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https://www.readbyqxmd.com/read/28822279/chemical-synthesis-of-guanosine-diphosphate-mannuronic-acid-gdp-mana-and-its-c-4-o-methyl-and-c-4-deoxy-congeners
#1
Qingju Zhang, P Lynne Howell, Herman S Overkleeft, Dmitri V Filippov, Gijsbert A van der Marel, Jeroen D C Codée
Described is the first synthesis of guanosine diphosphate mannuronic acid (GDP-ManA), the sugar donor used by algae and bacteria for the production of alginate, an anionic polysaccharide composed of β-d-mannuronic acid (ManA) and α-l-guluronic acid (GulA). Understanding the biosynthesis of these polyanionic polysaccharides on the molecular level, opens up avenues to use and modulate the biosynthesis machinery for biotechnological and therapeutic applications. The synthesis reported here delivers multi-milligram amounts of the GDP-ManA donor that can be used to study the polymerase (Alg8 in Pseudomonas aeruginosa) that generates the poly-ManA chain...
August 11, 2017: Carbohydrate Research
https://www.readbyqxmd.com/read/28818364/involvement-of-schrabgdi1-from-solanum-chilense-in-endocytic-trafficking-and-tolerance-to-salt-stress
#2
Alex San Martín-Davison, Ricardo Pérez-Díaz, Flavia Soto, José Madrid-Espinoza, Enrique González-Villanueva, Lorena Pizarro, Lorena Norambuena, Jaime Tapia, Hiromi Tajima, Eduardo Blumwald, Simón Ruiz-Lara
Physiological responses of plants to salinity stress requires the coordinated activation of many genes. A salt-induced gene was isolated from roots of the wild tomato species Solanum chilense and named SchRabGDI1 because it encodes a protein with high identity to GDP dissociation inhibitors of plants. These proteins are regulators of the RabGTPase cycle that play key roles in intracellular vesicular trafficking. The expression pattern of SchRabGDI1 showed an early up-regulation in roots and leaves under salt stress...
October 2017: Plant Science: An International Journal of Experimental Plant Biology
https://www.readbyqxmd.com/read/28812835/impact-of-health-research-systems-on-under-5-mortality-rate-a-trend-analysis
#3
Bahareh Yazdizadeh, Mahboubeh Parsaeian, Reza Majdzadeh, Sima Nikooee
BACKGROUND: Between 1990 and 2015, under-5 mortality rate (U5MR) declined by 53%, from an estimated rate of 91 deaths per 1000 live births to 43, globally. The aim of this study was to determine the share of health research systems in this decrease alongside other influential factors. METHODS: We used random effect regression models including the 'random intercept' and 'random intercept and random slope' models to analyze the panel data from 1990 to 2010. We selected the countries with U5MRs falling between the first and third quartiles in 1990...
November 26, 2016: International Journal of Health Policy and Management
https://www.readbyqxmd.com/read/28812834/cost-effectiveness-of-rural-incentive-packages-for-graduating-medical-students-in-lao-pdr
#4
Eric Keuffell, Wanda Jaskiewicz, Khampasong Theppanya, Kate Tulenko
BACKGROUND: The dearth of health workers in rural settings in Lao People's Democratic Republic (PDR) and other developing countries limits healthcare access and outcomes. In evaluating non-wage financial incentive packages as a potential policy option to attract health workers to rural settings, understanding the expected costs and effects of the various programs ex ante can assist policy-makers in selecting the optimal incentive package. METHODS: We use discrete choice experiments (DCEs), costing analyses and recent empirical results linking health worker density and health outcomes to estimate the future location decisions of physicians and determine the cost-effectiveness of 15 voluntary incentives packages for new physicians in Lao PDR...
October 29, 2016: International Journal of Health Policy and Management
https://www.readbyqxmd.com/read/28809931/the-cost-of-entry-an-analysis-of-pharmaceutical-registration-fees-in-low-middle-and-high-income-countries
#5
Steven G Morgan, Brandon Yau, Murray M Lumpkin
BACKGROUND: Advances in pharmaceuticals offer improved health outcomes for a wide range of illnesses, yet medicines are often inaccessible for many patients worldwide. One potential barrier to making medicines available to all is the cost of product registration, the fees for regulatory review and licensing for the sale of medicines beyond the cost of clinical trials, if needed. METHODS AND FINDINGS: We performed a cross-sectional analysis of pharmaceutical registration fees in low-, middle-, and high-income countries...
