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https://www.readbyqxmd.com/read/27909398/an-amyloid-like-pathological-conformation-of-tdp-43-is-stabilized-by-hypercooperative-hydrogen-bonds
#1
Miguel Mompeán, Marco Baralle, Emanuele Buratti, Douglas V Laurents
TDP-43 is an essential RNA-binding protein forming aggregates in almost all cases of sporadic amyotrophic lateral sclerosis (ALS) and many cases of frontotemporal lobar dementia (FTLD) and other neurodegenerative diseases. TDP-43 consists of a folded N-terminal domain with a singular structure, two RRM RNA-binding domains, and a long disordered C-terminal region which plays roles in functional RNA regulatory assemblies as well as pernicious aggregation. Evidence from pathological mutations and seeding experiments strongly suggest that TDP-43 aggregates are pathologically relevant through toxic gain-of-harmful-function and/or harmful loss-of-native-function mechanisms...
2016: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/27908619/correlation-of-dna-repair-gene-polymorphisms-with-clinical-outcome-in-patients-with-locally-advanced-non-small-cell-lung-cancer-receiving-induction-chemotherapy-followed-by-surgery
#2
Mariacarmela Santarpia, Jose Luis Ramirez, Itziar de Aguirre, Pilar Garrido, Maria Pérez Cano, Cristina Queralt, Jose Luis Gonzalez-Larriba, Amelia Insa, Mariano Provencio, Dolores Isla, Carlos Camps, Remei Blanco, Teresa Moran, Rafael Rosell
OBJECTIVE: The aim of this study was to evaluate whether xeroderma pigmentosum group D (XPD) and ribonucleotide reductase subunit M1 (RRM1) polymorphisms influenced clinical outcome in patients with stage IIIA-B non-small-cell lung cancer (NSCLC) treated with neoadjuvant gemcitabine/cisplatin/docetaxel followed by surgery. MATERIALS AND METHODS: A total of 109 patients with stage IIIA and IIIB NSCLC were prospectively genotyped to examine a potential association between XPD 312 (aspartic acid [Asp]/asparagine [Asn]), XPD 751 (lysine [Lys]/glutamine [Gln]), and RRM1 (-37 C/A) polymorphisms with response and survival...
November 9, 2016: Clinical Lung Cancer
https://www.readbyqxmd.com/read/27906990/surveillance-of-helicobacter-pylori-antibiotic-susceptibility-in-indonesia-different-resistance-types-among-regions-and-with-novel-genetic-mutations
#3
Muhammad Miftahussurur, Ari Fahrial Syam, Iswan Abbas Nusi, Dadang Makmun, Langgeng Agung Waskito, Lukman Hakim Zein, Fardah Akil, Willy Brodus Uwan, David Simanjuntak, I Dewa Nyoman Wibawa, Jimmy Bradley Waleleng, Alexander Michael Joseph Saudale, Fauzi Yusuf, Syifa Mustika, Pangestu Adi, Ummi Maimunah, Hasan Maulahela, Yudith Annisa Ayu Rezkitha, Phawinee Subsomwong, Nasronudin, Dadik Rahardjo, Rumiko Suzuki, Junko Akada, Yoshio Yamaoka
Information regarding Helicobacter pylori antibiotic resistance in Indonesia was previously inadequate. We assessed antibiotic susceptibility for H. pylori in Indonesia, and determined the association between virulence genes or genetic mutations and antibiotic resistance. We recruited 849 dyspeptic patients who underwent endoscopy in 11 cities in Indonesia. E-test was used to determine the minimum inhibitory concentration of five antibiotics. PCR-based sequencing assessed mutations in 23S rRNA, rdxA, gyrA, gyrB, and virulence genes...
