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https://www.readbyqxmd.com/read/29161763/quantifying-the-relationship-between-inhibition-of-vegfr-2-drug-induced-blood-pressure-elevation-and-hypertension
#1
Teresa Collins, Kelly Gray, Michal Bista, Matt Skinner, Christopher Hardy, Haiyun Wang, Jerome T Mettetal, Alexander R Harmer
BACKGROUND AND PURPOSE: Several anti-angiogenic cancer drugs that inhibit VEGF receptor (VEGFR) signalling for efficacy are associated with a 15-60% incidence of hypertension. Tyrosine kinase inhibitors (TKIs) that have off-target activity at VEGFR-2 may also cause blood pressure elevation as an undesirable side effect. Therefore, the ability to translate VEGFR-2 off-target potency into blood pressure elevation would be useful in development of novel TKIs. EXPERIMENTAL APPROACH: We sought to quantify the relationship between VEGFR-2 inhibition and blood pressure elevation for a range of kinase inhibitors...
November 21, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29161659/lipopolysaccharide-lps-mediated-priming-of-toll-like-receptor-4-enhances-oxidant-induced-prostaglandin-e2-biosynthesis-in-primary-murine-macrophages
#2
Yan Zhang, Orisa J Igwe
Agonists and pseudo-agonists for toll-like receptor 4 (TLR4) are common in our environment. Thus, human exposure to these agents may result in "priming or sensitization" of TLR4. A body of evidence suggests that LPS-mediated sensitization of TLR4 can increase the magnitude of responses to exogenous agents in multiple tissues. We have previously shown that reactive oxygen and nitrogen species (RONS) stimulate TLR4. There is no evidence that LPS-primed TLR4 can influence the magnitude of responses to oxidants from either endogenous or exogenous sources...
November 18, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29161537/association-of-h3k79-monomethylation-an-epigenetic-signature-with-arsenic-induced-skin-lesions
#3
Pritha Bhattacharjee, Somnath Paul, Sandip Bhattacharjee, Ashok K Giri, Pritha Bhattacharjee
Arsenic, a non mutagenic carcinogen, poses a profound health risk upon prolonged exposure. The objective of the study was to analyze the post-translational modifications of the major histone H3 and the associated molecular crosstalk to identify the epigenetic signature of arsenic susceptibility. Herein, we identified significant upregulation of H3K79me1, in individuals with arsenic-induced skin lesion (WSL), and H3K79me1 was found to be regulated by the upstream methyltransferase DOT1L. Moreover, the downstream target molecule 53BP1, a tumor suppressor protein that has a docking preference for H3K79me1 at a site of a double-strand break (DSB), was downregulated, indicating greater DNA damage in the WSL group...
November 14, 2017: Mutation Research
https://www.readbyqxmd.com/read/29161365/genome-scale-analysis-ofescherichia-coliwith-a-comprehensive-prokaryotic-sequence-based-biophysical-model-of-translation-initiation-and-elongation
#4
Gilad Shaham, Tamir Tuller
Translation initiation in prokaryotes is affected by the mRNA folding and interaction of the ribosome binding site with the ribosomal RNA. The elongation rate is affected, among other factors, by the local biophysical properties of the coding regions, the decoding rates of different codons, and the interactions among ribosomes. Currently, there is no comprehensive biophysical model of translation that enables the prediction of mRNA translation dynamics based only on the transcript sequence and while considering all of these fundamental aspects of translation...
November 17, 2017: DNA Research: An International Journal for Rapid Publication of Reports on Genes and Genomes
https://www.readbyqxmd.com/read/29161344/nuclear-localization-of-eif4g3-suggests-a-role-for-the-xy-body-in-translational-regulation-during-spermatogenesis-in-mice
#5
Jianjun Hu, Fengyun Sun, Mary Ann Handel
Eukaryotic translation initiation factor 4G (EIF4G) is an important scaffold protein in the translation initiation complex. In mice mutation of the Eif4g3 gene causes male infertility, with arrest of meiosis at the end of meiotic prophase. This study documents features of the developmental expression and sub-cellular localization of EIF4G3 that might contribute to its highly specific role in meiosis and spermatogenesis. Quite unexpectedly, EIF4G3 is located in the nucleus of spermatocytes, where it is highly enriched in the XY body, the chromatin domain formed by the transcriptionally inactive sex chromosomes...
