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21.
Irene Pichler Fabiola Del Greco M. Martin G?gele Christina M. Lill Lars Bertram Chuong B. Do Nicholas Eriksson Tatiana Foroud Richard H. Myers PD GWAS Consortium Michael Nalls Margaux F. Keller International Parkinson's Disease Genomics Consortium Wellcome Trust Case Control Consortium Beben Benyamin John B. Whitfield Genetics of Iron Status Consortium Peter P. Pramstaller Andrew A. Hicks John R. Thompson Cosetta Minelli 《PLoS medicine》2013,10(6)
Background
Although levels of iron are known to be increased in the brains of patients with Parkinson disease (PD), epidemiological evidence on a possible effect of iron blood levels on PD risk is inconclusive, with effects reported in opposite directions. Epidemiological studies suffer from problems of confounding and reverse causation, and mendelian randomization (MR) represents an alternative approach to provide unconfounded estimates of the effects of biomarkers on disease. We performed a MR study where genes known to modify iron levels were used as instruments to estimate the effect of iron on PD risk, based on estimates of the genetic effects on both iron and PD obtained from the largest sample meta-analyzed to date.Methods and Findings
We used as instrumental variables three genetic variants influencing iron levels, HFE rs1800562, HFE rs1799945, and TMPRSS6 rs855791. Estimates of their effect on serum iron were based on a recent genome-wide meta-analysis of 21,567 individuals, while estimates of their effect on PD risk were obtained through meta-analysis of genome-wide and candidate gene studies with 20,809 PD cases and 88,892 controls. Separate MR estimates of the effect of iron on PD were obtained for each variant and pooled by meta-analysis. We investigated heterogeneity across the three estimates as an indication of possible pleiotropy and found no evidence of it. The combined MR estimate showed a statistically significant protective effect of iron, with a relative risk reduction for PD of 3% (95% CI 1%–6%; p = 0.001) per 10 µg/dl increase in serum iron.Conclusions
Our study suggests that increased iron levels are causally associated with a decreased risk of developing PD. Further studies are needed to understand the pathophysiological mechanism of action of serum iron on PD risk before recommendations can be made. Please see later in the article for the Editors'' Summary 相似文献22.
Abstract Opportunistic sightings and strandings of Caperea marginata (n=196) from the vicinity of Australia and New Zealand (1884 to early 2007) were used to relate geographic and temporal patterns to oceanographic and broad-scale climatic variability. Records were not uniformly distributed along the coast and more (69%) were from Australia than New Zealand. Seven coastal whale ‘hotspots’ were identified which accounted for 61% of records with locality data. Half of the hotspot records were from southeast (37) and northwest (20) Tasmania—others each had 9–15 events. Upwelling and/or high zooplankton abundance has been documented near all whale hotspots. Records of C. marginata occurred in all months, with 75% in spring and summer. Inter-annual variability showed broad agreement between increased whale records (usually in spring/summer) and strongly positive ‘Niño 3.4’ during 1980–1995 but not thereafter. Coastal upwelling and productivity increase during climatic phenomena such as El Niño and are likely to be quickly beneficial to plankton-feeding whales such as C. marginata. 相似文献
23.
T. Ripperger B. Schlegelberger PD Dr. rer. nat. D. Steinemann 《Medizinische Genetik》2012,24(1):33-39
Juvenile myelomonocytic leukemia (JMML) is a unique myeloproliferative disorder of early childhood in which mutations in NRAS, KRAS, PTPN11, NF1 and CBL are frequently found. Using high-resolution oligo array-based comparative genomic hybridization (aCGH), 20 JMML samples were investigated for submicroscopic genomic copy number alterations. Besides known cytogenetic aberrations, ten samples displayed additional submicroscopic alterations. Interestingly, an almost identical gain of chromosome 8 was identified in two patients. Subsequently, fluorescence in situ hybridization indicated a constitutional partial trisomy 8 mosaic (cT8M) in both patients. A survey on 27 cT8M patients with reported malignancies showed a predominance of myeloid malignancies including JMML. Our results dramatically reduce the critical region on chromosome 8 to 8p11.21q11.21. To determine how constitutional partial trisomy 8 mosaicisms may contribute to leukemogenesis in different mutational subtypes of JMML and other myeloid malignancies, further investigations are required. 相似文献
24.
