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https://www.readbyqxmd.com/read/28432913/spontaneously-formed-redox-and-ph-sensitive-polymersomes-by-mpeg-based-cytocompatible-random-copolymers
#1
Partha Laskar, Joykrishna Dey, Sudip Kumar Ghosh
Stimuli-sensitive polymersomes are one of the important vehicles and have been extensively studied as smart drug delivery system. Polymersomes have added advantage over the micelles because of having the ability to carry not only hydrophobic but also hydrophilic guest in their aqueous core. Among various stimuli, the change of pH and redox reaction is very important for drug delivery purpose especially for anticancer drug. Therefore, in this work, two poly(ethylene glycol) methyl ether methacrylate (mPEG) containing hydrophilic random anionic copolymers, poly[(2-hydroxyethyl methacrylate-3,3'-dithiodipropanoic acid)x-co-(poly(ethylene glycol) methyl ether methacrylate)y], poly[(HEMA-DTDPA)x-co-mPEGy] with different copolymer ratios were designed and synthesized...
April 12, 2017: Journal of Colloid and Interface Science
https://www.readbyqxmd.com/read/28432761/protein-s-sulfhydration-by-hydrogen-sulfide-in-cardiovascular-system
#2
REVIEW
Guoliang Meng, Shuang Zhao, Liping Xie, Yi Han, Yong Ji
Hydrogen sulfide (H2 S), independent on any specific transporters, plays a number of biological effects on cardiovascular systems. However, the detailed mechanism of H2 S is not yet clear until now. Recently, a novel post-translational modification induced by H2 S, named S-sulfhydration, has been proposed. S-sulfhydration is a chemical modification on specific cysteine residues of target proteins by H2 S. There are several methods for S-sulfhydration detection, such as modified biotin switch assay, maleimide assay with fluorescent thiol modifying regents, tag-switch method and mass spectrometry...
April 22, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28432648/rationale-for-new-checkpoint-inhibitor-combinations-in-melanoma-therapy
#3
Mario Mandalà, Carlo Tondini, Barbara Merelli, Daniela Massi
The use of monoclonal antibodies that block immunologic checkpoints, which mediate adaptive immune resistance, has revolutionized the treatment of metastatic melanoma patients. Specifically, targeting single immune suppressive molecules such as cytotoxic T lymphocyte-associated protein 4 (CTLA-4), or programmed cell death protein 1 (PD-1) expressed on T cells or its primary ligand, programmed cell death ligand 1 (PD-L1), resulted in pronounced clinical benefit for a subset of melanoma patients. Although single-agent immune checkpoint inhibitor therapy has demonstrated promising clinical activity in metastatic melanoma patients, there is still a significant proportion of patients who show primary resistance to these therapies...
April 21, 2017: American Journal of Clinical Dermatology
https://www.readbyqxmd.com/read/28432532/a-portable-battery-powered-microfluidic-impedance-cytometer-with-smartphone-readout-towards-personal-health-monitoring
#4
Niloy Talukder, Abbas Furniturewalla, Tuan Le, Matthew Chan, Shreyas Hirday, Xinnan Cao, Pengfei Xie, Zhongtian Lin, Azam Gholizadeh, Steve Orbine, Mehdi Javanmard
We present a portable system for personalized blood cell counting consisting of a microfluidic impedance cytometer and portable analog readout electronics, feeding into an analog-to-digital converter (ADC), and being transmitted via Bluetooth to a user-accessible mobile application. We fabricated a microfluidic impedance cytometer with a novel portable analog readout. The novel design of the analog readout, which consists of a lock-in-amplifier followed by a high-pass filter stage for subtraction of drift and DC offset, and a post-subtraction high gain stage, enables detection of particles and cells as small as 1 μm in diameter, despite using a low-end 8-bit ADC...
June 2017: Biomedical Microdevices
https://www.readbyqxmd.com/read/28432258/lil3-a-light-harvesting-complex-protein-links-terpenoid-and-tetrapyrrole-biosynthesis
#5
Daniel Hey, Maxi Rothbart, Josephine Herbst, Peng Wang, Jakob Müller, Daniel Wittmann, Kirsten Gruhl, Bernhard Grimm
LIL3 of Arabidopsis thaliana belongs to the light-harvesting complex (LHC) family, which also includes the light-harvesting chlorophyll-binding proteins of photosystems 1 and 2, the early-light-inducible proteins, PsbS involved in non-photochemical quenching, the one-helix-proteins and their cyanobacterial homologs designated high-light-inducible proteins. Each member of this family is characterized by one or two LHC transmembrane domains (referred to as the LHC motif) to which potential functions such as chlorophyll binding, protein interaction and integration of interacting partners into the plastid membranes have been attributed...
