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https://www.readbyqxmd.com/read/29029085/impairment-of-elastic-properties-of-the-aorta-in-bicuspid-aortic-valve-relationship-between-biomolecular-and-aortic-strain-patterns
#1
Luca Longobardo, Maria Ludovica Carerj, Gabriele Pizzino, Alessandra Bitto, Maurizio Cusma Piccione, Marta Zucco, Lilia Oreto, Maria Chiara Todaro, Maria Pia Calabrò, Francesco Squadrito, Gianluca Di Bella, Giuseppe Oreto, Bijoy K Khandheria, Scipione Carerj, Concetta Zito
Aims: Bicuspid aortic valve (BAV) is associated with aortic wall alterations. We aimed to detect any correlation between aortic elasticity and genetic and biomolecular patterns of elastin. Methods and results: Forty-nine BAV patients (mean age: 38 ± 17.05) were prospectively enrolled. A blood sample was drawn for analysis of a single nucleotide polymorphism of elastin gene (ELN rs2071307) responsible for misfolding of elastin, and for the amount of elastin soluble fragments (ESF) in the plasma...
September 23, 2017: European Heart Journal Cardiovascular Imaging
https://www.readbyqxmd.com/read/29028684/toxic-metals-increase-serum-tumor-necrosis-factor-%C3%AE-levels-modified-by-essential-elements-and-different-types-of-tumor-necrosis-factor-%C3%AE-promoter-single-nucleotide-polymorphisms
#2
Yung-Cheng Huang, Wei-Chiao Chang, Ya-Han Shan, Chao-Yi Lin, Chao-Ling Wang, Chia-Yen Dai, Chi-Kung Ho, Ming-Tsang Wu, Hung-Yi Chuang
BACKGROUND: Lead (Pb), cadmium (Cd), and arsenic (As) could cause health issues through oxidative stress that is indicated in the elevated tumor necrosis factor-alpha (TNF-α). However, some of the essential elements-selenium (Se), zinc (Zn), cobalt (Co), and copper (Cu)-are cofactors or structural components of antioxidant enzymes. It is suggested that single-nucleotide polymorphisms (SNPs) in the TNF-α gene have different TNF-α responses. This study aims to evaluate the effect of serum TNF-α levels through the interactions between toxic metals and essential elements and how the interactions between the toxic metals and TNF-α SNPs (-1031 T > C, -863 C > A, -857 C > T, -308 G > A, -238 G > A) influence serum TNF-α levels...
October 2017: Epidemiology
https://www.readbyqxmd.com/read/29024007/snp-mutations-occurring-in-thyroid-hormone-receptor-influenced-individual-susceptibility-to-triiodothyronine-molecular-dynamics-and-site-directed-mutagenesis-approaches
#3
Yaquan Liu, Kaili Qu, Ying Hai, Xin Li, Lei Zhao, Chunyan Zhao
The increasing evidences have suggested that expression of single nucleotide polymorphisms (SNP) coded thyroid hormone receptors (THR) generally are associated with individual susceptibility to chemicals. In the present research, multiple molecular dynamics simulations on four SNP mutants (G332R, T337△, G345R and G347E) were performed to investigate the structural and dynamical altering, which could lead to a binding capability variation to triiodothyronine (T3). It proved the structures of two SNP mutants (G345R and T337△) occurring in the THR proteins had experienced conformational change to a great extend, which also led to a significant decreasing in binding ability with T3...
October 11, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29024003/molecular-characterization-of-the-llama-fgf5-gene-and-identification-of-putative-loss-of-function-mutations
#4
M S Daverio, L Vidal-Rioja, E N Frank, F Di Rocco
Llama, the most numerous domestic camelid in Argentina, has good fiber-production ability. Although a few genes related to other productive traits have been characterized, the molecular genetic basis of fiber growth control in camelids is still poorly understood. Fibroblast growth factor 5 (FGF5) is a secreted signaling protein that controls hair growth in humans and other mammals. Mutations in the FGF5 gene have been associated with long-hair phenotypes in several species. Here, we sequenced the llama FGF5 gene, which consists of three exons encoding 813 bp...
