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https://www.readbyqxmd.com/read/27912088/enhancing-stem-cell-transplantation-with-nutri-technology
#1
Valter D Longo, Salvatore Cortellino
It is necessary to employ myeloablative irradiation or chemotherapy to deplete the HSC niche to optimize hematopoietic stem cell transplantation. In a recent issue of Science, Taya and colleagues provide evidence for an alternative to the toxic chemoirradiative procedure by showing that a valine-restricted diet is sufficient to empty the bone marrow niche.
December 1, 2016: Cell Stem Cell
https://www.readbyqxmd.com/read/27907077/transcriptome-and-multivariable-data-analysis-of-corynebacterium-glutamicum-under-different-dissolved-oxygen-conditions-in-bioreactors
#2
Yang Sun, Wenwen Guo, Fen Wang, Feng Peng, Yankun Yang, Xiaofeng Dai, Xiuxia Liu, Zhonghu Bai
Dissolved oxygen (DO) is an important factor in the fermentation process of Corynebacterium glutamicum, which is a widely used aerobic microbe in bio-industry. Herein, we described RNA-seq for C. glutamicum under different DO levels (50%, 30% and 0%) in 5 L bioreactors. Multivariate data analysis (MVDA) models were used to analyze the RNA-seq and metabolism data to investigate the global effect of DO on the transcriptional distinction of the substance and energy metabolism of C. glutamicum. The results showed that there were 39 and 236 differentially expressed genes (DEGs) under the 50% and 0% DO conditions, respectively, compared to the 30% DO condition...
2016: PloS One
https://www.readbyqxmd.com/read/27905109/a-lethal-neonatal-phenotype-of-mitochondrial-short-chain-enoyl-coa-hydratase-1-deficiency
#3
F Al Mutairi, H E Shamseldin, M Alfadhel, R J Rodenburg, F S Alkuraya
Short-chain enoyl-CoA hydratase (SCEH) is a mitochondrial enzyme involved in the oxidation of fatty acids and the catabolic pathway of valine and, to a lesser extent, isoleucine. Deficiency of this enzyme was recently shown to cause an early childhood Leigh syndrome phenotype. The few reported patients were compound heterozygotes for two missense or missense with truncating variants in ECHS1 that encodes SCEH. We describe two siblings with severe refractory lactic acidosis and death within the first 2 days of life...
October 13, 2016: Clinical Genetics
https://www.readbyqxmd.com/read/27902285/raineyella-antarctica-gen-nov-sp-nov-a-novel-psychrotolerant-d-amino-acid-utilizing-anaerobe-isolated-from-two-geographic-locations-of-the-southern-hemisphere
#4
Elena V Pikuta, Rodolfo Javier Menes, Alisa Michelle Bruce, Zhe Lyu, Nisha Patel, Yuchen Liu, Richard Brice Hoover, Hans Jürgen Busse, Paul A Lawson, William Barney Whitman
Gram-positive bacterium, strain LZ-22T, was isolated from a rhizosphere of moss Leptobryum sp. collected at the shore of Lake Zub in Antarctica. Cells were motile, straight or pleomorphic rods with sizes of 0.6-1.0 x 3.5-10 μm. The new isolate was a facultatively anaerobic, catalase positive, psychrotolerant mesophile. Growth was observed at 3-41 oC (optimum 24-30 oC), 0-7 % NaCl, w/v (optimum, 0.25 %) and pH 4.0-9.0 (optimum 7.8). The quinone system of strain LZ-22T possessed predominately menaquinones MK-9(H4)...
October 12, 2016: International Journal of Systematic and Evolutionary Microbiology
https://www.readbyqxmd.com/read/27900589/intrinsic-her2-v777l-mutation-mediates-resistance-to-trastuzumab-in-a-breast-cancer-patient
#5
Yosuke Hirotsu, Hiroshi Nakagomi, Kenji Amemiya, Toshio Oyama, Masayuki Inoue, Hitoshi Mochizuki, Masao Omata
HER2 (ERBB2) is an oncogene and 20% of breast cancers display HER2 amplification. The HER2 monoclonal antibody, trastuzumab, is used to treat breast cancers that display HER2 amplification, with good responses in 80-90% of cases; however, 10% of tumours develop resistance to trastuzumab. In this study, we collected data of primary breast cancer patients who treated at hospital during 2004-2014. In our cohort, 205 of 1497 primary breast cancer patients showed HER2-amplification, and 20 experienced recurrence after trastuzumab therapy...