April 21, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28431990/a-common-polymorphism-decreases-lrp1-mrna-stability-and-is-associated-with-increased-plasma-factor-viii-levels
#6
Jiann-Der Lee, Kuang-Ming Hsiao, Pey-Jium Chang, Chih-Cheng Chen, Ya-Wen Kuo, Yen-Chu Huang, Huan-Lin Hsu, Ya-Hui Lin, Chih-Ying Wu, Ying-Chih Huang, Meng Lee, Chia-Yu Hsu, Yi-Ting Pan, Chih-Yu Kuo, Chun-Hsien Lin
The low-density lipoprotein receptor-related protein 1 (LRP1) gene is associated with increased levels of plasma factor VIII (FVIII). We aimed to explore eight functional genetic LRP1 variants for their potential roles in regulating FVIII levels and acute ischemic stroke (AIS). This genetic association study enrolled 192 patients with AIS and 134 controls. There were no significant differences in the genetic frequency of the eight functional single-nucleotide polymorphisms (SNPs) between the control and AIS groups...
April 18, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28431774/limited-compensation-at-the-following-meal-for-protein-and-energy-intake-at-a-lunch-meal-in-healthy-free-living-older-adults
#7
K M Appleton
Various interventions have previously been found to increase protein intakes in older adults, but in free-living individuals, compensation for increased intakes at one meal may easily negate these effects resulting in limited long term benefit. This study investigated the impact of adding sauce to an older person's lunch meal on intakes at that meal, at the following meal and overall (lunch + evening meal). Using a repeated measures design, 52 participants consumed both a lunch meal with sauce and the same lunch meal without sauce on two separate occasions, and intake at this meal and at the following meal were measured...
April 7, 2017: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/28431259/allosteric-regulation-of-metabolism-in-cancer-endogenous-mechanisms-and-considerations-for-drug-design
#8
REVIEW
Jamie A Macpherson, Dimitrios Anastasiou
Alterations in metabolic processes have been linked to various diseases, including cancer. Although gene expression can dictate long-term metabolic adaptation, many metabolic changes found in cancer are associated with altered allosteric properties of the underlying enzymes. Small molecule-protein interactions and intracellular signalling converge to orchestrate these allosteric mechanisms, which, emerging evidence suggests, constitute a promising therapeutic avenue. In this review we focus on glucose and energy metabolism to illustrate the role of allostery in cancer physiology and we discuss approaches to streamline the process of targeting aberrant allosteric pathways with small molecules...
April 18, 2017: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/28431209/drug-delivery-systems-based-on-hydroxyethyl-starch
#9
Constantinos M Paleos, Zili Sideratou, Dimitris Tsiourvas
Τhe advantageous biological properties of hydroxyethyl starch (HES) triggered research interest towards design and synthesis of Drug Delivery Systems (DDSs) based on this polysaccharide. Convenient reaction schemes, including one-step reactions, led to the synthesis of HES conjugates with selected anticancer molecules or therapeutic proteins. Nanocapsules and hydrogels based on HES were also prepared and studied as prospective drug delivery systems. Formulations originating from these drug conjugates and also from nanocapsules and hydrogels loaded with drugs were characterized, highlighting on the extension of their half-life in plasma which is a critical property as far as their efficacy is concerned...
April 21, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28431197/serum-c-reactive-protein-procalcitonin-and-lactate-dehydrogenase-for-the-diagnosis-of-pancreatic-necrosis
#10
REVIEW
Oluyemi Komolafe, Stephen P Pereira, Brian R Davidson, Kurinchi Selvan Gurusamy
BACKGROUND: The treatment of people with pancreatic necrosis differs from that of people with oedematous pancreatitis. It is important to know the diagnostic accuracy of serum C-reactive protein (CRP), serum procalcitonin, and serum lactate dehydrogenase (LDH) as a triage test for the detection of pancreatic necrosis in people with acute pancreatitis, so that an informed decision can be made as to whether the person with pancreatic necrosis needs further investigations such as computed tomography (CT) scan or magnetic resonance imaging (MRI) scan and treatment for pancreatic necrosis started...
