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https://www.readbyqxmd.com/read/29668033/sexual-dimorphism-in-postnatal-gonadotropin-levels-in-infancy-reflects-diverse-maturation-of-the-ovarian-and-testicular-hormone-synthesis
#1
Tanja Kuiri-Hänninen, Leo Dunkel, Ulla Sankilampi
BACKGROUND: The postnatal gonadotropin surge is sexually dimorphic: FSH levels predominate in girls and LH levels in boys. However, in preterm (PT) girls, both gonadotropin levels are higher than in PT boys. OBJECTIVE: To evaluate how gonadal maturation contributes to the sex differences in FSH and LH. DESIGN: Monthly follow-up of 58 full-term (FT, 29 boys) and 67 PT (33 boys) infants from one week (D7) to six months of age (M1-M6). Analyses were also done according to postmenstrual (PM) age in PT infants...
April 18, 2018: Clinical Endocrinology
https://www.readbyqxmd.com/read/29667811/in-vitro-and-in-vivo-studies-of-the-electrophilicity-of-physcion-and-its-oxidative-metabolites
#2
Xiaotong Qin, Ying Peng, Jiang Zheng
Physcion (1,8-dihydroxy-3-methoxy-6-methyl-9,10-anthracenedione) is a bioactive component found in Polygoni Multiflori Radix (PMR) which has been widely used as traditional Chinese medicine. Unfortunately, studies showed hepatotoxicity of PMR during its clinical use. The mechanisms of its toxic action remain unknown. The major objectives of this study were to characterize oxidative metabolites of physcion in vitro and in vivo and to determine the electrophilicity of the parent compound and its oxidative metabolites...
April 18, 2018: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/29666467/ascorbic-acid-induces-global-epigenetic-reprogramming-to-promote-meiotic-maturation-and-developmental-competence-of-porcine-oocytes
#3
Xiao-Xia Yu, Yun-Hua Liu, Xiao-Man Liu, Pei-Chao Wang, Shuai Liu, Jia-Kun Miao, Zhi-Qiang Du, Cai-Xia Yang
L-ascorbic acid (Vitamin C) can enhance the meiotic maturation and developmental competence of porcine oocytes, but the underlying molecular mechanism remains obscure. Here we show the role of ascorbic acid in regulating epigenetic status of both nucleic acids and chromatin to promote oocyte maturation and development in pigs. Supplementation of 250 μM L-ascorbic acid 2-phosphate sesquimagnesium salt hydrate (AA2P) during in vitro maturation significantly enhanced the nuclear maturation (as indicated by higher rate of first polar body extrusion and increased Bmp15 mRNA level), reduced level of reactive oxygen species, and promoted developmental potency (higher cleavage and blastocyst rates of parthenotes, and decreased Bax and Caspase3 mRNA levels in blastocysts) of pig oocytes...
April 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29665901/-clinical-efficacy-of-nopho-aml-2004-regimen-for-treatment-of-children-with-acute-myelocytic-leukemia-non-m3
#4
Kun-Yin Qiu, Xiong-Yu Liao, Ke Huang, Yang Li, Wen-Jun Weng, Hong-Gui Xu, Jian-Pei Fang, Ruo-Hao Wu, Dun-Hua Zhou
OBJECTIVE: To investigate the efficacy and safety of NOPHO-AML 2004 chemotherapy regimen for treatment of children with acute myelocytic leukemia(non-M3). METHODS: Thirty-three patients aged 1-13 with acute myelocytic leukemia (non-M3) were diagnosed from January 2013 to June 2017. FAB typing showed that 1 case in M0, 4 cases in M1, 12 cases in M2, 5 cases in M4, 8 cases in M5, 1 case in M6, and 2 cases in M7; Risk stratification showed that: 19 cases in standard risk, and 14 cases in high risk...
April 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29660473/increasing-thermal-stability-of-glutamate-decarboxylase-from-escherichia-coli-by-site-directed-saturation-mutagenesis-and-its-application-in-gaba-production
#5
Li-Qiang Fan, Ming-Wei Li, Yong-Jun Qiu, Qi-Ming Chen, Si-Jing Jiang, Yu-Jie Shang, Li-Ming Zhao
Gamma-amino butyric acid (GABA) is an important bio-product used in pharmaceuticals, functional foods, and a precursor of the biodegradable plastic polyamide 4 (Nylon 4). Glutamate decarboxylase B (GadB) from Escherichia. coli is a highly active biocatalyst that can convert L-glutamate to GABA. However, its practical application is limited by the poor thermostability and only active under acidic conditions of GadB. In this study, we performed site-directed saturation mutagenesis of the N-terminal residues of GadB from Escherichia coli to improve its thermostability...
