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https://www.readbyqxmd.com/read/27922637/a-human-carboxypeptidase-e-nf-%C3%AE-1-gene-mutation-in-an-alzheimer-s-disease-patient-leads-to-dementia-and-depression-in-mice
#1
Y Cheng, N X Cawley, T Yanik, S R K Murthy, C Liu, F Kasikci, D Abebe, Y P Loh
Patients with Alzheimer's disease (AD), a common dementia among the aging population, often also suffer from depression. This comorbidity is poorly understood. Although most forms of AD are not genetically inherited, we have identified a new human mutation in the carboxypeptidase E (CPE)/neurotrophic factor-α1 (NF-α1) gene from an AD patient that caused memory deficit and depressive-like behavior in transgenic mice. This mutation consists of three adenosine inserts, introducing nine amino acids, including two glutamines into the mutant protein, herein called CPE-QQ...
December 6, 2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27919681/mutational-analysis-of-kex2-recognition-sites-and-a-disulfide-bond-in-tannase-from-aspergillus-oryzae
#2
Takuya Koseki, Motohiro Otsuka, Toshiyuki Mizuno, Yoshihito Shiono
Aspergillus oryzae tannase (AoTanA), which contains two Kex2 recognition sites at positions Arg311 and Arg316, consists of two subunits that are generated by the cleavage of tannase gene product by the Kex2 protease. Based on the crystal structure of feruloyl esterase from Aspergillus oryzae (AoFaeB), which has been classified as a member of the fungal tannase family, the catalytic triad residues of AoTanA are predicted to be Ser195, Asp455, and His501, with the serine and histidine residues brought together by a disulfide bond of the neighboring cysteines, Cys194 and Cys502...
December 2, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27917750/cowpox-in-a-human-russia-2015
#3
A Y Popova, R A Maksyutov, O S Taranov, T V Tregubchak, A V Zaikovskaya, A A Sergeev, I V Vlashchenko, S A Bodnev, V A Ternovoi, N S Alexandrova, A L Tarasov, N V Konovalova, A A Koroleva, L E Bulychev, O V Pyankov, Y V Demina, A P Agafonov, S N Shchelkunov, V N Miheev
We investigated the first laboratory-confirmed human case of cowpox virus infection in Russia since 1991. Phylogenetic studies of haemagglutinin, TNF-α receptor-like protein and thymidine kinase regions showed significant differences with known orthopoxviruses, including unique amino-acid substitutions and deletions. The described cowpox virus strain, taking into account differences, is genetically closely related to strains isolated years ago in the same geographical region (European part of Russia and Finland), which suggests circulation of viral strains with common origin in wild rodents without spread over long distances and appearance in other parts of the world...
December 5, 2016: Epidemiology and Infection
https://www.readbyqxmd.com/read/27916792/elevated-o%C3%A2-and-tylcv-infection-reduce-the-suitability-of-tomato-as-a-host-for-the-whitefly-bemisia-tabaci
#4
Hongying Cui, Yucheng Sun, Fajun Chen, Youjun Zhang, Feng Ge
The effects of elevated atmospheric ozone (O₃) levels on herbivorous insects have been well studied, but little is known about the combined effects of elevated O₃ and virus infection on herbivorous insect performance. Using open-top chambers in the field, we determined the effects of elevated O₃ and Tomato yellow leaf curl virus (TYLCV) infection on wild-type (Wt) tomato and 35S tomato (jasmonic acid (JA) defense-enhanced genotype) in association with whitefly, Bemisia tabaci Gennadius biotype B. Elevated O₃ and TYLCV infection, alone and in combination, significantly reduced the contents of soluble sugars and free amino acids, increased the contents of total phenolics and condensed tannins, and increased salicylic acid (SA) content and the expression of SA-related genes in leaves...
November 28, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27915248/comparative-proteomic-analysis-unravels-a-role-for-esrb-in-the-regulation-of-reactive-oxygen-species-stress-responses-in-edwardsiella-piscicida
#5
Kaiyu Yin, Qiyao Wang, Jingfan Xiao, Yuanxing Zhang
As a leading pathogen, Edwardsiella piscicida can cause hemorrhagic septicemia in fish and gastro-intestinal infections in humans. The two-component regulatory system EsrA-EsrB plays essential roles in pathogenesis through the type III and type VI secretion systems, and hemolysin production in E. piscicida It is unclear whether other virulence- or stress response-associated genes are regulated by EsrA-EsrB. In this study, the proteomes of wild type E. piscicida EIB202 and esrB mutant strains were compared to reveal EsrB regulon components after growth in LB...
