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Maxim Igaev, Helmut Grubmüller
Microtubules (MTs) are key components of the cytoskeleton and play a central role in cell division and development. MT assembly is known to be associated with a structural change in αβ-tubulin dimers from kinked to straight conformations. How GTP binding renders individual dimers polymerization-competent, however, is still unclear. Here, we have characterized the conformational dynamics and energetics of unassembled tubulin using atomistic molecular dynamics and free energy calculations. Contradictory to existing allosteric and lattice models, we find that GTP-tubulin favors a broad range of almost isoenergetic curvatures, whereas GDP-tubulin has a much lower bending flexibility...
April 13, 2018: ELife
Huiming Zhu, Hang Xia, Yawei Guo, Cheng Peng
This paper empirically examines the effects of urbanization and income inequality on CO2 emissions in the BRICS economies (i.e., Brazil, Russia, India, China, and South Africa) during the periods 1994-2013. The method we used is the panel quantile regression, which takes into account the unobserved individual heterogeneity and distributional heterogeneity. Our empirical results indicate that urbanization has a significant and negative impact on carbon emissions, except in the 80th , 90th , and 95th quantiles...
April 12, 2018: Environmental Science and Pollution Research International
Ana Iolanda Voda, Ionel Bostan
Expenditure and financing aspects in the healthcare system in general, and in cancer care in particular, are subjects of increasing concern to the medical community. Nowadays, it is imperative for the healthcare system to respond to the challenge of universal access to quality healthcare, by measuring the financial resources within the healthcare sector. The purpose of this review is to highlight the major gaps in the healthcare expenditures for all types of care, as well as on cancer and anti-cancer drugs across 28 European Union member states...
April 12, 2018: Cancers
Pedro A Laires, Helena Canhão, Ana M Rodrigues, Mónica Eusébio, Miguel Gouveia, Jaime C Branco
BACKGROUND: Osteoarthritis (OA) is a leading cause of pain and disability, which may be a source of productivity losses. The objectives of this study were to describe the impact of OA, namely through pain and physical disability, on early exit from work and to calculate its economic burden. METHODS: We analysed data from the national, cross-sectional, population-based EpiReumaPt study (Sep2011-Dec2013) in which 10,661 individuals were randomly surveyed in order to capture all cases of rheumatic diseases...
April 11, 2018: BMC Public Health
Miriam Schöpel, Oleksandr Shkura, Jana Seidel, Klaus Kock, Xueyin Zhong, Stefanie Löffek, Iris Helfrich, Hagen S Bachmann, Jürgen Scherkenbeck, Christian Herrmann, Raphael Stoll
The protein family of small GTPases controls cellular processes by acting as a binary switch between an active and an inactive state. The most prominent family members are H-Ras, N-Ras, and K-Ras isoforms, which are highly related and frequently mutated in cancer. Bisphenols are widespread in modern life because of their industrial application as plasticisers. Bisphenol A (BPA) is the best-known member and has gained significant scientific as well as public attention as an endocrine disrupting chemical, a fact that eventually led to its replacement...
April 10, 2018: International Journal of Molecular Sciences
Qi Hu, Kevan M Shokat
The single most frequent cancer-causing mutation across all heterotrimeric G proteins is R201C in Gαs. The current model explaining the gain-of-function activity of the R201 mutations is through the loss of GTPase activity and resulting inability to switch off to the GDP state. Here, we find that the R201C mutation can bypass the need for GTP binding by directly activating GDP-bound Gαs through stabilization of an intramolecular hydrogen bond network. Having found that a gain-of-function mutation can convert GDP into an activator, we postulated that a reciprocal mutation might disrupt the normal role of GTP...
April 1, 2018: Cell
P V Mc Crory
The British Orthodontic Society (BOS) recently published a number of news articles aimed at drawing attention to its 'Hold that Smile' campaign which promotes lifelong retainer wear. The BOS's stated intention is to 'generate a viral #HoldthatSmile campaign in order to build awareness of its message that retainers are for life'. The campaign also seeks to recruit the support of GDPs and DCPs, including nurses, in motivating patients to wear retainers for life. It suggests that orthodontists and GDPs need to work collaboratively and suggests that dentists would need to check patients are taking care of their retainers over the long term...
April 6, 2018: British Dental Journal
Nicole Bates, Emily Callander, Daniel Lindsay, Kerrianne Watt
BACKGROUND: In Australia, 40% of people diagnosed with cancer will be of working age (25-64 years). A cancer diagnosis may lead to temporary or permanent changes in a person's labour force participation, which has an economic impact on both the individual and the economy. However, little is known about this economic impact of cancer due to lost productivity in Australia. This paper aims to determine the labour force participation characteristics of people with cancer, to estimate the indirect cost due to lost productivity, and to identify any inequality in the distribution of labour force absence in Australia...