January 2017: Medical Oncology
https://www.readbyqxmd.com/read/27898893/effect-of-phase-feeding-and-valine-to-lysine-ratio-during-lactation-on-sow-and-piglet-performance
#6
A Craig, W Henry, E Magowan
The potential of piglets to grow before weaning is greater than the sow can support, and as such, improving the performance of the lactating sow is a key driver of whole-farm efficiency. This study aimed to investigate the impact of 1) adopting a phased feeding approach during lactation and 2) the ratio of Val to Lys on sow and piglet performance. Multiparious sows ( = 109) were assigned to treatment at 108 d of gestation. Dietary treatments were arranged in a 2 × 2 + 1 factorial design. Dietary treatments included 2 dietary regimes: "Flat" (14...
September 2016: Journal of Animal Science
https://www.readbyqxmd.com/read/27898682/genetic-predisposition-to-an-impaired-metabolism-of-the-branched-chain-amino-acids-and-risk-of-type-2-diabetes-a-mendelian-randomisation-analysis
#7
Luca A Lotta, Robert A Scott, Stephen J Sharp, Stephen Burgess, Jian'an Luan, Therese Tillin, Amand F Schmidt, Fumiaki Imamura, Isobel D Stewart, John R B Perry, Luke Marney, Albert Koulman, Edward D Karoly, Nita G Forouhi, Rasmus J O Sjögren, Erik Näslund, Juleen R Zierath, Anna Krook, David B Savage, Julian L Griffin, Nishi Chaturvedi, Aroon D Hingorani, Kay-Tee Khaw, Inês Barroso, Mark I McCarthy, Stephen O'Rahilly, Nicholas J Wareham, Claudia Langenberg
BACKGROUND: Higher circulating levels of the branched-chain amino acids (BCAAs; i.e., isoleucine, leucine, and valine) are strongly associated with higher type 2 diabetes risk, but it is not known whether this association is causal. We undertook large-scale human genetic analyses to address this question. METHODS AND FINDINGS: Genome-wide studies of BCAA levels in 16,596 individuals revealed five genomic regions associated at genome-wide levels of significance (p < 5 × 10-8)...
November 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27898008/research-on-the-relationships-between-endogenous-biomarkers-and-exogenous-toxic-substances-of-acute-toxicity-in-radix-aconiti
#8
Haonan Zhou, Pengjie Zhang, Zhiguo Hou, Jiabin Xie, Yuming Wang, Bin Yang, Yanyan Xu, Yubo Li
Radix Aconiti, a classic traditional Chinese medicine (TCM), has been widely used throughout China for disease treatment due to its various pharmacological activities, such as anti-inflammatory, cardiotonic, and analgesic effects. However, improper use of Radix Aconiti often generated severe acute toxicity. Currently, research on the toxic substances of Radix Aconiti is not rare. In our previous study, acute toxic biomarkers of Radix Aconiti have been found. However, few studies were available to find the relationships between these endogenous biomarkers and exogenous toxic substances...
November 25, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27894270/evaluation-of-tolerability-with-the-co-formulation-elvitegravir-cobicistat-emtricitabine-and-tenofovir-disoproxil-fumarate-for-post-hiv-exposure-prophylaxis
#9
Nadia Valin, Laurent Fonquernie, Anne Daguenel, Pauline Campa, Theresita Anthony, Marguerite Guiguet, Pierre Marie Girard, Marie Caroline Meyohas
BACKGROUND: The preferred regimen for HIV post-exposure prophylaxis (PEP) is based mainly on safety and tolerability because it is given to immunocompetent people without HIV infection for a limited time (28 days). The frequency of adverse events (AEs) may be > 60%. Although AEs are generally not severe, they can lead to lack of adherence and failure to complete the regimen. We evaluated the co-formulation elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate (Stribild(®)) prescribed as one pill taken once daily for HIV PEP in terms of tolerability and adherence...
November 29, 2016: BMC Infectious Diseases
https://www.readbyqxmd.com/read/27892771/a-trna-derived-fragment-competes-with-mrna-for-ribosome-binding-and-regulates-translation-during-stress
#10
Jennifer Gebetsberger, Leander Wyss, Anna M Mleczko, Julia Reuther, Norbert Polacek
Posttranscriptional processing of RNA molecules is a common strategy to enlarge the structural and functional repertoire of RNomes observed in all three domains of life. Fragmentation of RNA molecules of basically all functional classes has been reported to yield smaller non-protein coding RNAs (ncRNAs) that typically possess different roles compared to their parental transcripts. Here we show that a valine tRNA-derived fragment (Val-tRF) that is produced under certain stress conditions in the halophilic archaeon Haloferax volcanii is capable of binding to the small ribosomal subunit...
