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https://www.readbyqxmd.com/read/28822858/comparison-of-genome-engineering-using-the-crispr-cas9-system-in-c-glabrata-wild-type-and-lig4-strains
#1
Yuke Cen, Bea Timmermans, Ben Souffriau, Johan M Thevelein, Patrick Van Dijck
Candida glabrata is reported as the second most prevalent human opportunistic fungal pathogen in North America and is threatening patients all over the world. Its incidence is rising, while it has developed resistance to the most widely used antifungal drugs, necessitating new approaches based on better insight into the biology of the organism. Despite its close phylogenetic relationship with Saccharomyces cerevisiae, generating precise genomic alterations in this species is problematic. Previously we have shown that deletion of LIG4, which encodes an enzyme involved in Non-Homologous End Joining (NHEJ), strongly enhances the probability of obtaining correctly modified transformants...
August 16, 2017: Fungal Genetics and Biology: FG & B
https://www.readbyqxmd.com/read/28821266/endogenous-hydrogen-sulphide-attenuates-nlrp3-inflammasome-mediated-neuroinflammation-by-suppressing-the-p2x7-receptor-after-intracerebral-haemorrhage-in-rats
#2
Hengli Zhao, Pengyu Pan, Yang Yang, Hongfei Ge, Weixiang Chen, Jie Qu, Jiantao Shi, Gaoyu Cui, Xin Liu, Hua Feng, Yujie Chen
BACKGROUND: Emerging studies have demonstrated the important physiological and pathophysiological roles of hydrogen sulphide (H2S) as a gasotransmitter for NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome-associated neuroinflammation in the central nervous system. However, the effects of H2S on neuroinflammation after intracerebral haemorrhage (ICH), especially on the NLRP3 inflammasome, remain unknown. METHODS: We employed a Sprague-Dawley rat of collagenase-induced ICH in the present study...
August 18, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28820582/pathogenic-mutations-induce-partial-structural-changes-in-native-%C3%AE-sheet-structure-of-transthyretin-and-accelerate-aggregation
#3
Kwang Hun Lim, Anvesh K R Dasari, Renze Ma, Ivan Hung, Zhehong Gan, Jeffery W Kelly, Michael C Fitzgerald
Amyloid formation of natively folded proteins involves global and/or local unfolding of the native state to form aggregation-prone intermediates. Here we report solid-state NMR structural studies of amyloid derived from wild-type (WT) and more aggressive mutant forms of transthyretin (TTR) to investigate the structural changes associated with effective TTR aggregation. We employed selective 13C-labeling schemes to investigate structural features of β-structured core regions in amyloid states of WT and two mutant forms (V30M and L55P) of TTR...
August 18, 2017: Biochemistry
https://www.readbyqxmd.com/read/28820476/biosynthesis-of-s-adenosylmethionine-by-magnetically-immobilized-escherichia-coli-cells-highly-expressing-a-methionine-adenosyltransferase-variant
#4
Chunli Yin, Tao Zheng, Xin Chang
S-Adenosylmethionine (SAM) is a natural metabolite having important uses in the treatment of various diseases. To develop a simple and effective way to produce SAM, immobilized Escherichia coli cells highly expressing an engineered variant of methionine adenosyltransferase (MAT) were employed to synthesize SAM. The recombinant I303V MAT variant was successfully produced at approximately 900 mg/L in a 10-L bioreactor and exhibited significantly less product inhibition and had a four-fold higher specific activity (14...
August 18, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28820136/protective-effect-of-val129-prp-against-bovine-spongiform-encephalopathy-but-not-variant-creutzfeldt-jakob-disease
#5
Natalia Fernández-Borges, Juan Carlos Espinosa, Alba Marín-Moreno, Patricia Aguilar-Calvo, Emmanuel A Asante, Tetsuyuki Kitamoto, Shirou Mohri, Olivier Andréoletti, Juan María Torres
Bovine spongiform encephalopathy (BSE) is the only known zoonotic prion that causes variant Creutzfeldt-Jakob disease (vCJD) in humans. The major risk determinant for this disease is the polymorphic codon 129 of the human prion protein (Hu-PrP), where either methionine (Met129) or valine (Val129) can be encoded. To date, all clinical and neuropathologically confirmed vCJD cases have been Met129 homozygous, with the exception of 1 recently reported Met/Val heterozygous case. Here, we found that transgenic mice homozygous for Val129 Hu-PrP show severely restricted propagation of the BSE prion strain, but this constraint can be partially overcome by adaptation of the BSE agent to the Met129 Hu-PrP...
