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961.
Shiyan Yu Yingchao Nie Byron Knowles Ryotaro Sakamori Ewa Stypulkowski Chirag Patel Soumyashree Das Veronique Douard Ronaldo P Ferraris Edward M Bonder James R Goldenring Yicktung Tony Ip Nan Gao 《The EMBO journal》2014,33(17):1882-1895
Compartmentalization of Toll‐like receptors (TLRs) in intestinal epithelial cells (IECs) regulates distinct immune responses to microbes; however, the specific cellular machinery that controls this mechanism has not been fully identified. Here we provide genetic evidences that the recycling endosomal compartment in enterocytes maintains a homeostatic TLR9 intracellular distribution, supporting mucosal tolerance to normal microbiota. Genetic ablation of a recycling endosome resident small GTPase, Rab11a, a gene adjacent to a Crohn's disease risk locus, in mouse IECs and in Drosophila midgut caused epithelial cell‐intrinsic cytokine production, inflammatory bowel phenotype, and early mortality. Unlike wild‐type controls, germ‐free Rab11a‐deficient mouse intestines failed to tolerate the intraluminal stimulation of microbial agonists. Thus, Rab11a endosome controls intestinal host‐microbial homeostasis at least partially via sorting TLRs. 相似文献
962.
Chizu Nakamoto Soh-Leh Kuan Amy S. Findlay Elaine Durward Zhufeng Ouyang Ewa D. Zakrzewska Takuma Endo Masaru Nakamoto 《Molecular biology of the cell》2014,25(2):234-244
For correct functioning of the nervous system, the appropriate number and complement of neuronal cell types must be produced during development. However, the molecular mechanisms that regulate the production of individual classes of neurons are poorly understood. In this study, we investigate the function of the thrombospondin-1–like glycoprotein, Nel (neural epidermal growth factor [EGF]-like), in the generation of retinal ganglion cells (RGCs) in chicks. During eye development, Nel is strongly expressed in the presumptive retinal pigment epithelium and RGCs. Nel overexpression in the developing retina by in ovo electroporation increases the number of RGCs, whereas the number of displaced amacrine cells decreases. Conversely, knockdown of Nel expression by transposon-mediated introduction of RNA interference constructs results in decrease in RGC number and increase in the number of displaced amacrine cells. Modifications of Nel expression levels do not appear to affect proliferation of retinal progenitor cells, but they significantly alter the progression rate of RGC differentiation from the central retina to the periphery. Furthermore, Nel protects RGCs from apoptosis during retinal development. These results indicate that Nel positively regulates RGC production by promoting their differentiation and survival during development. 相似文献
963.
964.
Magdalena Bartnik Beata Nowakowska Katarzyna Derwińska Barbara Wiśniowiecka-Kowalnik Marta Kędzior Joanna Bernaciak Kamila Ziemkiewicz Tomasz Gambin Maciej Sykulski Natalia Bezniakow Lech Korniszewski Anna Kutkowska-Kaźmierczak Jakub Klapecki Krzysztof Szczałuba Chad A. Shaw Tadeusz Mazurczak Anna Gambin Ewa Obersztyn Ewa Bocian Paweł Stankiewicz 《Journal of applied genetics》2014,55(1):125-144
We used whole-genome exon-targeted oligonucleotide array comparative genomic hybridization (array CGH) in a cohort of 256 patients with developmental delay (DD)/intellectual disability (ID) with or without dysmorphic features, additional neurodevelopmental abnormalities, and/or congenital malformations. In 69 patients, we identified 84 non-polymorphic copy-number variants, among which 41 are known to be clinically relevant, including two recently described deletions, 4q21.21q21.22 and 17q24.2. Chromosomal microarray analysis revealed also 15 potentially pathogenic changes, including three rare deletions, 5q35.3, 10q21.3, and 13q12.11. Additionally, we found 28 copy-number variants of unknown clinical significance. Our results further support the notion that copy-number variants significantly contribute to the genetic etiology of DD/ID and emphasize the efficacy of the detection of novel candidate genes for neurodevelopmental disorders by whole-genome array CGH. 相似文献
965.