November 17, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/29161176/translation-and-cultural-adaptation-of-the-japanese-version-of-the-interprofessional-facilitation-scale
#6
Junji Haruta, Raoul Breugelmans, Hiroshi Nishigori
Effective interaction in interprofessional collaboration requires skills in interprofessional facilitation. The need for interprofessional learning and practice in Japan is highlighted by Japan's status as one of the most rapidly aging societies because good care for elderly people with complex needs requires effective collaboration between different professional groups. The development of interprofessional facilitation skills (including management of the additional complexities) among learners or professionals enhances interprofessional learning and consensus building and empowers them to make appropriate commitments when faced with difficult challenges...
November 21, 2017: Journal of Interprofessional Care
https://www.readbyqxmd.com/read/29161091/dealing-with-stress-defective-metabolic-adaptation-in-chronic-obstructive-pulmonary-disease-pathogenesis
#7
Charalambos Michaeloudes, Pankaj K Bhavsar, Sharon Mumby, Kian Fan Chung, Ian M Adcock
The mitochondrion is the main site of energy production and a hub of key signaling pathways. It is also central in stress-adaptive response due to its dynamic morphology and ability to interact with other organelles. In response to stress, mitochondria fuse into networks to increase bioenergetic efficiency and protect against oxidative damage. Mitochondrial damage triggers segregation of damaged mitochondria from the mitochondrial network through fission and their proteolytic degradation by mitophagy. Post-translational modifications of the mitochondrial proteome and nuclear cross-talk lead to reprogramming of metabolic gene expression to maintain energy production and redox balance...
November 2017: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/29161047/mapping-extracellular-matrix-proteins-in-formalin-fixed-paraffin-embedded-tissues-by-maldi-imaging-mass-spectrometry
#8
Peggi M Angel, Susana Comte-Walters, Lauren E Ball, Kacey Talbot, Anand Mehta, Kelvin G M Brockbank, Richard R Drake
Collagens and elastin form the fundamental framework of all tissues and organs and their expression and post-translational processing are tightly regulated in disease and health. Due to their unique structural composition and properties, it is a recognized challenge to access these protein structures within the complex tissue microenvironment to understand how localized changes modulate tissue health. We describe a new workflow using a combination of matrix-assisted laser desorption /ionization imaging mass spectrometry (MALDI IMS) with collagenase and matrix metalloproteinase (MMP) enzymes to access and report on spatial localization of collagen and elastin sequences in formalin-fixed, paraffin-embedded (FFPE) tissues...
November 21, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/29161028/exploring-the-active-centre-of-lsd1-corest-complex-by-molecular-dynamics-simulation-utilizing-its-co-crystallized-cofactor-tetrahydrofolate-as-a-probe
#9
Waleed A A Zalloum, Hiba M Zalloum
Epigenetic targeting of cancer is a recent era to manipulate the gene without destroying the genetic material. Lysine-specific demethylase 1 (LSD1) is one of the enzymes associated with the chromatin for post-translational modifications, where it demethylates lysine amino acid in the chromatin H3 tail. Many studies showed that inhibiting LSD1 could potentially be used to treat cancer epigenetically. LSD1 is associated with its corepressor protein CoREST, and uses tetrahydrofolate as a cofactor to accept CH2 from the demethylation process...
November 21, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/29161012/top-down-proteomics-ready-for-prime-time
#10
Bifan Chen, Kyle A Brown, Ziqing Lin, Ying Ge
In the post-genomics era, the study of proteins is critical for understanding cellular functions at the molecular level.1-5 Beyond the genetic code, the human proteome is greatly diversified by various genetic variations, alternative splicing of RNA transcripts, and post-translational modifi-cations (PTMs).6,7 In 2013, the term "proteoform" was designated to describe "all of the different molecular forms in which the protein product of a single gene can be found",6 clearing up the confusion in nomenclature and joining research efforts to develop methodologies for pro-teoform characterization...