2016: PloS One
https://www.readbyqxmd.com/read/27904890/using-signal-amplification-by-reversible-exchange-sabre-to-hyperpolarise-119-sn-and-29-si-nmr-nuclei
#4
Alexandra M Olaru, Alister Burt, Peter J Rayner, Sam J Hart, Adrian C Whitwood, Gary G R Green, Simon B Duckett
The hyperpolarisation of the (119)Sn and (29)Si nuclei in 5-(tributylstannyl)pyrimidine (ASn) and 5-(trimethylsilyl)pyrimidine (BSi) is achieved through their reaction with [IrCl(COD)(IMes)] (1a) or [IrCl(COD)(SIMes)] (1b) and parahydrogen via the SABRE process. 1a exhibits superior activity in both cases. The two inequivalent pyrimidine proton environments of ASn readily yielded signal enhancements totalling ∼2300-fold in its (1)H NMR spectrum at a field strength of 9.4 T, with the corresponding (119)Sn signal being 700 times stronger than normal...
December 1, 2016: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/27903647/the-production-and-utilization-of-gdp-glucose-in-the-biosynthesis-of-trehalose-6-phosphate-by-streptomyces-venezuelae
#5
Matías D Asencion Diez, Farzana Miah, Clare E M Stevenson, David M Lawson, Alberto A Iglesias, Stephen Bornemann
Trehalose-6-phosphate synthase OtsA from streptomycetes is unusual in that it uses GDP-glucose as the donor substrate rather than the more commonly used UDP-glucose. We now confirm that OtsA from Streptomyces venezuelae has such a preference for GDP-glucose and can utilise ADP-glucose to some extent too. A crystal structure of the enzyme shows that it shares twin Rossmann-like domains with the UDP-glucose-specific OtsA from Escherichia coli However, it is structurally more similar to Streptomyces hygroscopicus VldE, a GDP-valienol-dependent pseudo-glycosyltransferase enzyme...
November 30, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27896447/novel-extended-sequons-of-human-n-glycosylation-sites-improve-the-precision-of-qualitative-predictions-an-alignment-free-study-of-pattern-recognition-using-protdcal-protein-features
#6
Yasser B Ruiz-Blanco, Yovani Marrero-Ponce, Enrique García-Hernández, James Green
N-Glycosylation is a common post-translational modification that plays an important role in the proper folding and function of many proteins. This modification is largely dependent on the presence of a sequence motif called a "sequon" defined as Asn-Xxx-Ser/Thr. However, evidence has shown that the presence of such a "sequon" is insufficient to determine the occurrence of N-glycosylation with high precision. This study aims to elucidate patterns that can more accurately predict N-glycosylation sites in human proteins...
November 28, 2016: Amino Acids
https://www.readbyqxmd.com/read/27895582/introduction-of-an-n-glycosylation-site-into-udp-glucuronosyltransferase-2b3-alters-its-sensitivity-to-cytochrome-p450-3a1-dependent-modulation
#7
Tatsuro Nakamura, Naho Yamaguchi, Yuu Miyauchi, Tomoki Takeda, Yasushi Yamazoe, Kiyoshi Nagata, Peter I Mackenzie, Hideyuki Yamada, Yuji Ishii
Our previous studies have demonstrated functional protein-protein interactions between cytochrome P450 (CYP) 3A and UDP-glucuronosyltransferase (UGT). However, the role of carbohydrate chains of UGTs in the interaction with CYP is not well understood. To address this issue, we examined whether CYP3A1 modulates the function of UGT2B3 which lacks potential glycosylation sites. We also examined whether the introduction of N-glycosylation to UGT2B3 affects CYP3A-dependent modulation of UGT function. To introduce a potential glycosylation site into UGT2B3, Ser 316 of UGT2B3 was substituted with Asn by site-directed mutagenesis...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27894812/enhanced-legumain-recognition-and-nir-controlled-released-of-cisplatin-indocyanine-nanosphere-against-gastric-carcinoma
#8
Tianyi Shi, Lianshuai Gu, Yu Sun, Senlin Wang, Chaoqun You, Xiangyang Zhang, Jin Zhu, Baiwang Sun
Cisplatin-therapy has faced limitations in the gastric cancer therapy. To settle the bottleneck, enhanced specificity and controlled-release property are choosen. We synthesize cisplatin and indocyanine green (ICG) loaded PLGA-(DSPE-PEG2000) nanoparticles, which is abbreviated as CINPs. And we conjugate the Gly-Cys-Gly-Ala-Ala-Asn-Leu (GCGAANL) heptapeptide upon the surface of CINPs, the product is abbreviated as ACINPs. ACINPs with nearly 110nm exhibit good monodispersity and size stability. The EE (efficiency of encapsulation) and LE (loading of encapsulation) of cisplatin loaded into ACINPs are optimized as 29...
