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51.
Markus Draaken Michael Knapp Tracie Pennimpede Johanna M. Schmidt Anne-Karolin Ebert Wolfgang R?sch Raimund Stein Boris Utsch Karin Hirsch Thomas M. Boemers Elisabeth Mangold Stefanie Heilmann Kerstin U. Ludwig Ekkehart Jenetzky Nadine Zwink Susanne Moebus Bernhard G. Herrmann Manuel Mattheisen Markus M. N?then Michael Ludwig Heiko Reutter 《PLoS genetics》2015,11(3)
The bladder exstrophy-epispadias complex (BEEC) represents the severe end of the uro-rectal malformation spectrum, and is thought to result from aberrant embryonic morphogenesis of the cloacal membrane and the urorectal septum. The most common form of BEEC is isolated classic bladder exstrophy (CBE). To identify susceptibility loci for CBE, we performed a genome-wide association study (GWAS) of 110 CBE patients and 1,177 controls of European origin. Here, an association was found with a region of approximately 220kb on chromosome 5q11.1. This region harbors the ISL1 (ISL LIM homeobox 1) gene. Multiple markers in this region showed evidence for association with CBE, including 84 markers with genome-wide significance. We then performed a meta-analysis using data from a previous GWAS by our group of 98 CBE patients and 526 controls of European origin. This meta-analysis also implicated the 5q11.1 locus in CBE risk. A total of 138 markers at this locus reached genome-wide significance in the meta-analysis, and the most significant marker (rs9291768) achieved a P value of 2.13 × 10−12. No other locus in the meta-analysis achieved genome-wide significance. We then performed murine expression analyses to follow up this finding. Here, Isl1 expression was detected in the genital region within the critical time frame for human CBE development. Genital regions with Isl1 expression included the peri-cloacal mesenchyme and the urorectal septum. The present study identified the first genome-wide significant locus for CBE at chromosomal region 5q11.1, and provides strong evidence for the hypothesis that ISL1 is the responsible candidate gene in this region. 相似文献
52.
Riegler B Besenboeck C Bauer R Nimpf J Schneider WJ 《Biochemical and biophysical research communications》2011,(2):257-261
In laying hens, massive hepatic mobilization of fatty acids is required for the synthesis of oocyte-targeted very-low density lipoproteins (VLDL). The current study aims at identification of enzymes that hydrolyze hepatic acylglycerol stores regulated in a fashion compatible with supporting enhanced VLDL synthesis. We show that unlike mammals, chickens express adipose triglyceride lipase (ATGL) also in liver, where it is upregulated by fasting, while the enzyme patatin-like phospholipase domain-containing lipase 3 (PNPLA3) is suppressed. For the first time in any system, we show that hepatic arylacetamide deacetylase (AADA) is upregulated by fasting, and that its affinity for an insoluble carboxylester substrate is compatible with an in-vivo function similar to that of ATGL. Unknown heretofore, hepatic expression of chicken AADA is estrogen-responsive, and is induced to the same degree as the stimulation of VLDL-production by estrogen. These observations support roles of chicken ATGL, PNPLA3, and AADA in acylglycerol metabolism related to the high rates of VLDL synthesis that are essential for reproduction. 相似文献
53.
