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101.
Sun L Dimitromanolakis A Faye LL Paterson AD Waggott D;DCCT/EDIC Research Group Bull SB 《Human genetics》2011,129(5):545-552
The detrimental effects of the winner’s curse, including overestimation of the genetic effects of associated variants and
underestimation of sufficient sample sizes for replication studies are well-recognized in genome-wide association studies
(GWAS). These effects can be expected to worsen as the field moves from GWAS into whole genome sequencing. To date, few studies
have reported statistical adjustments to the naive estimates, due to the lack of suitable statistical methods and computational
tools. We have developed an efficient genome-wide non-parametric method that explicitly accounts for the threshold, ranking,
and allele frequency effects in whole genome scans. Here, we implement the method to provide bias-reduced estimates via bootstrap
re-sampling (BR-squared) for association studies of both disease status and quantitative traits, and we report the results
of applying BR-squared to GWAS of psoriasis and HbA1c. We observed over 50% reduction in the genetic effect size estimation for many associated
SNPs. This translates into a greater than fourfold increase in sample size requirements for successful replication studies,
which in part explains some of the apparent failures in replicating the original signals. Our analysis suggests that adjusting
for the winner’s curse is critical for interpreting findings from whole genome scans and planning replication and meta-GWAS
studies, as well as in attempts to translate findings into the clinical setting. 相似文献
102.
Apostolos Kapranas Brian A. Federici Robert F. Luck Jeffrey Johnson 《Biological Control》2009,48(1):1-5
The parasitic wasp, Metaphycus luteolus Timberlake, is an endoparasitoid of various soft scale insects including brown soft scale, Coccus hesperidum L. Development of this parasitoid in scale hosts is hindered by encapsulation. In the present study, using transmission and scanning electron microscopy, we show that hemocytes are responsible for encapsulation, which is mediated by the direct deposition of cells and melanin on the surface of M. luteolus eggs. By 12 h post-oviposition, scale hemocytes, presumably granulocytes, aggregate, spread and directly lyse on the surface of parasitoid eggs. This process continues for at least 1 day and results in the gradual formation of a capsule. Two to three days post-oviposition, a melanized capsule is well formed and signs of chemical deposition are evident by examination of the outer surface of the capsule. These results demonstrate that soft scale insects are fully capable of melanotic encapsulation of foreign material mediated by hemocytes. 相似文献
103.
104.
Anna Panagopoulou Apostolos Kyritsis Anna-Maria Aravantinou Dionysios Nanopoulos Roser Sabater i Serra Jose Luis G��mez Ribelles Naoki Shinyashiki Polycarpos Pissis 《Food biophysics》2011,6(2):199-209
Differential scanning calorimetry (DSC) and two dielectric techniques, broadband dielectric relaxation spectroscopy and thermally
stimulated depolarization currents (TSDC), were employed to study glass transition and water and protein dynamics in mixtures
of water and a globular protein, lysozyme, in wide ranges of water content, both solutions, and hydrated solid samples. In
addition, water equilibrium sorption isotherms (ESI) measurements were performed at room temperature. The main objective was
to correlate results by different techniques to each other and to determine critical water contents for various processes.
From ESI measurements the content of water directly bound to primary hydration sites was determined to 0.088 (grams of water
per grams of dry protein), corresponding to 71 water molecules per protein molecule, and that where clustering becomes significant
to about 0.25. Crystallization and melting events of water were first observed at water contents 0.270 and 0.218, respectively,
and the amount of uncrystallized water was found to increase with increasing water content. Two populations of ice crystals
were observed by DSC, primary and bulk ice crystals, which give rise to two separate relaxations in dielectric measurements.
In addition, the relaxation of uncrystallized water was observed, superimposed on a local relaxation of polar groups on the
protein surface. The glass transition temperature, determined by DSC and TSDC in rather good agreement to each other, was
found to decrease significantly with increasing water content and to stabilize at about −90 °C for water contents higher than
about 0.25. This is a novel result of this study with potential impact on cryoprotection and pharmaceutics. 相似文献
105.
