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Seu Ping Guiraud, Ivan Montoliu, Laeticia Da Silva, Loïc Dayon, Antonio Núñez Galindo, John Corthésy, Martin Kussmann, Francois-Pierre Martin
The methionine cycle is a key pathway contributing to the regulation of human health, with well-established involvement in cardiovascular diseases and cognitive function. Changes in one-carbon cycle metabolites have also been associated with mild cognitive decline, vascular dementia, and Alzheimer's disease. Today, there is no single analytical method to monitor both metabolites and co-factors of the methionine cycle. To address this limitation, we here report for the first time a new method for the simultaneous quantitation of 17 metabolites in the methionine cycle, which are homocysteic acid, taurine, serine, cysteine, glycine, homocysteine, riboflavin, methionine, pyridoxine, cystathionine, pyridoxamine, S-adenosylhomocysteine, S-adenosylmethionine, betaine, choline, dimethylglycine, and 5-methyltetrahydrofolic acid...
October 18, 2016: Analytical and Bioanalytical Chemistry
Robert N Kirchdoerfer, Crystal L Moyer, Dafna M Abelson, Erica Ollmann Saphire
Filoviruses are capable of causing deadly hemorrhagic fevers. All nonsegmented negative-sense RNA-virus nucleocapsids are composed of a nucleoprotein (NP), a phosphoprotein (VP35) and a polymerase (L). However, the VP30 RNA-synthesis co-factor is unique to the filoviruses. The assembly, structure, and function of the filovirus RNA replication complex remain unclear. Here, we have characterized the interactions of Ebola, Sudan and Marburg virus VP30 with NP using in vitro biochemistry, structural biology and cell-based mini-replicon assays...
October 2016: PLoS Pathogens
Justin Parreno, Sneha Raju, Po-Han Wu, Rita A Kandel
Chondrocyte culture as a monolayer for cell number expansion results in dedifferentiation whereby expanded cells acquire contractile features and increased actin polymerization status. This study determined whether the actin polymerization based signaling pathway, myocardin-related transcription factor-a (MRTF-A) is involved in regulating this contractile phenotype. Serial passaging of chondrocytes in monolayer culture to passage 2 resulted in increased gene and protein expression of the contractile molecules alpha-smooth muscle actin, transgelin and vinculin compared to non-passaged, primary cells...
October 14, 2016: Matrix Biology: Journal of the International Society for Matrix Biology
Lan He, Priscilla T Y Law, Siaw Shi Boon, Chuqing Zhang, Wendy C S Ho, Lawrence Banks, C K Wong, Juliana C N Chan, Paul K S Chan
Epidemiological evidence supports that infection with high-risk types of human papillomavirus (HPV) can interact with host and environmental risk factors to contribute to the development of cervical, oropharyngeal, and other anogenital cancers. In this study, we established a mouse epithelial cancer cell line, designated as Chinese University Papillomavirus-1 (CUP-1), from C57BL/KsJ mice through persistent expression of HPV-16 E7 oncogene. After continuous culturing of up to 200 days with over 60 passages, we showed that CUP-1 became an immortalized and transformed epithelial cell line with continuous E7 expression and persistent reduction of retinoblastoma protein (a known target of E7)...
2016: PloS One
L C Kim, R S Cook, J Chen
The mammalian target of rapamycin (mTOR) is a crucial signaling node that integrates environmental cues to regulate cell survival, proliferation and metabolism, and is often deregulated in human cancer. mTOR kinase acts in two functionally distinct complexes, mTOR complex 1 (mTORC1) and 2 (mTORC2), whose activities and substrate specificities are regulated by complex co-factors. Deregulation of this centralized signaling pathway has been associated with a variety of human diseases including diabetes, neurodegeneration and cancer...
October 17, 2016: Oncogene
Marie Duranteau, Jean-Jacques Montagne, Zohra Rahmani
The Spindle Assembly Checkpoint (SAC) is a surveillance mechanism that ensures accurate segregation of chromosomes into two daughter cells. BubR1, a key component of the SAC, play also a role in the mitotic timing since depletion of BubR1 leads to an accelerated mitosis. We previously found that, unlike what was reported in mammalian cells, mutation of the KEN1-box domain of Drosophila BubR1 (bubR1-KEN1 mutant) that affects the binding of BubR1 to Cdc20, the activating co-factor of the APC/C, did not accelerate the mitotic timing despite resulting in a defective SAC...
October 14, 2016: Biology Open
Martin Zeile, Artur Bakal, Jan Eden Volkmer, Gregor A Stavrou, Philip Dautel, Jan Hoeltje, Axel Stang, Karl J Oldhafer, Roland Brüning
OBJECTIVES: The purpose of this retrospective study was to monitor hypertrophy of the future liver remnant (FLR) following portal vein embolization (PVE) before planned extended right hepatectomy (ERH). However, because individual responses to PVE are highly variable, our focus was to identify co-factors of successful hypertrophy. METHODS: 28 patients with primary or secondary liver tumors, mean age 64.1±12.9 years, underwent PVE. Volumetric analysis of hypertrophy before and after PVE (median 39...
