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https://www.readbyqxmd.com/read/28921378/chemistry-and-chemical-equilibrium-dynamics-of-bmaa-and-its-carbamate-adducts
#1
Pedro Diaz-Parga, Joy J Goto, V V Krishnan
Beta-N-methylamino-L-alanine (BMAA) has been demonstrated to contribute to the onset of the ALS/Parkinsonism-dementia complex (ALS/PDC) and is implicated in the progression of other neurodegenerative diseases. While the role of BMAA in these diseases is still debated, one of the suggested mechanisms involves the activation of excitatory glutamate receptors. In particular, the excitatory effects of BMAA are shown to be dependent on the presence of bicarbonate ions, which in turn forms carbamate adducts in physiological conditions...
September 18, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28911206/identification-of-the-molecular-dysfunction-caused-by-glutamate-dehydrogenase-s445l-mutation-responsible-for-hyperinsulinism-hyperammonemia
#2
Mariagrazia Grimaldi, Melis Karaca, Livia Latini, Estelle Brioudes, Thomas Schalch, Pierre Maechler
Congenital hyperinsulinism/hyperammonemia (HI/HA) syndrome gives rise to unregulated protein-induced insulin secretion from pancreatic beta-cells, fasting hypoglycemia and elevated plasma ammonia levels. Mutations associated with HI/HA were identified in the Glud1 gene, encoding for glutamate dehydrogenase (GDH). We aimed at identifying the molecular causes of dysregulation in insulin secretion and ammonia production conferred by the most frequent HI/HA mutation Ser445Leu. Following transduction with adenoviruses carrying the human GDH-wild type or GDH-S445L-mutant gene, immunoblotting showed efficient expression of the transgenes in all the investigated cell types...
September 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28887542/genome-wide-analysis-of-health-related-biomarkers-in-the-uk-household-longitudinal-study-reveals-novel-associations
#3
Bram P Prins, Karoline B Kuchenbaecker, Yanchun Bao, Melissa Smart, Delilah Zabaneh, Ghazaleh Fatemifar, Jian'an Luan, Nick J Wareham, Robert A Scott, John R B Perry, Claudia Langenberg, Michaela Benzeval, Meena Kumari, Eleftheria Zeggini
Serum biomarker levels are associated with the risk of complex diseases. Here, we aimed to gain insights into the genetic architecture of biomarker traits which can reflect health status. We performed genome-wide association analyses for twenty serum biomarkers involved in organ function and reproductive health. 9,961 individuals from the UK Household Longitudinal Study were genotyped using the Illumina HumanCoreExome array and variants imputed to the 1000 Genomes Project and UK10K haplotypes. We establish a polygenic heritability for all biomarkers, confirm associations of fifty-four established loci, and identify five novel, replicating associations at genome-wide significance...
September 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28862181/identification-of-a-novel-homozygous-mutation-in-transmembrane-channel-like-1-tmc1-gene-one-of-the-second-tier-hearing-loss-genes-after-gjb2-in-india
#4
Pawan Kumar Singh, Manju Ghosh, Shipra Sharma, Shivaram Shastri, Neerja Gupta, Madhumita Roy Chowdhury, Anuranjan Anand, Madhulika Kabra
BACKGROUND & OBJECTIVES: Hearing impairment is a common and heterogeneous sensory disorder in humans. Among about 90 genes, which are known to be associated with hearing impairment, mutations in the GJB2 (gap junction protein beta 2) gene are the most prevalent in individuals with hereditary hearing loss. Contribution of the other deafness-causing genes is relatively poorly understood. Here, we present our findings on two families with transmembrane channel like 1 (TMC1) gene variants of the 47 families with nonsyndromic hearing loss (NSHL) studied...
April 2017: Indian Journal of Medical Research
https://www.readbyqxmd.com/read/28861087/alanine-mutagenesis-in-the-complementarity-determining-region-3-of-the-mtb-and-hiv-1-peptide-bispecific-t-cell-receptor-beta-chain-affects-ligand-recognition
#5
Chao-Ying Zhou, Rui-Ning Wang, Qian Wen, Wen-Ting He, Shi-Meng Zhang, Xia-Lin Du, Jia-Hui Yang, Li Ma
Mycobacterium tuberculosis/human immunodeficiency virus (MTB/HIV) coinfection presents a special challenge to the prevention and treatment of tuberculosis and HIV/AIDS. Adoptive transfer of high-affinity T cell receptor (TCR) gene-modified T cells against MTB and HIV antigens is a promising approach to treating MTB/HIV coinfected patients whose cellular immunity is obviously disordered. We have previously successfully identified that a bispecific TCR screened out from peripheral blood mononuclear cells of a HLA-A*0201(+) healthy individual using the complementarity determining region 3 (CDR3) spectratype analysis recognizes both MTB Ag85B199-207 and HIV-1 Env120-128 peptide...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28837265/exposure-to-bmaa-mirrors-molecular-processes-linked-to-neurodegenerative-disease
#6
Joshua Beri, Tara Nash, Rubia M Martin, Michael S Bereman
The goal of this study is to investigate the molecular pathways perturbed by in vitro exposure of beta-methylamino-L-alanine (BMAA) to NSC-34 cells via contemporary proteomics. Our analysis of differentially regulated proteins reveals significant enrichment (p < 0.01) of pathways related to ER stress, protein ubiquitination, the unfolded protein response, and mitochondrial dysfunction. Upstream regulator analysis indicates that exposure to BMAA induces activation of transcription factors (X-box binding protein 1; nuclear factor 2 erythroid like 2; promyelocytic leukemia) involved in regulation of the UPR, oxidative stress, and cellular senescence...