Aleksandra Biedrzycka Andrzej Zalewski Magdalena Bartoszewicz Henryk Okarma Ewa Jędrzejewska 《Biological invasions》2014,16(8):1611-1625
Invasions of non-native species are of great concern as they have a devastating impact on native biodiversity and can also affect the economy of a region. Multiple introductions in several locations of a new range greatly promote the success of non-native species. The raccoon (Procyon lotor) is an omnivore whose native distribution extends from southern Canada to Panama. It has been successfully introduced in many European countries. We examined the microsatellite and mitochondrial diversity of raccoon populations in Central Europe (Germany, Poland, and Czech Republic) in order to determine their introduction sources and pathways as well as the factors affecting genetic structure in this invasive species. We found low diversity of the mtDNA control region and moderate diversity of microsatellite markers. Raccoon showed three hierarchic levels of genetic structure which separate at different levels sampled from Czech Republic, Germany and raccoon inhabiting two different habitats in Poland. In Poland the raccoon population was established through migration from Germany to Czech Republic. Analysis of the intensity of migration between two different habitat types indicated source-sink dynamics in the Polish populations of raccoons. Our results confirm the high intensity of the raccoon invasion in Central Europe and point to specific measures needed as part of an effective management strategy. 相似文献
966.
Ewa Przybytkowski Elizabeth Lenkiewicz Michael T Barrett Kathleen Klein Sheida Nabavi Celia MT Greenwood Mark Basik 《BMC genomics》2014,15(1)
Background
Chromosomal breakage followed by faulty DNA repair leads to gene amplifications and deletions in cancers. However, the mere assessment of the extent of genomic changes, amplifications and deletions may reduce the complexity of genomic data observed by array comparative genomic hybridization (array CGH). We present here a novel approach to array CGH data analysis, which focuses on putative breakpoints responsible for rearrangements within the genome.Results
We performed array comparative genomic hybridization in 29 primary tumors from high risk patients with breast cancer. The specimens were flow sorted according to ploidy to increase tumor cell purity prior to array CGH. We describe the number of chromosomal breaks as well as the patterns of breaks on individual chromosomes in each tumor. There were differences in chromosomal breakage patterns between the 3 clinical subtypes of breast cancers, although the highest density of breaks occurred at chromosome 17 in all subtypes, suggesting a particular proclivity of this chromosome for breaks. We also observed chromothripsis affecting various chromosomes in 41% of high risk breast cancers.Conclusions
Our results provide a new insight into the genomic complexity of breast cancer. Genomic instability dependent on chromosomal breakage events is not stochastic, targeting some chromosomes clearly more than others. We report a much higher percentage of chromothripsis than described previously in other cancers and this suggests that massive genomic rearrangements occurring in a single catastrophic event may shape many breast cancer genomes.Electronic supplementary material
The online version of this article (doi:10.1186/1471-2164-15-579) contains supplementary material, which is available to authorized users. 相似文献967.
968.
Pawel Romaszko Ewa M. Slominska Ryszard T. Smolenski 《Nucleosides, nucleotides & nucleic acids》2014,33(4-6):333-337
We recently described a new nicotinamide derivative: 4-pyridone-3-carboxamide ribonucleoside (4PYR) and its conversion to intracellular metabolites (4PYR monophosphate: 4PYMP and 4PYR adenylate diphosphate: 4PYRAD). The aim of this study was to clarify the metabolism and physiological effects of brief exposure to 4PYR in perfused rat heart. Rat hearts were perfused in Langendorff mode. After 15 min equilibration, 100 μM 4PYR (or solvent in controls) was infused into coronary circulation for 5 min. Coronary flow was recorded with electromagnetic flow meter and left ventricular mechanical function was assessed with intraventricular baloon by constructing pressure–volume relations. After perfusion hearts were freeze-clamped and analyzed using HPLC for phosphocreatine, creatine, ATP with metabolites as well as 4PYR metabolites. 4PYR infused into the coronary circulation was rapidly converted in the heart into 4PYMP and 4PYRAD with concentrations reaching 85.6 ± 46.9 and 43.9 ± 6.4 nmol/g dry weight, respectively, while control concentrations were below 20 nmol/g. 4PYR had no effect on baseline coronary flow (11.9 ± 2.3 ml/min versus 11.0 ± 2.7 ml/min in control) or stimulated by shear stress (23.2 ± 4.5 ml/min versus 23.1 ± 5.2 ml/min in control). Both systolic and diastolic left ventricular mechanical function were not affected by 4PYR. No difference was noted for heart rate. Myocardial concentrations of ATP or phosphocreatine were also not affected by 4PYR. We conclude that 4PYR has no immediate effect on coronary endothelium or cardiomyocyte functions such as coronary flow, rhythm, diastolic properties, or contractility despite rapid incorporation into intracellular metabolites. This study also indicates the lack of effect on purinergic receptors. 相似文献
969.
