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151.
Xunjun Xiao Michael R. Ferguson Kelsey E. Magee Pamela D. Hale Yan Wang Mark E. Lowe 《Journal of lipid research》2013,54(2):514-521
Colipase is essential for efficient fat digestion. An arginine-to-cysteine polymorphism at
position 92 of colipase (Arg92Cys) associates with an increased risk for developing type-2 diabetes
through an undefined mechanism. To test our hypothesis that the extra cysteine increases colipase
misfolding, thereby altering its intracellular trafficking and function, we expressed Cys92 colipase
in HEK293T cells. Less Cys92 colipase is secreted and more is retained intracellularly in an
insoluble form compared with Arg92 colipase. Nonreducing gel electrophoresis suggests the folding of
secreted Cys92 colipase differs from Arg92 colipase. Cys92 colipase misfolding does not trigger the
unfolded protein response (UPR) or endoplasmic reticulum (ER) stress. The ability of secreted Cys92
colipase to stimulate pancreatic triglyceride lipase (PTL) is reduced with all substrates tested,
particularly long-chain triglycerides. The reaction of Cys92 colipase with triolein and Intralipid
has a much longer lag time, reflecting decreased ability to anchor PTL on those substrates. Our data
predicts that humans with the Arg92Cys substitution will secrete less functional colipase into the
duodenum and have less efficient fat digestion. Whether inefficient fat digestion or another
property of colipase contributes to the risk for developing diabetes remains to be clarified. 相似文献
152.
Dan H. Barouch Kathryn E. Stephenson Erica N. Borducchi Kaitlin Smith Kelly Stanley Anna G. McNally Jinyan Liu Peter Abbink Lori F. Maxfield Michael S. Seaman Anne-Sophie Dugast Galit Alter Melissa Ferguson Wenjun Li Patricia L. Earl Bernard Moss Elena E. Giorgi James J. Szinger Leigh Anne Eller Erik A. Billings Mangala Rao Sodsai Tovanabutra Eric Sanders-Buell Mo Weijtens Maria G. Pau Hanneke Schuitemaker Merlin L. Robb Jerome H. Kim Bette T. Korber Nelson L. Michael 《Cell》2013
153.
The present article deals with the efficacy of seed hairs of poplar trees (Populus spp.) as a potent natural airborne pollen trap. Different species of Populus are commonly found planted along the streets in the cities of North China. The seed hairs and pericarp of poplar trees were collected from the trees and on the ground in Beijing Botanical Garden of Chinese Academy of Sciences and around Miyun Reservoir during May 2005 for pollen analysis. Different pollen spectra are recorded from different samples and are characterised by dominant occurrence of pollen grains of arboreal and anemophilous plants. In addition, pollen grains of non‐arboreal plants including grasses are also found trapped. Among the 46 trapped pollen grains, 26 are known to be allergenic. This study suggests that poplar seed hairs possibly make people feel uncomfortable due to the presence of allergenic pollen trapped in the hairs. 相似文献
154.
Yingjie Li Shilpa Bali Sarah Borg Emanuel Katzmann Stuart J. Ferguson Dirk Schüler 《Journal of bacteriology》2013,195(18):4297-4309
The alphaproteobacterium Magnetospirillum gryphiswaldense synthesizes magnetosomes, which are membrane-enveloped crystals of magnetite. Here we show that nitrite reduction is involved in redox control during anaerobic biomineralization of the mixed-valence iron oxide magnetite. The cytochrome cd1-type nitrite reductase NirS shares conspicuous sequence similarity with NirN, which is also encoded within a larger nir cluster. Deletion of any one of these two nir genes resulted in impaired growth and smaller, fewer, and aberrantly shaped magnetite crystals during nitrate reduction. However, whereas nitrite reduction was completely abolished in the ΔnirS mutant, attenuated but significant nitrite reduction occurred in the ΔnirN mutant, indicating that only NirS is a nitrite reductase in M. gryphiswaldense. However, the ΔnirN mutant produced a different form of periplasmic d1 heme that was not noncovalently bound to NirS, indicating that NirN is required for full reductase activity by maintaining a proper form of d1 heme for holo-cytochrome cd1 assembly. In conclusion, we assign for the first time a physiological function to NirN and demonstrate that effective nitrite reduction is required for biomineralization of wild-type crystals, probably by contributing to oxidation of ferrous iron under oxygen-limited conditions. 相似文献
155.
