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Protein design

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https://www.readbyqxmd.com/read/28941399/comparison-of-uv-led-and-low-pressure-uv-for-water-disinfection-photoreactivation-and-dark-repair-of-escherichia-coli
#1
Guo-Qiang Li, Wen-Long Wang, Zheng-Yang Huo, Yun Lu, Hong-Ying Hu
Studies on ultraviolet light-emitting diode (UV-LED) water disinfection have shown advantages, such as safety, flexible design, and lower starting voltages. However, information about reactivation after UV-LED disinfection is limited, which is an important issue of UV light-based technology. In this study, the photoreactivation and dark repair of Escherichia coli after UV-LEDs and low pressure (LP) UV disinfection were compared. Four UV-LED units, 265 nm, 280 nm, the combination of 265 + 280 (50%), and 265 + 280 (75%) were tested...
September 17, 2017: Water Research
https://www.readbyqxmd.com/read/28939533/comparative-mapping-of-on-targets-and-off-targets-for-the-discovery-of-anti-trypanosomatid-folate-pathway-inhibitors
#2
Joanna Panecka-Hofman, Ina Pöhner, Francesca Spyrakis, Talia Zeppelin, Flavio Di Pisa, Lucia Dello Iacono, Alessio Bonucci, Antonio Quotadamo, Alberto Venturelli, Stefano Mangani, Maria Paola Costi, Rebecca C Wade
BACKGROUND: Multi-target approaches are necessary to properly analyze or modify the function of a biochemical pathway or a protein family. An example of such a problem is the repurposing of the known human anti-cancer drugs, antifolates, as selective anti-parasitic agents. This requires considering a set of experimentally validated protein targets in the folate pathway of major pathogenic trypanosomatid parasites and humans: (i) the primary parasite on-targets: pteridine reductase 1 (PTR1) (absent in humans) and bifunctional dihydrofolate reductase-thymidylate synthase (DHFR-TS), (ii) the primary off-targets: human DHFR and TS, and (iii) the secondary on-target: human folate receptor β, a folate/antifolate transporter...
September 20, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28938793/effects-of-protein-or-amino-acid-supplementation-on-the-physical-growth-of-young-children-in-low-income-countries
#3
Joanne E Arsenault, Kenneth H Brown
Child growth stunting is common in low-income countries, possibly due to insufficient protein intakes. Most previous studies have concluded that children's protein intakes are adequate in relation to estimated requirements, but these studies did not consider issues of protein digestibility and effects of infection on dietary protein utilization. Using an alternative approach to assess the possible role of protein inadequacy in children's growth restriction, the results of 18 intervention trials in which supplementary protein or amino acids were provided to children ages 6-35 months and growth outcomes were reviewed...
September 1, 2017: Nutrition Reviews
https://www.readbyqxmd.com/read/28938766/dietary-effects-of-bacillus-subtilis-fmbj-on-the-antioxidant-capacity-of-broilers-at-an-early-age
#4
Lili Zhang, Kaiwen Bai, Jingfei Zhang, Wen Xu, Qiang Huang, Tian Wang
This study was designed to evaluate the usage of Bacillus subtilis fmbj (BS fmbj) in broiler diets, and its effects on the antioxidant capacity of broilers at an early age. A total of 240 day-old male Arbor Acres (AA) broilers were randomly assigned to 4 groups, namely the control (CON) group (fed basal diets with 0 cfu/kg BS fmbj), the BS-1 group (fed basal diet with 0.2 × 1011 cfu/kg BS fmbj), BS-2 group (fed basal diet with 0.3 × 1011 cfu/kg BS fmbj), and BS-3 group (fed basal diet with 0.4 × 1011 cfu/kg BS fmbj)...
October 1, 2017: Poultry Science
https://www.readbyqxmd.com/read/28938543/predictive-clinical-model-of-tumor-response-after-chemoradiation-in-rectal-cancer
#5
Marisa D Santos, Cristina Silva, Anabela Rocha, Carlos Nogueira, Fernando Castro-Poças, António Araujo, Eduarda Matos, Carina Pereira, Rui Medeiros, Carlos Lopes
Survival improvement in rectal cancer treated with neoadjuvant chemoradiotherapy (nCRT) is achieved only if pathological response occurs. Mandard tumor regression grade (TRG) proved to be a valid system to measure nCRT response. The ability to predict tumor response before treatment may significantly have impact the selection of patients for nCRT in rectal cancer. The aim is to identify potential predictive pretreatment factors for Mandard response and build a clinical predictive model design. 167 patients with locally advanced rectal cancer were treated with nCRT and curative surgery...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938434/fgf21-is-an-insulin-dependent-postprandial-hormone-in-adult-humans
#6
Ricardo J Samms, Jo E Lewis, Luke Norton, Francis B Stephens, Christopher J Gaffney, Tony Butterfield, Dennis Smith, Christine Cheng, James W Perfield, Andrew C Adams, Francis J P Ebling, Kostas Tsintzas
Context: Fibroblast growth factor 21 (FGF21) secretion has been shown to respond directly to carbohydrate consumption, with glucose, fructose and sucrose all reported to increase plasma levels of FGF21 in rodents and humans. However, carbohydrate consumption also results in secretion of insulin. Objective: The aim of this study was to examine the combined and independent effects of hyperglycemia and hyperinsulinemia on total and bioactive FGF21 in the postprandial period in humans, and determine whether this effect is attenuated in conditions of altered insulin secretion and action...
