, Ryan L Kyle, Lana Vandersarren, Jonathan D Curtis, Annette E Patterson, Simon Lawless, Katarzyna Grzes, Jing Qiu, David E Sanin, Oliver Kretz, Tobias B Huber, Sophie Janssens, Bart N Lambrecht, Angelika S Rambold, Edward J Pearce, Erika L Pearce
T cell receptor (TCR) signaling without CD28 can elicit primary effector T cells, but memory T cells generated during this process are anergic, failing to respond to secondary antigen exposure. We show that, upon T cell activation, CD28 transiently promotes expression of carnitine palmitoyltransferase 1a (Cpt1a), an enzyme that facilitates mitochondrial fatty acid oxidation (FAO), before the first cell division, coinciding with mitochondrial elongation and enhanced spare respiratory capacity (SRC). microRNA-33 (miR33), a target of thioredoxin-interacting protein (TXNIP), attenuates Cpt1a expression in the absence of CD28, resulting in cells that thereafter are metabolically compromised during reactivation or periods of increased bioenergetic demand...
October 5, 2017: Cell
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