November 21, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/29160910/epithelial-disruptions-but-not-immune-cell-invasion-induced-secretory-dysfunction-following-innate-immune-activation-in-a-novel-model-of-acute-salivary-gland-injury
#11
Abeer Shaalan, Guy Carpenter, Gordon Proctor
BACKGROUND: Salivary gland (SG) injurious agents are all translated into loss of salivation (xerostomia). An association has been established between activation of innate immunity and salivary gland injury and dysfunction. However, it remains unclear how the secretory epithelia respond by halting saliva production. METHODS: C57BL/6 submandibular glands (SMGs) were acutely challenged using a single dose of the innate immune stimulant: polyinosinic-polycytidylic acid (poly (I:C))...
November 21, 2017: Journal of Oral Pathology & Medicine
https://www.readbyqxmd.com/read/29160822/how-secondary-and-tertiary-amide-moieties-are-molecular-stations-for-dibenzo-24-crown-8-in-2-rotaxane-molecular-shuttles
#12
Benjamin Riss-Yaw, Justine Morin, Caroline Clavel, Frédéric Coutrot
Interlocked molecular machines like [2]rotaxanes are intriguing aesthetic molecules. The control of the localization of the macrocycle, which surrounds a molecular axle, along the thread leads to translational isomers of very different properties. Although many moieties have been used as sites of interactions for crown ethers, the very straightforwardly obtained amide motif has more rarely been envisaged as molecular station. In this article, we report the use of secondary and tertiary amide moieties as efficient secondary molecular station in pH-sensitive molecular shuttles...
November 21, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29160808/interplay-between-colistin-resistance-virulence-and-fitness-in-acinetobacter-baumannii
#13
REVIEW
Gabriela Jorge Da Silva, Sara Domingues
Acinetobacter baumannii is an important opportunistic nosocomial pathogen often resistant to multiple antibiotics classes. Colistin, an "old" antibiotic, is now considered a last-line treatment option for extremely resistant isolates. In the meantime, resistance to colistin has been reported in clinical A. baumannii strains. Colistin is a cationic peptide that disrupts the outer membrane (OM) of Gram-negative bacteria. Colistin resistance is primarily due to post-translational modification or loss of the lipopolysaccharide (LPS) molecules inserted into the outer leaflet of the OM...
November 21, 2017: Antibiotics
https://www.readbyqxmd.com/read/29160707/molecular-structure-inhibiting-synergism-in-charged-surfactant-mixtures-an-atomistic-molecular-dynamics-simulation-study
#14
Gözde Ergin, Mária Lbadaoui-Darvas, Satoshi Takahama
Synergistic and non-synergistic surfactant-water mixtures of sodium dodecyl sulfate (SDS), lauryl betaine (C12B) and cocoamidopropyl betaine (CAPB) systems are studied using molecular simulation to understand the role of interactions among headgroups, tailgroups, and water on structural and thermodynamic properties at the air-water interface. SDS is an anionic surfactant while C12B and CAPB are zwitterionic; CAPB differs from C12B by an amide group in the tail. While the lowest surface tensions at high surface concentrations in the SDS-C12B synergistic system could not be reproduced by simulation, estimated partitioning between surface and bulk show trends consistent with synergism...
November 21, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/29160602/mitochondrial-ribosome-bl34-mutants-present-diminished-translation-of-cytochrome-c-oxidase-subunits
#15
Raquel Fonseca Guedes-Monteiro, José Ribamar Ferreira-Junior, Lucas Bleicher, Francisco G Nóbrega, Antoni Barrientos, Mario H Barros
Saccharomyces cerevisiae mitoribosomes are specialized in the translation of a few number of highly hydrophobic membrane proteins, components of the oxidative phosphorylation system. Mitochondrial characteristics, such as the membrane system and its redox state driven mitoribosomes evolution through great diversion from their bacterial and cytosolic counterparts. Therefore, mitoribosome presents a considerable number of mitochondrial-specific proteins, as well as new protein extensions. In this work we characterize temperature sensitive mutants of the subunit bL34 present in the 54S large subunit...