Kouyianou K De Bock PJ Müller SA Nikolaki A Rizos A Krzyžánek V Aktoudianaki A Vandekerckhove J Engel A Gevaert K Tsiotis G 《Proteomics》2011,11(14):2867-2880
Chlorosomes, the antenna complexes of green bacteria, are unique antenna systems in which pigments are organized in aggregates. Studies on isolated chlorosomes from Chlorobaculum tepidum based on SDS-PAGE, immunoblotting and molecular biology have revealed that they contain ten chlorosomal proteins, but no comprehensive information is available about the protein composition of the entire organelle. To extend these studies, chlorosomes were isolated from C. tepidum using three related and one independent isolation protocol and characterized by absorption spectroscopy, tricine SDS-PAGE, dynamic light scattering (DLS) and electron microscopy. Tricine SDS-PAGE showed the presence of more than 20 proteins with molecular weights ranging between 6 and 70 kDa. The chlorosomes varied in size. Their hydrodynamic radius (R(h) ) ranged from 51 to 75 nm and electron microscopy indicated that they were on average 140 nm wide and 170 nm long. Furthermore, the mass of 184 whole chlorosome organelles determined by scanning transmission electron microscopy ranged from 27 to 237 MDa being on average 88 (±28) MDa. In contrast their mass-per-area was independent of their size, indicating that there is a strict limit to chlorosome thickness. The average protein composition of the C. tepidum chlorosome organelles was obtained by MS/MS-driven proteomics and for the first time a detailed protein catalogue of the isolated chlorosomal proteome is presented. Based on the proteomics results for chlorosomes isolated by different protocols, four proteins that are involved in the electron or ion transport are proposed to be tightly associated with or incorporated into C. tepidum chlorosomes as well as the ten Csm proteins known to date. 相似文献
106.
Ioannis Ganopoulos Filippos A. Aravanopoulos Anagnostis Argiriou Apostolos Kalivas Athanasios Tsaftaris 《Tree Genetics & Genomes》2011,7(6):1299-1313
Wild cherry (Prunus avium L.) is a widespread, partially asexual, noble hardwood European species characterized by a scattered distribution, small population sizes, and human exploitation for its valuable wood. These characteristics, especially at the southern limits of the species natural distribution where additional varying stresses may occur, render P. avium populations prone to potential stochastic, genetic, and demographic events. In this study, we used dominant inter simple sequence repeat (ISSR) and codominant simple sequence repeat (SSR) markers to infer the genetic structure of P. avium. Five populations from northern Greece were evaluated based on 46 ISSR and 11 SSR loci. Populations presented a relatively high level of genetic variation, with a mean genetic diversity of H e?=?0.166 and H e?=?0.740 regarding ISSR and SSR analysis, respectively. We observed moderate population differentiation for ISSR (G ST?=?0.113) and SSR (F ST?=?0.097) markers. AMOVA also detected significant differentiation among populations for ISSRs (?? ST?=?0.338) and SRRs (?? ST?=?0.162). According to linkage disequilibrium analysis, estimates of effective population size were generally sufficient for maintaining extant genetic variability and evolutionary potential. A possible bottleneck was detected for only one population. In general, it appears that despite the particular characteristics of the P. avium populations studied, genetic stochasticity events were not apparent. The studied populations, located at the rear edge of the species European distribution, reveal a wealth of genetic variation that is very valuable for the genetic conservation of local adaptive gene complexes, especially under contemporary climatic change scenarios. 相似文献
107.