Mason A. Chilmonczyk Peter A. Kottke Hazel Y. Stevens Robert E. Guldberg Andrei G. Fedorov 《Biotechnology and bioengineering》2019,116(1):121-131
Large-scale manufacturing of therapeutic cells requires bioreactor technologies with online feedback control enabled by monitoring of secreted biomolecular critical quality attributes (CQAs). Electrospray ionization mass spectrometry (ESI-MS) is a highly sensitive label-free method to detect and identify biomolecules, but requires extensive sample preparation before analysis, making online application of ESI-MS challenging. We present a microfabricated, monolithically integrated device capable of continuous sample collection, treatment, and direct infusion for ESI-MS detection of biomolecules in high-salt solutions. The dynamic mass spectrometry probe (DMSP) uses a microfluidic mass exchanger to rapidly condition samples for online MS analysis by removing interfering salts, while concurrently introducing MS signal enhancers to the sample for sensitive biomolecular detection. Exploiting this active conditioning capability increases MS signal intensity and signal-to-noise ratio. As a result, sensitivity for low-concentration biomolecules is significantly improved, and multiple proteins can be detected from chemically complex samples. Thus, the DMSP has significant potential to serve as an enabling portion of a novel analytical tool for discovery and monitoring of CQAs relevant to therapeutic cell manufacturing. 相似文献
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Mádi A Hoffrogge R Blaskó B Glocker MO Fésüs L 《Biochemical and biophysical research communications》2004,315(4):1064-1069
Transglutaminase dependent cross-linking of proteins has been implicated in a wide range of biological phenomena occurring in both extracellular and intracellular compartments. Clarification of the physiological role of transglutaminases requires identification of substrate molecules. Here we report the detection, purification, and identification by mass spectrometry of proteins, the glutamate dehydrogenase, a protein disulfide isomerase, and aldehyde dehydrogenase as amine donor substrates for the transglutaminase activity of the nematode Caenorhabditis elegans utilizing a novel biotinylated oligoglutamine peptide as a substrate. We also purified and identified streptavidin-binding proteins of the worm. 相似文献
58.
Kuznetsov AV Troppmair J Sucher R Hermann M Saks V Margreiter R 《Biochimica et biophysica acta》2006,1757(5-6):686-691
Heterogeneity of mitochondria has been reported for a number of various cell types. Distinct mitochondrial subpopulations may be present in the cell and may be differently involved in physiological and pathological processes. However, the origin and physiological roles of mitochondrial heterogeneity are still unknown. In mice skeletal muscle, a much higher oxidized state of subsarcolemmal mitochondria as compared with intermyofibrillar mitochondria has been demonstrated. Using confocal imaging technique, we present similar phenomenon for rat soleus and gastrocnemius muscles, where higher oxidative state of mitochondrial flavoproteins correlates also with elevated mitochondrial calcium. Moreover, subsarcolemmal mitochondria demonstrate distinct arrangement and organization. In HL-1 cardiomyocytes, long thread mitochondria and small grain mitochondria are observed irrespective of a particular cellular region, showing also heterogeneous membrane potential and ROS production. Possible physiological roles of intracellular mitochondrial heterogeneity and specializations are discussed. 相似文献
59.
Lutz A Müller Tobias E Nowak Michael V?lk Rocco P Pitto David Pfander Raimund Forst Rainer Schmidt Stephan Eichinger 《Biomedizinische Technik》2006,51(3):139-144
AIMS: We prospectively analyzed the cancellous and cortical periprosthetic femoral bone reaction after implantation of a cementless total hip arthroplasty with computertomography assisted osteodensitometry after a mean of 1 and 6 years. MATERIALS AND METHODS: Twenty-one patients (? age at implantation: 52 years) with osteoarthrits of the hip joint received 21 cementless hip prostheses with a three-dimensionally tapered design. All patients were analyzed clinically, with CT-osteodensitometry and plain radiography after a mean of 10 days, at 1 and 6 years postoperatively. Cancellous and cortical bone density was evaluated automatically using a special software tool. RESULTS: The proximal region of the stem showed progessive cortical (? -15% 1 year, -25% 6 years post-OP) and cancellous (? -26% 1 year, -49% 6 years post-OP) bone density loss. Cortical bone density loss was lower and non-progressive at the diaphysis (? -7% 1 year, -9% 6 years post-OP) and the distal region (? -6% 1 year, -4% 6 years post-OP) of the stem. All stems showed no signs of loosening on plain radiography and good clinical results according to the Harris hip score. CONCLUSION: Computertomography assisted osteodensitometry is the only method which allows discrimination between periprosthetic cortical and cancellous bone density changes in vivo. The analyzed uncemented stem fixates at the diaphysis and distal region. Due to the changed biomechanical loading after stem implantation, progressive proximal cancellous bone density loss was measured for the first time in vivo. Its role in the pathogenesis of implant loosening is still unknown and needs to be further elucidated. 相似文献
60.
Martin Hoffmann Dirk Pohlers Dirk Koczan Hans-Jürgen Thiesen Stefan Wölfl Raimund W Kinne 《BMC bioinformatics》2006,7(1):369-16