April 21, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28431137/trapp-webserver-predicting-protein-binding-site-flexibility-and-detecting-transient-binding-pockets
#11
Antonia Stank, Daria B Kokh, Max Horn, Elena Sizikova, Rebecca Neil, Joanna Panecka, Stefan Richter, Rebecca C Wade
The TRAnsient Pockets in Proteins (TRAPP) webserver provides an automated workflow that allows users to explore the dynamics of a protein binding site and to detect pockets or sub-pockets that may transiently open due to protein internal motion. These transient or cryptic sub-pockets may be of interest in the design and optimization of small molecular inhibitors for a protein target of interest. The TRAPP workflow consists of the following three modules: (i) TRAPP structure- generation of an ensemble of structures using one or more of four possible molecular simulation methods; (ii) TRAPP analysis-superposition and clustering of the binding site conformations either in an ensemble of structures generated in step (i) or in PDB structures or trajectories uploaded by the user; and (iii) TRAPP pocket-detection, analysis, and visualization of the binding pocket dynamics and characteristics, such as volume, solvent-exposed area or properties of surrounding residues...
April 20, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28431131/dnaprodb-an-interactive-tool-for-structural-analysis-of-dna-protein-complexes
#12
Jared M Sagendorf, Helen M Berman, Remo Rohs
Many biological processes are mediated by complex interactions between DNA and proteins. Transcription factors, various polymerases, nucleases and histones recognize and bind DNA with different levels of binding specificity. To understand the physical mechanisms that allow proteins to recognize DNA and achieve their biological functions, it is important to analyze structures of DNA-protein complexes in detail. DNAproDB is a web-based interactive tool designed to help researchers study these complexes. DNAproDB provides an automated structure-processing pipeline that extracts structural features from DNA-protein complexes...
April 20, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28430800/the-burden-of-trisomy-21-disrupts-the-proteostasis-network-in-down-syndrome
#13
Stefanos Aivazidis, Christina M Coughlan, Abhishek K Rauniyar, Hua Jiang, L Alexander Liggett, Kenneth N Maclean, James R Roede
Down syndrome (DS) is a genetic disorder caused by trisomy of chromosome 21. Abnormalities in chromosome number have the potential to lead to disruption of the proteostasis network (PN) and accumulation of misfolded proteins. DS individuals suffer from several comorbidities, and we hypothesized that disruption of proteostasis could contribute to the observed pathology and decreased cell viability in DS. Our results confirm the presence of a disrupted PN in DS, as several of its elements, including the unfolded protein response, chaperone system, and proteasomal degradation exhibited significant alterations compared to euploid controls in both cell and mouse models...
2017: PloS One
https://www.readbyqxmd.com/read/28430779/a-coevolution-analysis-for-identifying-protein-protein-interactions-by-fourier-transform
#14
Changchuan Yin, Stephen S-T Yau
Protein-protein interactions (PPIs) play key roles in life processes, such as signal transduction, transcription regulations, and immune response, etc. Identification of PPIs enables better understanding of the functional networks within a cell. Common experimental methods for identifying PPIs are time consuming and expensive. However, recent developments in computational approaches for inferring PPIs from protein sequences based on coevolution theory avoid these problems. In the coevolution theory model, interacted proteins may show coevolutionary mutations and have similar phylogenetic trees...
2017: PloS One
https://www.readbyqxmd.com/read/28430426/the-rosetta-all-atom-energy-function-for-macromolecular-modeling-and-design
#15
Rebecca Faye Alford, Andrew Leaver-Fay, Jeliazko R Jeliazkov, Matthew J O'Meara, Frank P DiMaio, Hahnbeom Park, Maxim V Shapovalov, P Douglas Renfrew, Vikram Khipple Mulligan, Kalli Kappel, Jason W Labonte, Michael Steven Pacella, Richard Bonneau, Philip Bradley, Roland L Dunbrack, Rhiju Das, David Baker, Brian Kuhlman, Tanja Kortemme, Jeffrey J Gray
Over the past decade, the Rosetta biomolecular modeling suite has informed diverse biological questions and engineering challenges ranging from interpretation of low-resolution structural data to design of nanomaterials, protein therapeutics, and vaccines. Central to Rosetta's success is the energy function: a model parameterized from small molecule and X-ray crystal structure data used to approximate the energy associated with each biomolecule conformation. This paper describes the mathematical models and physical concepts that underlie the latest Rosetta Energy Function, REF15...
