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https://www.readbyqxmd.com/read/29651930/molecular-insights-into-the-irreversible-mechanical-behavior-of-sickle-hemoglobin
#1
Sumith Yesudasan, Simone A Douglas, Manu O Platt, Xianqiao Wang, Rodney D Averett
Sickle cell disease is caused by the amino acid substitution of glutamic acid to valine, which leads to the polymerization of deoxygenated sickle hemoglobin (HbS) into long strands. These strands are responsible for the sickling of red blood cells (RBCs), making blood hyper-coagulable leading to an increased chance of vaso-occlusive crisis. The conformational changes in sickled RBCs traveling through narrow blood vessels in a highly viscous fluid are critical in understanding; however, there are few studies that investigate the origins of the molecular mechanical behavior of sickled RBCs...
April 13, 2018: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/29644075/regulation-of-amino-acid-transporters-in-the-mammary-gland-from-late-pregnancy-to-peak-lactation-in-the-sow
#2
Fang Chen, Shihai Zhang, Zixiao Deng, Qiqi Zhou, Lin Cheng, Sung Woo Kim, Jun Chen, Wutai Guan
Background: Milk protein is crucial for milk quality in sows and health of newborn piglets. Plasma amino acids (AA) in sows are important precursors for milk protein synthesis in the mammary gland. In order to study the regulation of AA transported in sow mammary glands and possible underlying mechanisms, we measured the expression of genes coding for milk proteins, AA transporter expressions, and plasma AA concentrations in sows at three different physiological stages (D-17, D1 and D17 of lactation), and then further investigated the regulation of AA transport across the cell membrane by adaptive mechanisms using pig mammary epithelial cells (PMEC) as an in vitro model...
2018: Journal of Animal Science and Biotechnology
https://www.readbyqxmd.com/read/29628983/-fcrr3a-158-polymorphism-and-stromal-tumor-infiltrating-lymphocytes-and-survival-among-patients-with-metastatic-her2-positive-breast-cancer-receiving-trastuzumab-based-treatment
#3
Heejung Chae, Changhoon Yoo, Jung-A Yoon, Hee Jin Lee, Kyu-Pyo Kim, Jeong-Eun Kim, Jin-Hee Ahn, Kyung Hae Jung, Gyungyub Gong, Sung-Bae Kim
Purpose: The prognosis of human epidermal growth factor receptor 2 (HER2)-positive breast cancer has markedly improved since the introduction of trastuzumab. We aimed to evaluate the association between stromal tumor-infiltrating lymphocyte (sTIL) or FcrR polymorphisms and survival among patients with metastatic HER2-positive breast cancer who were treated with trastuzumab. Methods: A total of 56 women with recurrent or metastatic HER2-positive breast cancer who received the trastuzumab-taxane combination as first-line treatment were included in this retrospective analysis...
March 2018: Journal of Breast Cancer
https://www.readbyqxmd.com/read/29625175/magi-proteins-can-differentially-regulate-the-signaling-pathways-of-5-ht-2a-r-by-enhancing-receptor-trafficking-and-plc-recruitment
#4
Maha M Hammad, Henry A Dunn, Stephen S G Ferguson
MAGI proteins are Membrane-Associated Guanylate Kinase Inverted proteins that belong to the MAGUK family. They are scaffolding proteins that were shown to mediate the trafficking and signaling of various G protein-coupled receptors (GPCRs). They contain PDZ domains in their structure and most GPCRs interact with these proteins via the PDZ motifs on the carboxyl terminal end of a receptor. In a PDZ overlay assay performed with the carboxyl terminal tail of 5-HT2A R, we were able to detect all three members of the MAGI subfamily, MAGI-1, MAGI-2 and MAGI-3 as interacting PDZ proteins...
April 3, 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29622678/calcium-induced-structural-rearrangements-release-autoinhibition-in-the-rap-gef-caldag-gefi
#5
Aaron A Cook, Wei Deng, Jinqi Ren, Renhao Li, John Sondek, Wolfgang Bergmeier
Platelets are recruited to sites of vascular injury where they are activated and aggregate to form a hemostatic plug. This process requires the activation of the small GTPase Rap1B by its cognate guanine nucleotide exchange factor CalDAG-GEFI. Studies on platelet function suggest that CalDAG-GEFI activity is regulated by changes in cytosolic calcium, but the exact molecular mechanism is poorly understood. Here, we show that purified CalDAG-GEFI is autoinhibited and directly regulated by calcium. Substitutions of putative calcium-binding residues within the canonical EF hands of CalDAG-GEFI diminish its capacity to activate Rap1B...
