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Frank Szulzewsky, Sonali Arora, Lot de Witte, Thomas Ulas, Darko Markovic, Joachim L Schultze, Eric C Holland, Michael Synowitz, Susanne A Wolf, Helmut Kettenmann
Glioblastoma (GBM) is the most aggressive brain tumor in adults. It is strongly infiltrated by microglia and peripheral monocytes that support tumor growth. In the present study we used RNA sequencing to compare the expression profile of CD11b(+) human glioblastoma-associated microglia/monocytes (hGAMs) to CD11b(+) microglia isolated from non-tumor samples. Hierarchical clustering and principal component analysis showed a clear separation of the two sample groups and we identified 334 significantly regulated genes in hGAMs...
August 2016: Glia
Chiara Pontremoli, Alessandra Mozzi, Diego Forni, Rachele Cagliani, Uberto Pozzoli, Giorgia Menozzi, Jacopo Vertemara, Nereo Bresolin, Mario Clerici, Manuela Sironi
Dietary shifts can drive molecular evolution in mammals and a major transition in human history, the agricultural revolution, favored carbohydrate consumption. We investigated the evolutionary history of nine genes encoding brush-border proteins involved in carbohydrate digestion/absorption. Results indicated widespread adaptive evolution in mammals, with several branches experiencing episodic selection, particularly strong in bats. Many positively selected sites map to functional protein regions (e.g., within glucosidase catalytic crevices), with parallel evolution at SI (sucrase-isomaltase) and MGAM (maltase-glucoamylase)...
September 2015: Genome Biology and Evolution
Xiaofang Cao, Chen Zhang, Yangyang Dong, Peng Geng, Fang Bai, Gang Bai
In human, digestion of cooked starch mainly involves breaking down of α-amylase to α-limit dextrins and small linear malto-oligosaccharides, which are in turn hydrolyzed to glucose by the gut mucosal maltase-glucoamylase (MGAM). Human pancreatic α-amylase (HPA), amino- and carboxyl-terminal portions of MGAM (ntMGAM and ctMGAM) catalyze the hydrolysis of α-D-(1,4) glycosidic linkages in starch, playing a crucial role in the production of glucose in the human lumen. Accordingly, these enzymes are effective drug targets for the treatments of type 2 diabetes and obesity...
September 23, 2015: Carbohydrate Research
Meric Simsek, Roberto Quezada-Calvillo, Mario G Ferruzzi, Buford L Nichols, Bruce R Hamaker
In this study, it was hypothesized that dietary phenolic compounds selectively inhibit the individual C- and N-terminal (Ct, Nt) subunits of the two small intestinal α-glucosidases, maltase-glucoamylase (MGAM) and sucrase-isomaltase (SI), for a modulated glycemic carbohydrate digestion. The inhibition by chlorogenic acid, caffeic acid, gallic acid, (+)-catechin, and (-)-epigallocatechin gallate (EGCG) on individual recombinant human Nt-MGAM and Nt-SI and on mouse Ct-MGAM and Ct-SI was assayed using maltose as the substrate...
April 22, 2015: Journal of Agricultural and Food Chemistry
Samuel G Younkin, Robert B Scharpf, Holger Schwender, Margaret M Parker, Alan F Scott, Mary L Marazita, Terri H Beaty, Ingo Ruczinski
BACKGROUND: DNA copy number variants play an important part in the development of common birth defects such as oral clefts. Individual patients with multiple birth defects (including oral clefts) have been shown to carry small and large chromosomal deletions. METHODS: We investigated the role of polymorphic copy number deletions by comparing transmission rates of deletions from parents to offspring in case-parent trios of European ancestry ascertained through a cleft proband with trios ascertained through a normal offspring...