December 2, 2016: FEMS Microbiology Letters
https://www.readbyqxmd.com/read/27914300/structure-based-analysis-of-bacilli-and-plasmid-dihydrofolate-reductase-evolution
#6
Mona Alotaibi, Ben Delos Reyes, Tin Le, Phuong Luong, Faramarz Valafar, Robert P Metzger, Gary B Fogel, David Hecht
Dihydrofolate reductase (DHFR), a key enzyme in tetrahydrofolate-mediated biosynthetic pathways, has a structural motif known to be highly conserved over a wide range of organisms. Given its critical role in purine and amino acid synthesis, DHFR is a well established therapeutic target for treating a wide range of prokaryotic and eukaryotic infections as well as certain types of cancer. Here we present a structural-based computer analysis of bacterial (Bacilli) and plasmid DHFR evolution. We generated a structure-based sequence alignment using 7 wild-type DHFR x-ray crystal structures obtained from the RCSB Protein Data Bank and 350 chromosomal and plasmid homology models we generated from sequences obtained from the NCBI Protein Database...
November 22, 2016: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/27914062/computational-design-of-ligand-binding-proteins
#7
Christine E Tinberg, Sagar D Khare
The ability to design novel small-molecule binding sites in proteins is a stringent test of our understanding of the principles of molecular recognition, and would have many practical applications, in synthetic biology and medicine. Here, we describe a computational method in the context of the macromolecular modeling suite Rosetta to designing proteins with sites featuring predetermined interactions to ligands of choice. The required inputs for the method are a model of the small molecule and the desired interactions (e...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27913996/altered-gut-microbiota-composition-and-immune-response-in-experimental-steatohepatitis-mouse-models
#8
Mitsuaki Ishioka, Kouichi Miura, Shinichiro Minami, Yoichiro Shimura, Hirohide Ohnishi
BACKGROUND: Although several types of diet have been used in experimental steatohepatitis models, comparison of gut microbiota and immunological alterations in the gut among diets has not yet been performed. AIM: We attempted to clarify the difference in the gut environment between mice administrated several experimental diets. METHODS: Male wild-type mice were fed a high-fat (HF) diet, a choline-deficient amino acid-defined (CDAA) diet, and a methionine-choline-deficient (MCD) diet for 8 weeks...
December 2, 2016: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/27910898/hydrogen-overproducing-nitrogenases-obtained-by-random-mutagenesis-and-high-throughput-screening
#9
Emma Barahona, Emilio Jiménez-Vicente, Luis M Rubio
When produced biologically, especially by photosynthetic organisms, hydrogen gas (H2) is arguably the cleanest fuel available. An important limitation to the discovery or synthesis of better H2-producing enzymes is the absence of methods for the high-throughput screening of H2 production in biological systems. Here, we re-engineered the natural H2 sensing system of Rhodobacter capsulatus to direct the emission of LacZ-dependent fluorescence in response to nitrogenase-produced H2. A lacZ gene was placed under the control of the hupA H2-inducible promoter in a strain lacking the uptake hydrogenase and the nifH nitrogenase gene...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27909574/characterization-of-5-2-18-f-fluoroethoxy-l-tryptophan-for-pet-imaging-of-the-pancreas
#10
Ahmed Abbas, Christine Beamish, Rebecca McGirr, John Demarco, Neil Cockburn, Dawid Krokowski, Ting-Yim Lee, Michael Kovacs, Maria Hatzoglou, Savita Dhanvantari
Purpose: In diabetes, pancreatic beta cell mass declines significantly prior to onset of fasting hyperglycemia. This decline may be due to endoplasmic reticulum (ER) stress, and the system L amino acid transporter LAT1 may be a biomarker of this process. In this study, we used 5-(2- (18)F-fluoroethoxy)-L-tryptophan ( (18)F-L-FEHTP) to target LAT1 as a potential biomarker of beta cell function in diabetes. Procedures: Uptake of (18)F-L-FEHTP was determined in wild-type C57BL/6 mice by ex vivo biodistribution...