Oliver JA Maarouf O Cheema FH Liu C Zhang QY Kraus C Zeeshan Afzal M Firdous M Klinakis A Efstratiadis A Al-Awqati Q 《American journal of physiology. Renal physiology》2012,302(11):F1362-F1373
The adult kidney contains a population of low-cycling cells that resides in the papilla. These cells retain for long periods S-phase markers given as a short pulse early in life; i.e., they are label-retaining cells (LRC). In previous studies in adult rat and mice, we found that shortly after acute kidney injury many of the quiescent papillary LRC started proliferating (Oliver JA, Klinakis A, Cheema FH, Friedlander J, Sampogna RV, Martens TP, Liu C, Efstratiadis A, Al-Awqati Q. J Am Soc Nephrol 20: 2315-2327, 2009; Oliver JA, Maarouf O, Cheema FH, Martens TP, Al-Awqati Q. J Clin Invest 114: 795-804, 2004) and, with cell-tracking experiments, we found upward migration of some papillary cells including LRC (Oliver JA, Klinakis A, Cheema FH, Friedlander J, Sampogna RV, Martens TP, Liu C, Efstratiadis A, Al-Awqati Q. J Am Soc Nephrol 20: 2315-2327, 2009). To identify molecular cues involved in the activation (i.e., proliferation and/or migration) of the papillary LRC that follows injury, we isolated these cells from the H2B-GFP mice and found that they migrated and proliferated in response to the cytokine stromal cell-derived factor-1 (SDF-1). Moreover, in a papillary organ culture assay, the cell growth out of the upper papilla was dependent on the interaction of SDF-1 with its receptor Cxcr4. Interestingly, location of these two proteins in the kidney revealed a complementary location, with SDF-1 being preferentially expressed in the medulla and Cxcr4 more abundant in the papilla. Blockade of Cxcr4 in vivo prevented mobilization of papillary LRC after transient kidney ischemic injury and worsened its functional consequences. The data indicate that the SDF-1/Cxcr4 axis is a critical regulator of papillary LRC activation following transient kidney injury and during organ repair. 相似文献
108.
Spanou CI Veskoukis AS Stagos D Liadaki K Aligiannis N Angelis A Skaltsounis AL Anastasiadi M Haroutounian SA Kouretas D 《Journal of physiology and biochemistry》2012,68(1):37-45
Legumes are considered to have beneficial health implications, which have been attributed to their phytochemical content.
Polyphenols are considered the most important phytochemical compounds extensively studied for their antioxidant properties.
The aim of the present study was to examine the effects of potent antioxidant legume plant extracts on xanthine oxidase (XO),
catalase (CAT) and superoxide dismutase (SOD) activities. XO exerts a dual role, as it is the major contributor of free radicals
during exercise while it generates uric acid, the most potent antioxidant molecule in plasma. CAT and SOD are two of the main
enzymes of the antioxidant defence of tissues. We demonstrate that the majority of the extracts inhibited XO activity, but
they had no effect on CAT inhibition and SOD induction when used at low concentrations. These results imply that the tested
extracts may be considered as possible source of novel XO inhibitors. However, we have shown that allopurinol administration,
a known XO inhibitor, before exercise reduces performance and induces oxidative stress in rats. Considering the fact that
the extracts examined had an inhibitory effect on XO activity, possibly posing a restriction in their characterization as
antioxidants, phytochemical antioxidant administration before exercise should probably be reconsidered. 相似文献
109.
Panteloglou AG Smart KA Cook DJ 《Journal of industrial microbiology & biotechnology》2012,39(6):813-822
Premature yeast flocculation (PYF) is a sporadic problem for the malting and brewing industries which can have significant financial and logistical implications. The condition is characterised by abnormally heavy (and sometimes early) flocculation of yeast during brewery fermentations. The resulting low suspended yeast cell counts towards the end of the fermentation can result in flavour defects and incomplete attenuation (fermentation of sugars to alcohol). Despite several decades of research into the phenomenon, its precise nature and mechanisms have not been fully elucidated. In part this is because the term PYF has become a 'catch-all' syndrome which can have multiple origins. Furthermore, there are complex interactions in the malting and brewing processes which together mean that the PYF status of a malt sample is hard to predict at a generic level. Whether or not PYF is observed depends not only on barley quality, but on process factors in the maltings and to a substantial extent on the brewing yeast strain concerned. This article highlights the significance of PYF, and reviews current knowledge relating to the origins of this complex phenomenon. 相似文献
110.