April 21, 2017: Journal of Chemical Theory and Computation
https://www.readbyqxmd.com/read/28430394/structure-based-design-of-a-new-scaffold-for-cell-penetrating-peptidic-inhibitors-of-the-histone-demethylase-phf8
#16
Jerzy Dorosz, Lars Olsen, Signe Teuber Seger, Cornelia Steinhauer, Giorgos Bouras, Charlotte Helgstrand, Anders Wiuf, Michael Gajhede
The histone demethylase PHF8 catalyzes demethylation of mono- and di-methylated lysine 9 on histone H3 (H3K9me1/2) and is a transcriptional activator involved in development and cancer. Affinity and specificity of PHF8 towards H3K9me2 substrate is affected by interaction with both the catalytic domain and a PHD reader domain. The latter specifically recognizes tri-methylated lysine 4 on histone H3. A fragment of the histone H3 tail with tri-methylated lysine 4 was used as template for structure based design of a cyclic, cell-penetrating peptide that exhibits micromolar binding affinity to PHF8 in biochemical assays...
April 21, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28430104/dissection-of-the-interaction-between-the-intrinsically-disordered-yap-protein-and-the-transcription-factor-tead
#17
Yannick Mesrouze, Fedir Bokhovchuk, Marco Meyerhofer, Patrizia Fontana, Catherine Zimmermann, Typhaine Martin, Clara Delaunay, Dirk Erdmann, Tobias Schmelzle, Patrick Chène
TEAD (TEA/ATTS domain) transcription factors are the most distal effectors of the Hippo pathway. YAP (Yes-associated protein) is a coactivator protein which, upon binding to TEAD proteins, stimulates their transcriptional activity. Since the Hippo pathway is deregulated in various cancers, designing inhibitors of the YAP:TEAD interaction is an attractive therapeutic strategy for oncology. Understanding the molecular events that take place at the YAP:TEAD interface is therefore important not only to devise drug discovery approaches, but also to gain knowledge on TEAD regulation...
April 21, 2017: ELife
https://www.readbyqxmd.com/read/28429994/ileal-endogenous-losses-in-pigs-feeding-a-protein-free-diet-or-diets-with-different-contents-of-casein-or-crystalline-amino-acids
#18
Matej Brestenský, Soňa Nitrayová, Peter Patráš
The common usage of protein-free diets to estimate unspecific AA losses has been criticised as unphysiological and incorrect. Therefore, in this study different diets were tested for the determination of endogenous losses (EL) of amino acids (AA) and nitrogen (N) assuming a complete absorption in the small intestine. Seven cannulated gilts received a protein-free diet (Diet PF) or diets with 3%, 6% or 10% crude protein (CP) from crystalline AA (Diets CA) or casein (Diets CAS) according to a 7 × 7 Latin square design...
June 2017: Archives of Animal Nutrition
https://www.readbyqxmd.com/read/28429955/matrix-metalloproteinase-8-and-tissue-inhibitor-of-matrix-metalloproteinase-1-predict-incident-cardiovascular-disease-events-and-all-cause-mortality-in-a-population-based-cohort
#19
Immi Kormi, Mikko T Nieminen, Aki S Havulinna, Tanja Zeller, Stefan Blankenberg, Taina Tervahartiala, Timo Sorsa, Veikko Salomaa, Pirkko J Pussinen
Background Extracellular matrix degrading proteases and their regulators play an important role in atherogenesis and subsequent plaque rupture leading to acute cardiovascular manifestations. Design and methods In this prospective cohort study, we investigated the prognostic value of circulating matrix metalloproteinase-8, tissue inhibitor of matrix metalloproteinase-1 concentrations, the ratio of matrix metalloproteinase-8/ tissue inhibitor of matrix metalloproteinase-1 and, for comparison, myeloperoxidase and C-reactive protein concentrations for incident cardiovascular disease endpoints...
January 1, 2017: European Journal of Preventive Cardiology
https://www.readbyqxmd.com/read/28429896/production-of-a-conjugate-between-the-rk346-antigen-from-leishmania-infantum-and-the-horseradish-peroxidase-c-for-the-detection-of-rk346-antibodies
#20
Juan Rengifo-González, Yollyseth Medina-Mora, Sasha Silva-Barrios, María Elizabeth Márquez-Contreras, María Tibisay Ruiz, Ana J Cáceres, Juan Luis Concepción, Wilfredo Quiñones
It was designed and characterized a reporter system to be captured by an- tibodies bound to ELISA plates. The system was designed with the rK346 from Leishmania infantum, a highly antigenic and specific protein. The rK346 was coupled to the horseradish peroxidase C (HRPc) from Armoracia rusticana using glutaraldehyde or sulfo-SMCC. Gluta- raldehyde conjugation was performed in two steps. Separation of conjugates was carried out using a Sepharose S-200 in size exclusion chromatography (SEC); fractions were analyzed via HRPc activity and through ELISA plates sensitized with polyclonal anti-rK346 IgG puri- fied from rabbit serum...
June 2016: Investigación Clínica
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