2016: F1000Research
https://www.readbyqxmd.com/read/27909291/engineering-of-a-thermostable-esterase-est816-to-improve-its-quorum-quenching-activity-and-the-underlying-structural-basis
#11
Xiwen Liu, Li-Chuang Cao, Xin-Jiong Fan, Yu-Huan Liu, Wei Xie
N-acyl-homoserine lactones (AHLs) are small diffusible molecules called autoinducers that mediate cell-to-cell communications. Enzymatic degradation of AHLs is a promising bio-control strategy known as quorum-quenching. To improve the quorum-quenching activity of a thermostable esterase Est816, which had been previously cloned, we have engineered the enzyme by random mutagenesis. One of the mutants M2 with double amino acid substitutions (A216V/K238N) showed 3-fold improvement on catalytic efficiency. Based on the crystal structure determined at 2...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27906504/combination-of-two-epitope-identification-techniques-enables-the-rational-design-of-soy-allergen-gly-m-4-mutants
#12
Heide Havenith, Karolin Kern, Paul Rautenberger, Holger Spiegel, Michael Szardenings, Elke Ueberham, Jörg Lehmann, Matthias Buntru, Simon Vogel, Regina Treudler, Rainer Fischer, Stefan Schillberg
BACKGROUND: Detailed IgE-binding epitope analysis is a key requirement for the understanding and development of diagnostic and therapeutic agents to address food allergies. METHODS: We combined an IgE-specific linear peptide microarray with random phage peptide display for the high-resolution mapping of IgE-binding epitopes of the major soybean allergen Gly m 4, which is a homologue to the birch pollen allergen Bet v1. RESULTS: Three epitopes were identified and mapped to a resolution of four key amino acids, allowing the rational design and the production of three Gly m 4 mutants with the aim to abolish or reduce the binding of epitope-specific IgE...
December 1, 2016: Biotechnology Journal
https://www.readbyqxmd.com/read/27904971/mutations-in-slc5a6-associated-with-brain-immune-bone-and-intestinal-dysfunction-in-a-young-child
#13
Veedamali S Subramanian, Alexandru R Constantinescu, Paul J Benke, Hamid M Said
The human sodium-dependent multivitamin transporter (hSMVT) is a product of the SLC5A6 gene and mediates biotin, pantothenic acid, and lipoate uptake in a variety of cellular systems. We report here the identification of mutations R94X, a premature termination, and R123L, a dysfunctional amino acid change, both in exon 3 of the SLC5A6 gene in a child using whole genome-scanning. At 15 months of age, the child showed failure to thrive, microcephaly and brain changes on MRI, cerebral palsy and developmental delay, variable immunodeficiency, and severe gastro-esophageal reflux requiring a gastrostomy tube/fundoplication, osteoporosis, and pathologic bone fractures...
November 30, 2016: Human Genetics
https://www.readbyqxmd.com/read/27903963/cdh1-regulates-e2f1-degradation-in-response-to-differentiation-signals-in-keratinocytes
#14
Randeep K Singh, Lina Dagnino
The E2F1 transcription factor plays key roles in skin homeostasis. In the epidermis, E2F1 expression is essential for normal proliferation of undifferentiated keratinocytes, regeneration after injury and DNA repair following UV radiation-induced photodamage. Abnormal E2F1 expression promotes nonmelanoma skin carcinoma. In addition, E2F1 must be downregulated for proper keratinocyte differentiation, but the relevant mechanisms involved remain poorly understood. We show that differentiation signals induce a series of post-translational modifications in E2F1 that are jointly required for its downregulation...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27902899/endemic-variation-of-h9n2-avian-influenza-virus-in-china
#15
Yu-Fu Liu, Han-Zhang Lai, Lin Li, Yu-Peng Liu, Wen-Yan Zhang, Ren Gao, Wen-Ke Huang, Qin-Fang Luo, Yan Gao, Qiong Luo, Xiao-Yu Xie, Jia-Hua Xu, Rui-Ai Chen
Forty-two H9N2 subtype AIV strains were isolated from vaccinated commercial chickens in China from 2012 to 2015. Their HA genes had nucleotide sequence homology from 86.7% to 99.7%, and similarity to the classic vaccine strain was 88.6%-92.6%. A comparison was carried out with published HA genes (410 H9 strains) and whole genomes (306 strains) isolated in China during 2012-2015. Interestingly, 99.1% (448/452) of Chinese H9N2 AIV belonged to lineage h9.4.2, and 98.5% (445/452) of the viruses belonged to h9.4...