November 25, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27883185/water-dynamics-of-ser-his-glu-cys-asn-powder-and-effects-of-moisture-absorption-on-its-chemical-properties
#9
Songyi Lin, Peiyu Xue, Shuailing Yang, Xingfang Li, Xiuping Dong, Feng Chen
BACKGROUND: This study has elucidated moisture dynamics in the soybean peptide, Ser-His-Glu-Cys-Asn (SHECN) powder by using dynamic vapor sorption (DVS) and NMR. We also tried to investigate the effects of moisture absorption on the biological activity and chemical properties of SHECN with some effective methods such like mid-infrared spectroscopy (MIR) and GC-MS. RESULTS: The DVS results showed the maximum moisture absorption of SHECN could reached 33% and the SHECN powder after synthesis actually existed in a trihydrate state of SHECN·3H2 O...
November 24, 2016: Journal of the Science of Food and Agriculture
https://www.readbyqxmd.com/read/27879392/characterization-of-class-iii-peroxidases-from-switchgrass
#10
Timothy W Moural, Kevin M Lewis, Carlo Barnaba, Fang Zhu, Nathan A Palmer, Gautam Sarath, Erin D Scully, Jeffrey P Jones, Scott E Sattler, ChulHee Kang
Class III peroxidases (CIIIPRX) catalyze the oxidation of monolignols, generate radicals, and ultimately lead to the formation of lignin. In general, CIIIPRX genes encode a large number of isozymes with ranges of in vitro substrate specificities. In order to elucidate the mode of substrate specificity of these enzymes, we characterized one of the CIIIPRXs (PviPRX9) from switchgrass (Panicum virgatum), a strategic plant for 2nd generation biofuels. The crystal structure, kinetic experiments, molecular docking, as well as expression patterns of PviPRX9 across multiple tissues and treatments, along with its levels of coexpression with the majority of genes in the monolignol biosynthesis pathway, revealed the function of PviPRX9 in lignification...
November 15, 2016: Plant Physiology
https://www.readbyqxmd.com/read/27871003/magnetic-mesoporous-nanospheres-anchored-with-lyp-1-as-an-efficient-pancreatic-cancer-probe
#11
Yongjian Jiang, Shaojun Liu, Yu Zhang, Hengchao Li, Hang He, Juntao Dai, Tao Jiang, Weihang Ji, Daoying Geng, Ahmed A Elzatahry, Abdulaziz Alghamdi, Deliang Fu, Yonghui Deng, Dongyuan Zhao
Immobilization of a ligand that selectively interacts with cancer cells to nanomaterials can enhance their diagnostic and therapeutic efficiency. In this study, we firstly demonstrate the high expression of receptor for cyclic nine-amino acid peptide LyP-1 (Cys-Gly-Asn-Lys-Arg-Thr-Arg-Gly-Cys) in both mouse and human pancreatic cancer. Based on these findings, sub-50 nm multifunctional superparamagnetic mesoporous nanospheres with surface modified with LyP-1 are rationally designed. Theses nanospheres have a core of silica-protected magnetite nanoparticle and a shell of FITC-labeled mesoporous silica, and they are able to specifically recognize and conjugate with the pancreatic cancer cell in vitro, as verified by the combined techniques of fluorescent imaging and T2 weight magnetic resonance imaging...