Hui Xiong Melinda Foulk Lisa Aschenbrenner Jun Fan Choi-Lai Tiong-Yip Kenneth D. Johnson Demetri Moustakas Paul R. Fleming Dean G. Brown Minli Zhang Douglas Ferguson Dedong Wu Qin Yu 《Bioorganic & medicinal chemistry letters》2013,23(24):6789-6793
Targeting viral polymerases has been a proven and attractive strategy for antiviral drug discovery. Herein we describe our effort in improving the antiviral activity and physical properties of a series of benzothienoazepine compounds as respiratory syncytial virus (RSV) RNA polymerase inhibitors. The antiviral activity and spectrum of this class was significantly improved by exploring the amino substitution of the pyridine ring, resulting in the discovery of the most potent RSV A polymerase inhibitors reported to date. 相似文献
156.
157.
Sarah J. Stock Evelyn Ferguson Andrew Duffy Ian Ford James Chalmers Jane E. Norman 《PloS one》2013,8(4)
Background
There is evidence that induction of labour (IOL) around term reduces perinatal mortality and caesarean delivery rates when compared to expectant management of pregnancy (allowing the pregnancy to continue to await spontaneous labour or definitive indication for delivery). However, it is not clear whether IOL in women with a previous caesarean section confers the same benefits. The aim of this study was to describe outcomes of IOL at 39–41 weeks in women with one previous caesarean delivery and to compare outcomes of IOL or planned caesarean delivery to those of expectant management.Methods and Findings
We performed a population-based retrospective cohort study of singleton births greater than 39 weeks gestation, in women with one previous caesarean delivery, in Scotland, UK 1981–2007 (n = 46,176). Outcomes included mode of delivery, perinatal mortality, neonatal unit admission, postpartum hemorrhage and uterine rupture. 40.1% (2,969/7,401) of women who underwent IOL 39–41 weeks were ultimately delivered by caesarean. When compared to expectant management IOL was associated with lower odds of caesarean delivery (adjusted odds ratio [AOR] after IOL at 39 weeks of 0.81 [95% CI 0.71–0.91]). There was no significant effect on the odds of perinatal mortality but greater odds of neonatal unit admission (AOR after IOL at 39 weeks of 1.29 [95% CI 1.08–1.55]). In contrast, when compared with expectant management, elective repeat caesarean delivery was associated with lower perinatal mortality (AOR after planned caesarean at 39 weeks of 0.23 [95% CI 0.07–0.75]) and, depending on gestation, the same or lower neonatal unit admission (AOR after planned caesarean at 39 weeks of 0.98 [0.90–1.07] at 40 weeks of 1.08 [0.94–1.23] and at 41 weeks of 0.77 [0.60–1.00]).Conclusions
A more liberal policy of IOL in women with previous caesarean delivery may reduce repeat caesarean delivery, but increases the risks of neonatal complications. 相似文献158.