October 12, 2016: British Journal of Radiology
Carolina Schencke, Adriana Vasconcellos, Cristian Sandoval, Paulina Torres, Francisca Acevedo, Mariano Del Sol
BACKGROUND: In the context of the search for cost-efficient treatments, Ulmo (Eurcyphia cordifolia) honey is an excellent alternative for treating burn wounds and could have a profound medical, social, and economic impact. Ascorbic acid is an enzymatic co-factor necessary for the synthesis of collagen and the proliferation of fibroblasts and has been proposed as a coadjuvant to strengthen the healing effects of honey. The aim of this work was to evaluate by morphometric studies the healing wounds caused by burns treated with Ulmo honey alone and supplemented with ascorbic acid in guinea pig (Cavia porcellus)...
2016: Burns and trauma
Jacob I Ayers, Benjamin McMahon, Sabrina Gill, Herman L Lelie, Susan Fromholt, Hilda Brown, Joan Selverstone Valentine, Julian P Whitelegge, David R Borchelt
A common property of Cu/Zn superoxide dismutase 1 (SOD1), harboring mutations associated with amyotrophic lateral sclerosis (ALS), is a high propensity to misfold and form abnormal aggregates. The aggregation of mutant SOD1 has been demonstrated in vitro, with purified proteins, in mouse models, in human tissues, and in cultured cell models. In vitro translation studies have determined that SOD1 with ALS mutations is slower to mature, and thus perhaps vulnerable to off-pathway folding that could generate aggregates...
October 11, 2016: Journal of Neurochemistry
W Bruinsma, M Aprelia, I García-Santisteban, J Kool, Y J Xu, R H Medema
When cells in G2 phase are challenged with DNA damage, several key mitotic regulators such as Cdk1/Cyclin B, Aurora A and Plk1 are inhibited to prevent entry into mitosis. Here we have studied how inhibition of Plk1 is established after DNA damage. Using a Förster resonance energy transfer (FRET)-based biosensor for Plk1 activity, we show that inhibition of Plk1 after DNA damage occurs with relatively slow kinetics and is entirely dependent on loss of Plk1-T210 phosphorylation. As T210 is phosphorylated by the kinase Aurora A in conjunction with its co-factor Bora, we investigated how they are affected by DNA damage...
October 10, 2016: Oncogene
Helene McNulty, J J Strain, Catherine F Hughes, Mary Ward
Hypertension is the leading risk factor contributing to mortality worldwide, primarily from cardiovascular disease (CVD), while effective treatment of hypertension is proven to reduce CVD events. Along with the well recognized nutrition and lifestyle determinants, genetic factors are implicated in the development and progression of hypertension. In recent years genome-wide association studies have identified a region near the gene encoding the folate-metabolizing enzyme methylenetetrahydrofolate reductase (MTHFR) among eight loci associated with blood pressure...
October 6, 2016: Molecular Aspects of Medicine
Joshua P Moatt, Shinichi Nakagawa, Malgorzata Lagisz, Craig A Walling
BACKGROUND: Dietary restriction (DR), a reduction in the amount of food or particular nutrients eaten, is the most consistent environmental manipulation to extend lifespan and protect against age related diseases. Current evolutionary theory explains this effect as a shift in the resolution of the trade-off between lifespan and reproduction. However, recent studies have questioned the role of reproduction in mediating the effect of DR on longevity and no study has quantitatively investigated the effect of DR on reproduction across species...
October 7, 2016: BMC Evolutionary Biology
Rafael Barros de Souza, Rayssa Karla Silva, Dayvison Soares Ferreira, Sérgio de Sá Leitão Paiva Junior, Will de Barros Pita, Marcos Antonio de Morais Junior
In a recent work we showed that magnesium (Mg(II)) plays an important role in industrial ethanol production, overcoming the negative effect of the excess of minerals, particularly copper, present in sugarcane juice, with a consequent increase in ethanol yield. This cation has been reported to be involved in several steps of yeast metabolism, acting mainly as a co-factor of several enzymes of fermentation metabolism and protecting yeast cells from stressful conditions. However, despite many physiological investigations, its effect in the molecular mechanisms that control such metabolic activities remains unclear and to date no information concerning its influence on gene expression has been provided...
October 7, 2016: Metallomics: Integrated Biometal Science
Na Zhang, Feiming Ye, Wei Zhu, Dexing Hu, Changchen Xiao, Jinliang Nan, Sheng'an Su, Yingchao Wang, Mingfei Liu, Kanglu Gao, Xinyang Hu, Jinghai Chen, Hong Yu, Xiaojie Xie, Jian'an Wang
Cardiac ankyrin repeat protein (CARP) is a nuclear transcriptional co-factor that has additional functions in the myoplasm as a component of the muscle sarcomere. Previous studies have demonstrated increased expression of CARP in cardiovascular diseases, however, its role in cardiomyocyte apoptosis is unclear and controversial. In the present study, we investigated possible roles of CARP in hypoxia/reoxygenation (H/R) -induced cardiomyocyte apoptosis and the underlying mechanisms. Neonatal mouse ventricular cardiomyocytes were isolated and infected with adenovirus encoding Flag-tagged CARP (Ad-CARP) and lentivirus encoding CARP targeted shRNA (sh-CARP), respectively...