April 2015: Birth Defects Research. Part A, Clinical and Molecular Teratology
Kayoko Kawakami, Peng Li, Misugi Uraji, Tadashi Hatanaka, Hideyuki Ito
α-Glucosidase inhibitors are currently used in the treatment of type 2 diabetes. In this study, we investigated the inhibitory activities of aril and pericarp extracts from pomegranates obtained various regions against recombinant human maltase-glucoamylase (MGAM). The inhibitory activities of the aril extracts tended to be stronger than those of the pericarp extracts. The Iranian aril extract was the most effective inhibitor. We investigated the polyphenol content of the pomegranate extracts using the Folin-Ciocalteu method...
September 2014: Journal of Food Science
Hanzhang Chen, Xia Fang, Hailong Zhu, Shuai Li, Jian He, Pan Gu, Deshen Fan, Fei Han, Yu Zeng, Xiaotin Yu, Benfang Luo, Haodong Xu, Xianghua Yi
OBJECTIVE: Idiopathic interstitial pneumonias (IIPs) are a group of diffuse parenchymal lung diseases of unknown etiology characterized by the presence of various degrees of inflammation and fibrosis. We aimed to screen the differences among IIPs subtypes in the gene level by using the microarray expression profiles of normal lung tissue and IIPs tissue for the key genes associated with early diagnosis and treatment of IIPs. METHODS: The gene expression profile of six kinds of IIPs (GSE 32537) subtypes tissue and normal lung tissues were downloaded...
October 2014: Experimental Lung Research
Amy Hui-Mei Lin, Zihua Ao, Roberto Quezada-Calvillo, Buford L Nichols, Chi-Tien Lin, Bruce R Hamaker
To produce sufficient amounts of glucose from food starch, both α-amylase and mucosal α-glucosidases are required. We found previously that the digestion rate of starch is influenced by its susceptibility to mucosal α-glucosidases. In the present study, six starches and one glycogen were pre-hydrolyzed by α-amylase for various time periods, and then further hydrolyzed with the mucosal α-glucosidase, the N-terminal subunit of maltase-glucoamylase (Nt-MGAM), to generate free glucose. Results showed that α-amylase amplified the Nt-MGAM glucogenesis, and that the amplifications differed in various substrates...
October 13, 2014: Carbohydrate Polymers
Youtian Cui, Wenjing Cui, Zhongmei Liu, Li Zhou, Michihiko Kobayashi, Zhemin Zhou
Nitrile hydratase (NHase), which catalyzes the hydration of nitriles to amides, is the key enzyme for the production of amides in industries. However, the poor stability of this enzyme under the reaction conditions is a drawback of its industrial application. In this study, we aimed to improve the stability of NHase (PpNHase) from Pseudomonas putida NRRL-18668 using a homologous protein fragment swapping strategy. One thermophilic NHase fragment from Comamonas testosteroni 5-MGAM-4D and two fragments from Pseudonocardia thermophila JCM3095 were selected to swap the corresponding fragments of PpNHase...
July 18, 2014: Biochemical and Biophysical Research Communications
Liqiang Wanga, Qingxin Cui, Yuanyuan Hou, Fang Bai, Jixue Sun, Xiaofang Cao, Pi Liu, Min Jiang, Gang Bai
We propose a strategy that integrates ultra-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry (UPLC/Q-TOF-MS) and virtual docking to identify inhibitors of multiple human -glucosidases. UPLC yielded AIB656, an acarviostatin-containing complex, which was analyzed by Q-TOF-MS to acquire structural information and was tested for inhibition of N-terminal (MGAM-N), C-terminal (MGAM-C) catalytic domain of maltase-glucoamylase, and human pancreatic -amylase (HPA).A systematic computational study was performed to evaluate the inhibition activity for 51 identified acarviostatins with various sizes, including trace or difficult-to-prepare ingredients...