2017: PloS One
https://www.readbyqxmd.com/read/28803992/p-rex1-amplification-promotes-progression-of-cutaneous-melanoma-via-the-pak1-p38-mmp-2-pathway
#6
Jinhua Wang, Hajime Hirose, Guanhua Du, Kelly Chong, Eiji Kiyohara, Isaac P Witz, Dave S B Hoon
P-REX1 (PIP3-dependent Rac exchange factor-1) is a guanine nucleotide exchange factor that activates Rac by catalyzing exchange of GDP for GTP bound to Rac. Aberrant up-regulation of P-REX1 expression has a role in metastasis however, copy number (CN) and function of P-REX1 in cutaneous melanoma are unclear. To explore the role of P-REX1 in melanoma, SNP 6.0 and Exon 1.0 ST microarrays were assessed. There was a higher CN (2.82-fold change) of P-REX1 in melanoma cells than in melanocytes, and P-REX1 expression was significantly correlated with P-REX1 CN...
August 10, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28798252/pollen-induced-oxidative-dna-damage-response-regulates-mirnas-controlling-allergic-inflammation
#7
Leopoldo Aguilera-Aguirre, Wenjing Hao, Lang Pan, Xiaoxue Li, Alfredo Saavedra-Molina, Attila Bacsi, Zsolt Radak, Sanjiv Sur, Allan R Brasier, Xueqing Ba, Istvan Boldogh
A mucosal oxidative burst is a hallmark response to pollen exposure that promotes allergic inflammatory responses. Reactive species constituents of oxidative stress signal via the modification of cellular molecules including nucleic acids. One of the most abundant oxidative genomic base damage is 8-oxo-7,8-dihydroguanine (8-oxoG), which is removed from DNA by 8-oxoguanine DNA glycosylase1 (OGG1). OGG1 in complex with 8-oxoG acts as a GDP-GTP exchange factor and induces acute inflammation; however, the mechanism(s) by which OGG1 signaling regulates allergic airway inflammation is not known...
August 10, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28796563/indirect-costs-of-diabetes-and-its-impact-on-the-public-finance-the-case-of-poland
#8
Andrzej Torój, Aneta Mela
BACKGROUND: Growing public and private expenditure on healthcare results i.a. from the spreading of chronic diseases. Diabetes belongs to the most frequent ones, beyond neoplasms and cardiological diseases, and hence generates a significant burden for the public finance in terms of the direct costs, leading e.g. to the occurrence of opportunity cost of missed public investment. However, the economy suffers also from the indirect cost of diabetes that manifests itself in the loss in Gross Domestic Product (GDP) and general government revenues...
August 10, 2017: Expert Review of Pharmacoeconomics & Outcomes Research
https://www.readbyqxmd.com/read/28795341/adjuvant-trastuzumab-therapy-for-early-her2-positive-breast-cancer-in-iran-a-cost-effectiveness-and-scenario-analysis-for-an-optimal-treatment-strategy
#9
Amir Ansaripour, Carin A Uyl-de Groot, W Ken Redekop
INTRODUCTION: Clinical guidelines have recommended a 1-year trastuzumab regimen as standard care for early human epidermal growth factor receptor 2 (HER2)-positive breast cancer; however, this recommendation can have a dramatic impact on total drug expenditures in middle-income countries (MICs). We performed a cost-effectiveness analysis from the Iranian healthcare perspective to find an optimum duration of trastuzumab use in Iran. METHOD: We compared four treatment strategies comprising chemotherapy and varying durations of trastuzumab use (no trastuzumab, 6, 9 months, and 1 year), and a Markov model and probabilistic sensitivity analysis were used to estimate the costs and effects of the strategies...
August 9, 2017: PharmacoEconomics
https://www.readbyqxmd.com/read/28792956/projected-climate-change-threatens-pollinators-and-crop-production-in-brazil
#10
Tereza Cristina Giannini, Wilian França Costa, Guaraci Duran Cordeiro, Vera Lucia Imperatriz-Fonseca, Antonio Mauro Saraiva, Jacobus Biesmeijer, Lucas Alejandro Garibaldi
Animal pollination can impact food security since many crops depend on pollinators to produce fruits and seeds. However, the effects of projected climate change on crop pollinators and therefore on crop production are still unclear, especially for wild pollinators and aggregate community responses. Using species distributional modeling, we assessed the effects of climate change on the geographic distribution of 95 pollinator species of 13 Brazilian crops, and we estimated their relative impacts on crop production...