November 28, 2016: RNA Biology
https://www.readbyqxmd.com/read/27890855/linker-stability-influences-the-anti-tumor-activity-of-acetazolamide-drug-conjugates-for-the-therapy-of-renal-cell-carcinoma
#11
Samuele Cazzamalli, Alberto Dal Corso, Dario Neri
Small molecule-drug conjugates (SMDCs) are increasingly being considered as an alternative to antibody-drug conjugates (ADCs) for the selective delivery of anticancer agents to the tumor site, sparing normal tissues. Carbonic anhydrase IX (CAIX) is a membrane-bound enzyme, which is over-expressed in the majority of renal cell carcinomas and which can be efficiently targeted in vivo, using charged derivatives of acetazolamide, a small heteroaromatic sulfonamide. Here, we show that SMDC products, obtained by the coupling of acetazolamide with monomethyl auristatin E (MMAE) using dipeptide linkers, display a potent anti-tumoral activity in mice bearing xenografted SKRC-52 renal cell carcinomas...
November 24, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/27889941/an-adductomic-approach-to-identify-electrophiles-in-vivo
#12
Henrik Carlsson, Margareta Törnqvist
Humans are exposed to many reactive electrophiles, both formed endogenously and from exogenous exposures. Such compounds could react with cellular biomolecules and form stable reaction products, adducts, at nucleophilic sites in proteins and DNA, constituting a risk for toxic effects. Adductomic approaches aim to study the totality of adducts, to specific biomolecules, by mass spectrometric screening. This MiniReview focuses on the development and application of an adductomic approach for the screening of unknown adducts to N-terminal valine (Val) in hemoglobin (Hb) by liquid chromatography tandem mass spectrometry (LC-MS/MS)...
November 27, 2016: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/27884058/efficiency-of-silencing-rna-for-removal-of-transthyretin-v30m-in-a-ttr-leptomeningeal-animal-model
#13
Paula Gonçalves, Helena Martins, Susete Costelha, Luis F Maia, Maria Joao Saraiva
Some TTR mutants target the central nervous system (CNS). Familial amyloid polyneuropathy (FAP) with leptomeningeal involvement has been described in 9% of transthyretin (TTR) mutations and in valine for methionine at position 30 (V30M) patients. These individuals present dementia, ataxia, brain hemorrhages and focal neurological episodes (FNEs). FNEs occurred also in V30M FAP patients with longer disease duration, who have undergone liver transplant to remove the source of plasma mutant TTR as a form of treatment...
December 2016: Amyloid: the International Journal of Experimental and Clinical Investigation
https://www.readbyqxmd.com/read/27882195/design-and-synthesis-of-tesirine-a-clinical-antibody-drug-conjugate-pyrrolobenzodiazepine-dimer-payload
#14
Arnaud C Tiberghien, Jean-Noel Levy, Luke A Masterson, Neki V Patel, Lauren R Adams, Simon Corbett, David G Williams, John A Hartley, Philip W Howard
Pyrrolobenzodiazepine dimers are an emerging class of warhead in the field of antibody-drug conjugates (ADCs). Tesirine (SG3249) was designed to combine potent antitumor activity with desirable physicochemical properties such as favorable hydrophobicity and improved conjugation characteristics. One of the reactive imines was capped with a cathepsin B-cleavable valine-alanine linker. A robust synthetic route was developed to allow the production of tesirine on clinical scale, employing a flexible, convergent strategy...
November 10, 2016: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27881392/higher-serum-phenylalanine-concentration-is-associated-with-more-rapid-telomere-shortening-in-men
#15
Johan G Eriksson, Maria-Angela Guzzardi, Patricia Iozzo, Eero Kajantie, Hannu Kautiainen, Minna K Salonen
BACKGROUND: Telomere length and telomere shortening are associated with age-related health outcomes. Only a few studies have been able to longitudinally report on factors that are associated with changes in telomere length in an aging population. OBJECTIVE: We studied the longitudinal relation between telomere length, the change in telomere length, and circulating amino acids. DESIGN: A total of 812 subjects from the Helsinki Birth Cohort Study (born from 1934 to 1944), who underwent 3 clinical visits during a 10-y interval that included measurements of cardiometabolic risk factors, were included in the study...