December 6, 2013: Journal of Chromatography. A
Debasish Roy, Vinod Kumar, Kshitish K Acharya, Kavitha Thirumurugan
Human maltase glucoamylase (MGAM) is a potent molecular target for controlling post prandial glucose surplus in type 2 diabetes. Binding of small molecules from Syzygium sp. with α-glucosidase inhibitory potential in MGAM has been investigated in silico. Our results suggest that myricetin was the most potent inhibitor with high binding affinity for both N- and C-terminals of MGAM. Molecular dynamics revealed that myricetin interacts in its stretched conformation through water-mediated interactions with C-terminal of MGAM and by normal hydrogen bonding with the N-terminal...
January 2014: Applied Biochemistry and Biotechnology
Sankar Mohan, Razieh Eskandari, B Mario Pinto
In humans, four different enzymes mediate the digestion of ingested carbohydrates. First salivary and pancreatic α-amylases, the two endoacting retaining glucosidases, break down the complex starch molecules into smaller linear maltose-oligomers (LM) and branched α-limit dextrins (αLDx). Then two retaining exoglucosidases, maltase-glucoamylase (MGAM) and sucrase-isomaltase (SI), convert those molecules into glucose in the small intestine. The small intestinal brush-border epithelial cells anchor MGAM and SI, and each contains a catalytic N- and C-terminal subunit, ntMGAM, ctMGAM, ntSI, and ctSI, respectively...
January 21, 2014: Accounts of Chemical Research
Melanie M Ivancic, Edward L Huttlin, Xiaodi Chen, Jennifer K Pleiman, Amy A Irving, Adrian D Hegeman, William F Dove, Michael R Sussman
Current screening procedures for colorectal cancer are imperfect and highly invasive and result in increased mortality rates due to low compliance. The goal of the experiments reported herein is to identify potential blood-based biomarkers indicative of early stage intestinal cancers using the ApcMin/+ mouse model of intestinal cancer as an experimental system. Serum proteins from tumor-bearing ApcMin/+ mice were quantitatively compared to tumor-free Apc+/+ wild-type mice via in anima metabolic labeling with 14N/15N-labeled Spirulina algae and an LTQ Orbitrap mass spectrometer...
September 6, 2013: Journal of Proteome Research
Maricela Diaz-Sotomayor, Roberto Quezada-Calvillo, Stephen E Avery, Shaji K Chacko, Li-Ke Yan, Amy Hui-Mei Lin, Zi-hua Ao, Bruce R Hamaker, Buford L Nichols
OBJECTIVES: Six enzyme activities are needed to digest starch to absorbable free glucose; 2 luminal α-amylases (AMY) and 4 mucosal maltase-glucoamylase (MGAM) and sucrase-isomaltase (SI) subunit activities are involved in the digestion. The AMY activities break down starch to soluble oligomeric dextrins; mucosal MGAM and SI can either directly digest starch to glucose or convert the post-α-amylolytic dextrins to glucose. We hypothesized that MGAM, with higher maltase than SI, drives digestion on ad limitum intakes and SI, with lower activity but more abundant amount, constrains ad libitum starch digestion...
December 2013: Journal of Pediatric Gastroenterology and Nutrition
Weiping Ma, Xiaodong Sun, Yanyan Song, Fangfang Tao, Wei Feng, Yi He, Naiqing Zhao, Zhengan Yuan
BACKGROUND: Association between bacillary dysentery (BD) disease and temperature has been reported in some studies applying Poisson regression model, however the effect estimation might be biased due to the data autocorrelation. Furthermore the temperature effect distributed in the time of different lags has not been studied either. The purpose of this work was to obtaining the association between the BD counts and the climatic factors such as temperature in the form of the weighted averages, concerning the autocorrelation pattern of the model residuals, and to make short term predictions using the model...
2013: PloS One
Satomi Umeda-Yano, Ryota Hashimoto, Hidenaga Yamamori, Takeya Okada, Yuka Yasuda, Kazutaka Ohi, Motoyuki Fukumoto, Akira Ito, Masatoshi Takeda
ZNF804A has been implicated in susceptibility to schizophrenia by several genome-wide association studies (GWAS), follow-up association studies and meta-analyses. However, the biological functions of ZNF804A are not entirely understood. To identify the genes that are affected by ZNF804A, we manipulated the expression of the ZNF804A protein in HEK293 human embryonic kidney cell lines and performed a cDNA microarray analysis followed by qPCR. We found that ZNF804A-overexpression up-regulated four genes (ANKRD1, INHBE, PIK3AP1, and DDIT3) and down-regulated three genes (CLIC2, MGAM, and BIRC3)...