2017: PloS One
https://www.readbyqxmd.com/read/28792949/does-environmental-policy-affect-scaling-laws-between-population-and-pollution-evidence-from-american-metropolitan-areas
#11
Nicholas Z Muller, Akshaya Jha
Modern cities are engines of production, innovation, and growth. However, urbanization also increases both local and global pollution from household consumption and firms' production. Do emissions change proportionately to city size or does pollution tend to outpace or lag urbanization? Do emissions scale differently with population versus economic growth or are emissions, population, and economic growth inextricably linked? How are the scaling relationships between emissions, population, and economic growth affected by environmental regulation? This paper examines the link between urbanization, economic growth and pollution using data from Metropolitan Statistical Areas (MSAs) in the United States between 1999 and 2011...
2017: PloS One
https://www.readbyqxmd.com/read/28776959/development-of-substrate-derived-mechanistic-sirtuin-inhibitors-with-potential-anti-cancer-activity
#12
Michael Lammers, Nora Kuhlmann, Linda Baldus, Ines Neundorf, Constance Chollet
RhoGDIα is a key regulator for Rho-proteins coordinating their GTP/GDP- and membrane/cytosol-cycle. Recently, it was demonstrated by quantitative mass spectrometry that RhoGDIα is heavily targeted by post-translational lysine-acetylation. For one site in its N-terminal domain, namely K52, we reported that acetylation completely switches off RhoGDIα function. Here, we show that K52-acetylated RhoGDIα is specifically deacetylated by the sirtuin deacetylase Sirt2.. We show that acetylation at K52 decelerates cervical cancer cell proliferation, suggesting RhoGDIα acetylation to be a promising therapeutic target...
August 4, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28775002/kindlin-2-association-with-rho-gdp-dissociation-inhibitor-%C3%AE-suppresses-rac1-activation-and-podocyte-injury
#13
Ying Sun, Chen Guo, Ping Ma, Yumei Lai, Fan Yang, Jun Cai, Zhehao Cheng, Kuo Zhang, Zhongzhen Liu, Yeteng Tian, Yue Sheng, Ruijun Tian, Yi Deng, Guozhi Xiao, Chuanyue Wu
Alteration of podocyte behavior is critically involved in the development and progression of many forms of human glomerular diseases. The molecular mechanisms that control podocyte behavior, however, are not well understood. Here, we investigated the role of Kindlin-2, a component of cell-matrix adhesions, in podocyte behavior in vivo Ablation of Kindlin-2 in podocytes resulted in alteration of actin cytoskeletal organization, reduction of the levels of slit diaphragm proteins, effacement of podocyte foot processes, and ultimately massive proteinuria and death due to kidney failure...
August 3, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28771021/income-redistribution-predicts-greater-life-satisfaction-across-individual-national-and-cultural-characteristics
#14
Felix Cheung
The widening income gap between the rich and the poor has important social implications. Governmental-level income redistribution through tax and welfare policies presents an opportunity to reduce income inequality and its negative consequences. The current longitudinal studies examined whether within-region changes in income redistribution over time relate to life satisfaction. Moreover, I examined potential moderators of this relationship to test the strong versus weak hypotheses of income redistribution...
August 3, 2017: Journal of Personality and Social Psychology
https://www.readbyqxmd.com/read/28767722/cost-effectiveness-analysis-of-population-based-tobacco-control-strategies-in-the-prevention-of-cardiovascular-diseases-in-tanzania
#15
Frida Ngalesoni, George Ruhago, Mary Mayige, Tiago Cravo Oliveira, Bjarne Robberstad, Ole Frithjof Norheim, Hideki Higashi
BACKGROUND: Tobacco consumption contributes significantly to the global burden of disease. The prevalence of smoking is estimated to be increasing in many low-income countries, including Tanzania, especially among women and youth. Even so, the implementation of tobacco control measures has been discouraging in the country. Efforts to foster investment in tobacco control are hindered by lack of evidence on what works and at what cost. AIMS: We aim to estimate the cost and cost-effectiveness of population-based tobacco control strategies in the prevention of cardiovascular diseases (CVD) in Tanzania...