September 2017: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/28819915/suppression-of-methionine-induced-colon-injury-of-young-rats-by-cysteine-and-n-acetyl-l-cysteine
#6
Marija Stojanović, Ljiljana Šćepanović, Dušan Todorović, Dušan Mitrović, Vuk Šćepanović, Radomir Šćepanović, Slobodan Ilić, Teja Šćepanović, Milica Labudović Borović, Živana Milićević, Vesna Dragutinović, Sunčica Borozan, Ivana Lalić, Sanja Despotović, Dragan Djuric
Changes in the methionine metabolism can cause a state called hyperhomocysteinemia, inducing oxidative stress in the gut. The production of free radicals is important in the colon damage caused by methionine. This study aimed at evaluating the effect of the use of L-cysteine and N-acetyl-L-cysteine on the colon morphometry of young rats treated with methionine. A total number of 32 male rats were distributed in a randomized experimental design in 4 groups: control group treated with saline; methionine group; cysteine + methionine group, and N-acetyl-L-cysteine + methionine group...
August 17, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28818801/development-and-validation-of-a-reliable-method-for-thiopurine-methyltransferase-tpmt-enzyme-activity-in-human-whole-blood-by-lc-ms-ms-an-application-for-phenotypic-and-genotypic-correlations
#7
Supaporn Wiwattanakul, Santirhat Prommas, Nuttawut Jenjirattithigarn, Siwalee Santon, Apichaya Puangpetch, Samart Pakakasama, Usanarat Anurathapan, Chonlaphat Sukasem
A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the determination of thiopurine methyltransferase (TPMT) activity in human whole blood lysate, based on conversion of 6-mercaptopurine (6-MP) by TPMT to 6-methylmercaptopurine (6-MMP) using S-adenosyl-l-methionine (SAM) as the methyl donor. This method was improved from the previous laborious method for washing of red cell lysate preparation to develop whole blood EDTA lysate. In addition, the TPMT incubation was optimized and the chromatography was performed in a short runtime of 7min on a C18-column by detection via triple quadrupole mass spectrometry...
August 4, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28818268/-metformin-resistant-folic-acid-producing-probiotics-or-folic-acid-against-metformin-s-adverse-effects-like-diarrhea
#8
Abdullah Olgun
Metformin, first line medication in the treatment of type2 diabetes by millions of patients worldwide, causes gastrointestinal adverse effects (i.e. diarrhea) in approximately 30% of patients, frequently leading to discontinuation. Interestingly, metformin was reported to increase life span in a microscopic worm, Caenorhabditis elegans, by decreasing folate and methionine production of bacteria that this worm uses as a food source. Metformin can be expected to have a similar effect on some microorganisms of human gut microbiota...
September 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28816346/homocysteine-lowering-interventions-for-preventing-cardiovascular-events
#9
REVIEW
Arturo J Martí-Carvajal, Ivan Solà, Dimitrios Lathyris, Mark Dayer
BACKGROUND: Cardiovascular disease, which includes coronary artery disease, stroke and peripheral vascular disease, is a leading cause of death worldwide. Homocysteine is an amino acid with biological functions in methionine metabolism. A postulated risk factor for cardiovascular disease is an elevated circulating total homocysteine level. The impact of homocysteine-lowering interventions, given to patients in the form of vitamins B6, B9 or B12 supplements, on cardiovascular events has been investigated...
August 17, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28816082/zeaxanthin-dipalmitate-alleviates-hepatic-injury-induced-by-superimposed-chronic-hepatitis-b-and-non-alcoholic-steatohepatitis-in-non-obese-mice
#10
Jing-Jing Li, Hao Gao, Yi Lv, Mian-Huan Li, Chao-Ran Ren, Kwok-Fai So, Jia Xiao
A hepatitis B virus (HBV) transgenic mice model was used to establish the fatty liver superimposed model by feeding the methionine choline-deficient (MCD) diet for 8 weeks, with or without the gavage of 2 mg/kg zeaxanthin dipalmitate (ZD) three times per week. Both wild-type and HBV transgenic mice, with MCD diet, gained typical non-obese non-alcoholic steatohepatitis (NASH) and HBV symptoms. Coadministration with ZD exhibited evident therapeutic effects through alleviating those pathological events. Moreover, long-term vehicle-ZD treatment was found to be safe...