October 11, 2017: Animal Genetics
https://www.readbyqxmd.com/read/29023092/effect-of-the-flexible-regions-of-the-oncoprotein-mouse-double-minute-x-on-inhibitor-binding-affinity
#5
Lingyun Qin, Huili Liu, Rong Chen, Jingjing Zhou, Xiyao Cheng, Yao Chen, Yongqi Huang, Zhengding Su
The oncoprotein MdmX (Mouse double minute X) is highly homologous to Mdm2 (Mouse double minute 2) regarding their amino acid sequences and three-dimensional conformations, but Mdm2 inhibitors exhibit very weak affinity for MdmX, providing an excellent model for exploring how protein conformation distinguishes and adapts inhibitor-binding. The intrinsic conformation flexibility of proteins plays pivotal roles in determining and predicting the binding properties and the design of inhibitors. Although the molecular dynamics simulation approach enables the understanding of protein-ligand interactions, the mechanism un-derlying how a flexible binding pocket adapts an inhibitor is less explored experimentally...
October 12, 2017: Biochemistry
https://www.readbyqxmd.com/read/29019072/mass-spectrometry-based-metabolomics-to-identify-taurine-modified-metabolites-in-heart
#6
Takashi Ito, Koei Okazaki, Daisuke Nakajima, Daisuke Shibata, Shigeru Murakami, Stephen Schaffer
Taurine is an abundant beta-amino acid found in high concentration in mammalian tissues. Taurine possesses many beneficial functions in mammalian cells. There are also a variety of taurine-conjugated products formed between taurine and bile acids, fatty acids, chloramine, mitochondrial tRNA, etc., and some of these have been identified as functional compounds. In the present study, we identified taurine-conjugated metabolites using LC-MS-based metabolome analysis of heart extracts prepared from hearts of wild-type and taurine transporter-knockout (TauTKO) mice, the latter being severely taurine deficient...
October 10, 2017: Amino Acids
https://www.readbyqxmd.com/read/29018423/the-microbiome-of-seriola-lalandi-of-wild-and-aquaculture-origin-reveals-differences-in-composition-and-potential-function
#7
Carolina Ramírez, Jaime Romero
Seriola lalandi is an economically important species that is globally distributed in temperate and subtropical marine waters. Aquaculture production of this species has had problems associated with intensive fish farming, such as disease outbreaks or nutritional deficiencies causing high mortalities. Intestinal microbiota has been involved in many processes that benefit the host, such as disease control, stimulation of the immune response, and the promotion of nutrient metabolism, among others. However, little is known about the potential functionality of the microbiota and the differences in the composition between wild and aquacultured fish...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28994436/engineering-a-periplasmic-binding-protein-for-amino-acid-sensors-with-improved-binding-properties
#8
Wooseok Ko, Sanggil Kim, Hyun Soo Lee
Periplasmic binding proteins (PBPs) are members of a widely distributed protein superfamily found in bacteria and archaea, and are involved in the cellular uptake of solutes. In this report, a leucine-binding PBP was engineered to detect l-Leu based on a fluorescence resonance energy transfer (FRET) change upon ligand binding. A fluorescent unnatural amino acid, l-(7-hydroxycoumarin-4-yl)ethylglycine (CouA), was genetically incorporated into the protein as a FRET donor, and a yellow fluorescent protein (YFP) was fused with its N-terminus as a FRET acceptor...
October 10, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28994223/multiple-taf-subunits-of-tfiid-interact-with-ino2-activation-domains-and-contribute-to-expression-of-genes-required-for-yeast-phospholipid-biosynthesis
#9
Stefan Hintze, Maike Engelhardt, Laura van Diepen, Eric Witt, Hans-Joachim Schüller
Expression of phospholipid biosynthetic genes in yeast requires activator protein Ino2 which can bind to the UAS element ICRE (inositol/choline-responsive element) and trigger activation of target genes, using two separate transcriptional activation domains, TAD1 and TAD2. However, it is still unknown which cofactors mediate activation by TADs of Ino2. Here we show that multiple subunits of basal transcription factor TFIID (TBP-associated factors Taf1, Taf4, Taf6, Taf10 and Taf12) are able to interact in vitro with activation domains of Ino2...
October 10, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28993610/evolution-of-host-adaptation-in-the-salmonella-typhoid-toxin
#10
Xiang Gao, Lingquan Deng, Gabrielle Stack, Hai Yu, Xi Chen, Yuko Naito-Matsui, Ajit Varki, Jorge E Galán
The evolution of virulence traits is central for the emergence or re-emergence of microbial pathogens and for their adaptation to a specific host (1-5) . Typhoid toxin is an essential virulence factor of the human-adapted bacterial pathogen Salmonella Typhi (6,7) , the cause of typhoid fever in humans (8-12) . Typhoid toxin has a unique A2B5 architecture with two covalently linked enzymatic 'A' subunits, PltA and CdtB, associated with a homopentameric 'B' subunit made up of PltB, which has binding specificity for the N-acetylneuraminic acid (Neu5Ac) sialoglycans (6,13) predominantly present in humans (14) ...
