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Protein design

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https://www.readbyqxmd.com/read/28231703/effects-of-water-addition-to-total-mixed-ration-on-water-intake-nutrient-digestibility-wool-cortisol-and-blood-indices-in-corriedale-ewes
#1
Jalil Ghassemi Nejad, Byong-Wan Kim, Bae-Hun Lee, Kyung Il Sung, Ji-Yung Kim
Objective: The objective of this study was to determine the effect of adding water to total mixed ration (TMR) on fresh water intake, nutrient digestibility, wool cortisol, and blood indices in Corriedale ewes under hot and humid conditions. Methods: Nine non-pregnant Corriedale ewes (ave. BW = 41 ± 3.5 kg) were individually fed diets based on maintenance requirements in metabolic crates. Ewes were assigned to three treatment groups according to a triplicate 3×3 Latin Square design for 3 periods of 21 days duration each (9 ewes per treatment, 27 replications)...
February 23, 2017: Asian-Australasian Journal of Animal Sciences
https://www.readbyqxmd.com/read/28231545/aqueous-extract-of-cortex-dictamni-protects-h9c2-cardiomyocytes-from-hypoxia-reoxygenation-induced-oxidative-stress-and-apoptosis-by-pi3k-akt-signaling-pathway
#2
Lin Li, Yunfeng Zhou, Yanlin Li, Lili Wang, Lan Sun, Lidong Zhou, Hiderori Arai, Yun Qi, Yang Xu
Ischemia-reperfusion injury is the major manifestation of ischemic heart disease, which facilitates cardiac arrhythmias, heart failure and death. Oxidative stress and apoptosis have been involved in the pathogenesis of myocardial ischemia-reperfusion injury. Modern pharmacological studies have indicated that the extracts and active compounds of Cortex Dictamni exhibit antioxidative and cardiovascular protective activities. This study was designed to investigate the protective effect of aqueous extract of Cortex Dictamni (CDAE) on regulating hypoxia/reoxygenation (H/R)-induced cardiomyocytes oxidative stress and apoptosis...
February 20, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28231524/discovery-of-novel-cdk8-inhibitors-using-multiple-crystal-structures-in-docking-based-virtual-screening
#3
Taijin Wang, Zhuang Yang, Yongguang Zhang, Wei Yan, Fang Wang, Linhong He, Yuanyuan Zhou, Lijuan Chen
The cyclin dependent kinase CDK8, along with Med12 and Med13, form the kinase module of the Mediator complex. CDK8 expression associates with the activation of β-catenin in colon and gastric cancers. Herein, we applied docking-based virtual screening (VS) using the multiple crystal structures to identify several potent CDK8 inhibitors. The appropriate use of multiple crystal structures obtained a better enrichment of CDK8 conformations to cope with the protein flexibility. Later on, the 2D similarity search was used to find the derivatives of the high inhibitory CDK8 inhibitors we discovered by VS...
February 9, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28231509/a-single-injection-of-protein-loaded-coacervate-gel-significantly-improves-cardiac-function-post-infarction
#4
H K Awada, D W Long, Z Wang, M P Hwang, K Kim, Y Wang
After myocardial infarction (MI), the heart undergoes fibrotic pathological remodeling instead of repair and regeneration. With multiple pathologies developing after MI, treatment using several proteins is expected to address this range of pathologies more effectively than a single-agent therapy. A factorial design of experiments study guided us to combine three complementary factors in one injection: tissue inhibitor of metalloproteinases-3 (TIMP-3) was embedded in a fibrin gel for signaling in the initial phase of the treatment, while basic fibroblast growth factor (FGF-2) and stromal cell-derived factor 1-alpha (SDF-1α) were embedded in heparin-based coacervates for sustained release and distributed within the same fibrin gel to exert their effects over a longer period...
February 17, 2017: Biomaterials
https://www.readbyqxmd.com/read/28231312/analysis-of-the-t-cell-response-to-zika-virus-and-identification-of-a-novel-cd8-t-cell-epitope-in-immunocompetent-mice
#5
Ryan D Pardy, Maaran M Rajah, Stephanie A Condotta, Nathan G Taylor, Selena M Sagan, Martin J Richer
Zika virus (ZIKV) is an emerging arbovirus of the Flaviviridae family. Although ZIKV infection is typically mild and self-limiting in healthy adults, infection has been associated with neurological symptoms such as Guillain-Barré syndrome, and a causal link has been established between fetal microcephaly and ZIKV infection during pregnancy. These risks, and the magnitude of the ongoing ZIKV pandemic, have created an urgent need for the development of animal models to study the immune response to ZIKV infection...