April 13, 2018: Journal of Biotechnology
https://www.readbyqxmd.com/read/29656373/evaluation-of-disease-activity-in-patients-with-rheumatoid-arthritis-treated-with-tofacitinib-by-rapid3-post-hoc-analyses-from-two-phase-3-trials
#6
Vibeke Strand, Eun Bong Lee, Yusuf Yazici, Ara Dikranian, Bethanie Wilkinson, Liza Takiya, Chuanbo Zang, Eustratios Bananis, Martin J Bergman
Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. We evaluated the relationship between disease activity, according to Routine Assessment of Patient Index Data 3 (RAPID3) after 6-month treatment with tofacitinib, and long-term outcomes at 24 months. This was a post hoc analysis of two 24-month, phase 3, randomized controlled trials in methotrexate (MTX)-naïve (ORAL Start [NCT01039688]) or MTX-inadequate responder patients (ORAL Scan [NCT00847613]) receiving tofacitinib 5 or 10 mg twice daily (BID) as monotherapy or with background MTX...
April 14, 2018: Clinical Rheumatology
https://www.readbyqxmd.com/read/29643844/emerging-roles-of-n-6-methyladenosine-on-hiv-1-rna-metabolism-and-viral-replication
#7
REVIEW
Sebastián Riquelme-Barrios, Camila Pereira-Montecinos, Fernando Valiente-Echeverría, Ricardo Soto-Rifo
N6 -methyladenosine (m6 A) is the most abundant internal modification present in Eukaryotic mRNA. The functions of this chemical modification are mediated by m6 A-binding proteins (m6 A readers) and regulated by methyltransferases (m6 A writers) and demethylases (m6 A erasers), which together are proposed to be responsible of a new layer of post-transcriptional control of gene expression. Despite the presence of m6 A in a retroviral genome was reported more than 40 years ago, the recent development of sequencing-based technologies allowing the mapping of m6 A in a transcriptome-wide manner made it possible to identify the topology and dynamics of m6 A during replication of HIV-1 as well as other viruses...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29610101/metdiff-a-novel-differential-rna-methylation-analysis-for-merip-seq-data
#8
Xiaodong Cui, Lin Zhang, Jia Meng, Manjeet K Rao, Yidong Chen, Yufei Huang
N6-Methyladenosine (m6 A) transcriptome methylation is an exciting new research area that just captures the attention of research community. We present in this paper, MeTDiff, a novel computational tool for predicting differential m6 A methylation sites from Methylated RNA immunoprecipitation sequencing (MeRIP-Seq) data. Compared with the existing algorithm exomePeak, the advantages of MeTDiff are that it explicitly models the reads variation in data and also devices a more power likelihood ratio test for differential methylation site prediction...
March 2018: IEEE/ACM Transactions on Computational Biology and Bioinformatics
https://www.readbyqxmd.com/read/29605996/molecular-clusters-nanoscale-building-blocks-for-solid-state-materials
#9
Andrew Pinkard, Anouck M Champsaur, Xavier Roy
The programmed assembly of nanoscale building blocks into multicomponent hierarchical structures is a powerful strategy for the bottom-up construction of functional materials. To develop this concept, our team has explored the use of molecular clusters as superatomic building blocks to fabricate new classes of materials. The library of molecular clusters is rich with exciting properties, including diverse functionalization, redox activity, and magnetic ordering, so the resulting cluster-assembled solids, which we term superatomic crystals (SACs), hold the promise of high tunability, atomic precision, and robust architectures among a diverse range of other material properties...
March 31, 2018: Accounts of Chemical Research
https://www.readbyqxmd.com/read/29595119/cytochrome-p450-3a4-induction-lumacaftor-versus-ivacaftor-potentially-resulting-in-significantly-reduced-plasma-concentration-of-ivacaftor
#10
Elena K Schneider
Since release of ivacaftor-lumacaftor several red-flags have been raised that highlight the clinical efficacy of this combination strategy may be be limited due to antagonistic drug-drug interactions. </p><p> Method: The effect of ivacaftor, its major metabolites M1 and M6, lumacaftor and the novel cystic fibrosis transmembrane conductance regulator (CFTR) modulator tezacaftor at 10 µg/mL on the enzymatic activity of the major xenobiotic metabolizing enzymes CYP1A2 and CYP3A4 as well as the minor enzymes CYP2B6 and CYP2C9 was assayed...
