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191.
Brendan Collins Simon Capewell Martin O’Flaherty Hannah Timpson Abdul Razzaq Sylvia Cheater Robin Ireland Helen Bromley 《PloS one》2015,10(6)
Background
Increasing evidence associates excess refined sugar intakes with obesity, Type 2 diabetes and heart disease. Worryingly, the estimated volume of sugary drinks purchased in the UK has more than doubled between 1975 and 2007, from 510ml to 1140ml per person per week. We aimed to estimate the potential impact of a duty on sugar sweetened beverages (SSBs) at a local level in England, hypothesising that a duty could reduce obesity and related diseases.Methods and Findings
We modelled the potential impact of a 20% sugary drinks duty on local authorities in England between 2010 and 2030. We synthesised data obtained from the British National Diet and Nutrition Survey (NDNS), drinks manufacturers, Office for National Statistics, and from previous studies. This produced a modelled population of 41 million adults in 326 lower tier local authorities in England. This analysis suggests that a 20% SSB duty could result in approximately 2,400 fewer diabetes cases, 1,700 fewer stroke and coronary heart disease cases, 400 fewer cancer cases, and gain some 41,000 Quality Adjusted Life Years (QALYs) per year across England. The duty might have the biggest impact in urban areas with young populations.Conclusions
This study adds to the growing body of evidence suggesting health benefits for a duty on sugary drinks. It might also usefully provide results at an area level to inform local price interventions in England. 相似文献192.
Clara?D. van?Karnebeek William?S. Sly Colin?J. Ross Ramona Salvarinova Joy Yaplito-Lee Saikat Santra Casper Shyr Gabriella?A. Horvath Patrice Eydoux Anna?M. Lehman Virginie Bernard Theresa Newlove Henry Ukpeh Anupam Chakrapani Mary?Anne Preece Sarah Ball James Pitt Hilary?D. Vallance Marion Coulter-Mackie Hien Nguyen Lin-Hua Zhang Amit?P. Bhavsar Graham Sinclair Abdul Waheed Wyeth?W. Wasserman Sylvia Stockler-Ipsiroglu 《American journal of human genetics》2014,94(3):453-461
Four children in three unrelated families (one consanguineous) presented with lethargy, hyperlactatemia, and hyperammonemia of unexplained origin during the neonatal period and early childhood. We identified and validated three different CA5A alterations, including a homozygous missense mutation (c.697T>C) in two siblings, a homozygous splice site mutation (c.555G>A) leading to skipping of exon 4, and a homozygous 4 kb deletion of exon 6. The deleterious nature of the homozygous mutation c.697T>C (p.Ser233Pro) was demonstrated by reduced enzymatic activity and increased temperature sensitivity. Carbonic anhydrase VA (CA-VA) was absent in liver in the child with the homozygous exon 6 deletion. The metabolite profiles in the affected individuals fit CA-VA deficiency, showing evidence of impaired provision of bicarbonate to the four enzymes that participate in key pathways in intermediary metabolism: carbamoylphosphate synthetase 1 (urea cycle), pyruvate carboxylase (anaplerosis, gluconeogenesis), propionyl-CoA carboxylase, and 3-methylcrotonyl-CoA carboxylase (branched chain amino acids catabolism). In the three children who were administered carglumic acid, hyperammonemia resolved. CA-VA deficiency should therefore be added to urea cycle defects, organic acidurias, and pyruvate carboxylase deficiency as a treatable condition in the differential diagnosis of hyperammonemia in the neonate and young child. 相似文献
193.
Sylvia Deppe Anne Ripperger Johanna Weiss Süleyman Ergün Ralf A. Benndorf 《Biochemical and biophysical research communications》2014
The ATP-binding cassette transporter ABCG2 plays a prominent role in cardiovascular and cancer pathophysiology, is involved in the pathogenesis of gout, and affects pharmacokinetics of numerous drugs. Telmisartan, a widely used AT1 receptor antagonist, inhibits the transport capacity of ABCG2 and may cause drug–drug interactions, especially in individuals carrying polymorphism that facilitate the telmisartan–ABCG2 interaction. Thus, the aim of this study was to identify ABCG2 polymorphisms and somatic mutations with relevance for the telmisartan–ABCG2 interaction. For this purpose, a cellular system for the conditional expression of ABCG2 was established. ABCG2 variants were generated via site-directed mutagenesis. Interaction of telmisartan with these ABCG2 variants was investigated in HEK293-Tet-On cells using the pheophorbide A efflux assay. Moreover, expression of ABCG2 variants was studied in these cells. Importantly, protein levels of the Q141K and F489L variant were significantly reduced, a phenomenon that was partly reversed by pharmacological proteasome inhibition. Moreover, basal pheophorbide A efflux capacity of S248P, F431L, and F489L variants was significantly impaired. Interestingly, inhibition of ABCG2-mediated pheophorbide A transport by telmisartan was almost abolished in cells expressing the R482G variant, whereas it was largely increased in cells expressing the F489L variant. We conclude that the arginine residue at position 482 of the ABCG2 molecule is of major importance for the interaction of telmisartan with this ABC transporter. Furthermore, individuals carrying the F489L polymorphism may be at increased risk of developing adverse drug reactions in multi-drug regimens involving ABCG2 substrates and telmisartan. 相似文献
194.
