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https://www.readbyqxmd.com/read/29049491/dermal-hyperneury-and-multiple-sclerotic-fibromas-in-multiple-endocrine-neoplasia-type-2a-syndrome
#1
Victoria Alegría-Landa, Margarita Jo-Velasco, Mercedes Robledo, Luis Requena
Importance: Multiple endocrine neoplasia type 2 (MEN 2) syndrome is an autosomal dominant, hereditary cancer disorder caused by germline mutations in the RET (formerly MEN2A, MEN2B) proto-oncogene located on chromosomal band 10q11.21. Two distinct clinical forms have been described as the following phenotypes: multiple endocrine neoplasia type 2A (MEN 2A) and multiple endocrine neoplasia type 2B (MEN 2B) syndromes. The common and necessary nexus that defines these 2 phenotypes is the presence of medullary thyroid carcinoma (MTC)...
October 18, 2017: JAMA Dermatology
https://www.readbyqxmd.com/read/29046337/cathepsin-b-is-dispensable-for-cellular-processing-of-cathepsin-b-cleavable-antibody-drug-conjugates
#2
Niña G Caculitan, Josefa Dela Cruz Chuh, Yong Ma, Donglu Zhang, Katherine R Kozak, Yichin Liu, Thomas H Pillow, Jack Sadowsky, Tommy K Cheung, Qui Phung, Benjamin Haley, Byoung-Chul Lee, Robert Akita, Mark X Sliwkowski, Andrew G Polson
Antibody-drug conjugates (ADCs) are designed to selectively bind to tumor antigens via the antibody and release their cytotoxic payload upon internalization. Controllable payload release through judicious design of the linker has been an early technological milestone. Here, we examine the effect of the protease-cleavable valine-citrulline (VC(S)) linker on ADC efficacy. The VC(S) linker was designed to be cleaved by cathepsin B, a lysosomal cysteine protease. Surprisingly, suppression of cathepsin B expression via CRISPR-Cas9 gene deletion or shRNA knockdown had no effect on the efficacy of ADCs with VC(S) linkers armed with a monomethyl auristatin E (MMAE) payload...
October 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/29046328/genetic-support-for-a-causal-role-of-insulin-resistance-on-circulating-branched-chain-amino-acids-and-inflammation
#3
Qin Wang, Michael V Holmes, George Davey Smith, Mika Ala-Korpela
OBJECTIVE: Insulin resistance has deleterious effects on cardiometabolic disease. We used Mendelian randomization analyses to clarify the causal relationships of insulin resistance (IR) on circulating blood-based metabolites to shed light on potential mediators of the IR to cardiometabolic disease relationship. RESEARCH DESIGN AND METHODS: We used 53 single nucleotide polymorphisms associated with IR from a recent genome-wide association study (GWAS) to explore their effects on circulating lipids and metabolites...
October 18, 2017: Diabetes Care
https://www.readbyqxmd.com/read/29046316/evidence-for-the-presence-in-rainbow-trout-brain-of-amino-acid-sensing-systems-involved-in-the-control-of-food-intake
#4
Sara Comesana, Cristina Velasco, Rosa M Ceinos, Marcos A Lopez-Patiño, Jesus M Miguez, Sofia Morais, Jose L Soengas
To assess the existence of central amino acid sensing systems in fish we carried out two experiments in rainbow trout. In the first one, we injected ICV two different branched-chain amino acids (BCAA), leucine and valine, and assessed food intake up to 48 h later. Leucine decreased and valine increased food intake. In a second experiment, 6h after similar ICV treatment we determined changes in parameters related to putative amino acid sensing systems. Amino acid sensing systems respond to leucine in hypothalamus and telencephalon, and to valine in telencephalon...
October 18, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/29044433/pregnancy-induced-changes-in-metabolome-and-proteome-in-ovine-uterine-flushings
#5
Jared J Romero, Bethany E Liebig, Corey D Broeckling, Jessica E Prenni, Thomas R Hansen
Mass spectrometry (MS) approaches were used herein to identify metabolites and proteins in uterine flushings (UF) that may contribute to nourishing the conceptus. Ovine uteri collected on Day 12 of the estrous cycle (n = 5 ewes exposed to vasectomized ram) or Days 12 (n = 4), 14 (n = 5), or 16 (n = 5) of pregnancy (bred with fertile ram) were flushed using buffered saline. Metabolites were extracted using 80% methanol and profiled using ultraperformance liquid chromatography (LC) tandem mass spectrometry. The proteome was examined by digestion with trypsin, followed by the analysis of peptides with LC-MS/MS...