March 27, 2018: Drug Metabolism Letters
https://www.readbyqxmd.com/read/29593291/structural-insights-into-the-rna-methyltransferase-domain-of-mettl16
#11
Agnieszka Ruszkowska, Milosz Ruszkowski, Zbigniew Dauter, Jessica A Brown
N6 -methyladenosine (m6 A) is an abundant modification in messenger RNA and noncoding RNAs that affects RNA metabolism. Methyltransferase-like protein 16 (METTL16) is a recently confirmed m6 A RNA methyltransferase that methylates U6 spliceosomal RNA and interacts with the 3'-terminal RNA triple helix of MALAT1 (metastasis-associated lung adenocarcinoma transcript 1). Here, we present two X-ray crystal structures of the N-terminal methyltransferase domain (residues 1-291) of human METTL16 (METTL16_291): an apo structure at 1...
March 28, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29587823/multiple-functions-of-m-6-a-rna-methylation-in-cancer
#12
REVIEW
Yutian Pan, Pei Ma, Yu Liu, Wei Li, Yongqian Shu
First identified in 1974, m6 A RNA methylation, which serves as a predominant internal modification of RNA in higher eukaryotes, has gained prodigious interest in recent years. Modifications of m6 A are dynamic and reversible in mammalian cells, which have been proposed as another layer of epigenetic regulation similar to DNA and histone modifications. m6 A RNA methylation is involved in all stages in the life cycle of RNA, ranging from RNA processing, through nuclear export, translation modulation to RNA degradation, which suggests its potential of influencing a plurality of aspects of RNA metabolism...
March 27, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29567479/loop-engineering-reveals-the-importance-of-active-site-decorating-loops-and-gating-residue-in-substrate-affinity-modulation-of-arginine-deiminase-an-anti-tumor-enzyme
#13
Feng Cheng, Jianhua Yang, Marco Bocola, Ulrich Schwaneberg, Leilei Zhu
Protein engineering of enzyme loop regions is an effective strategy to improve enzymatic properties. Previous studies that aimed to boost the activity of PpADI (an arginine deiminase from Pseudomonas plecoglossicida) under physiological conditions yielded several significantly improved variants that harbor substitutions predominantly located in active-site-decorating loops. A multi-site saturation mutagenesis at four positions in loop 1 (37, 38, 42, and 43) and three positions in loop 4 (402, 403, and 404) was performed to elucidate the importance of these loops in modulating the substrate affinity of PpADI...
March 19, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29560360/the-potentially-beneficial-central-nervous-system-activity-profile-of-ivacaftor-and-its-metabolites
#14
Elena K Schneider, Rachel M McQuade, Vincenzo C Carbone, Felisa Reyes-Ortega, John W Wilson, Brenda Button, Ayame Saito, Daniel P Poole, Daniel Hoyer, Jian Li, Tony Velkov
Ivacaftor-lumacaftor and ivacaftor are two new breakthrough cystic fibrosis transmembrane conductance modulators. The interactions of ivacaftor and its two metabolites hydroxymethylivacaftor (iva-M1) and ivacaftorcarboxylate (iva-M6) with neurotransmitter receptors were investigated in radioligand binding assays. Ivacaftor displayed significant affinity to the 5-hydroxytryptamine (5-HT; serotonin) 5-HT2C receptor (p K i =6.06±0.03), β3 -adrenergic receptor (p K i =5.71±0.07), δ-opioid receptor (p K i =5...
January 2018: ERJ Open Research
https://www.readbyqxmd.com/read/29555988/groundwater-oxygen-isotope-anomaly-before-the-m6-6-tottori-earthquake-in-southwest-japan
#15
Satoki Onda, Yuji Sano, Naoto Takahata, Takanori Kagoshima, Toshihiro Miyajima, Tomo Shibata, Daniele L Pinti, Tefang Lan, Nak Kyu Kim, Minoru Kusakabe, Yoshiro Nishio
Geochemical monitoring of groundwater in seismically-active regions has been carried out since 1970s. Precursors were well documented, but often criticized for anecdotal or fragmentary signals, and for lacking a clear physico-chemical explanation for these anomalies. Here we report - as potential seismic precursor - oxygen isotopic ratio anomalies of +0.24‰ relative to the local background measured in groundwater, a few months before the Tottori earthquake (M 6.6) in Southwest Japan. Samples were deep groundwater located 5 km west of the epicenter, packed in bottles and distributed as drinking water between September 2015 and July 2017, a time frame which covers the pre- and post-event...
March 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29555775/identification-and-biosynthesis-of-thymidine-hypermodifications-in-the-genomic-dna-of-widespread-bacterial-viruses
#16
Yan-Jiun Lee, Nan Dai, Shannon E Walsh, Stephanie Müller, Morgan E Fraser, Kathryn M Kauffman, Chudi Guan, Ivan R Corrêa, Peter R Weigele
Certain viruses of bacteria (bacteriophages) enzymatically hypermodify their DNA to protect their genetic material from host restriction endonuclease-mediated cleavage. Historically, it has been known that virion DNAs from the Delftia phage ΦW-14 and the Bacillus phage SP10 contain the hypermodified pyrimidines α-putrescinylthymidine and α-glutamylthymidine, respectively. These bases derive from the modification of 5-hydroxymethyl-2'-deoxyuridine (5-hmdU) in newly replicated phage DNA via a pyrophosphorylated intermediate...