April 5, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29621136/complex-regulatory-networks-governing-production-of-the-glycopeptide-a40926
#6
REVIEW
Rosa Alduina, Margherita Sosio, Stefano Donadio
Glycopeptides (GPAs) are an important class of antibiotics, with vancomycin and teicoplanin being used in the last 40 years as drugs of last resort to treat infections caused by Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus . A few new GPAs have since reached the market. One of them is dalbavancin, a derivative of A40926 produced by the actinomycete Nonomuraea sp. ATCC 39727, recently classified as N. gerenzanensis . This review summarizes what we currently know on the multilevel regulatory processes governing production of the glycopeptide A40926 and the different approaches used to increase antibiotic yields...
April 5, 2018: Antibiotics
https://www.readbyqxmd.com/read/29620688/effects-of-branched-chain-amino-acid-supplementation-on-spontaneous-seizures-and-neuronal-viability-in-a-model-of-mesial-temporal-lobe-epilepsy
#7
Shaun E Gruenbaum, Roni Dhaher, Amedeo Rapuano, Hitten P Zaveri, Amber Tang, Nihal de Lanerolle, Tore Eid
BACKGROUND: The essential branched-chain amino acids (BCAAs) leucine, isoleucine, and valine have recently emerged as a potential novel treatment for medically refractory epilepsy. Blood-derived BCAAs can readily enter the brain, where they contribute to glutamate biosynthesis and may either suppress or trigger acute seizures. However, the effects of BCAAs on chronic (ie, spontaneous recurrent) seizures and epilepsy-associated neuron loss are incompletely understood. MATERIALS AND METHODS: Sixteen rats with mesial temporal lobe epilepsy were randomized into 2 groups that could drink, ad libitum, either a 4% solution of BCAAs in water (n=8) or pure water (n=8)...
April 3, 2018: Journal of Neurosurgical Anesthesiology
https://www.readbyqxmd.com/read/29614759/high-glucose-induced-cardiomyocyte-death-may-be-linked-to-unbalanced-branched-chain-amino-acids-and-energy-metabolism
#8
Xi Zhang, Qiuting Lin, Jiuxia Chen, Tingting Wei, Chen Li, Liangcai Zhao, Hongchang Gao, Hong Zheng
High glucose-induced cardiomyocyte death is a common symptom in advanced-stage diabetic patients, while its metabolic mechanism is still poorly understood. The aim of this study was to explore metabolic changes in high glucose-induced cardiomyocytes and the heart of streptozotocin-induced diabetic rats by ¹H-NMR-based metabolomics. We found that high glucose can promote cardiomyocyte death both in vitro and in vivo studies. Metabolomic results show that several metabolites exhibited inconsistent variations in vitro and in vivo...
April 1, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29610385/coordinating-agmip-data-and-models-across-global-and-regional-scales-for-1-5%C3%A2-c-and-2-0%C3%A2-c-assessments
#9
Cynthia Rosenzweig, Alex C Ruane, John Antle, Joshua Elliott, Muhammad Ashfaq, Ashfaq Ahmad Chatta, Frank Ewert, Christian Folberth, Ibrahima Hathie, Petr Havlik, Gerrit Hoogenboom, Hermann Lotze-Campen, Dilys S MacCarthy, Daniel Mason-D'Croz, Erik Mencos Contreras, Christoph Müller, Ignacio Perez-Dominguez, Meridel Phillips, Cheryl Porter, Rubi M Raymundo, Ronald D Sands, Carl-Friedrich Schleussner, Roberto O Valdivia, Hugo Valin, Keith Wiebe
The Agricultural Model Intercomparison and Improvement Project (AgMIP) has developed novel methods for Coordinated Global and Regional Assessments (CGRA) of agriculture and food security in a changing world. The present study aims to perform a proof of concept of the CGRA to demonstrate advantages and challenges of the proposed framework. This effort responds to the request by the UN Framework Convention on Climate Change (UNFCCC) for the implications of limiting global temperature increases to 1.5°C and 2...
May 13, 2018: Philosophical Transactions. Series A, Mathematical, Physical, and Engineering Sciences
https://www.readbyqxmd.com/read/29603657/changes-in-plasma-metabolite-concentrations-after-a-low-glycemic-index-diet-intervention
#10
Pablo Hernández-Alonso, Simona Giardina, Daniel Cañueto, Jordi Salas-Salvadó, Nicolau Cañellas, Mònica Bulló
SCOPE: To examine whether a low-glycemic index (LGI) diet improves a set of plasma metabolites related to different metabolic diseases and compared to a high-glycemic index (HGI) diet and a low-fat (LF) diet. METHODS AND RESULTS: We conducted a parallel, randomized trial with three intervention diets: a LGI diet, a HGI diet and a LF diet. A total of 122 adult overweight and obese subjects were enrolled in the study for 6 months. Blood samples were collected at baseline and at the end of the intervention...