November 11, 2016: Biomaterials
https://www.readbyqxmd.com/read/27866911/structural-insight-into-the-enzymatic-formation-of-bacterial-stilbene
#12
Takahiro Mori, Takayoshi Awakawa, Koichiro Shimomura, Yuri Saito, Dengfeng Yang, Hiroyuki Morita, Ikuro Abe
In contrast to stilbene biosynthesis by type III polyketide synthase in plants, in bacteria stilbene is produced by the collaboration of two enzymes in Photorhabdus luminescens: the unusual β-ketosynthase StlD catalyzes the condensation of the β-ketoacyl starter with an α,β-unsaturated-acyl substrate (two C-C bond-forming reactions) to produce isopropylstyrylcyclohexanedione, which is subsequently converted to stilbene by the aromatase StlC. Here we report the in vitro characterizations of StlD and StlC, and the X-ray crystal structures of StlD...
November 9, 2016: Cell Chemical Biology
https://www.readbyqxmd.com/read/27866376/reduction-in-dietary-acrylamide-exposure-impact-of-potatoes-with-low-acrylamide-potential
#13
Nga L Tran, Leila M Barraj, Susan Collinge
Acrylamide forms primarily from a reaction between reducing sugars (e.g., glucose and fructose) and an amino acid (asparagine, Asn) formed naturally in foods, including potatoes. This reaction occurs when carbohydrate-rich foods are heated at temperatures above 120 °C. Multiple potato varieties were transformed with potato genomic DNA that results in down-regulation of the expression of the asparagine synthetase-1 gene (Asn1), significantly reducing synthesis of free Asn, and consequently lowering the potential to form acrylamide during cooking...
November 20, 2016: Risk Analysis: An Official Publication of the Society for Risk Analysis
https://www.readbyqxmd.com/read/27864899/n-glycosylation-at-asn-402-stabilizes-n-cadherin-and-promotes-cell-cell-adhesion-of-glioma-cells
#14
Yaolin Xu, Ruiqi Chang, Fulin Xu, Yan Gao, Fuming Yang, Can Wang, Jin Xiao, Zuopeng Su, Yongyan Bi, Liying Wang, Xiliang Zha
Cadherin is crucial for cell-cell adhesion and N-glycosylation of N-cadherin has been implicated in the process of mammary, renal, and ovarian carcinogenesis. However, whether N-glycosylation of N-cadherin plays a role in glioma remains unknown. Previous studies had indicated that N-glycosylation could occur at three asparagine residues of N-cadherin. By generating and over-expressing N-glycosylation-deficient N-cadherin mutants in the human glioma cell lines SHG66 and U87, we found that mutation of N402 but not of the other potentially N-glycosylated residues destabilized N-cadherin and led to its ubiquitylation and subsequent proteasomal degradation...
November 19, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27863716/antibodies-against-the-c-terminus-of-%C3%AE-synuclein-modulate-its-fibrillation
#15
Cagla Sahin, Nikolai Lorenzen, Lasse Lemminger, Gunna Christiansen, Ian Max Møller, Louise Buur Vesterager, Lars Østergaard Pedersen, Karina Fog, Pekka Kallunki, Daniel E Otzen
The 140-residue natively disordered protein α-synuclein (aSN) is a central component in the development of a family of neurodegenerative diseases termed synucleinopathies. This is attributed to its ability to form cytotoxic aggregates such as oligomers and amyloid fibrils. Consequently there have been intense efforts to avoid aggregation or reroute the aggregation pathway using pharmaceutical agents such as small molecules, chaperones and antibodies. aSN's lack of persistent structure in the monomeric state, as well as the multitude of different oligomeric and even different fibrillar states, makes it difficult to raise antibodies that would be efficacious in neutralizing all conformations of aSN...
January 2017: Biophysical Chemistry
https://www.readbyqxmd.com/read/27858705/epitope-analysis-of-japanese-cedar-pollen-allergen-cry-j2-with-a-human-igm-class-monoclonal-antibody-404-117
#16
Seiya Chiba, Haruka Yokoyama, Ayane Kumazawa, Michie Shimmoto, Yasunori Naganawa, Hiroshi Shinmoto
Japanese cedar pollen allergen Cry j2 is a causal allergen of seasonal pollinosis in Japan. To analyze B cell epitopes of Cry j2, we established two human-mouse hybridomas secreting IgM class human monoclonal antibodies to Cry j2. A pin-peptide enzyme-linked immunosorbent assay with synthesized icosa peptides showed that 404-117 monoclonal antibody bound to peptides #11-13 with cry j2 amino acid sequence of 101F-L140. Detailed analysis with octa peptides and alanine substituted peptides indicated that an amino acid sequence of 118FKVD121 was an essential for antibody binding...