March 19, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29555755/xio-is-a-component-of-the-drosophila-sex-determination-pathway-and-rna-n-6-methyladenosine-methyltransferase-complex
#17
Jian Guo, Hong-Wen Tang, Jing Li, Norbert Perrimon, Dong Yan
N 6 -methyladenosine (m6 A), the most abundant chemical modification in eukaryotic mRNA, has been implicated in Drosophila sex determination by modifying Sex-lethal ( Sxl ) pre-mRNA and facilitating its alternative splicing. Here, we identify a sex determination gene, CG7358 , and rename it xio according to its loss-of-function female-to-male transformation phenotype. xio encodes a conserved ubiquitous nuclear protein of unknown function. We show that Xio colocalizes and interacts with all previously known m6 A writer complex subunits (METTL3, METTL14, Fl(2)d/WTAP, Vir/KIAA1429, and Nito/Rbm15) and that loss of xio is associated with phenotypes that resemble other m6 A factors, such as sexual transformations, Sxl splicing defect, held-out wings, flightless flies, and reduction of m6 A levels...
March 19, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29550433/structural-and-biochemical-insights-into-the-substrate-binding-mechanism-of-a-novel-glycoside-hydrolase-family-134-%C3%AE-mannanase
#18
Xin You, Zhen Qin, Yan-Xiao Li, Qiao-Juan Yan, Bin Li, Zheng-Qiang Jiang
Mannan is one of the major constituent groups of hemicellulose, which is a renewable resource from higher plants. β-Mannanases are enzymes capable of degrading lignocellulosic biomass. Here, an endo-β-mannanase from Rhizopus microsporus (RmMan134A) was cloned and expressed. The recombinant RmMan134A showed maximal activity at pH 5.0 and 50 °C, and exhibited high specific activity towards locust bean gum (2337 U/mg). To gain insight into the substrate-binding mechanism of RmMan134A, four complex structures (RmMan134A-M3, RmMan134A-M4, RmMan134A-M5 and RmMan134A-M6) were further solved...
March 14, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29548567/metabolic-study-of-methylstenbolone-in-horses-using-liquid-chromatography-high-resolution-mass-spectrometry-and-gas-chromatography-mass-spectrometry
#19
Timmy L S Choi, Jenny K Y Wong, Wai Him Kwok, Peter Curl, Stewart Mechie, Terence S M Wan
Methylstenbolone (2,17α-dimethyl-5α-androst-1-en-17β-ol-3-one) is a synthetic anabolic and androgenic steroid (AAS) sold as an oral 'nutritional supplement' under the brand names 'Ultradrol', 'M-Sten' and 'Methyl-Sten'. Like other AASs, methylstenbolone is a prohibited substance in both human and equine sports. This paper describes the studies of the in vitro and in vivo metabolism of methylstenbolone in horses using LC/HRMS, GC/MS and GC/MS/MS. Phase I in vitro metabolic study of methylstenbolone was performed using homogenised horse liver...
February 21, 2018: Journal of Chromatography. A
https://www.readbyqxmd.com/read/29547716/zc3h13-regulates-nuclear-rna-m-6-a-methylation-and-mouse-embryonic-stem-cell-self-renewal
#20
Jing Wen, Ruitu Lv, Honghui Ma, Hongjie Shen, Chenxi He, Jiahua Wang, Fangfang Jiao, Hang Liu, Pengyuan Yang, Li Tan, Fei Lan, Yujiang Geno Shi, Chuan He, Yang Shi, Jianbo Diao
N6 -methyladenosine (m6 A) is an abundant modification in eukaryotic mRNA, regulating mRNA dynamics by influencing mRNA stability, splicing, export, and translation. However, the precise m6 A regulating machinery still remains incompletely understood. Here we demonstrate that ZC3H13, a zinc-finger protein, plays an important role in modulating RNA m6 A methylation in the nucleus. We show that knockdown of Zc3h13 in mouse embryonic stem cell significantly decreases global m6 A level on mRNA. Upon Zc3h13 knockdown, a great majority of WTAP, Virilizer, and Hakai translocate to the cytoplasm, suggesting that Zc3h13 is required for nuclear localization of the Zc3h13-WTAP-Virilizer-Hakai complex, which is important for RNA m6 A methylation...
March 15, 2018: Molecular Cell
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