Ewa Kaniewska Alicja Sielicka Padmini Sarathchandra Iwona Pelikant-Małecka Mariola Olkowicz Ewa M. Słomińska 《Nucleosides, nucleotides & nucleic acids》2014,33(4-6):305-312
Extracellular nucleotides control mechanisms such as thrombosis or inflammation that are important in several pathologies, including heart valve disease and calcification. Ectonucleoside triphosphate diphosphohydrolase 1 (eNTPD1, CD39) and ecto-5′-nucleotidase (e5NT, CD73) are ectoenzymes that convert adenosine triphosphate to adenosine diphosphate, adenosine monophosphate and finally to adenosine. Changes in activities of these enzymes influence extracellular nucleotide concentrations and therefore could be involved in valve pathology. This study aimed to analyze type of cells, specific area, level of expression and biochemical function of CD39 and CD73 in pig aortic valves. Samples were collected from aortic valves of domestic pigs. Histological sections were cut from paraffin embedded tissue blocks. Following incubation with primary antibody against CD39 or CD73, washing and secondary goat anti-rabbit secondary antibodies, slides were viewed with NanoZoomer scanner. Substantial expression CD39 and CD73 was observed in two main types of valve cells: endothelial and valve interstitial cells. Subsequently, biochemical function of CD39 and CD73 was evaluated in cells cultured from pig aortic valve. Breakdown of extracellular nucleotides added to cell medium was analyzed with high performance liquid chromatography. In the interstitial cells, the CD73 products formation was much faster than in endothelium, while for the CD39 activity this relation was opposite. Expression and high concentration of CD39 and CD73 products in endothelium are expected, but presence of CD73 in valve interstitial cells is a surprise. We conclude that CD39 and CD73 and their enzymatic activities that convert extracellular nucleotides are highly expressed and could have special function in the valve. 相似文献
970.
Thomas Tilling Ewa Wladykowski Antonio Virgilio Failla Pia Houdek Johanna M. Brandner Ingrid Moll 《Histochemistry and cell biology》2014,141(4):407-421
Merkel cells, the neurosecretory cells of skin, are essential for light-touch responses and may probably fulfill additional functions. Whether these cells derive from an epidermal or a neural lineage has been a matter of dispute for a long time. In mice, recent studies have clearly demonstrated an epidermal origin of Merkel cells. Given the differences in Merkel cell distribution between human and murine skin, it is, however, unclear whether the same holds true for human Merkel cells. We therefore attempted to gain insight into the human Merkel cell lineage by co-immunodetection of the Merkel cell marker protein cytokeratin 20 (CK20) with various proteins known to be expressed either in epidermal or in neural stem cells of the skin. Neither Sox10 nor Pax3, both established markers of the neural crest lineage, exhibited any cell co-labeling with CK20. By contrast, β1 integrin, known to be enriched in epidermal stem cells, was found in nearly 70 % of interfollicular epidermal and 25 % of follicular Merkel cells. Moreover, LRIG1, also enriched in epidermal stem cells, displayed significant co-immunolabeling with CK20 as well (approximately 20 % in the interfollicular epidermis and 7 % in the hair follicle, respectively). Further epidermal markers were detected in sporadic Merkel cells. Cells co-expressing CK20 with epidermal markers may represent a transitory state between stem cells and differentiated cells. β1 integrin is probably also synthesized by a large subset of mature Merkel cells. Summarizing, our data suggest that human Merkel cells may originate from epidermal rather than neural progenitors. 相似文献