October 9, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28992303/dominant-allele-phylogeny-and-constitutive-subgenome-haplotype-inference-in-bananas-using-mitochondrial-and-nuclear-markers
#11
Kariuki Samwel Muiruri, Anne Britt, Nelson Onzere Amugune, Edward Nguu, Simon Chan, Leena Tripathi
Cultivated bananas (Musa spp.) have undergone domestication patterns involving crosses of wild progenitors followed by long periods of clonal propagation. Majority of cultivated bananas are polyploids with different constitutive subgenomes and knowledge on phylogenies to their progenitors at the species and subspecies levels is essential. Here, the mitochondrial (NAD1) and nuclear (CENH3) markers were used to phylogenetically position cultivated banana genotypes to diploid progenitors. The CENH3 nuclear marker was used to identify a minimum representative haplotype number in polyploids and diploid bananas based on single nucleotide polymorphisms...
October 1, 2017: Genome Biology and Evolution
https://www.readbyqxmd.com/read/28992260/simulations-of-cyp51a-from-aspergillus-fumigatus-in-a-model-bilayer-provide-insights-into-triazole-drug-resistance
#12
Anthony Nash, Johanna Rhodes
Azole antifungal drugs target CYP51A in Aspergillus fumigatus by binding with the active site of the protein, blocking ergosterol biosynthesis. Resistance to azole antifungal drugs is now common, with a leucine to histidine amino acid substitution at position 98 the most frequent, predominantly conferring resistance to itraconazole, although cross-resistance has been reported in conjunction with other mutations. In this study, we create a homology model of CYP51A using a recently published crystal structure of the paralog protein CYP51B...
September 9, 2017: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
https://www.readbyqxmd.com/read/28991437/structural-insight-into-acyl-acp-thioesterase-towards-substrate-specificity-design
#13
Yanbin Feng, Yayue Wang, Jiao Liu, Yinghui Liu, Xupeng Cao, Song Xue
Acyl-ACP thioesterase (TE) catalyzes the hydrolysis of thioester bonds during type II fatty acid synthesis and directly determines fatty acid chain length. Most TEs are responsible for recognition of 16:0 and 18:1 substrates, while specific TEs interrupt acyl-ACP elongation at C8-C14. However, the acyl selection mechanism of TE has not been thoroughly elucidated to date. In this study, the crystal structure of the C12-specific thioesterase FatB from Umbellularia californica, which consists of two independent hotdog domains, was determined...
October 9, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28988868/characterization-of-the-dna-mismatch-repair-proteins-muts-and-mutl-in-hypermutator-acinetobacter-baumannii
#14
Behnaz Deiham, Malihe Hassanzadeh, Nazanin Zahra Shafiei-Jandaghi, Massoud Amanlou, Masoumeh Douraghi
Mutations of mutS and mutL genes have been linked with the emergence of hypermutator (HPM) phenotype in several bacteria. Nevertheless, there is scarce evidence that these mutations occurred in HPM Acinetobacter baumannii, therefore, it remains unknown whether the mutations located in domains mediating the functions of MutS and MutL. To address this information gap, the nucleotide sequence of mutS and mutL was characterized and their mutations were identified. Additionally, we proposed in silico models of mutated proteins and analyzed the secondary and tertiary structures, and interaction interfaces of MutL and MutS...
October 5, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28988317/identification-of-critical-amino-acids-in-the-proximal-c-terminal-of-trek-2-k-channel-for-activation-by-acidic-phi-and-atp-dependent-inhibition
#15
Joohan Woo, Young Keul Jun, Yin-Hua Zhang, Joo Hyun Nam, Dong Hoon Shin, Sung Joon Kim
TWIK-related two-pore domain K(+) channels (TREKs) are regulated by intracellular pH (pHi) and Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2). Previously, Glu(306) in proximal C-terminal (pCt) of mouse TREK-1 was identified as the pHi-sensing residue. The direction of PI(4,5)P2 sensitivity is controversial, and we have recently shown that TREKs are inhibited by intracellular ATP via endogenous PI(4,5)P2 formation. Here we investigate the anionic and cationic residues of pCt for the pHi and ATP-sensitivity in human TREK-2 (hTREK-2)...