Marshall K. Tulloch-Reid Novie O. Younger Trevor S. Ferguson Damian K. Francis Abdullahi O. Abdulkadri Georgiana M. Gordon-Strachan Shelly R. McFarlane Colette A. Cunningham-Myrie Rainford J. Wilks Simon G. Anderson 《PloS one》2013,8(6)
Background
Black Caribbean women have a higher burden of cardiovascular disease (CVD) risk factors than their male counterparts. Whether this results in a difference in incident cardiovascular events is unknown. The aim of this study was to estimate the 10 year World Health Organization/International Society for Hypertension (WHO/ISH) CVD risk score for Jamaica and explore the effect of sex as well as obesity, physical activity and socioeconomic status on these estimates.Methods and Findings
Data from 40–74 year old participants in the 2007/08 Jamaica Health and Lifestyle Survey were used. Trained interviewers administered questionnaires and measured anthropometrics, blood pressure, fasting glucose and cholesterol. Education and occupation were used to assess socioeconomic status. The Americas B tables were used to estimate the WHO/ISH 10 year CVD risk scores for the population. Weighted prevalence estimates were calculated. Data from 1,432 (450 men, 982 women) participants were analysed, after excluding those with self-reported heart attack and stroke. The women had a higher prevalence of diabetes (19%W;12%M), hypertension (49%W;47%M), hypercholesterolemia (25%W;11%M), obesity (46%W;15%M) and physical inactivity (59%W;29%M). More men smoked (6%W;31%M). There was good agreement between the 10-year cardiovascular risk estimates whether or not cholesterol measurements were utilized for calculation (kappa –0.61). While 90% had a 10 year WHO/ISH CVD risk of less than 10%, approximately 2% of the population or 14,000 persons had a 10 year WHO/ISH CVD risk of ≥30%. As expected CVD risk increased with age but there was no sex difference in CVD risk distribution despite women having a greater risk factor burden. Women with low socioeconomic status had the most adverse CVD risk profile.Conclusion
Despite women having a higher prevalence of CVD risk factors there was no sex difference in 10-year WHO/ISH CVD risk in Jamaican adults. 相似文献159.
Andrea S. Foulkes Gregory J. Matthews Ujjwal Das Jane F. Ferguson Rongheng Lin Muredach P. Reilly 《PloS one》2013,8(2)
Informing missing heritability for complex disease will likely require leveraging information across multiple SNPs within a gene region simultaneously to characterize gene and locus-level contributions to disease phenotypes. To this aim, we introduce a novel strategy, termed Mixed modeling of Meta-Analysis P-values (MixMAP), that draws on a principled statistical modeling framework and the vast array of summary data now available from genetic association studies, to test formally for locus level association. The primary inputs to this approach are: (a) single SNP level p-values for tests of association; and (b) the mapping of SNPs to genomic regions. The output of MixMAP is comprised of locus level estimates and tests of association. In application of MixMAP to summary data from the Global Lipids Gene Consortium, we suggest twelve new loci (PKN, FN1, UGT1A1, PPARG, DMDGH, PPARD, CDK6, VPS13B, GAD2, GAB2, APOH and NPC1) for low-density lipoprotein cholesterol (LDL-C), a causal risk factor for cardiovascular disease and we also demonstrate the potential utility of MixMAP in small data settings. Overall, MixMAP offers novel and complementary information as compared to SNP-based analysis approaches and is straightforward to implement with existing open-source statistical software tools. 相似文献
160.
Arash Chitsazan Blake Ferguson Ramesh Ram Pamela Mukhopadhyay Herlina Y. Handoko Brian Gabrielli Peter H Soyer Graeme J. Walker 《Pigment cell & melanoma research》2016,29(4):459-464
Congenital nevi develop before birth and sometimes cover large areas of the body. They are presumed to arise from the acquisition of a gene mutation in an embryonic melanocyte that becomes trapped in the dermis during development. Mice bearing the Cdk4R24C::Tyr‐NRASQ61K transgenes develop congenital nevus‐like lesions by post‐natal day 10, from melanocytes escaping the confines of hair follicles. We interbred these mice with the collaborative cross (CC), a resource that enables identification of modifier genes for complex diseases (those where multiple genes are involved). We examined variation in nevus cell density in 66 CC strains and mapped a large‐effect quantitative trait locus (QTL) controlling nevus cell density to murine chromosome 9. The best candidate for a gene that exacerbates congenital nevus development in the context of an NRAS mutation is Cdon, a positive regulator of sonic hedgehog (Shh) that is expressed mainly in keratinocytes. 相似文献