October 3, 2016: Biochimica et Biophysica Acta
Ying Li, Yeou-Cherng Bor, Mark P Fitzgerald, Kevin S Lee, David Rekosh, Marie-Louise Hammarskjold
The Nxf1 protein is a major nuclear export receptor for the transport of mRNA and it also is essential for export of retroviral mRNAs with retained introns. In the latter case, it binds to RNA elements known as Constitutive Transport Elements (CTEs) and functions in conjunction with a cofactor known as Nxt1. The NXF1 gene also regulates expression of its own intron-containing RNA through the use of a functional CTE within intron 10. mRNA containing this intron is exported to the cytoplasm where it can be translated into the 356 amino acid short Nxf1(sNxf1) protein, despite the fact that it is a prime candidate for nonsense mediated decay (NMD)...
October 5, 2016: Molecular Biology of the Cell
Jolyn Fernandes, Li Hao, Kaiser M Bijli, Joshua D Chandler, Michael Orr, Xin Hu, Dean P Jones, Young-Mi Go
Manganese (Mn) is an abundant redox-active metal with well-characterized mitochondrial accumulation and neurotoxicity due to excessive exposures. Mn is also an essential co-factor for the mitochondrial antioxidant protein, superoxide dismutase-2 (SOD2), and the range for adequate intake established by the Institute of Medicine Food and Nutrition Board is 20% of the interim guidance value for toxicity by the Agency for Toxic Substances and Disease Registry, leaving little margin for safety. To study toxic mechanisms over this critical dose range, we treated human neuroblastoma SH-SY5Y cells with a series of MnCl2 concentrations (from 0 to 100 μM) and measured cellular content to compare to human brain Mn content...
October 4, 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
E Artoni, G L Sighinolfi, A M Gatti, M Sebastiani, M Colaci, D Giuggioli, C Ferri
BACKGROUND: Mixed cryoglobulinemia (MC) is a rare multisystem disease whose aetiopathogenesis is not completely understood. Hepatitis C virus (HCV) infection may have a causative role, and genetic and/or environmental factors may also contribute. AIMS: To investigate the presence and possible role of environmental agents in MC. METHODS: We recruited 30 HCV-infected MC patients with different clinical manifestations and a control group of 30 healthy, sex-/age-matched volunteers...
September 30, 2016: Occupational Medicine
Nina Koenecke, Jeff Johnston, Bjoern Gaertner, Malini Natarajan, Julia Zeitlinger
BACKGROUND: Drosophila dorso-ventral (DV) patterning is one of the best-understood regulatory networks to date, and illustrates the fundamental role of enhancers in controlling patterning, cell fate specification, and morphogenesis during development. Histone acetylation such as H3K27ac is an excellent marker for active enhancers, but it is challenging to obtain precise locations for enhancers as the highest levels of this modification flank the enhancer regions. How to best identify tissue-specific enhancers in a developmental system de novo with a minimal set of data is still unclear...
September 27, 2016: Genome Biology
Hui Wang, Michael P Matise
The generation of functionally distinct neuronal subtypes within the vertebrate central nervous system (CNS) requires the precise regulation of progenitor gene expression in specific neuronal territories during early embryogenesis. Accumulating evidence has implicated histone deacetylase (HDAC) proteins in cell specification, proliferation, and differentiation in diverse embryonic and adult tissues. However, although HDAC proteins have shown to be expressed in the developing vertebrate neural tube, their specific role in CNS neural progenitor fate specification remains unclear...
2016: PloS One
Noriko Miyake, Ryoko Fukai, Chihiro Ohba, Takahiro Chihara, Masayuki Miura, Hiroshi Shimizu, Akiyoshi Kakita, Eri Imagawa, Masaaki Shiina, Kazuhiro Ogata, Jiu Okuno-Yuguchi, Noboru Fueki, Yoshifumi Ogiso, Hiroshi Suzumura, Yoshiyuki Watabe, George Imataka, Huey Yin Leong, Aviva Fattal-Valevski, Uri Kramer, Satoko Miyatake, Mitsuhiro Kato, Nobuhiko Okamoto, Yoshinori Sato, Satomi Mitsuhashi, Ichizo Nishino, Naofumi Kaneko, Akira Nishiyama, Tomohiko Tamura, Takeshi Mizuguchi, Mitsuko Nakashima, Fumiaki Tanaka, Hirotomo Saitsu, Naomichi Matsumoto
We describe four families with affected siblings showing unique clinical features: early-onset (before 1 year of age) progressive diffuse brain atrophy with regression, postnatal microcephaly, postnatal growth retardation, muscle weakness/atrophy, and respiratory failure. By whole-exome sequencing, we identified biallelic TBCD mutations in eight affected individuals from the four families. TBCD encodes TBCD (tubulin folding co-factor D), which is one of five tubulin-specific chaperones playing a pivotal role in microtubule assembly in all cells...
October 6, 2016: American Journal of Human Genetics
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