October 8, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28986109/x-protein-variants-of-the-autochthonous-latin-american-hepatitis-b-virus-f-genotype-promotes-human-hepatocyte-death-by-the-induction-of-apoptosis-and-autophagy
#16
María Mercedes Elizalde, Rodolfo Héctor Campos, Luciana Barbini
The hepatitis B virus X protein (HBV-X) is a multifunctional regulatory protein associated with the pathogenesis of liver disease in chronic HBV infection. Basal core promoter mutations (BCP), associated with the clinical course of chronic HBV infection, affect HBV-X at 130-131 positions. The role of these mutations on HBV-X biological activity remains largely unknown. The aim of this study was to analyze the impact of the presence of different amino acids at 130-131 positions of HBV-X on the biological activity of the protein...
October 3, 2017: Virus Research
https://www.readbyqxmd.com/read/28984228/substitutions-at-residues-300-and-389-of-the-vp2-capsid-protein-serve-as-the-minimal-determinant-of-attenuation-for-canine-parvovirus-vaccine-strain-9985-46
#17
Go Sehata, Hiroaki Sato, Morimasa Yamanaka, Takuo Takahashi, Risa Kainuma, Tatsuhiko Igarashi, Sho Oshima, Taichi Noro, Eiji Oishi
Identifying molecular determinants of virulence attenuation in live attenuated canine parvovirus (CPV) vaccines is important for assuring their safety. To this end, we identified mutations in the attenuated CPV 9985-46 vaccine strain that arose during serial passage in Crandell-Rees feline kidney cells by comparison with the wild-type counterpart, as well as minimal determinants of the loss of virulence. Four amino acid substitutions (N93K, G300V, T389N and V562L) in VP2 of strain 9985-46 significantly restricted infection in canine A72 cells...
October 6, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28983723/engineering-a-carotenoid-binding-site-in-dokdonia-sp-pro95-na-translocating-rhodopsin-by-a-single-amino-acid-substitution
#18
Viktor A Anashkin, Yulia V Bertsova, Adalyat M Mamedov, Mahir D Mamedov, Alexander M Arutyunyan, Alexander A Baykov, Alexander V Bogachev
Light-driven H(+), Cl(-) and Na(+) rhodopsin pumps all use a covalently bound retinal molecule to capture light energy. Some H(+)-pumping rhodopsins (xanthorhodopsins; XRs) additionally contain a carotenoid antenna for light absorption. Comparison of the available primary and tertiary structures of rhodopsins pinpointed a single Thr residue (Thr216) that presumably prevents carotenoid binding to Na(+)-pumping rhodopsins (NaRs). We replaced this residue in Dokdonia sp. PRO95 NaR with Gly, which is found in the corresponding position in XRs, and produced a variant rhodopsin in a ketocarotenoid-synthesising Escherichia coli strain...
October 5, 2017: Photosynthesis Research
https://www.readbyqxmd.com/read/28982731/studies-in-genetically-modified-mice-implicate-maternal-hdl-as-a-mediator-of-fetal-growth
#19
Sandra L Rebholz, John T Melchior, W Sean Davidson, Helen N Jones, Jeffrey A Welge, Andrew M Prentice, Sophie E Moore, Laura A Woollett
Studies in humans have shown a direct association between maternal plasma cholesterol concentrations and infant birthweight. Similarly, previous studies in our laboratory have shown that chow-fed mice lacking apolipoprotein (apo) A-I, the major protein in HDL, have low HDL-cholesterol (HDL-C) concentrations and smaller fetuses in midgestation. In the current study, we measured fetal weights in mice with varying levels of apoA-I gene dose (knockout, wild-type, and transgenic) and examined metabolic pathways known to affect fetal growth...
October 5, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28982592/human-amyloid-%C3%AE-peptide-and-tau-co-expression-impairs-behavior-and-causes-specific-gene-expression-changes-in-caenorhabditis-elegans
#20
Chenyin Wang, Valeria Saar, Ka Lai Leung, Liang Chen, Garry Wong
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the presence of extracellular amyloid plaques consisting of Amyloid-β peptide (Aβ) aggregates and neurofibrillary tangles formed by aggregation of hyperphosphorylated microtubule-associated protein tau. We generated a novel invertebrate model of AD by crossing Aβ1-42 (strain CL2355) with either pro-aggregating tau (strain BR5270) or anti-aggregating tau (strain BR5271) pan-neuronal expressing transgenic Caenorhabditis elegans...
October 2, 2017: Neurobiology of Disease
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