PD Dr. med. Hanspeter Rohr Ute Seitter Jürgen Schmalbeck 《Cell and tissue research》1968,85(3):376-397
Zusammenfassung Einer weiblichen Maus wurde 3 Tage post partum 750 C 3H-Leucin i. p. injiziert. Zu verschiedenen Zeiten nach der Leucinapplikation wurden dem leicht narkotisierten Tier Gewebeteile der Milchdrüse entnommen und zu elektronenmikroskopischen Autoradiogrammen verarbeitet. An Hand der dabei gewonnenen Ergebnisse wurde versucht, den zeitlichen Ablauf der Milcheiweißbildung rechnerisch zu erfassen. 5 und 15 min nach der 3H-Leucinapplikation kann die Aktivität über dem rauhen endoplasmatischen Retikulum, nach 30 min über dem Golgi-Feld, und nach 240 min zur Hauptsache über den Lumina der Ausführungsgänge beobachtet werden. Die Halbwertszeit von markierten Proteinen im Ergastoplasma errechnete sich zu etwa 22 min, diejenige im Golgi-Feld zu etwa 3 Std.Die Voraussetzungen und derzeitigen Grenzen einer quantitativen elektronenmikroskopischen Autoradiographie werden diskutiert. Wegen der vielen möglichen Fehlerquellen wird die Berechnung der Kinetik der Milcheiweißbildung lediglich als Modell gewertet.
Ausgeführt mit Unterstützung durch die Deutsche Forschungsgemeinschaft.
Wesentliche Teile der Arbeit werden Von Ute Seitter der Medizinischen Fakultät der Universität Freiburg i. Br. als Inaugural-Dissertation vorgelegt. 相似文献
Summary A female mouse, 3 days post partum, was injected with 3H-leucine. After various intervals parts of the mammary gland were processed for electronmicroscopic autoradiograms, the results of which were mathematically evaluated in order to understand the temporal course of milk protein formation. After 5 and 15 minutes the leucine-activity is located mainly in the rough endoplasmic reticulum, after 30 minutes in the Golgi field and after 240 minutes in the lumina of the mammary ducts. The half-live time of labelled proteins in the rough endoplasmic reticulum is about 22 minutes, in the Golgi field about 3 hours.The preconditions and limitations of quantitative electronmicroscopic autoradiography are discussed. Because of the many possible sources of error, the calculations of the kinetics of protein synthesis and secretion in the mammary gland are merely regarded as a model.
Ausgeführt mit Unterstützung durch die Deutsche Forschungsgemeinschaft.
Wesentliche Teile der Arbeit werden Von Ute Seitter der Medizinischen Fakultät der Universität Freiburg i. Br. als Inaugural-Dissertation vorgelegt. 相似文献
25.
26.
Dipl. Geol. Volker Thiel Dr. Martina Merz-Preiß Prof. Dr. Joachim Reitner PD Dr. Walter Michaelis 《Facies》1997,36(1):163-172
Summary Biomarker investigations are applied to the free lipid fractions of a naturally grown freshwater microbial mat, constructed
by calcifying cyanobacteria (Scytonema sp. andSchizothrix sp.). The absolute and relative concentrations of hydrocarbons, free alcohols and carboxylic acids are studied and their
probable biological precursors are discussed. A significant signal of cyanobacterial lipids is recognized by the strong predominance
ofn-heptadecane (C17),n-heptadecene, two monomethyl-heptadecanes, and the pentacyclic triterpenoid diploptene. Their occurrences parallel the lipid
distributions found in pure cultured cyanobacteria and in recent cyanobacterial mats grown in particular environments (hypersaline,
lagoonal, hot spring). The observed compound signature appears to be a suitable reference for environments, where cyanobacteria
are directly associated with theloci of carbonate precipitation and thus, rock formation. In the studied material, a significant contribution of organic matter
from other sources, especially higher plants is characterized by the occurrence of several specific marker compounds, namely
lup-20(29)-ene-3-ol, high molecular weightn-alkanes and carboxylic acids. Although these components comprise a notably high portion of the sample’s lipid inventory,
they are shown to be distinguished easily from the signal left by the predominant mat building organisms. 相似文献
27.
28.
Rick PD; Hubbard GL; Kitaoka M; Nagaki H; Kinoshita T; Dowd S; Simplaceanu V; Ho C 《Glycobiology》1998,8(6):557-567
The polysaccharide chains of enterobacterial common antigen (ECA) consist
of linear trisaccharide repeat units with the structure -->3)-
alpha-d-Fuc4NAc-(1-->4)-beta-d-ManNAcA-(1-->
4)-alpha-d-GlcNAc-(1-->, where Fuc4NAc is 4-acetamido-4,
6-dideoxy-d-galactose, ManNAcA is N - acetyl-d- mannosaminuronic acid, and
GlcNAc is N -acetyl-d-glucosamine. The major form of ECA (ECAPG) consists
of polysaccharide chains that are believed to be covalently linked to
diacylglycerol through phosphodiester linkage; the phospholipid moiety
functions to anchor molecules in the outer membrane. The ECA trisaccharide
repeat unit is assembled as a polyisoprenyl-linked intermediate which has
been tentatively identified as Fuc4NAc-ManNAcA-GlcNAc-
pyrophosphorylundecaprenol (lipid III). Subsequent chain-elongation
presumably occurs by a block-polymerization mechanism. However, the
identity of the polyisoprenoid carrier-lipid has not been established.