August 4, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28938164/multifunctional-superparamagnetic-nanoparticles-conjugated-with-fluorescein-labeled-designed-ankyrin-repeat-protein-as-an-efficient-her2-targeted-probe-in-breast-cancer
#7
Dong-Li Li, Jian-Er Tan, Ying Tian, Shun Huang, Peng-Hui Sun, Meng Wang, Yan-Jiang Han, Hong-Sheng Li, Hu-Bing Wu, Xing-Mei Zhang, Yi-Kai Xu, Quan-Shi Wang
Based on the discordance of human epidermal growth factor receptor-2 (HER2) expression between primary and metastatic/recurrent breast cancer, HER2 molecular imaging, which had potential to systemically assess and dynamically monitor HER2 expression, might improve the selection of patients for anti-HER2 therapy. In this study, designed ankyrin repeat protein (DARPin) G3, a novel binding protein with picomolar affinity for HER2, was used and multifunctional superparamagnetic nanoparticles modified with fluorescein-5-maleimide-labeled DARPin G3 (SPIO-G3-5MF) were developed for HER2 imaging...
September 8, 2017: Biomaterials
https://www.readbyqxmd.com/read/28938075/the-human-plasma-proteome-draft-of-2017-building-on-the-human-plasma-peptideatlas-from-mass-spectrometry-and-complementary-assays
#8
Jochen M Schwenk, Gilbert S Omenn, Zhi Sun, David S Campbell, Mark S Baker, Christopher M Overall, Ruedi Aebersold, Robert L Moritz, Eric W Deutsch
Human blood plasma provides a highly accessible window to the proteome of any individual in health and disease. Since its inception in 2002, the Human Proteome Organization's Human Plasma Proteome Project (HPPP) has been promoting advances in the study and understanding of the full protein complement of human plasma and on determining the abundance and modifications of its components. In 2017, we review the history of the HPPP and the advances of human plasma proteomics in general, including several recent achievements...
September 22, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28938069/molecular-recognition-of-agonists-and-antagonists-by-the-nucleotide-activated-g-protein-coupled-p2y2-receptor
#9
Muhammad Rafehi, Alexander Neumann, Younis Baqi, Enas M Malik, Michael Wiese, Vigneshwaran Namasivayam, Christa E Müller
A homology model of the nucleotide-activated P2Y2R was created based on the X-ray structures of the P2Y1 and P2Y12 receptors. Docking studies were performed, and receptor mutants were created to probe the identified binding interactions. Mutation of residues predicted to interact with the ribose (Arg110) and the phosphates of the nucleotide agonists (Arg265, Arg292) or that contribute indirectly to binding (Tyr288) abolished activity. The Y114F, R194A, and F261A mutations led to inactivity of diadenosine tetraphosphate and to a reduced response of UTP...
September 22, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28938067/a-single-chain-photoswitchable-crispr-cas9-architecture-for-light-inducible-gene-editing-and-transcription
#10
Xin X Zhou, Xinzhi Zou, Hokyung K Chung, Yuchen Gao, Yanxia Liu, Lei S Qi, Michael Z Lin
Optical control of CRISPR-Cas9-derived proteins would be useful for restricting gene editing or transcriptional regulation to desired times and places. Optical control of Cas9 functions has been achieved with photouncageable unnatural amino acids or by using light-induced protein interactions to reconstitute Cas9-mediated functions from two polypeptides. However, these methods have only been applied to one Cas9 species and have not been used for optical control of different perturbations at two genes. Here, we use photodissociable dimeric fluorescent protein domains to engineer single-chain photoswitchable Cas9 (ps-Cas9) proteins in which the DNA-binding cleft is occluded at baseline and opened upon illumination...