July 24, 2017: Proteomics
https://www.readbyqxmd.com/read/28836148/anti-diabetic-actions-of-esculentin-2cha-1-30-and-its-stable-analogues-in-a-diet-induced-model-of-obesity-diabetes
#7
Srividya Vasu, Opeolu O Ojo, R Charlotte Moffett, J Michael Conlon, Peter R Flatt, Yasser H A Abdel-Wahab
Actions of esculentin-2CHa(1-30) (GFSSIFRGVAKFASKGLGKDLAKLGVDLVA) and its analogues, ([D-Arg(7), D-Lys(15), D-Lys(23)]-esculentin-2CHa(1-30) and [Lys(15)-octanoate]-esculentin-2CHa(1-30), were evaluated in high-fat fed NIH Swiss mice with impaired glucose tolerance and insulin resistance. Twice-daily i.p. administration of the esculentin-2CHa(1-30) peptides (75 nmol/kg body weight) or exendin-4 (25 nmol/kg) for 28 days reduced body weight, without altering cumulative energy intake. All peptides reduced blood glucose levels by 6-12 mmol/l concomitant with lower plasma insulin levels, with significance evident from day 6...
August 23, 2017: Amino Acids
https://www.readbyqxmd.com/read/28828081/effects-of-plyometric-training-and-beta-alanine-supplementation-on-maximal-intensity-exercise-and-endurance-in-female-soccer-players
#8
Fabián Rosas, Rodrigo Ramírez-Campillo, Cristian Martínez, Alexis Caniuqueo, Rodrigo Cañas-Jamet, Emma McCrudden, Cesar Meylan, Jason Moran, Fábio Y Nakamura, Lucas A Pereira, Irineu Loturco, Daniela Diaz, Mikel Izquierdo
Plyometric training and beta-alanine supplementation are common among soccer players, although its combined use had never been tested. Therefore, a randomized, double-blind, placebo-controlled trial was conducted to compare the effects of a plyometric training program, with or without beta-alanine supplementation, on maximal-intensity and endurance performance in female soccer players during an in-season training period. Athletes (23.7 ± 2.4 years) were assigned to either a plyometric training group receiving a placebo (PLACEBO, n = 8), a plyometric training group receiving beta-alanine supplementation (BA, n = 8), or a control group receiving placebo without following a plyometric training program (CONTROL, n = 9)...
September 2017: Journal of Human Kinetics
https://www.readbyqxmd.com/read/28818411/long-term-supplementation-with-egcg-and-beta-alanine-decreases-mortality-but-does-not-affect-cognitive-or-muscle-function-in-aged-mice
#9
Brandt D Pence, Tushar K Bhattacharya, Pul Park, Jennifer L Rytych, Jacob M Allen, Yi Sun, Robert H McCusker, Keith W Kelley, Rodney W Johnson, Justin S Rhodes, Jeffrey A Woods
We have previously shown that 6weeks of a diet containing epigallocatechin gallate (EGCG) and beta-alanine (B-ALA) was not effective in improving either cognitive or muscle function in aged (18month) mice (Gibbons et al. Behav Brain Res 2014). However, diet reduced oxidative stress in the brain, and previous studies using longer-term interventions have documented beneficial effects in cognitive, but not muscle, function. Therefore, we investigated the effect of 6months of feeding on measures of cognitive and muscle function in mice...
August 14, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28806173/the-%C3%AE-alanine-transporter-balat-is-required-for-visual-neurotransmission-in-drosophila
#10
Yongchao Han, Liangyao Xiong, Ying Xu, Tian Tian, Tao Wang
The recycling of neurotransmitters is essential for sustained synaptic transmission. In Drosophila, histamine recycling is required for visual synaptic transmission. Synaptic histamine is rapidly taken up by laminar glia, and is converted to carcinine. After delivered back to photoreceptors, carcinine is hydrolyzed to release histamine and β-alanine. This histamine is repackaged into synaptic vesicles, but it is unclear how the β-alanine is returned to the laminar glial cells. Here, we identified a new β-alanine transporter, which we named BalaT (Beta-alanine Transporter)...