February 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28231300/detection-and-partial-discrimination-of-atypical-and-classical-bovine-spongiform-encephalopathies-in-cattle-and-primates-using-real-time-quaking-induced-conversion-assay
#6
Etienne Levavasseur, Anne-Gaëlle Biacabe, Emmanuel Comoy, Audrey Culeux, Katarina Grznarova, Nicolas Privat, Steve Simoneau, Benoit Flan, Véronique Sazdovitch, Danielle Seilhean, Thierry Baron, Stéphane Haïk
The transmission of classical bovine spongiform encephalopathy (C-BSE) through contaminated meat product consumption is responsible for variant Creutzfeldt-Jakob disease (vCJD) in humans. More recent and atypical forms of BSE (L-BSE and H-BSE) have been identified in cattle since the C-BSE epidemic. Their low incidence and advanced age of onset are compatible with a sporadic origin, as are most cases of Creutzfeldt-Jakob disease (CJD) in humans. Transmissions studies in primates and transgenic mice expressing a human prion protein (PrP) indicated that atypical forms of BSE may be associated with a higher zoonotic potential than classical BSE, and require particular attention for public health...
2017: PloS One
https://www.readbyqxmd.com/read/28231180/evolution-of-the-maillard-reaction-in-glutamine-or-arginine-dextrinomaltose-model-systems
#7
Silvia Pastoriza, José Ángel Rufián-Henares, Belén García-Villanova, Eduardo Guerra-Hernández
Enteral formulas are foods designed for medical uses to feed patients who are unable to eat normally. They are prepared by mixing proteins, amino acids, carbohydrates and fats and submitted to sterilization. During thermal treatment, the Maillard reaction takes place through the reaction of animo acids with reducing sugars. Thus, although glutamine and arginine are usually added to improve the nutritional value of enteral formulas, their final concentration may vary. Thus, in the present paper the early, intermediate, and advanced states of the Maillard reaction were studied in model systems by measuring loss of free amino acids through the decrease of fluorescence intensity with o-phtaldialdehyde (OPA), 5-Hydroximethylfurfural (HMF), furfural, glucosylisomaltol, fluorescence, and absorbance at 420 nm...
December 7, 2016: Foods (Basel, Switzerland)
https://www.readbyqxmd.com/read/28230992/novel-design-of-heptad-amphiphiles-to-enhance-cell-selectivity-salt-resistance-anti-biofilm-properties-and-their-membrane-disruptive-mechanism
#8
Xiujing Dou, Xin Zhu, Jiajun Wang, Na Dong, Anshan Shan
Coiled-coil, a basic folding pattern of native proteins, was previously demonstrated to be associated with the specific spatial recognition, association, and dissociation of proteins and can be used to perfect engineering peptide model. Thus, in this study, a series of amphiphiles composed of heptads repeats with coiled-coil structures was constructed, and the designed peptides exhibited a broad spectrum of antimicrobial activities. Circular dichroism and biological assays showed that the heptad repeats and length of the linker between the heptads largely influenced the amphiphile's helical propensity and cell selectivity...
February 23, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28230923/predicting-phenotype-from-genotype-improving-accuracy-through-more-robust-experimental-and-computational-modeling
#9
Jonathan Gallion, Amanda Koire, Panagiotis Katsonis, Anne-Marie Schoenegge, Michel Bouvier, Olivier Lichtarge
Computational prediction yields efficient and scalable initial assessments of how variants of unknown significance (VUS) may affect human health. However, when discrepancies between these predictions and direct experimental measurements of functional impact arise, inaccurate computational predictions are frequently assumed as the source. Here we present a methodological analysis indicating that shortcomings in both computational and biological data can contribute to these disagreements. We demonstrate that incomplete assaying of multifunctional proteins can affect the strength of correlations between prediction and experiments; a variant's full impact on function is better quantified by considering multiple assays that probe an ensemble of protein functions...
February 23, 2017: Human Mutation
https://www.readbyqxmd.com/read/28230868/tuning-calcium-biosensors-with-a-single-site-mutation-structural-dynamics-insights-from-femtosecond-raman-spectroscopy
#10
Sean R Tachibana, Longteng Tang, Yanli Wang, Liangdong Zhu, Weimin Liu, Chong Fang
Fluorescent protein biosensors are popular reporters for biological processes and life sciences, but their fundamental working mechanisms remain unclear. To characterize the functional fluorescence events on their native timescales, we implemented wavelength-tunable femtosecond stimulated Raman spectroscopy (FSRS) to shed light on a blue-green emission-ratiometric fluorescent protein based Ca(2+) biosensor with a single Pro377Arg mutation. The transient Raman modes of the embedded chromophore from ca. 1000-1650 cm(-1) exhibit characteristic intensity and frequency dynamics which infer the underlying atomic motions and photochemical reaction stages...