November 21, 2017: Cell Biology International
https://www.readbyqxmd.com/read/29160600/current-evidence-of-cannabinoid-based-analgesia-obtained-in-preclinical-and-human-experimental-settings
#16
REVIEW
J Lötsch, I Weyer-Menkhoff, I Tegeder
Cannabinoids have a long record of recreational and medical use and become increasingly approved for pain therapy. This development is based on preclinical and human experimental research summarized in this review. Cannabinoid CB1 receptors are widely expressed throughout the nociceptive system. Their activation by endogenous or exogenous cannabinoids modulates the release of neurotransmitters. This is reflected in antinociceptive effects of cannabinoids in preclinical models of inflammatory, cancer and neuropathic pain, and by nociceptive hypersensitivity of cannabinoid receptor-deficient mice...
November 21, 2017: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/29160489/cross-cultural-adaptation-of-the-filial-responsibility-protocol-for-use-in-brazil
#17
Marines Aires, Fernanda Laís Fengler Dal Pizzol, Duane Mocellin, Idiane Rosset, Eliane Pinheiro de Morais, Lisiane Manganelli Girardi Paskulin
OBJECTIVE: To carry out a cross-cultural adaptation of the Filial Responsibility protocol for use in Brazil with adult child caregivers for elderly parents. METHOD: A methodological study that included the steps of initial translation, synthesis of translations, back-translation, committee of experts, pre-test, evaluation of psychometric measures and submission to authors. The protocol comprises a qualitative step, closed questions and seven scales: Filial Expectation, Subsidiary Compassion, Caregiver burden, Life Satisfaction, Personal Well-being and Quality of Relationships...
November 2017: Revista Brasileira de Enfermagem
https://www.readbyqxmd.com/read/29160476/cultural-adaptation-of-the-end-stage-renal-disease-adherence-questionnaire-for-hemodialysis-patients
#18
Silvia Maria de Sá Basilio Lins, Josete Luzia Leite, Simone de Godoy, Patrícia Dos Santos Claro Fuly, Silvia Teresa Carvalho de Araújo, Ítalo Rodolfo Silva
OBJECTIVE: To describe the stages in the cultural adaptation of "The End-Stage Renal Disease Adherence Questionnaire" for use in Brazil. METHOD: A descriptive, transversal study with a quantitative approach. The cultural adaptation followed the steps of translation, professional committee, back translation, panel of patients and pretest. RESULTS: the translation stage created a version in Portuguese that was analyzed by specialists, who suggested alterations in the title, seven sentences in the questions and three sets of answers...
November 2017: Revista Brasileira de Enfermagem
https://www.readbyqxmd.com/read/29160431/classification-of-deaths-in-women-with-human-immunodeficiency-virus-acquired-immunodeficiency-syndrome-in-pregnancy-and-childbirth
#19
Manuella Coutinho Brayner, Sandra Valongueiro Alves
OBJECTIVE: To reclassify deaths of women infected with the human immunodeficiency virus/acquired immunodeficiency syndrome in pregnancy and childbirth in the State of Pernambuco, Brazil, from 2000 to 2010. METHODS: A descriptive exploratory study, developed from the following steps: translation to Portuguese of the item "HIV and aids" of the United Nations document "The WHO application of ICD-10 to deaths during pregnancy, childbirth and the puerperium: DCI MM 2012"; development of a classification algorithm of deaths of women living with the human immunodeficiency virus/acquired immunodeficiency syndrome in pregnancy and childbirth; and reclassification of deaths by a group of experts...
July 2017: Revista Brasileira de Epidemiologia, Brazilian Journal of Epidemiology
https://www.readbyqxmd.com/read/29160381/quality-of-communication-questionnaire-for-copd-patients-receiving-palliative-care-translation-and-cross-cultural-adaptation-for-use-in-brazil
#20
Flávia Del Castanhel, Suely Grosseman
OBJECTIVE: To translate the Quality of Communication Questionnaire (QOC) to Portuguese and adapt it for use in Brazil in COPD patients receiving palliative care. METHODS: After approval from the first author of the original QOC and the local research ethics committee, the original, 13-item version of the questionnaire was independently translated to Brazilian Portuguese by two Brazilian translators fluent in English. The two translations were analyzed by a bilingual physician and the two Brazilian translators, who reached a consensus and produced another Portuguese version of the QOC...
September 2017: Jornal Brasileiro de Pneumologia: Publicaça̋o Oficial da Sociedade Brasileira de Pneumologia e Tisilogia
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