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131.
Nalls MA Couper DJ Tanaka T van Rooij FJ Chen MH Smith AV Toniolo D Zakai NA Yang Q Greinacher A Wood AR Garcia M Gasparini P Liu Y Lumley T Folsom AR Reiner AP Gieger C Lagou V Felix JF Völzke H Gouskova NA Biffi A Döring A Völker U Chong S Wiggins KL Rendon A Dehghan A Moore M Taylor K Wilson JG Lettre G Hofman A Bis JC Pirastu N Fox CS Meisinger C Sambrook J Arepalli S Nauck M Prokisch H Stephens J Glazer NL Cupples LA Okada Y Takahashi A Kamatani Y Matsuda K Tsunoda T Tanaka T Kubo M 《PLoS genetics》2011,7(6):e1002113
White blood cell (WBC) count is a common clinical measure from complete blood count assays, and it varies widely among healthy individuals. Total WBC count and its constituent subtypes have been shown to be moderately heritable, with the heritability estimates varying across cell types. We studied 19,509 subjects from seven cohorts in a discovery analysis, and 11,823 subjects from ten cohorts for replication analyses, to determine genetic factors influencing variability within the normal hematological range for total WBC count and five WBC subtype measures. Cohort specific data was supplied by the CHARGE, HeamGen, and INGI consortia, as well as independent collaborative studies. We identified and replicated ten associations with total WBC count and five WBC subtypes at seven different genomic loci (total WBC count-6p21 in the HLA region, 17q21 near ORMDL3, and CSF3; neutrophil count-17q21; basophil count- 3p21 near RPN1 and C3orf27; lymphocyte count-6p21, 19p13 at EPS15L1; monocyte count-2q31 at ITGA4, 3q21, 8q24 an intergenic region, 9q31 near EDG2), including three previously reported associations and seven novel associations. To investigate functional relationships among variants contributing to variability in the six WBC traits, we utilized gene expression- and pathways-based analyses. We implemented gene-clustering algorithms to evaluate functional connectivity among implicated loci and showed functional relationships across cell types. Gene expression data from whole blood was utilized to show that significant biological consequences can be extracted from our genome-wide analyses, with effect estimates for significant loci from the meta-analyses being highly corellated with the proximal gene expression. In addition, collaborative efforts between the groups contributing to this study and related studies conducted by the COGENT and RIKEN groups allowed for the examination of effect homogeneity for genome-wide significant associations across populations of diverse ancestral backgrounds. 相似文献
132.
Johannes Pr?ll Martin Danzer Stephanie Stabentheiner Norbert Niklas Christa Hackl Katja Hofer Sabine Atzmüller Peter Hufnagl Christian Gülly Hanns Hauser Otto Krieger Christian Gabriel 《DNA research》2011,18(4):201-210
How cells coordinate the immune system activities is important for potentially life-saving organ or stem cell transplantations. Polymorphic immunoregulatory genes, many of them located in the human major histocompatibility complex, impact the process and assure the proper execution of tolerance-versus-activity mechanisms. In haematopoietic stem cell transplantation, on the basis of fully human leukocyte antigen (HLA)-matched donor–recipient pairs, adverse effects like graft versus leukaemia and graft versus host are observed and difficult to handle. So far, high-resolution HLA typing was performed with Sanger sequencing, but for methodological reasons information on additional immunocompetent major histocompatibility complex loci has not been revealed. Now, we have used microarray sequence capture and targeted enrichment combined with next generation pyrosequencing for 3.5 million base pair human major histocompatibility complex resequencing in a clinical transplant setting and describe 3025 variant single nucleotide polymorphisms, insertions and deletions among recipient and donor in a single sequencing experiment. Taken together, the presented data show that sequence capture and massively parallel pyrosequencing can be used as a new tool for risk assessment in the setting of allogeneic stem cell transplantation. 相似文献
133.