September 22, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28937979/molecular-genomic-characterization-of-tick-and-human-derived-severe-fever-with-thrombocytopenia-syndrome-virus-isolates-from-south-korea
#11
Seok-Min Yun, Su-Jin Park, Sun-Whan Park, WooYoung Choi, Hye Won Jeong, Young-Ki Choi, Won-Ja Lee
BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne viral disease caused by the SFTS virus (SFTSV) from Bunyaviridae that is endemic in East Asia. However, the genetic and evolutionary characteristics shared between tick- and human-derived Korean SFTSV strains are still limited. METHODOLOGY/PRINCIPAL FINDINGS: In this study we identify, for the first time, the genome sequence of a tick (Haemaphysalis longicornis)-derived Korean SFTSV strain (designated as KAGWT) and compare this virus with recent human SFTSV isolates to identify the genetic variations and relationships among SFTSV strains...
September 22, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28937827/effect-of-saffron-on-metabolic-profile-and-retina-in-apolipoprotein-e-knockout-mice-fed-a-high-fat-diet
#12
Evangelos K Doumouchtsis, Aspasia Tzani, Ilias P Doulamis, Panagiotis Konstantopoulos, Korou Laskarina-Maria, Georgios Agrogiannis, Emmanouil Agapitos, Marilita M Moschos, Alkiviadis Kostakis, Despina N Perrea
Saffron is a spice that has been traditionally used as a regimen for a variety of diseases due to its potent antioxidant attributes. It is well documented that impaired systemic oxidative status is firmly associated with diverse adverse effects including retinal damage. The aim of this study was to investigate the role of saffron administration against the retinal damage in apoE -/- mice fed a high-fat diet, since they constitute a designated experimental model susceptible to oxidative stress. Twenty-one mice were allocated into three groups: Group A (control, n = 7 c57bl/6 mice) received standard chow diet; Group B (high-fat, n = 7 apoE -/- mice) received a high-fat diet; and Group C (high-fat and saffron, n = 7 apoE -/- mice) received a high-fat diet and saffron (25 mg/kg/d) through their drinking water...
September 22, 2017: Journal of Dietary Supplements
https://www.readbyqxmd.com/read/28937743/rational-design-of-an-anticalin-type-sugar-binding-protein-using-a-genetically-encoded-boronate-side-chain
#13
Selvakumar Edwardraja, Andreas Eichinger, Ina Theobald, Carina Andrea Sommer, Andreas J Reichert, Arne Skerra
The molecular recognition of carbohydrates plays a fundamental role in many biological processes. However, the development of carbohydrate-binding reagents for biomedical research and use poses a challenge due to the generally poor affinity of proteins towards sugars in aqueous solution. Here, we describe the effective molecular recognition of pyranose monosaccharides (in particular, galactose and mannose) by a rationally designed protein receptor based on the human lipocalin scaffold (Anticalin). Complexation relies on reversible covalent cis-diol boronate diester formation with a genetically encoded L-boronophenylalanine (Bpa) residue which was incorporated as a non-natural amino acid at a sterically permissive position in the binding site of the Anticalin, as confirmed by X-ray crystallography...
September 22, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28937696/chromophores-of-chromophores-a-bottom-up-h%C3%A3-ckel-picture-of-the-excited-states-of-photoactive-proteins
#14
Cate S Anstöter, Charlie R Dean, Jan R R Verlet
Many photoactive proteins contain chromophores based on para-substituted phenolate anions which are an essential component of their electronic structure. Here, we present a reductionist approach to gain fundamental insight into the evolution of electronic structure as the chromophore increases in complexity from phenolate to that in GFP. Using frequency- and angle-resolved photoelectron spectroscopy, in combination with electronic structure theory, the onset of excited states that are responsible for the characteristic spectroscopic features in biochromophores are determined...
September 22, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28937648/separation-and-enrichment-of-lectin-from-zihua-snap-bean-phaseolus-vulgaris-seeds-by-peg-600-ammonium-sulfate-aqueous-two-phase-system
#15
Bin Jiang, Yongqiang Yuan, Xiaoqing Zhang, Zhibiao Feng, Chunhong Liu
A fast and efficient method based on a polyethylene glycol (PEG) 600/(NH₄)₂SO₄ aqueous two-phase system for extracting lectin from Zihua snap-bean (Phaseolus vulgaris) seeds was established. According to a Box-Behnken design (BBD), involving four factors at three levels each subjected to analysis of variance (ANOVA) and response surface analysis, the protein recovery and the purification factor of lectin in the top phase were used as the response values of the variance analysis to acquire the multivariate quadratic regression model...