November 4, 2016: Human Antibodies
https://www.readbyqxmd.com/read/27856750/substrate-recognition-and-catalysis-by-gh47-%C3%AE-mannosidases-involved-in-asn-linked-glycan-maturation-in-the-mammalian-secretory-pathway
#17
Yong Xiang, Khanita Karaveg, Kelley W Moremen
Maturation of Asn-linked oligosaccharides in the eukaryotic secretory pathway requires the trimming of nascent glycan chains to remove all glucose and several mannose residues before extension into complex-type structures on the cell surface and secreted glycoproteins. Multiple glycoside hydrolase family 47 (GH47) α-mannosidases, including endoplasmic reticulum (ER) α-mannosidase I (ERManI) and Golgi α-mannosidase IA (GMIA), are responsible for cleavage of terminal α1,2-linked mannose residues to produce uniquely trimmed oligomannose isomers that are necessary for ER glycoprotein quality control and glycan maturation...
November 17, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27856189/n-linked-glycans-are-an-important-component-of-the-processive-machinery-of-cellobiohydrolases
#18
Alexander V Gusakov, Anna S Dotsenko, Aleksandra M Rozhkova, Arkady P Sinitsyn
Cellobiohydrolases (CBHs), belonging to glycoside hydrolase families 6 and 7 (GH6 and GH7), are the major components of cellulase systems of filamentous fungi involved in biodegradation of cellulose in nature. Previous studies demonstrated that N-linked glycans in the catalytic domains of GH7 CBHs significantly affect the enzyme activity against cellulosic substrates. The influence of N-linked glycans on the activity and processivity of recombinant GH6 CBH II from Penicillium verruculosum (PvCel6A) was studied using site-directed mutagenesis of the respective Asn residues...
November 14, 2016: Biochimie
https://www.readbyqxmd.com/read/27847342/molecular-cloning-and-functional-characterization-of-cathepsin-b-from-the-sea-cucumber-apostichopus-japonicus
#19
Huahui Chen, Miao Lv, Zhimeng Lv, Chenghua Li, Wei Xu, Weiwei Zhang, Xuelin Zhao, Xuemei Duan, Chunhua Jin
Cathepsin B (CTSB), a member of lysosomal cysteine protease, is involved in multiple levels of physiological and biological processes, and also plays crucial roles in host immune defense against pathogen infection in vertebrates. However, the function of CTSB within the innate immune system of invertebrates, particularly in marine echinoderms, has been poorly documented. In this study, the immune function of CTSB in Apostichopus japonicus (designated as AjCTSB), a commercially important and disease vulnerable aquaculture specie, was investigated by integrated molecular and protein approaches...
November 12, 2016: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/27845046/arabidopsis-plastidial-folylpolyglutamate-synthetase-is-required-for-nitrogen-metabolism-under-nitrate-limited-condition-in-darkness
#20
Hongyan Meng, Bosi Xu, Chunyi Zhang, Ling Jiang
Folates play an important role in plant metabolism. Here we report a T-DNA insertion mutant (atdfb-3) of the plastidial folylpolyglutamate synthetase gene (AtDFB) was defective in folate metabolism and nitrogen metabolism under nitrate-limited conditions in darkness. Exogenous applied 5-formyl-tetrahydrofolate (5-F-THF) completely restored nitrogen content, soluble protein, total amino acids, individual amino acids including Glu, Gln, Asp, Asn, Pro, Arg and Met, nitrate, and endogenous 5-F-THF in atdfb-3 to the wild-type level...
November 12, 2016: Biochemical and Biophysical Research Communications
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