March 30, 2018: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29601791/biofilm-production-by-clinical-isolates-of-pseudomonas-aeruginosa-and-structural-changes-in-lasr-protein-of-isolates-non-biofilm-producing
#11
Jailton Lobo da Costa Lima, Lilian Rodrigues Alves, Paula Regina Luna de Araújo Jacomé, João Pacífico Bezerra Neto, Maria Amélia Vieira Maciel, Marcia Maria Camargo de Morais
INTRODUCTION: Biofilm production is an important mechanism for the survival of Pseudomonas aeruginosa and its relationship with antimicrobial resistance represents a challenge for patient therapeutics. P. aeruginosa is an opportunistic pathogen frequently associated to nosocomial infections, especially in imunocompromised hosts. OBJECTIVES: Analyze the phenotypic biofilm production in P. aeruginosa isolates, describe clonal profiles, and analyze quorum sensing (QS) genes and the occurrence of mutations in the LasR protein of non-biofilm producing isolates...
March 27, 2018: Brazilian Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29595366/dabrafenib-in-combination-with-trametinib-in-the-treatment-of-patients-with-braf-v600-positive-advanced-or-metastatic-non-small-cell-lung-cancer-clinical-evidence-and-experience
#12
Arjun Khunger, Monica Khunger, Vamsidhar Velcheti
Mutations in the BRAF oncogene are found in 2-4% of all non-small cell lung cancer (NSCLC) patients. The most common activating mutation present within the BRAF oncogene is associated with valine substitution for glutamate at position 600 (V600E) within the BRAF kinase. BRAF-targeted therapies are effective in patients with melanoma and NSCLC harboring BRAF V600E mutation. In both melanoma and NSCLC, dual inhibition of both BRAF and the downstream mitogen-activated protein kinase (MEK) improves response rates compared with BRAF inhibition alone...
January 2018: Therapeutic Advances in Respiratory Disease
https://www.readbyqxmd.com/read/29594358/production-of-l-valine-from-metabolically-engineered-corynebacterium-glutamicum
#13
REVIEW
Xiaoyuan Wang, Hailing Zhang, Peter J Quinn
L-Valine is one of the three branched-chain amino acids (valine, leucine, and isoleucine) essential for animal health and important in metabolism; therefore, it is widely added in the products of food, medicine, and feed. L-Valine is predominantly produced through microbial fermentation, and the production efficiency largely depends on the quality of microorganisms. In recent years, continuing efforts have been made in revealing the mechanisms and regulation of L-valine biosynthesis in Corynebacterium glutamicum, the most utilitarian bacterium for amino acid production...
March 29, 2018: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29594134/the-comt-val158met-polymorphism-and-exploratory-behavior-in-bipolar-mania
#14
Arpi Minassian, Jared W Young, Mark A Geyer, John R Kelsoe, William Perry
Background: The catechol-O-methyltransferase (COMT) Val158Met gene influences cognition and behavior in psychiatric illnesses; its low-activity allele, methionine (Met), may be associated with behavior reflecting catecholamine overactivity. Heightened motor activity and increased positive valence are central features of bipolar disorder (BD) and have been quantified in the human Behavioral Pattern Monitor (hBPM), an exploration paradigm based upon the rodent open field. We examined whether hBPM behavior was related to the COMT gene in a small sample of manic BD patients...
February 2018: Molecular Neuropsychiatry
https://www.readbyqxmd.com/read/29584425/leucine-promotes-the-growth-of-fetal-pigs-by-increasing-protein-synthesis-through-the-mtor-signaling-pathway-in-longissimus-dorsi-muscle-at-late-gestation
#15
Chaoxian Wang, Fang Chen, Wenfei Zhang, Shihai Zhang, Kui Shi, Hanqing Song, Yijiang Wang, Sun Woo Kim, Wutai Guan
Leucine (Leu) plays an important role in protein synthesis and metabolism. The present study tested whether Leu supplementation in the diet for sows during late pregnancy could improve piglet birth weight, and also investigated the possible underlying mechanism. Two hundreds sows at day 70 of pregnancy were selected and assigned to four groups fed with following four diets until farrowing respectively: corn and soybean meal-based diet group (CON), CON + 0.40% Leu, CON + 0.80% Leu and CON + 1.20% Leu. We found that supplementing with 0...