The physicochemical properties of cellular environments with a high macromolecular content have been systematically characterized to explain differences observed in the diffusion coefficients, kinetics parameters, and thermodynamic properties of proteins inside and outside of cells. However, much less attention has been given to the effects of macromolecular crowding on cell physiology. Here, we review recent findings that shed some light on the role of crowding in various cellular processes, such as reduction of biochemical activities, structural reorganization of the cytoplasm, cytoplasm fluidity, and cellular dormancy. We conclude by presenting some unresolved problems that require the attention of biophysicists, biochemists, and cell physiologists. Although it is still underappreciated, macromolecular crowding plays a critical role in life as we know it. 相似文献
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198.
Olivier Corminboeuf Olivier Bezençon Corinna Grisostomi Ľuboš Remeň Sylvia Richard-Bildstein Daniel Bur Lars Prade Patrick Hess Panja Strickner Walter Fischli Beat Steiner Alexander Treiber 《Bioorganic & medicinal chemistry letters》2010,20(21):6286-6290
The discovery of a new series of piperidine-based renin inhibitors is described herein. SAR optimization upon the P3 renin sub-pocket is described, leading to the discovery of 9 and 41, two bioavailable renin inhibitors orally active at low doses in a transgenic rat model of hypertension. 相似文献
199.
Henryk Flachowsky Iris Szankowski Thilo C. Fischer Klaus Richter Andreas Peil Monika Höfer Claudia Dörschel Sylvia Schmoock Achim E. Gau Heidrun Halbwirth Magda-Viola Hanke 《Planta》2010,231(3):623-635
Transgenic apple plants (Malus × domestica cv. ‘Holsteiner Cox’) overexpressing the Leaf Colour (Lc) gene from maize (Zea mays) exhibit strongly increased production of anthocyanins and flavan-3-ols (catechins, proanthocyanidins). Greenhouse plants investigated in this study exhibit altered phenotypes with regard to growth habit and resistance traits. Lc-transgenic plants show reduced size, transversal gravitropism of lateral shoots, reduced trichome development, and frequently reduced shoot diameter and abnormal leaf development with fused leaves. Such phenotypes seem to be in accordance with a direct or an indirect effect on polar-auxin-transport in the transgenic plants. Furthermore, leaves often develop necrotic lesions resembling hypersensitive response lesions. In tests, higher resistance against fire blight (caused by the bacterium Erwinia amylovora) and against scab (caused by the fungus Venturia inaequalis) is observed. These phenotypes are discussed with respect to the underlying altered physiology of the Lc-transgenic plants. The results are expected to be considered in apple breeding strategies. 相似文献
200.
Elizabeth J. Faul Celestine N. Wanjalla Mehul S. Suthar Michael Gale Jr Christoph Wirblich Matthias J. Schnell 《PLoS pathogens》2010,6(7)
As with many viruses, rabies virus (RABV) infection induces type I interferon (IFN) production within the infected host cells. However, RABV has evolved mechanisms by which to inhibit IFN production in order to sustain infection. Here we show that RABV infection of dendritic cells (DC) induces potent type I IFN production and DC activation. Although DCs are infected by RABV, the viral replication is highly suppressed in DCs, rendering the infection non-productive. We exploited this finding in bone marrow derived DCs (BMDC) in order to differentiate which pattern recognition receptor(s) (PRR) is responsible for inducing type I IFN following infection with RABV. Our results indicate that BMDC activation and type I IFN production following a RABV infection is independent of TLR signaling. However, IPS-1 is essential for both BMDC activation and IFN production. Interestingly, we see that the BMDC activation is primarily due to signaling through the IFNAR and only marginally induced by the initial infection. To further identify the receptor recognizing RABV infection, we next analyzed BMDC from Mda-5−/− and RIG-I−/− mice. In the absence of either receptor, there is a significant decrease in BMDC activation at 12h post infection. However, only RIG-I−/− cells exhibit a delay in type I IFN production. In order to determine the role that IPS-1 plays in vivo, we infected mice with pathogenic RABV. We see that IPS-1−/− mice are more susceptible to infection than IPS-1+/+ mice and have a significantly increased incident of limb paralysis. 相似文献