August 1, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/29043205/an-extremely-rare-case-of-concurrent-braf-v600e-mutation-driven-hairy-cell-leukemia-and-melanoma-case-report-and-review-of-literature
#6
Amir Ghorbani-Aghbolaghi, Mirna Lechpammer, Saba F Ali, Nam K Ku, Denis M Dwyre, Hooman H Rashidi
BRAF protein is a serine/threonine kinase with 766 amino acids. Approximately 15% of human cancers harbor BRAF mutations as well as other BRAF anomalies (amplifications, fusions). Somatic mutations mainly occur in the catalytic kinase domain (CR3), and the predominant mutation is p.V600E which is the substitution of glutamic acid (E) for valine (V) as result of a mutation at codon 600 of the kinase domain. To our knowledge, the vast majority of the cancers have non-germline BRAF mutations. Here we describe a case of a 60-year-old female with a history of hairy cell leukemia (HCL) who presented with aphasia and forgetfulness...
July 2017: Autopsy & case reports
https://www.readbyqxmd.com/read/29039583/serum-metabolomic-profile-in-genetically-modified-cows-carrying-human-%C3%AE-%C3%A2-lactalbumin-gene
#7
Qin Wang, Wei Fu, Xiaofei Liu, Jianwu Wang, Chunyan Feng, Songyin Qiu, Xiaolin Li, Dandan Liu, Shuifang Zhu, Xiangmei Lin
The present study aimed to investigate the serum metabolomic profiles in genetically modified cows carrying and expressing human lactalbumin α (LALBA) and non‑LALBA cows, and identify altered metabolic characteristics following the genetic modification. Serum biochemistry indexes were measured according to protocols recommended by International Federation of Clinical Chemistry. The metabolomic profiles were determined using the serum samples collected from LALBA (n=6) and non‑LALBA cows (n=6). Welch's two‑sample t‑test was used to identify the metabolites that significantly differed between the LALBA and non‑LALBA groups (fold‑change ≠ 1 and P<0...
October 11, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29038046/multiple-reversals-of-strand-asymmetry-in-molluscs-mitochondrial-genomes-and-consequences-for-phylogenetic-inferences
#8
Shao'e Sun, Qi Li, Lingfeng Kong, Hong Yu
Strand asymmetry in nucleotide composition is a remarkable feature of animal mitochondrial genomes. The strand-specific bias in the nucleotide composition of the mtDNA has been known to be highly problematic for phylogenetic analyses. Here, the strand asymmetry was compared across 140 mollusc species and analyzed for a mtDNA fragment including twelve protein-coding genes. The analyses show that almost all species in Gastropoda (except Heterobranchia) and all species in Bivalvia present reversals of strand bias...
October 13, 2017: Molecular Phylogenetics and Evolution
https://www.readbyqxmd.com/read/29037781/uncovering-the-role-of-branched-chain-amino-acid-transaminases-in-saccharomyces-cerevisiae-isobutanol-biosynthesis
#9
Sarah K Hammer, José L Avalos
Isobutanol and other branched-chain higher alcohols (BCHAs) are promising advanced biofuels derived from the degradation of branched-chain amino acids (BCAAs). The yeast Saccharomyces cerevisiae is a particularly attractive host for the production of BCHAs due to its high tolerance to alcohols and prevalent use in the bioethanol industry. Degradation of BCAAs begins with transamination reactions, catalyzed by branched-chain amino acid transaminases (BCATs) located in the mitochondria (Bat1p) and cytosol (Bat2p)...
October 13, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/29035969/effects-of-medical-food-leucine-content-in-the-management-of-methylmalonic-and-propionic-acidemias
#10
Jennifer G Myles, Irini Manoli, Charles P Venditti
PURPOSE OF REVIEW: The current review highlights the varied effects of medical foods high in leucine (Leu) and devoid of valine (Val) and isoleucine (Ile) in the management of methylmalonic acidemia (MMA) and propionic acidemia and cobalamin C (cblC) deficiency, aiming to advance dietary practices. RECENT FINDINGS: Leu is a key metabolic regulator with a multitude of effects on different organ systems. Recent observational studies have demonstrated that these effects can have unintended consequences in patients with MMA as a result of liberal use of medical foods...