Accordingly, the current studies were conducted in an effort to
structurally characterize the polyisoprenyl lipid-carrier involved in ECA
synthesis. Isolation and characterization of the lipid carrier was
facilitated by the accumulation of a ManNAcA-GlcNAc-
pyrophosphorylpolyisoprenyl lipid (lipid II) in mutants of Salmonella
typhimurium defective in the synthesis of TDP-Fuc4NAc, the donor of Fuc4NAc
residues for ECA synthesis. Analyses of lipid II preparations by fast atom
bombardment tandem mass spectroscopy (FAB-MS/MS) resulted in the
identification of the lipid-carrier as the 55-carbon polyisoprenyl alcohol,
undecaprenol. These analyses also resulted in the identification of a novel
glycolipid which copurified with lipid II. FAB-MS/MS analyses of this
glycolipid revealed its structure to be 1,2-diacyl- sn
-glycero-3-pryophosphoryl-GlcNAc-ManNAcA (DGP- disaccharide). An
examination of purified ECAPGby phosphorus-31 nuclear magnetic resonance
spectroscopy confirmed that the polysaccharide chains are linked to
diacylglycerol through phosphodiester linkage. Thus, DGP-disaccharide does
not appear to be an intermediate in ECAPGsynthesis. Nevertheless, although
the available evidence clearly indicate that lipid II is a precursor of
DGP-disaccharide, the function of this novel glycolipid is not yet known,
and it may be an intermediate in the biosynthesis of a molecule other than
ECAPG.
相似文献
29.
Colin PD Birch Ambrose C Chikukwa Kieran Hyder Victor J Del Rio Vilas 《BMC veterinary research》2009,5(1):1-14
Background
This paper explores the spatial distribution of sampling within the active surveillance of sheep scrapie in Great Britain. We investigated the geographic distribution of the birth holdings of sheep sampled for scrapie during 2002 – 2005, including samples taken in abattoir surveys (c. 83,100) and from sheep that died in the field ("fallen stock", c. 14,600). We mapped the birth holdings by county and calculated the sampling rate, defined as the proportion of the holdings in each county sampled by the surveys. The Moran index was used to estimate the global spatial autocorrelation across Great Britain. The contributions of each county to the global Moran index were analysed by a local indicator of spatial autocorrelation (LISA). 相似文献30.
A novel role for p120 catenin in E-cadherin function 总被引:18,自引:0,他引:18
Ireton RC Davis MA van Hengel J Mariner DJ Barnes K Thoreson MA Anastasiadis PZ Matrisian L Bundy LM Sealy L Gilbert B van Roy F Reynolds AB 《The Journal of cell biology》2002,159(3):465-476
Indirect evidence suggests that p120-catenin (p120) can both positively and negatively affect cadherin adhesiveness. Here we show that the p120 gene is mutated in SW48 cells, and that the cadherin adhesion system is impaired as a direct consequence of p120 insufficiency. Restoring normal levels of p120 caused a striking reversion from poorly differentiated to cobblestone-like epithelial morphology, indicating a crucial role for p120 in reactivation of E-cadherin function. The rescue efficiency was enhanced by increased levels of p120, and reduced by the presence of the phosphorylation domain, a region previously postulated to confer negative regulation. Surprisingly, the rescue was associated with substantially increased levels of E-cadherin. E-cadherin mRNA levels were unaffected by p120 expression, but E-cadherin half-life was more than doubled. Direct p120-E-cadherin interaction was crucial, as p120 deletion analysis revealed a perfect correlation between E-cadherin binding and rescue of epithelial morphology. Interestingly, the epithelial morphology could also be rescued by forced expression of either WT E-cadherin or a p120-uncoupled mutant. Thus, the effects of uncoupling p120 from E-cadherin can be at least partially overcome by artificially maintaining high levels of cadherin expression. These data reveal a cooperative interaction between p120 and E-cadherin and a novel role for p120 that is likely indispensable in normal cells. 相似文献