November 23, 2016: American Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/27881338/-plasma-metabonomics-of-guifu-dihuang-wan-in-the-treatment-of-yang-deficiency
#16
Ya Xiao, Yuan Jing, Jie-Yu Chen, Fei Li, Jing-Ru Cheng, Jian-Lu Bi, Ren Luo, Xiao-Shan Zhao
OBJECTIVE: To assess the effect of Guifu Dihuang Wan (GFDHW) in the treatment of yang deficiency and explore the underlying molecular mechanism. METHODS: Sixty-two participants without diseases were randomized into control group (n=31) and experimental group (n=31) and were given lifestyle intervention additional GFDHW treatment for a month. NMR technology was used for metabonomics analysis. RESULTS: Intervention with GFDHW resulted in significantly decreased conversion scores of yang deficiency in the experimental group compared with the control group (P<0...
November 20, 2016: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/27879637/temperature-triggered-switchable-helix-helix-inversion-of-poly-phenylacetylene-bearing-l-valine-ethyl-ester-pendants-and-its-chiral-recognition-ability
#17
Yanli Zhou, Chunhong Zhang, Yuan Qiu, Lijia Liu, Taotao Yang, Hongxing Dong, Toshifumi Satoh, Yoshio Okamoto
A phenylacetylene containing the l-valine ethyl ester pendant (PAA-Val) was synthesized and polymerized by an organorhodium catalyst (Rh(nbd)BPh₄) to produce the corresponding one-handed helical cis-poly(phenylacetylene) (PPAA-Val). PPAA-Val showed a unique temperature-triggered switchable helix-sense in chloroform, while it was not observed in highly polar solvents, such as N,N'-dimethylformamide (DMF). By heating the solution of PPAA-Val in chloroform, the sign of the CD absorption became reversed, but recovered after cooling the solution to room temperature...
November 21, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27878569/assay-of-hemoglobin-a1c-using-lectin-from-aleuria-aurantia
#18
Masato Kabata, Erina Hase, Kouta Kimura, Yuka Kobayashi, Yasushi Ueno, Kazuaki Yoshimune
Hemoglobin A1c (HbA1c) has an N-terminal fructosyl valine on the β-chain, and this modification is caused by the non-enzymatic glycosylation of hemoglobin (Hb). The relative concentration ratio of HbA1c to total Hb is an important biomarker for the diagnosis of diabetes. HbA1c-binding lectins were screened from 29 sources of lectin, and the lectin from Aleuria aurantia (AAL) was revealed to have higher affinity to HbA1c than to Hb. The concentration of HbA1c was determined by lectin-based enzyme-linked immunosorbent assay (ELISA) using the AAL lectin...
December 2016: AMB Express
https://www.readbyqxmd.com/read/27874020/friedelin-synthase-from-maytenus-ilicifolia-leucine-482-plays-an-essential-role-in-the-production-of-the-most-rearranged-pentacyclic-triterpene
#19
Tatiana M Souza-Moreira, Thaís B Alves, Karina A Pinheiro, Lidiane G Felippe, Gustavo M A De Lima, Tatiana F Watanabe, Cristina C Barbosa, Vânia A F F M Santos, Norberto P Lopes, Sandro R Valentini, Rafael V C Guido, Maysa Furlan, Cleslei F Zanelli
Among the biologically active triterpenes, friedelin has the most-rearranged structure produced by the oxidosqualene cyclases and is the only one containing a cetonic group. In this study, we cloned and functionally characterized friedelin synthase and one cycloartenol synthase from Maytenus ilicifolia (Celastraceae). The complete coding sequences of these 2 genes were cloned from leaf mRNA, and their functions were characterized by heterologous expression in yeast. The cycloartenol synthase sequence is very similar to other known OSCs of this type (approximately 80% identity), although the M...
November 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27873460/sortase-a-generated-highly-potent-anti-cd20-mmae-conjugates-for-efficient-elimination-of-b-lineage-lymphomas
#20
Liqiang Pan, Wenbin Zhao, Jun Lai, Ding Ding, Qian Zhang, Xiaoyue Yang, Minmin Huang, Shijie Jin, Yingchun Xu, Su Zeng, James J Chou, Shuqing Chen
Antibody-drug conjugate (ADC) targeting antigens expressed on the surface of tumor cells are an effective approach for delivering drugs into the cells via antigen-mediated endocytosis. One of the well-known tumor antigens, the CD20 of B-lymphocyte, has long been suggested to be noninternalizing epitope, and is thus not considered a desirable target for ADCs. Here, sortase A (srtA)-mediated transpeptidation is used to specifically conjugate triple glycine-modified monomethyl auristatin E (MMAE), a highly toxic antimitotic agent, to anti-CD20 ofatumumab (OFA) equipped with a short C-terminal LPETG (5 amino acids) tag at heavy chain (HL), which generates ADCs that show extremely strong potency in killing CD20 positive cancer cells...
November 22, 2016: Small
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