September 2017: Journal of Asian Natural Products Research
https://www.readbyqxmd.com/read/28816060/the-broad-spectrum-antimicrobial-potential-of-mn-co-4-s2cnme-ch2co2h-a-water-soluble-co-releasing-molecule-corm-401-intracellular-accumulation-transcriptomic-and-statistical-analyses-and-membrane-polarization
#11
Lauren Katie Wareham, Samantha McLean, Ronald Begg, Namrata Rana, Salar Ali, John J Kendall, Guido Sanguinetti, Brian E Mann, Robert K Poole
AIMS: Carbon monoxide (CO)-releasing molecules (CORMs) are candidates for animal and antimicrobial therapeutics. We aimed to probe the antimicrobial potential of a novel manganese CORM. RESULTS: [Mn(CO)4S2CNMe(CH2CO2H)], CORM-401, inhibits growth of Escherichia coli and several antibiotic-resistant clinical pathogens. CORM-401 releases CO that binds oxidases in vivo but is an ineffective respiratory inhibitor. Extensive CORM accumulation (assayed as intracellular manganese) accompanies antimicrobial activity...
August 17, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28814091/the-effect-of-vitamin-d-on-mcf-7-breast-cancer-cell-metabolism
#12
B Saracligil, B Ozturk, A Unlu, S Abusoglu, G Tekin
The role of vitamin D in calcium absorption and bone health is known. The studies revealed that vitamin D modulates breast cancer cell growth and it is also associated with a reduced breast cancer risk. The primary objective of this study was to highlight the metabolic effect of Vitamin D on MCF-7 breast cancer cell line. For that purpose, we checked the apoptosis, energy, amino-acid and acylcarnitine levels in cancer cells, that the study propose, that 1α, 25(OH)2D3 could inhibit cell growth in a dose and time dependent manner...
2017: Bratislavské Lekárske Listy
https://www.readbyqxmd.com/read/28811969/k27m-mutant-histone-3-as-a-novel-target-for-glioma-immunotherapy
#13
Katharina Ochs, Martina Ott, Theresa Bunse, Felix Sahm, Lukas Bunse, Katrin Deumelandt, Jana K Sonner, Melanie Keil, Andreas von Deimling, Wolfgang Wick, Michael Platten
Mutation-specific vaccines have become increasingly important in glioma immunotherapy; however, shared neoepitopes are rare. For diffuse gliomas, a driver mutation in the gene for isocitrate dehydrogenase type-1 has been shown to produce an immunogenic epitope currently targeted in clinical trials. For highly aggressive midline gliomas, a recurrent point mutation in the histone-3 gene (H3F3A) causes an amino acid change from lysine to methionine at position 27 (K27M). Here, we demonstrate that a peptide vaccine against K27M-mutant histone-3 is capable of inducing effective, mutation-specific, cytotoxic T-cell- and T-helper-1-cell-mediated immune responses in a major histocompatibility complex (MHC)-humanized mouse model...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28811139/metabonomics-approach-to-assessing-the-metabolism-variation-and-gender-gap-of-drosophila-melanogaster-in-aging-process
#14
Yu-Zhi Zhou, Ming-Liang Yan, Li Gao, Jian-Qin Zhang, Xue-Mei Qin, Xiang Zhang, Guan-Hua Du
Drosophila melanogaster is increasingly used for study aging mechanism and evaluating anti-aging drugs, but the changes of metabolites and differences of metabolites change between male and female during the aging process are not well known. Metabolomics technology, a massive information provider, has promoted the understanding of metabolic profile and overall changes of metabolites in organism. In this study, (1)H NMR based metabonomics was employed to investigate the dynamic changes of metabolites in whole bodies of male and female Drosophila melanogaster at 3, 15, 30, 45days and to research the gender gap of metabolites changes in aging process...
August 12, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28809400/prenatal-one-carbon-metabolism-dysregulation-programs-schizophrenia-like-deficits
#15
A Alachkar, L Wang, R Yoshimura, A R Hamzeh, Z Wang, N Sanathara, S M Lee, X Xu, G W Abbott, O Civelli
The methionine-folate cycle-dependent one-carbon metabolism is implicated in the pathophysiology of schizophrenia. Since schizophrenia is a developmental disorder, we examined the effects that perturbation of the one-carbon metabolism during gestation has on mice progeny. Pregnant mice were administered methionine equivalent to double their daily intake during the last week of gestation. Their progeny (MET mice) exhibited schizophrenia-like social deficits, cognitive impairments and elevated stereotypy, decreased neurogenesis and synaptic plasticity, and abnormally reduced local excitatory synaptic connections in CA1 neurons...