August 14, 2017: ELife
https://www.readbyqxmd.com/read/28783594/antigenic-characterization-of-52-55kda-protein-isolated-from-trypanosoma-evansi-and-its-application-in-detection-of-equine-trypanosomosis
#11
S C Yadav, Ritesh Kumar, Jaideep Kumar, Meetali Singh, B C Bera, Rajender Kumar, U Tatu, Kanika Tehri
Trypanosoma evansi is a haemo-protozoan parasite responsible for the disease surra, an economically important disease of wide range of domestic and wild animals. The present diagnostic methods using soluble antigens have inherent problems like lack of standardized and reproducible antigens, as well as ethical issues. This entails further efforts for search of defined antigenic molecules with satisfying sensitivity and specificity for sero-epidemiology of trypanosomosis. In present investigation, we have identified and purified 52-55kDa immuno-dominant protein cluster in molecular mass ranges by preparatory SDS-PAGE methods from T...
August 1, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28766672/seabuckthorn-berry-polysaccharide-protects-against-carbon-tetrachloride-induced-hepatotoxicity-in-mice-via-anti-oxidative-and-anti-inflammatory-activities
#12
Wei Zhang, Xiaohui Zhang, Kai Zou, Jiming Xie, Shimin Zhao, Jingran Liu, Huan Liu, Jinling Wang, Yuzhen Wang
The berries of Seabuckthorn (Hippophae rhamnoides L.) are traditional medicinal foods that have been used by Tibetans and Mongolians for thousands of years. The polysaccharides are the main components of Seabuckthorn berries, possessing immune stimulating, anti-cancer and anti-fatigue activities. The present study focused on evaluating the protective effects and mechanisms of Seabuckthorn berry polysaccharide (SP) against carbon tetrachloride (CCl4)-induced hepatotoxicity. Mice were orally administrated with 50, 100 and 200 mg kg(-1) of SP once daily for 14 consecutive days prior to CCl4 challenge...
August 2, 2017: Food & Function
https://www.readbyqxmd.com/read/28754350/beneficial-metabolic-effects-of-dietary-epigallocatechin-gallate-alone-and-in-combination-with-exendin-4-in-high-fat-diabetic-mice
#13
Nupur M Pathak, Paul J B Millar, Varun Pathak, Peter R Flatt, Victor A Gault
OBJECTIVE: Significant attempts are being made to generate multifunctional, hybrid or peptide combinations as novel therapeutic strategies for type 2 diabetes, however this presents key challenges including design and pharmaceutical development. In this study, we evaluated metabolic properties of oral nutritional supplement epigallocatechin gallate (EGCG) in combination with GLP-1 agonist exendin-4 in a mouse model of dietary-induced diabetes and obesity. METHODS: EGCG, exendin-4 or combination of both were administered twice-daily over 28 days to high fat (HF) mice on background of low-dose streptozotocin...
July 25, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28747868/protective-effect-of-momordica-charantia-water-extract-against-liver-injury-in-restraint-stressed-mice-and-the-underlying-mechanism
#14
Yuanyuan Deng, Qin Tang, Yan Zhang, Ruifen Zhang, Zhencheng Wei, Xiaojun Tang, Mingwei Zhang
Background: Momordica charantia is used in China for its jianghuo (heat-clearing and detoxifying) effects. The concept of shanghuo (the antonym of jianghuo, excessive internal heat) in traditional Chinese medicine is considered a type of stress response of the body. The stress process involves internal organs, especially the liver. Objective: We hypothesized that Momordica charantia water extract (MWE) has a hepatoprotective effect and can protect the body from stress. The aim of this study was to investigate the possible effects of MWE against liver injury in restraint-stressed mice...
2017: Food & Nutrition Research
https://www.readbyqxmd.com/read/28741343/relationships-between-certain-metabolic-diseases-and-selected-serum-biochemical-parameters-in-seropositive-dairy-cows-against-neospora-caninum-infection-in-different-stages-of-lactation
#15
Myassar O. Alekish, Abdelsalam Q Talafha, Musa A Alshehabat, Zuhair A Bani Ismail
Neospora caninum is an important cause of abortion in dairy cattle. The general health of affected cows has not been investigated before. Therefore, the main objective of this study was to identify possible relationships between certain metabolic diseases and selected serum biochemical parameters in seropositive dairy cows against N. caninum antibodies in different stages of lactation. The study was carried out using 72 N. caninum seropositive cows and 61 seronegative dairy cows (control). Serum from all cows was tested to determine their N...