February 23, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28230856/ginsenoside-rg5-increases-cardiomyocyte-resistance-to-ischemic-injury-through-regulation-of-mitochondrial-hexokinase-ii-and-dynamin-related-protein-1
#11
Yi-Lin Yang, Jia Li, Kang Liu, Lei Zhang, Qun Liu, Baolin Liu, Lian-Wen Qi
Hexokinase-II (HK-II) and dynamin-related protein 1 (Drp1) regulate mitochondrial function differently. This study was designed to investigate the cardioprotective effect of ginsenoside Rg5 (Rg5) with emphasis on the regulation of mitochondrial HK-II and Drp1. Saturated acid palmitate (PA) stimulation increased lactate accumulation and induced cellular acidification by impairing the activity of pyruvate dehydrogenase (PDH) in cardiomyocytes, leading to HK-II dissociation from mitochondria. Rg5 improved PDH activity and prevented cellular acidification by combating fatty-acid oxidation, contributing to protecting mitochondrial HK-II...
February 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28230771/antibiotic-resistance-determinant-focused-acinetobacter-baumannii-vaccine-designed-using-reverse-vaccinology
#12
Zhaohui Ni, Yan Chen, Edison Ong, Yongqun He
As one of the most influential and troublesome human pathogens, Acinetobacter baumannii (A. baumannii) has emerged with many multidrug-resistant strains. After collecting 33 complete A. baumannii genomes and 84 representative antibiotic resistance determinants, we used the Vaxign reverse vaccinology approach to predict classical type vaccine candidates against A. baumannii infections and new type vaccine candidates against antibiotic resistance. Our genome analysis identified 35 outer membrane or extracellular adhesins that are conserved among all 33 genomes, have no human protein homology, and have less than 2 transmembrane helices...
February 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28230762/the-development-of-ck2-inhibitors-from-traditional-pharmacology-to-in-silico-rational-drug-design
#13
REVIEW
Giorgio Cozza
Casein kinase II (CK2) is an ubiquitous and pleiotropic serine/threonine protein kinase able to phosphorylate hundreds of substrates. Being implicated in several human diseases, from neurodegeneration to cancer, the biological roles of CK2 have been intensively studied. Upregulation of CK2 has been shown to be critical to tumor progression, making this kinase an attractive target for cancer therapy. Several CK2 inhibitors have been developed so far, the first being discovered by "trial and error testing". In the last decade, the development of in silico rational drug design has prompted the discovery, de novo design and optimization of several CK2 inhibitors, active in the low nanomolar range...
February 20, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28230606/secretions-of-bifidobacterium-infantis-and-lactobacillus-acidophilus-protect-intestinal-epithelial-barrier-function
#14
Shuangshuang Guo, Tyler Gillingham, Yuming Guo, Di Meng, Weishu Zhu, W Allen Walker, Kriston Ganguli
OBJECTIVES: The secreted metabolites of probiotics are cytoprotective to intestinal epithelium and have been shown to attenuate inflammation and reduce gut permeability. The present study was designed to determine the protective effects of probiotic conditioned media (PCM) from Bifidobacterium infantis (BCM) and Lactobacillus acidophilus (LCM) on interleukin (IL)-1β-induced intestinal barrier compromise. METHODS: The epithelial barrier was determined by measuring the transepithelial electrical resistance (TER) across a Caco-2 cell monolayer using a Transwell model...
March 2017: Journal of Pediatric Gastroenterology and Nutrition
https://www.readbyqxmd.com/read/28230599/a-targeted-next-generation-genetic-sequencing-study-on-tetralogy-of-fallot-combined-with-cleft-lip-and-palate
#15
Lin Liu, Haisong Bu, Yifeng Yang, Zhiping Tan, Fei Zhang, Shijun Hu, Tianli Zhao
BACKGROUND: Congenital heart disease (CHD), plus cleft lip and palate (CLP) are currently the most common types of structural malformation in infants. Many genes have been investigated for their involvement in CHD with CLP. Targeted next-generation sequencing can analyze large amounts of genetic information rapidly, and thus address this question. METHODS: The authors designed a targeted, next-generation sequencing gene panel for 455 genes previously implicated in CHD or CLP...