August 15, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28809129/effect-of-methotrexate-vitamin-b12-on-dna-methylation-as-a-potential-factor-in-leukemia-treatment-related-neurotoxicity
#16
Victoria J Forster, Alex McDonnell, Rachel Theobald, Jill A McKay
Methotrexate (MTX) is administered to treat childhood acute lymphoblastic leukemia (ALL). It acts by inhibiting dihydrofolate reductase which reduces methyltetrahydrofolate, a key component in one carbon metabolism, thus reducing cell proliferation. Further perturbations to one carbon metabolism, such as reduced vitamin B12 levels via the use of nitrous oxide for sedation during childhood ALL treatment, may increase neurotoxicity risk. With B12 as an enzymatic cofactor, methyltetrahydrofolate is essential to produce methionine, which is critical for DNA methylation...
August 15, 2017: Epigenomics
https://www.readbyqxmd.com/read/28808922/backbone-resonance-assignments-for-the-set-domain-of-human-methyltransferase-nsd3-in-complex-with-its-cofactor
#17
Yan Li, Hui Qi Ng, Anna Ngo, Shuang Liu, Yih Wan Tan, Perlyn Zekui Kwek, Alvin W Hung, Joma Joy, Jeffrey Hill, Thomas H Keller, CongBao Kang
NSD3 is a histone H3 methyltransferase that plays an important role in chromatin biology. A construct containing the methyltransferase domain encompassing residues Q1049-K1299 of human NSD3 was obtained and biochemical activity was demonstrated using histone as a substrate. Here we report the backbone HN, N, Cα, C', and side chain Cβ assignments of the construct in complex with S-adenosyl-L-methionine (SAM). Based on these assignments, secondary structures of NSD3/SAM complex in solution were determined.
August 14, 2017: Biomolecular NMR Assignments
https://www.readbyqxmd.com/read/28808187/g-aminobutyric-acid-promotes-methionine-choline-deficient-diet-induced-nonalcoholic-steatohepatitis
#18
Yoon Seok Roh, Ara Cho, Zixiong Zhou, Hyuneui Jeong, Jeong-Eun Park, Youn-Soo Cha, Suk-Heung Oh, Chae-Woong Lim, Bumseok Kim
Nonalcoholic steatohepatitis (NASH) is one of the most common liver diseases and a major cause of liver fibrosis worldwide. G-Aminobutyric acid (GABA) is one of the most abundant inhibitory neurotransmitters in the central nervous system. Recently, it has been reported that GABAergic signaling pathways are found in various non-neuronal tissues including the immune system and play a functional role. In the present study, we investigated whether administration of GABA has effects on NASH through its immunomodulatory effects...
October 17, 2016: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28806970/transcriptomic-analysis-of-the-response-of-acropora-millepora-to-hypo-osmotic-stress-provides-insights-into-dmsp-biosynthesis-by-corals
#19
Catalina Aguilar, Jean-Baptiste Raina, Cherie A Motti, Sylvain Fôret, David C Hayward, Bruno Lapeyre, David G Bourne, David J Miller
BACKGROUND: Dimethylsulfoniopropionate (DMSP) is a small sulphur compound which is produced in prodigious amounts in the oceans and plays a pivotal role in the marine sulfur cycle. Until recently, DMSP was believed to be synthesized exclusively by photosynthetic organisms; however we now know that corals and specific bacteria can also produce this compound. Corals are major sources of DMSP, but the molecular basis for its biosynthesis is unknown in these organisms. RESULTS: Here we used salinity stress, which is known to trigger DMSP production in other organisms, in conjunction with transcriptomics to identify coral genes likely to be involved in DMSP biosynthesis...
August 14, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28803836/methionine-sulfoxide-reductase-a-protects-against-lipopolysaccharide-induced-septic-shock-via-negative-regulation-of-the-proinflammatory-responses
#20
Mahendra Pratap Singh, Ki Young Kim, Geun-Hee Kwak, Suk-Hwan Baek, Hwa-Young Kim
Methionine sulfoxide reductase A (MsrA) is a major antioxidant enzyme that specifically catalyzes the reduction of methionine S-sulfoxide. In this study, we used MsrA gene-knockout (MsrA(-/-)) mice and bone marrow-derived macrophages (BMDMs) to investigate the role of MsrA in the regulation of inflammatory responses induced by lipopolysaccharide (LPS). MsrA(-/-) mice were more susceptible to LPS-induced lethal shock than wild-type (MsrA(+/+)) mice. Serum levels of the proinflammatory cytokines IL-6 and TNF-α induced by LPS were higher in MsrA(-/-) than in MsrA(+/+) mice...
August 10, 2017: Archives of Biochemistry and Biophysics
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