March 27, 2018: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29581270/kv4-2-autism-and-epilepsy-mutation-enhances-inactivation-of-closed-channels-but-impairs-access-to-inactivated-state-after-opening
#16
Meng-Chin A Lin, Stephen C Cannon, Diane M Papazian
A de novo mutation in the KCND2 gene, which encodes the Kv4.2 K+ channel, was identified in twin boys with intractable, infant-onset epilepsy and autism. Kv4.2 channels undergo closed-state inactivation (CSI), a mechanism by which channels inactivate without opening during subthreshold depolarizations. CSI dynamically modulates neuronal excitability and action potential back propagation in response to excitatory synaptic input, controlling Ca2+ influx into dendrites and regulating spike timing-dependent plasticity...
March 26, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29576077/cystathionine-gamma-synthase-activity-in-rice-is-developmentally-regulated-and-strongly-correlated-with-sulfate
#17
Sarah J Whitcomb, Huu Cuong Nguyen, Franziska Brückner, Holger Hesse, Rainer Hoefgen
An important goal of rice cultivar development is improvement of protein quality, especially with respect to essential amino acids such as methionine. With the goal of increasing seed methionine content, we generated Oryza sativa ssp. japonica cv. Taipei 309 transgenic lines expressing a feedback-desensitized CYSTATHIONINE GAMMA-SYNTHASE from Arabidopsis thaliana (AtD-CGS) under the control of the maize ubiquitin promoter. Despite persistently elevated cystathionine gamma-synthase (CGS) activity in the AtD-CGS transgenic lines relative to untransformed Taipei, sulfate was the only sulfur-containing compound found to be elevated throughout vegetative development...
May 2018: Plant Science: An International Journal of Experimental Plant Biology
https://www.readbyqxmd.com/read/29575569/clinical-biochemical-and-genetic-features-of-four-patients-with-short-chain-enoyl-coa-hydratase-echs1-deficiency
#18
Patricia E Fitzsimons, Charlotte L Alston, Penelope E Bonnen, Joanne Hughes, Ellen Crushell, Michael T Geraghty, Martine Tetreault, Peter O'Reilly, Eilish Twomey, Yusra Sheikh, Richard Walsh, Hans R Waterham, Sacha Ferdinandusse, Ronald J A Wanders, Robert W Taylor, James J Pitt, Philip D Mayne
Short-chain enoyl-CoA hydratase (SCEH or ECHS1) deficiency is a rare inborn error of metabolism caused by biallelic mutations in the gene ECHS1 (OMIM 602292). Clinical presentation includes infantile-onset severe developmental delay, regression, seizures, elevated lactate, and brain MRI abnormalities consistent with Leigh syndrome (LS). Characteristic abnormal biochemical findings are secondary to dysfunction of valine metabolism. We describe four patients from two consanguineous families (one Pakistani and one Irish Traveler), who presented in infancy with LS...
March 25, 2018: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/29575058/amino-acids-as-chiral-derivatizing-agents-for-antiproliferative-substituted-n-benzyl-isoindolinones
#19
Tatyana A Grigoreva, Daria S Novikova, Maxim A Gureev, Alexander V Garabadzhiu, Vyacheslav G Tribulovich
The absolute configurations of the diastereomers of novel amino acid ester derivatives of 2,3-substituted isoindolinones, which are known as apoptosis activators due to their ability to inhibit the MDM2-p53 PPI, were assigned using NMR and computational methods. Procedures for diastereomer separation and determining the absolute configuration were developed to perform the study. The high significance of N-benzyl fragment for the determination of the diastereomer absolute configuration by NMR methods was established; it is determined by a number of factors inherent in this fragment and the structural features of the studied substrates...
March 25, 2018: Chirality
https://www.readbyqxmd.com/read/29573638/n-linoleoylamino-acids-as-chiral-probes-of-substrate-binding-by-soybean-lipoxygenase-1
#20
Charles H Clapp, Justin Pachuski, Natasha F Bassett, Kathleen A Bishop, Gillian Carter, Megan Young, Thomas Young, Yuhan Fu
Lipoxygenases catalyze the oxygenation of polyunsaturated fatty acids and their derivatives to produce conjugated diene hydroperoxides. Soybean lipoxygenase-1 (SBLO-1) has been the subject of intensive structural and mechanistic study, but the manner in which this enzyme binds substrates is uncertain. Previous studies suggest that the fatty acyl group of the substrate binds in an internal cavity near the catalytic iron with the polar end at the surface of the protein or perhaps external to the protein. To test this model, we have investigated two pairs of enantiomeric N-linoleoylamino acids as substrates for SBLO-1...
March 8, 2018: Bioorganic Chemistry
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