December 2016: Avian Diseases
https://www.readbyqxmd.com/read/27902777/the-two-component-system-arlrs-and-alterations-in-metabolism-enable-staphylococcus-aureus-to-resist-calprotectin-induced-manganese-starvation
#16
Jana N Radin, Jessica L Kelliher, Paola K Párraga Solórzano, Thomas E Kehl-Fie
During infection the host imposes manganese and zinc starvation on invading pathogens. Despite this, Staphylococcus aureus and other successful pathogens remain capable of causing devastating disease. However, how these invaders adapt to host-imposed metal starvation and overcome nutritional immunity remains unknown. We report that ArlRS, a global staphylococcal virulence regulator, enhances the ability of S. aureus to grow in the presence of the manganese-and zinc-binding innate immune effector calprotectin...
November 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27901068/nanomechanical-properties-of-distinct-fibrillar-polymorphs-of-the-protein-%C3%AE-synuclein
#17
Ali Makky, Luc Bousset, Jérôme Polesel-Maris, Ronald Melki
Alpha-synuclein (α-Syn) is a small presynaptic protein of 140 amino acids. Its pathologic intracellular aggregation within the central nervous system yields protein fibrillar inclusions named Lewy bodies that are the hallmarks of Parkinson's disease (PD). In solution, pure α-Syn adopts an intrinsically disordered structure and assembles into fibrils that exhibit considerable morphological heterogeneity depending on their assembly conditions. We recently established tightly controlled experimental conditions allowing the assembly of α-Syn into highly homogeneous and pure polymorphs...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27900595/overexpression-of-a-thaumatin-like-protein-gene-from-vitis-amurensis-improves-downy-mildew-resistance-in-vitis-vinifera-grapevine
#18
Rongrong He, Jiao Wu, Yali Zhang, Cecilia B Agüero, Xinlong Li, Shaoli Liu, Chaoxia Wang, M Andrew Walker, Jiang Lu
Downy mildew is a highly destructive disease in grapevine production. A gene encoding pathogenesis-related (PR) thaumatin-like protein was isolated from the downy mildew-resistant grapevine "Zuoshan-1," a clonal selection from wild Vitis amurensis Rupr. The predicted thaumatin-like protein (VaTLP) has 225 amino acids and it is acidic, with a calculated isoelectric point of 4.8. The full length of the VaTLP gene was transformed into somatic embryogenic calli of V. vinifera 'Thompson Seedless' via Agrobacterium tumefaciens...
November 30, 2016: Protoplasma
https://www.readbyqxmd.com/read/27899915/novel-h7n2-and-h5n6-avian-influenza-a-viruses-in-sentinel-chickens-a-sentinel-chicken-surveillance-study
#19
Teng Zhao, Yan-Hua Qian, Shan-Hui Chen, Guo-Lin Wang, Meng-Na Wu, Yong Huang, Guang-Yuan Ma, Li-Qun Fang, Gregory C Gray, Bing Lu, Yi-Gang Tong, Mai-Juan Ma, Wu-Chun Cao
In 2014, a sentinel chicken surveillance for avian influenza viruses was conducted in aquatic bird habitat near Wuxi City, Jiangsu Province, China. Two H7N2, one H5N6, and two H9N2 viruses were isolated. Sequence analysis revealed that the H7N2 virus is a novel reassortant of H7N9 and H9N2 viruses and H5N6 virus is a reassortant of H5N1 clade 2.3.4 and H6N6 viruses. Substitutions V186 and L226 (H3 numbering) in the hemagglutinin (HA) gene protein was found in two H7N2 viruses but not in the H5N6 virus. Two A138 and A160 mutations were identified in the HA gene protein of all three viruses but a P128 mutation was only observed in the H5N6 virus...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27899282/bindprofx-assessing-mutation-induced-binding-affinity-change-by-protein-interface-profiles-with-pseudo-counts
#20
Peng Xiong, Chengxin Zhang, Wei Zheng, Yang Zhang
Understanding how gene-level mutations affect the binding affinity of protein-protein interactions is a key issue of protein engineering. Due to the complexity of the problem, using physical force field to predict the mutation-induced binding free-energy change remains challenging. In this work, we present a renewed approach to calculate the impact of gene mutations on the binding affinity through the structure-based profiling of protein-protein interfaces, where the binding free-energy change (ΔΔG) is counted as the logarithm of relative probability of mutant amino acids over wild-type ones in the interface alignment matrix; three pseudo counts are introduced to alleviate the limit of the current interface library...
November 26, 2016: Journal of Molecular Biology
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