2017: Annals of Parasitology
https://www.readbyqxmd.com/read/28740597/is-hepatic-steatosis-associated-with-left-ventricular-mass-index-increase-in-the-general-population
#16
Katharina Piontek, Carsten O Schmidt, Sebastian E Baumeister, Markus M Lerch, Julia Mayerle, Marcus Dörr, Stephan B Felix, Henry Völzke
AIM: To investigate the association between hepatic steatosis and change in left ventricular mass index (LVMI) over five years, and examine whether systolic and diastolic blood pressures are mediators of the association between hepatic steatosis and LVMI using a general population sample. METHODS: We analyzed data from the Study of Health in Pomerania. The study population comprised 1298 individuals aged 45 to 81 years. Hepatic steatosis was defined as the presence of a hyperechogenic pattern of the liver together with elevated serum alanine transferase levels...
July 8, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/28737969/high-hydrostatic-pressure-extract-of-ginger-exerts-antistress-effects-in-immobilization-stressed-rats
#17
Sohee Moon, Mak-Soon Lee, Sunyoon Jung, Bori Kang, Seog-Young Kim, Seonyoung Park, Hye-Yeon Son, Chong-Tai Kim, Young-Hee Jo, In-Hwan Kim, Young Soon Kim, Yangha Kim
Stress contributes to physiological changes such as weight loss and hormonal imbalances. The aim of the present study was to investigate antistress effects of high hydrostatic pressure extract of ginger (HPG) in immobilization-stressed rats. Male Sprague-Dawley rats (n = 24) were divided into three groups as follows: control (C), immobilization stress (2 h daily, for 2 weeks) (S), and immobilization stress (2 h daily, for 2 weeks) plus oral administration of HPG (150 mg/kg body weight/day) (S+G). Immobilization stress reduced the body weight gain and thymus weight by 50...
September 2017: Journal of Medicinal Food
https://www.readbyqxmd.com/read/28687259/why-does-finland-have-the-highest-dementia-mortality-rate-environmental-factors-may-be-generalizable
#18
REVIEW
Arnold R Eiser
Finland has the highest death rate from dementia in the world and its environmental features can be instructive in understanding hidden causes of dementia. Environmental factors there include: 1) a climate that is both very cold and humid resulting in housing frequently harboring molds that are capable of producing a neurotoxic mycotoxin 2) the Gulf of Finland as well as Finnish lakes harbor cyanobacteria that produce the neurotoxin, beta-N-methyl amino-L-alanine, known to cause dementia and related disorders 3) the aforementioned toxins can be potentiated by the presence of mercury and methyl mercury which can be found in Finnish waters 4) soil in Finland is naturally low in selenium and selenium deficiency may reduce the quantity and effectiveness of glutathione's ability to protect against neurotoxins...
July 4, 2017: Brain Research
https://www.readbyqxmd.com/read/28669514/identification-of-urine-metabolites-associated-with-5-year-changes-in-biomarkers-of-glucose-homoeostasis
#19
N Friedrich, T Skaaby, M Pietzner, K Budde, B H Thuesen, M Nauck, A Linneberg
AIM: Metabolomics provides information on pathogenetic mechanisms and targets for interventions, and may improve risk stratification. During the last decade, metabolomics studies were used to gain deeper insight into the pathogenesis of diabetes mellitus. However, longitudinal metabolomics studies of possible subclinical states of disturbed glucose metabolism are limited. Therefore, the aim of this study was to analyze the associations between baseline urinary metabolites and 5-year changes in continuous markers of glucose homoeostasis, including fasting glucose, HbA1c and homoeostasis model assessment of insulin resistance (HOMA-IR) index values...
June 29, 2017: Diabetes & Metabolism
https://www.readbyqxmd.com/read/28659031/gypenosides-ameliorate-carbon-tetrachloride-induced-liver-fibrosis-by-inhibiting-the-differentiation-of-hepatic-progenitor-cells-into-myofibroblasts
#20
Jiamei Chen, Xuewei Li, Yonghong Hu, Wei Liu, Qun Zhou, Hua Zhang, Yongping Mu, Ping Liu
Gypenosides (GPs), the predominant components of Gynostemma pentaphyllum, exert antifibrotic effects; however, the mechanisms underlying their ability to ameliorate liver fibrosis are unclear. Liver fibrosis was induced in C57BL/6 mice via subcutaneous injection of 10% carbon tetrachloride (CCl[Formula: see text] three times a week for two weeks. Then, CCl4 was administered in conjunction with intragastric GPs for another three weeks. For in vitro analyses, WB-F344, hepatatic progenitor cells (HPCs) were treated with transforming growth factor beta 1 (TGF-β1) with or without GPs for 48[Formula: see text]h...
June 28, 2017: American Journal of Chinese Medicine
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