April 6, 2018: BMC Public Health
Kenneth A Freedberg, Nagalingeswaran Kumarasamy, Ethan D Borre, Eric L Ross, Kenneth H Mayer, Elena Losina, Soumya Swaminathan, Timothy P Flanigan, Rochelle P Walensky
Current Indian guidelines recommend twice-annual CD4 testing to monitor first-line antiretroviral therapy (ART), with a plasma HIV RNA test to confirm failure if CD4 declines, which would prompt a switch to second-line ART. We used a mathematical model to assess the clinical benefits and cost-effectiveness of alternative laboratory monitoring strategies in India. We simulated a cohort of HIV-infected patients initiating first-line ART and compared 11 strategies with combinations of CD4 and HIV RNA testing at varying frequencies...
March 12, 2018: AIDS Research and Human Retroviruses
Yaping Zhang, Xinfeng Wang, Yifei Liu, Chunfeng Sun, Wenyu Shi, Hongming Huang
CD5-positive (CD5+) diffuse large B-cell lymphoma (DLBCL) is associated with poor survival compared with CD5-negative DLBCL. The clinical characteristics of CD5+ DLBCL are different from both CD5-negative DLBCL and other CD5+ B cell lymphomas. There is currently no promising chemotherapy for CD5+ DLBCL. Herein, we report a 49-year-old Asian male with refractory CD5+ DLBCL. He complained of aggravated abdominal pain and weight loss. Computed tomography scan revealed abdominal masses, widespread lymphadenopathy, splenomegaly, and intussusception of the ileocecal junction with bowel wall thickening...
April 3, 2018: Cancer Biology & Therapy
Felix Pretis, Moritz Schwarz, Kevin Tang, Karsten Haustein, Myles R Allen
Empirical evidence suggests that variations in climate affect economic growth across countries over time. However, little is known about the relative impacts of climate change on economic outcomes when global mean surface temperature (GMST) is stabilized at 1.5°C or 2°C warming relative to pre-industrial levels. Here we use a new set of climate simulations under 1.5°C and 2°C warming from the 'Half a degree Additional warming, Prognosis and Projected Impacts' (HAPPI) project to assess changes in economic growth using empirical estimates of climate impacts in a global panel dataset...
May 13, 2018: Philosophical Transactions. Series A, Mathematical, Physical, and Engineering Sciences
Pradeep Bandaru, Yasushi Kondo, John Kuriyan
The guanine-nucleotide exchange factor (GEF) Son-of-Sevenless (SOS) plays a critical role in metazoan signaling by converting Ras•GDP (guanosine diphosphate) to Ras•GTP (guanosine triphosphate) in response to tyrosine kinase activation. Structural studies have shown that SOS differs from other Ras-specific GEFs in that SOS is itself activated by Ras•GTP binding to an allosteric site, distal to the site of nucleotide exchange. The activation of SOS involves membrane recruitment and conformational changes, triggered by lipid binding, that open the allosteric binding site for Ras•GTP...
April 2, 2018: Cold Spring Harbor Perspectives in Medicine
Yun Kong, Jiang Li, Xinyuan Hu, Yaoguang Wang, Qingyun Meng, Guofeng Gu, Peng George Wang, Min Chen
N-Glycosyltransferase (NGT) is an inverting glycosyltransferase for an unusual pathway of N-linked protein glycosylation and glycosylates polypeptides in the consensus sequon (N-(X≠P)-T/S) with hexose monosaccharides. Here, we expressed and characterized a novel N-glycosyltransferase from Aggregatibacter aphrophilus (named AaNGT). RP-HPLC and Mass Spectrometry were used to assay and quantify glycopeptide formation by AaNGT and determine its substrate specificities. AaNGT could utilize a variety of nucleotide-activated sugar donors, including UDP-Glc, UDP-Gal, UDP-Xyl, GDP-Glc, dGDP-Glc and UDP-GlcN, to glycosylate the tested peptides...
March 19, 2018: Carbohydrate Research
Liang Gao, Xiaoya Shan, Yuhao Qin, Senbin Yu, Lida Xu, Zi-You Gao
Previous works have shown the universality of allometric scaling under total and density values at the city level, but our understanding of the size effects of regions on the universality of allometric scaling remains inadequate. Here, we revisit the scaling relations between the gross domestic production (GDP) and the population based on the total and density values and first reveal that the allometric scaling under density values for different regions is universal. The scaling exponent β under the density value is in the range of (1...