Eva Schnabel Stefan Karrasch Holger Schulz Sven Gl?ser Christa Meisinger Margit Heier Annette Peters H-Erich Wichmann Jürgen Behr Rudolf M Huber Joachim Heinrich 《Respiratory research》2011,12(1):50
Background
Several studies showed that blood pressure and lung function are associated. Additionally, a potential effect of antihypertensive medication, especially beta-blockers, on lung function has been discussed. However, side effects of beta-blockers have been investigated mainly in patients with already reduced lung function. Thus, aim of this analysis is to determine whether hypertension and antihypertensive medication have an adverse effect on lung function in a general adult population.Methods
Within the population-based KORA F4 study 1319 adults aged 40-65 years performed lung function tests and blood pressure measurements. Additionally, information on anthropometric measurements, medical history and use of antihypertensive medication was available. Multivariable regression models were applied to study the association between blood pressure, antihypertensive medication and lung function.Results
High blood pressure as well as antihypertensive medication were associated with lower forced expiratory volume in one second (p = 0.02 respectively p = 0.05; R2: 0.65) and forced vital capacity values (p = 0.01 respectively p = 0.05, R2: 0.73). Furthermore, a detailed analysis of antihypertensive medication pointed out that only the use of beta-blockers was associated with reduced lung function, whereas other antihypertensive medication had no effect on lung function. The adverse effect of beta-blockers was significant for forced vital capacity (p = 0.04; R2: 0.65), while the association with forced expiratory volume in one second showed a trend toward significance (p = 0.07; R2: 0.73). In the same model high blood pressure was associated with reduced forced vital capacity (p = 0.01) and forced expiratory volume in one second (p = 0.03) values, too.Conclusion
Our analysis indicates that both high blood pressure and the use of beta-blockers, but not the use of other antihypertensive medication, are associated with reduced lung function in a general adult population. 相似文献134.
Ferdinand Bohlmann Christa Zdero Robert M. King Harold Robinson 《Phytochemistry》1984,23(7):1509-1511
A reinvestigation of the aerial parts of Conocliniopsis prasiifolia afforded two furoheliangolides, conoprasiolide-9-O,5′-O-diacetate and 相似文献
135.
Ferdinand Bohlmann Christa Zdero Robert M. King Harold Robinson 《Phytochemistry》1984,23(5):1185-1187
Perymenium featherstonei afforded, in addition to the known ent-kaurene derivative 4α, 15-dihydroencelin, two closely related epimeric acids. 相似文献
136.
Kayser M Lao O Anslinger K Augustin C Bargel G Edelmann J Elias S Heinrich M Henke J Henke L Hohoff C Illing A Jonkisz A Kuzniar P Lebioda A Lessig R Lewicki S Maciejewska A Monies DM Pawłowski R Poetsch M Schmid D Schmidt U Schneider PM Stradmann-Bellinghausen B Szibor R Wegener R Wozniak M Zoledziewska M Roewer L Dobosz T Ploski R 《Human genetics》2005,117(5):428-443
To test for human population substructure and to investigate human population history we have analysed Y-chromosome diversity using seven microsatellites (Y-STRs) and ten binary markers (Y-SNPs) in samples from eight regionally distributed populations from Poland (n=913) and 11 from Germany (n=1,215). Based on data from both Y-chromosome marker systems, which we found to be highly correlated (r=0.96), and using spatial analysis of the molecular variance (SAMOVA), we revealed statistically significant support for two groups of populations: (1) all Polish populations and (2) all German populations. By means of analysis of the molecular variance (AMOVA) we observed a large and statistically significant proportion of 14% (for Y-SNPs) and 15% (for Y-STRs) of the respective total genetic variation being explained between both countries. The same population differentiation was detected using Monmoniers algorithm, with a resulting genetic border between Poland and Germany that closely resembles the course of the political border between both countries. The observed genetic differentiation was mainly, but not exclusively, due to the frequency distribution of two Y-SNP haplogroups and their associated Y-STR haplotypes: R1a1*, most frequent in Poland, and R1*(xR1a1), most frequent in Germany. We suggest here that the pronounced population differentiation between the two geographically neighbouring countries, Poland and Germany, is the consequence of very recent events in human population history, namely the forced human resettlement of many millions of Germans and Poles during and, especially, shortly after World War II. In addition, our findings have consequences for the forensic application of Y-chromosome markers, strongly supporting the implementation of population substructure into forensic Y chromosome databases, and also for genetic association studies. 相似文献
137.