September 22, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28937220/a-fluorescence-polarization-activity-based-protein-profiling-assay-in-the-discovery-of-potent-selective-inhibitors-for-human-non-lysosomal-glucosylceramidase
#16
Daniel Lahav, Bing Liu, Richard J B H N van den Berg, Adrianus M C H van den Nieuwendijk, Tom Wennekes, Amar T Ghisaidoobe, Imogen Breen, Maria J Ferraz, Chi-Lin Kuo, Liang Wu, Paul P Geurink, Huib Ovaa, Gijsbert A van der Marel, Mario van der Stelt, Rolf G Boot, Gideon J Davies, Johannes M F G Aerts, Herman S Overkleeft
Human non-lysosomal glucosylceramidase (GBA2) is one of several enzymes that controls levels of glycolipids and whose activity is linked to several human disease states. There is a major need to design or discover selective GBA2 inhibitors both as chemical tools and as potential therapeutic agents. Here, we describe the development of a fluorescence polarization activity-based protein profiling (FluoPol-ABPP) assay for the rapid identification, from a 350+ library of iminosugars, of GBA2 inhibitors. A focused library is generated based on leads from the FluoPol-ABPP screen and assessed on GBA2 selectivity offset against the other glucosylceramide metabolizing enzymes, glucosylceramide synthase (GCS), lysosomal glucosylceramidase (GBA) and the cytosolic retaining β-glucosidase, GBA3...
September 22, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28936332/designing-brighter-near-infrared-fluorescent-proteins-insights-from-structural-and-biochemical-studies
#17
Mikhail Baloban, Daria M Shcherbakova, Sergei Pletnev, Vladimir Z Pletnev, J Clark Lagarias, Vladislav V Verkhusha
Brighter near-infrared (NIR) fluorescent proteins (FPs) are required for multicolor microscopy and deep-tissue imaging. Here, we present structural and biochemical analyses of three monomeric, spectrally distinct phytochrome-based NIR FPs, termed miRFPs. The miRFPs are closely related and differ by only a few amino acids, which define their molecular brightness, brightness in mammalian cells, and spectral properties. We have identified the residues responsible for the spectral red-shift, revealed a new chromophore bound simultaneously to two cysteine residues in the PAS and GAF domains in blue-shifted NIR FPs, and uncovered the importance of amino acid residues in the N-terminus of NIR FPs for their molecular and cellular brightness...
June 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28935886/stepwise-evolution-improves-identification-of-diverse-peptides-binding-to-a-protein-target
#18
Victor I Lyamichev, Lauren E Goodrich, Eric H Sullivan, Ryan M Bannen, Joerg Benz, Thomas J Albert, Jigar J Patel
Considerable efforts have been made to develop technologies for selection of peptidic molecules that act as substrates or binders to a protein of interest. Here we demonstrate the combination of rational peptide array library design, parallel screening and stepwise evolution, to discover novel peptide hotspots. These hotspots can be systematically evolved to create high-affinity, high-specificity binding peptides to a protein target in a reproducible and digitally controlled process. The method can be applied to synthesize both linear and cyclic peptides, as well as peptides composed of natural and non-natural amino acid analogs, thereby enabling screens in a much diverse chemical space...
September 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28935537/affibody-molecules-for-the-molecular-imaging-and-targeted-drug-delivery-in-the-management-of-breast-cancer
#19
REVIEW
Anindita De, Gowthamarajan Kuppusamy, Veera Venkata Satyanarayana Reddy Karri
Breast cancer is one of the leading reasons for the morbidity and mortality of cancer related death globally. The modern therapies are basically the combination of the breast-preserving surgeries or ablation with or without node biopsy or destroying the carcinoma cells adjuvant with chemotherapy, radiotherapy, hormonal or biological therapies depending upon the nature of the receptor of the cancerous cells, nature of the lymph node, as well as the tendency of the recurrence. For decade's carcinoma management suffered by the limitation of imagining, targeting and penetrability problem associated with management and cure of this deadly disease leads to unwanted chemo-toxicity and side effects...
September 18, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28935369/a-three-dimensional-model-of-rnase-p-in-the-hyperthermophilic-archaeon-pyrococcus-horikoshii-ot3
#20
Xuzhu Gao, Kosuke Oshima, Toshifumi Ueda, Takashi Nakashima, Makoto Kimura
Ribonuclease P (RNase P) is an endoribonuclease involved in maturation of the 5'-end of tRNA. We found previously that RNase P in the hyperthermophilic archaeon Pyrococcus horikoshii OT3 consists of a catalytic RNase P RNA (PhopRNA) and five protein cofactors designated PhoPop5, PhoRpp21, PhoRpp29, PhoRpp30, and PhoRpp38. The crystal structures of the five proteins have been determined, a three-dimensional (3-D) model of PhopRNA has been constructed, and biochemical data, including protein-RNA interaction sites, have become available...
September 18, 2017: Biochemical and Biophysical Research Communications
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