February 22, 2017: Journal of Craniofacial Surgery
https://www.readbyqxmd.com/read/28230233/establishment-and-growth-responses-of-nile-tilapia-embryonic-stem-like-cell-lines-under-feeder-free-condition
#16
Zhenhua Fan, Linyan Liu, Xiaohuan Huang, Yang Zhao, Linyan Zhou, Deshou Wang, Jing Wei
Embryonic stem (ES) cells provide an invaluable tool for molecular analysis of vertebrate development and a bridge linking genomic manipulations in vitro and functional analysis of target genes in vivo. Work towards fish ES cells so far has focused on zebrafish (Danio renio) and medaka (Oryzias latipes). Here we describe the derivation, pluripotency, differentiation and growth responses of ES cell lines from Nile tilapia (Oreochromis niloticus), a world-wide commercial farmed fish. These cell lines, designated as TES1-3, were initiated from blastomeres of Nile tilapia middle blastula embryos (MBE)...
February 23, 2017: Development, Growth & Differentiation
https://www.readbyqxmd.com/read/28230160/global-view-of-cognate-kinase-activation-by-the-human-pyruvate-dehydrogenase-complex
#17
Elena L Guevara, Luying Yang, Barbara Birkaya, Jieyu Zhou, Natalia S Nemeria, Mulchand S Patel, Frank Jordan
The human pyruvate dehydrogenase complex (PDC) comprises four multidomain components, E1, E3, E2 and an E3-binding protein (E3BP), the latter two forming the core as E2·E3BP sub-complex. Pyruvate flux through PDC is regulated via phosphorylation (inactivation) at E1 by four PDC kinases (PDKs), and reactivation by two PDC phosphatases. Up-regulation of PDK isoform gene expression is reported in several forms of cancer, while PDKs may be further activated by PDC by binding to the E2·E3BP core. Hence, the PDK: E2·E3BP interaction provides new therapeutic targets...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28230065/in-vivo-evaluation-of-a-novel-format-of-a-bivalent-her3-targeting-and-albumin-binding-therapeutic-affibody-construct
#18
Tarek Z Bass, Maria Rosestedt, Bogdan Mitran, Fredrik Y Frejd, John Löfblom, Vladimir Tolmachev, Stefan Ståhl, Anna Orlova
Overexpression of human epidermal growth factor receptor 3 (HER3) is involved in resistance to several therapies for malignant tumours. Currently, several anti-HER3 monoclonal antibodies are under clinical development. We introduce an alternative approach to HER3-targeted therapy based on engineered scaffold proteins, i.e. affibody molecules. We designed a small construct (22.5 kDa, denoted 3A3), consisting of two high-affinity anti-HER3 affibody molecules flanking an albumin-binding domain ABD, which was introduced for prolonged residence in circulation...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28229921/protective-effect-of-a-polysaccharide-from-anoectochilus-roxburghii-against-carbon-tetrachloride-induced-acute-liver-injury-in-mice
#19
Biyu Zeng, Minghua Su, Qingxi Chen, Qiang Chang, Wei Wang, Huihua Li
ETHNOPHARMACOLOGICAL RELEVANCE: Anoectochilus roxburghii (Wall.) Lindl. is traditionally used for the treatment of various types of chronic and acute hepatitis in China. Considering that Anoectochilus roxburghii polysaccharide (ARPT) is the main constituent of Anoectochilus roxburghii, the present study was designed to investigate the hepatoprotective effect of ARPT and its possible mechanism in carbon tetrachloride (CCl4)-induced mice. MATERIAL AND METHODS: The hepatoprotective activity of ARPT (150, 300 and 500 mg/kg) were investigated on CCl4-induced acute liver damage in mice...
February 13, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28229915/regulated-methionine-oxidation-by-monooxygenases
#20
REVIEW
Bruno Manta, Vadim N Gladyshev
Protein function can be regulated via post-translational modifications by numerous enzymatic and non-enzymatic mechanisms, including oxidation of cysteine and methionine residues. Redox-dependent regulatory mechanisms have been identified for nearly every cellular process, but the major paradigm has been that cellular components are oxidized (damaged) by reactive oxygen species (ROS) in a relatively unspecific way, and then reduced (repaired) by designated reductases. While this scheme may work with cysteine, it cannot be ascribed to other residues, such as methionine, whose reaction with ROS is too slow to be biologically relevant...
February 13, 2017: Free Radical Biology & Medicine
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