May 2013: Schizophrenia Research
Vui King Vincent-Chong, Arif Anwar, Lee Peng Karen-Ng, Sok Ching Cheong, Yi-Hsin Yang, Padmaja Jayaprasad Pradeep, Zainal Ariff Abdul Rahman, Siti Mazlipah Ismail, Zuraiza Mohamad Zaini, Narayanan Prepageran, Thomas George Kallarakkal, Anand Ramanathan, Nur Aaina Binti Mohd Mohayadi, Nurul Shielawati Binti Mohamed Rosli, Wan Mahadzir Wan Mustafa, Mannil Thomas Abraham, Keng Kiong Tay, Rosnah Binti Zain
Despite the advances in diagnosis and treatment of oral squamous cell carcinoma (OSCC), mortality and morbidity rates have not improved over the past decade. A major drawback in diagnosis and treatment of OSCC is the lack of knowledge relating to how genetic instability in oral cancer genomes affects oral carcinogenesis. Hence, the key aim of this study was to identify copy number alterations (CNAs) that may be cancer associated in OSCC using high-resolution array comparative genomic hybridization (aCGH). To our knowledge this is the first study to use ultra-high density aCGH microarrays to profile a large number of OSCC genomes (n = 46)...
2013: PloS One
Jason L Eccleston, Christopher Koh, Thomas C Markello, William A Gahl, Theo Heller
Single nucleotide polymorphism (SNP) arrays possess clinical potential due to their high throughput capacity, sensitivity and versatility. We used such an array to perform a genome-wide SNP analysis of a patient with a multi-system undiagnosed disease involving peripheral neuropathies and food intolerances. The patient had a homozygous deletion within the gene encoding maltase-glucoamylase (MGAM), an intestinal starch digestion enzyme, predicting absence of enzyme activity and potential starch indigestion. We then performed validation testing using a functional MGAM analysis that involved starch ingestion followed by measuring blood glucose and insulin levels as well as hydrogen breath levels...
December 2012: Molecular Genetics and Metabolism
Byung-Hoo Lee, Razieh Eskandari, Kyra Jones, Kongara Ravinder Reddy, Roberto Quezada-Calvillo, Buford L Nichols, David R Rose, Bruce R Hamaker, B Mario Pinto
Starch digestion involves the breakdown by α-amylase to small linear and branched malto-oligosaccharides, which are in turn hydrolyzed to glucose by the mucosal α-glucosidases, maltase-glucoamylase (MGAM) and sucrase-isomaltase (SI). MGAM and SI are anchored to the small intestinal brush-border epithelial cells, and each contains a catalytic N- and C-terminal subunit. All four subunits have α-1,4-exohydrolytic glucosidase activity, and the SI N-terminal subunit has an additional exo-debranching activity on the α-1,6-linkage...
September 14, 2012: Journal of Biological Chemistry
Masaya Shimada, Kazuki Mochizuki, Toshinao Goda
Methylated histone H3 at lysine 4 (K4) is associated with euchromatin and is involved in the transactivation of genes. However, it is unknown whether histone methylation is involved with changes in gene expression induced by nutrients. In this study, we examined whether methylations of histone H3 at K4 on maltase-glucoamylase (Mgam), which is responsible for the digestion of starch in the small intestine, as well as Mgam expression were altered by feeding rats an indigestible starch (resistant starch, RS). The mRNA and protein levels and the activities of MGAM were reduced in rats fed an RS diet compared with those fed a regular starch diet...
March 2013: Journal of Nutritional Biochemistry
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