Generalization and categorization of spectral colors in goldfish I. Experiments with one training wavelength 总被引:1,自引:1,他引:0
Manuela?Kitschmann Christa?NeumeyerEmail author 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》2005,191(11):1025-1036
Goldfish have a tetrachromatic color vision with a high discrimination ability for spectral colors as well as for object colors.
We investigate the question whether goldfish organize the high number of discriminable colors in terms of color categories,
i.e. in a few larger groups of colors independent of wavelength discrimination. Twenty-four goldfish were trained with food
reward, each fish on one out of 13 wavelengths between 371 nm and 630 nm. In transfer tests two different wavelengths were
presented, one shorter and one longer than the training wavelength, and the choice behavior was determined. Choice frequencies
of ≥50% were assumed to indicate similarity to the training color. The wavelength ranges ≥50% were about 100 nm and twice
as large as the just noticeable differences measured in wavelength discrimination tests (Fig. 7). The ranges were surprisingly
about the same for all training wavelengths, provided the data were plotted on a wavelength scale weighted according to discrimination
ability (Fig. 4). Thus, with the training method chosen goldfish showed a kind of categorization which, however, depends on
training wavelength and discrimination ability. Generalization tests in which training wavelength and test wavelengths were
shown separately for 2 min each gave the same results as wavelength discrimination tests (Figs. 5 and 6) and are, therefore,
not indicative for color categories. 相似文献
138.
In previous studies, we have shown that annual expression profiles of cambial and wood tissue with respect to the Shaker K+ channel PTORK correlate with cambial activity. To follow PTORK-gene activity on the cellular level, we isolated the respective promoter regions and generated transgenic Arabidopsis plants expressing the GUS gene under the control of the PTORK promoter. Cross-sections of petioles showed PTORK-driven signals predominantly in the xylem parenchyma surrounding the vessels and in the phloem. Antibodies raised against a unique N-terminal region of PTORK in histo-immunochemical analyses recognised this K+-release channel in growth-active poplar plants only. PTORK labelling was found in differentiating xylem cells (young fibres) and mature xylem (vessel-associated cells of the ray parenchyma). Patch-clamp measurements on fibre cell protoplasts, derived from young poplar twigs, identified outward-rectifying K+ channels as the major K+ conductance of this cell type, which resembled the biophysical properties of PTORK when expressed in Xenopus oocytes.Electronic Supplementary Material Supplementary material is available for this article at
Matthias Arend and Andrea Stinzing contributed equally to this work 相似文献
139.
N-cadherin is not typically expressed by epithelial cells. However, it is detected in breast cancers and increases tumor cell migration and invasion in vitro. To explore its misexpression, we generated transgenic mice with N-cadherin in the mammary epithelium. Mammary glands appeared normal and no tumors arose spontaneously. To investigate N-cadherin misexpression in mammary tumors, neu was overexpressed through breeding. Tumors developed in +/neu and N-cadherin/neu mice, although few tumors in bitransgenic mice expressed N-cadherin, and they did not differ from N-cadherin-negative tumors. 相似文献
140.
Craven C 《Medical anthropology quarterly》2005,19(2):194-215
Based on ethnographic research regarding public policy and grassroots organizing for midwifery in Virginia, this article explores how medical discourses around appropriate health care practices intersect with state discourses about what practices are considered "respectable" versus "pathological" for its citizens. In recent legislative debates about the legalization of direct-entry midwifery, medical officials have extended their criticism of midwifery and homebirth to mothers who resist state-sanctioned childbirth practices. This article examines how medical officials challenge the respectable mothering practices of homebirthers by linking them with women they deem pathological--child abusers, negligent mothers, and drug users--and placing them outside the cadre of "normal" American mothers who acknowledge the "logical" and "natural" superiority of biomedical childbirth practices. I also address homebirth mothers' responses, which assert that their political advocacy for midwives is a respectable mothering practice because they are responsible citizens who desire what they deem the best care for their children. 相似文献