March 2018: Chaos
Xu Tian, Hancheng Dai, Yong Geng, Jeffrey Wilson, Rui Wu, Yang Xie, Han Hao
Economic impact assessments of air pollution-related health effects from a sectoral perspective in China is still deficient. This study evaluates the PM2.5 pollution-related health impacts of the road transport sector on China's economy at both national and provincial levels in 2030 under various air mitigation technologies scenarios. Health impacts are estimated using an integrated approach that combines the Greenhouse Gas and Air Pollution Interactions and Synergies (GAINS) model, a computable general equilibrium (CGE) model and a health model...
March 28, 2018: Environment International
Sen Yu, Hongwei Lu
Urbanisation has increased the discharge of pollutants, altered water flow regimes, and modified the morphology of transboundary river basins. All these actions have resulted in multiple pressures on aquatic ecosystems of transboundary river basins, undermining the healthy development of their aquatic ecosystems as well as impairing the sustainable economic and social development associated therewith. Quantifying the relationship between socio-economic factors, and water environment systems, and understanding the multiple pressures in their combined impact on environmental fairness of transboundary river basins is challenging, and it is crucial to the strategic planning of the Belt and Road strategy...
March 26, 2018: Chemosphere
Paula M Luz, Benjamin Osher, Beatriz Grinsztejn, Rachel L Maclean, Elena Losina, Madeline E Stern, Claudio J Struchiner, Robert A Parker, Kenneth A Freedberg, Fabio Mesquita, Rochelle P Walensky, Valdilea G Veloso, A David Paltiel
INTRODUCTION: Men who have sex with men (MSM) and transgender women (TGW) in Brazil experience high rates of HIV infection. We examined the clinical and economic outcomes of implementing a pre-exposure prophylaxis (PrEP) programme in these populations. METHODS: We used the Cost-Effectiveness of Preventing AIDS Complications (CEPAC)-International model of HIV prevention and treatment to evaluate two strategies: the current standard of care (SOC) in Brazil, including universal ART access (No PrEP strategy); and the current SOC plus daily tenofovir/emtracitabine PrEP (PrEP strategy) until age 50...
March 2018: Journal of the International AIDS Society
Amy Zheng, Nagalingeswaran Kumarasamy, Mingshu Huang, A David Paltiel, Kenneth H Mayer, Bharat B Rewari, Rochelle P Walensky, Kenneth A Freedberg
INTRODUCTION: Dolutegravir (DTG)-based antiretroviral therapy (ART) is recommended for first-line HIV treatment in the US and Europe. Efavirenz (EFV)-based regimens remain the standard of care (SOC) in India. We examined the clinical and economic impact of DTG-based first-line ART in the setting of India's recent guidelines change to treating all patients with HIV infection regardless of CD4 count. METHODS: We used a microsimulation of HIV disease, the Cost-Effectiveness of Preventing AIDS Complications (CEPAC)-International model, to project outcomes in ART-naive patients under two strategies: (1) SOC: EFV/tenofovir disoproxil fumarate (TDF)/lamivudine (3TC); and (2) DTG: DTG + TDF/3TC...
March 2018: Journal of the International AIDS Society
Marta González-Sánchez, Teresa Díaz, Consuelo Pascual, Desiree Antequera, Alejandro Herrero-San Martín, Sara Llamas-Velasco, Alberto Villarejo-Galende, Fernando Bartolome, Eva Carro
Platelets are considered a good model system to study a number of elements associated with neuronal pathways as they share biochemical similarities. Platelets represent the major source of amyloid-β (Aβ) in blood contributing to the Aβ accumulation in the brain parenchyma and vasculature. Peripheral blood platelet alterations including cytoskeletal abnormalities, abnormal cytoplasmic calcium fluxes or increased oxidative stress levels have been related to Alzheimer's disease (AD) pathology. Therefore, platelets can be considered a peripheral model to study metabolic mechanisms occurring in AD...
March 30, 2018: Molecular Neurobiology
Mousumi Majumder, Pinki Nandi, Ahmed Omar, Kingsley Chukwunonso Ugwuagbo, Peeyush K Lala
G-protein-coupled receptors (GPCRs, also called seven-transmembrane or heptahelical receptors) are a superfamily of cell surface receptor proteins that bind to many extracellular ligands and transmit signals to an intracellular guanine nucleotide-binding protein (G-protein). When a ligand binds, the receptor activates the attached G-protein by causing the exchange of Guanosine-5'-triphosphate (GTP) for guanosine diphosphate (GDP). They play a major role in many physiological functions, as well as in the pathology of many diseases, including cancer progression and metastasis...
March 29, 2018: International Journal of Molecular Sciences
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