October 14, 2017: Current Opinion in Clinical Nutrition and Metabolic Care
https://www.readbyqxmd.com/read/29035325/advanced-prodrug-strategies-in-nucleoside-and-non-nucleoside-antiviral-agents-a-review-of-the-recent-five-years
#11
REVIEW
Hanadi Sinokrot, Tasneem Smerat, Anas Najjar, Rafik Karaman
Background: Poor pharmacokinetic profiles and resistance are the main two drawbacks from which currently used antiviral agents suffer, thus make them excellent targets for research, especially in the presence of viral pandemics such as HIV and hepatitis C. Methods: The strategies employed in the studies covered in this review were sorted by the type of drug synthesized into ester prodrugs, targeted delivery prodrugs, macromolecular prodrugs, other nucleoside conjugates, and non-nucleoside drugs. Results: Utilizing the ester prodrug approach a novel isopropyl ester prodrug was found to be potent HIV integrase inhibitor...
October 16, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29032784/spent-culture-medium-analysis-from-individually-cultured-bovine-embryos-demonstrates-metabolomic-differences
#12
Kayla J Perkel, Pavneesh Madan
Spent culture medium can provide valuable information regarding the physiological state of a bovine preimplantation embryos through non-invasive analysis of the sum/depleted metabolite constituents. Metabolomics has become of great interest as an adjunct technique to morphological and cleavage-rate assessment, but more importantly, in improving our understanding of metabolism. In this study, in vitro produced bovine embryos developing at different rates were evaluated using proton nuclear magnetic resonance (1H NMR)...
October 16, 2017: Zygote: the Biology of Gametes and Early Embryos
https://www.readbyqxmd.com/read/29032464/nutritional-composition-of-honey-bee-food-stores-vary-with-floral-composition
#13
Philip Donkersley, Glenn Rhodes, Roger W Pickup, Kevin C Jones, Eileen F Power, Geraldine A Wright, Kenneth Wilson
Sufficiently diverse and abundant resources are essential for generalist consumers, and form an important part of a suite of conservation strategies for pollinators. Honey bees are generalist foragers and are dependent on diverse forage to adequately meet their nutritional needs. Through analysis of stored pollen (bee bread) samples obtained from 26 honey bee (Apis mellifera L.) hives across NW-England, we quantified bee bread nutritional content and the plant species that produced these stores from pollen...
October 14, 2017: Oecologia
https://www.readbyqxmd.com/read/29026998/acetolactate-synthase-alss-in-bacillus-licheniformis-wx-02-enzymatic-properties-and-efficient-functions-for-acetoin-butanediol-and-l-valine-biosynthesis
#14
Yanli Huo, Yangyang Zhan, Qin Wang, Shunyi Li, Shihui Yang, Christopher T Nomura, Changjun Wang, Shouwen Chen
Acetolactate synthase catalyzes two molecules of pyruvates to form α-acetolactate, which is further converted to acetoin and 2,3-butanediol. In this study, by heterologous expression in Escherichia coli, the enzymatic properties of acetolactate synthase (AlsS) from Bacillus licheniformis WX-02 were characterized. Its K m and k cat for pyruvate were 3.96 mM and 514/s, respectively. It has the optimal activity at pH 6.5, 37 °C and was feedback inhibited by L-valine, L-leucine and L-isoleucine. Furthermore, the alsS-deficient strain could not produce acetoin, 2,3-butanediol, and L-valine, while the complementary strain was able to restore these capacities...
October 11, 2017: Bioprocess and Biosystems Engineering
https://www.readbyqxmd.com/read/29026156/metabolic-responses-of-eisenia-fetida-to-individual-pb-and-cd-contamination-in-two-types-of-soils
#15
Ronggui Tang, Changfeng Ding, Yibing Ma, Junsong Wang, Taolin Zhang, Xingxiang Wang
To characterize the potential toxicity of low Pb- and Cd-contaminated arable soils, earthworms were exposed to Pb contaminated ferrosol, cambosol or Cd contaminated ferrosol for two weeks. Polar metabolites of earthworms were detected by nuclear magnetic resonance. Data were then analyzed with principal component analysis followed by orthogonal signal correction-partial least squares-discriminant analysis and univariate analysis to determine possible mechanisms for the changes in metabolites. The survival rates, metal concentrations and bioaccumulation factor (BAF) of the earthworms were also measured and calculated as auxiliary data...