2017: PloS One
https://www.readbyqxmd.com/read/28760338/structural-dynamics-of-gi%C3%AE-protein-revealed-by-single-molecule-fret
#16
Yongping Zhu, Lei Zhang, Xuejun C Zhang, Yongfang Zhao
The heterotrimeric G proteins (Gαβγ) act as molecular switches to mediate signal transduction from G protein-coupled receptors to downstream effectors. Upon interaction with an activated receptor, G protein exchanges its bound GDP with GTP, stimulating downstream signal transmission. Release of GDP requires a structural rearrangement between the GTPase domain and helical domain of the Gα subunit. Here, we used single molecule fluorescence resonance energy transfer (smFRET) technique to study the conformational dynamics of these two domains in the apo state and in the binding of different ligands...
July 29, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28754887/antisymmetry-of-oceanic-eddies-across-the-kuroshio-over-a-shelfbreak
#17
Yu Liu, Changming Dong, Xiaohui Liu, Jihai Dong
From the analysis of oceanic eddies detected in the drifter trajectories of the Global Drifter Program (GDP) data set, it was found that oceanic eddies are asymmetrically distributed across the Kuroshio in the East China Sea: predominant cyclonic (anticyclonic) eddies are on the western (eastern) sides of Kuroshio. This distribution is confirmed by high-resolution numerical modeling output as well. Most of these eddies are 5~20 km in radius, less than the local first baroclinic deformation radius, thus categorized as submesoscale...
July 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28749644/the-cost-effectiveness-of-quadrivalent-human-papillomavirus-vaccination-in-indonesia
#18
Soewarta Kosen, Andrijono Andrijono, Dwiana Ocviyanti, Wresti Indriatmi
Objective: National cervical cancer prevention program has been initiated in Indonesia since April 2015 and the ministry of health has started efforts to integrate the HPV Vaccine in the national immunization program since Q4 2015. Thus, it becomes important to analyze the cost-effectiveness of HPV vaccine. The objective of this model is to examine the potential long-term epidemiologic and economic impact of quadrivalent HPV(qHPV;6/11/16/18) vaccination program in Indonesia. Methods: A previously validated transmission dynamic model was used to estimate the long-term epidemiologic and economic consequences of quadrivalent HPV vaccination by comparing cost-effectiveness of 2 dose qHPV vaccination strategy for girls 11-12 years old (with or without catch up; catch up dose for 12–26 years) versus Screening Only (Pap Smear) for reducing cost related to HPV type 6,11,16,18 (cervical cancer, CIN 1, CIN 2/3, and genital warts)...
July 27, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28747695/compounds-that-enhance-the-tailing-activity-of-moloney-murine-leukemia-virus-reverse-transcriptase
#19
Yoshiyuki Ohtsubo, Yuji Nagata, Masataka Tsuda
In a previous study, we showed that MMLV-RT has a strong terminal transferase activity, and that the C-, G-, and T-tailing activities are enhanced by dGMP, dCMP, and dAMP, respectively. In this study, to achieve faster reaction and higher tailing efficiency, we screened other compounds for the ability to enhance the tailing activities of MMLV-RT, and determined the corresponding optimal concentrations. The C-, G-, and T-tailing activities were enhanced by guanine, cytosine, and adenine, respectively, and by derivatives thereof, suggesting a transient Watson-Click base pairing between an enhancer molecule and the nucleotide to be incorporated...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28743912/structural-basis-for-dolichylphosphate-mannose-biosynthesis
#20
Rosaria Gandini, Tom Reichenbach, Tien-Chye Tan, Christina Divne
Protein glycosylation is a critical protein modification. In biogenic membranes of eukaryotes and archaea, these reactions require activated mannose in the form of the lipid conjugate dolichylphosphate mannose (Dol-P-Man). The membrane protein dolichylphosphate mannose synthase (DPMS) catalyzes the reaction whereby mannose is transferred from GDP-mannose to the dolichol carrier Dol-P, to yield Dol-P-Man. Failure to produce or utilize Dol-P-Man compromises organism viability, and in humans, several mutations in the human dpm1 gene lead to congenital disorders of glycosylation (CDG)...
July 25, 2017: Nature Communications
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