October 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29024237/sterol-content-in-the-artificial-diet-of-mythimna-separata-affects-the-metabolomics-of-arma-chinensis-fallou-as-determined-by-proton-nuclear-magnetic-resonance-spectroscopy
#16
Yi Guo, Chen-Xi Liu, Li-Sheng Zhang, Meng-Qing Wang, Hong-Yin Chen
Insects cannot synthesize sterols and must obtain them from plants. Therefore, reducing plant sterol content or changing sterol type might be an effective pest control strategy. However, the impacts of these changes on pests' natural predators remain unknown. Here, we fed artificial diets with reduced sterol content to Mythimna separata (Walker) (Lepidoptera: Noctuidae) and investigated the effects on its natural predator, Arma chinensis (Fallou) (Hemiptera: Pentatomidae). Reduced sterol content in M. separata (MS1, MS2, and MS5) was achieved by feeding them artificial diets prepared from a feed base subjected to one, two, or five cycles of sterol extractions, respectively...
October 11, 2017: Archives of Insect Biochemistry and Physiology
https://www.readbyqxmd.com/read/29017947/integrated-profiling-of-global-metabolomic-and-transcriptomic-responses-to-viral-hemorrhagic-septicemia-virus-infection-in-olive-flounder
#17
Se-Young Cho, Yong-Kook Kwon, Miso Nam, Bipin Vaidya, Seok Ryel Kim, Sunghoon Lee, Joseph Kwon, Duwoon Kim, Geum-Sook Hwang
Viral hemorrhagic septicemia virus (VHSV) is one of the most serious viral pathogen that infects farmed fish. In this study, we measured the replication of VHSV increased steadily at 9, 24, 72, and 120 h after infection and progression of necrosis was observed at 72 hpi. We performed transcriptomic and metabolomics profiling of kidney tissues collected at each infection time using Illumina HiSeq2000 and ultra-performance liquid chromatography/quadrupole time-of-flight mass spectroscopy to investigate the mechanisms of VHSV infection in the kidneys of olive flounder...
October 7, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29017613/a-multiplex%C3%A2-pcr-for-detection-of-knockdown-resistance-mutations-v1016g-and-f1534c-in-pyrethroid-resistant-aedes-aegypti
#18
Jassada Saingamsook, Atiporn Saeung, Jintana Yanola, Nongkran Lumjuan, Catherine Walton, Pradya Somboon
BACKGROUND: Mutation of the voltage-gated sodium channel (VGSC) gene, or knockdown resistance (kdr) gene, is an important resistance mechanism of the dengue vector Aedes aegypti mosquitoes against pyrethroids. In many countries in Asia, a valine to glycine substitution (V1016G) and a phenylalanine to cysteine substitution (F1534C) are common in Ae. aegypti populations. The G1016 and C1534 allele frequencies have been increasing in recent years, and hence there is a need to have a simple and inexpensive tool to monitor the alleles in large scale...
October 10, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28992356/uplc-hr-ms-ms-based-determination-study-on-the-metabolism-of-four-synthetic-cannabinoids-adb-fubica-ab-fubica-ab-bica-and-adb-bica-by-human-liver-microsomes
#19
Jing Li, Cuimei Liu, Tao Li, Zhendong Hua
Since 2012, several cannabimimetic indazole and indole derivatives with valine amino acid amide residue have emerged in the illicit drug market, and gradually replaced the old generations of synthetic cannabinoids (SCs) with naphthyl or adamantine groups. Among them, ADB-FUBICA, AB-FUBICA, AB-BICA and ADB-BICA were detected in China recently, but unfortunately no information about their in vitro human metabolism is available for now. Therefore, biomonitoring studies to screen their consumption lack any information about the potential biomarkers (e...
October 9, 2017: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/28990066/integrated-microarray-analysis-provided-novel-insights-to-the-pathogenesis-of-glaucoma
#20
Jinhui Wang, Daofei Qu, Jinghong An, Guoming Yuan, Yufu Liu
Glaucoma is characterized as a visual field defect, which is the second most common cause of blindness. The present study performed an integrated analysis of microarray studies of glaucoma derived from Gene Expression Omnibus (GEO). Following the identification of the differentially expressed genes (DEGs) in glaucoma compared with normal control (NC) tissues, the functional annotation, glaucoma‑specific protein‑protein interaction (PPI) network and transcriptional regulatory network constructions were performed...
October 4, 2017: Molecular Medicine Reports
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