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41.
Deficiency in expression of the signaling protein Sin/Efs leads to T-lymphocyte activation and mucosal inflammation 下载免费PDF全文
Donlin LT Danzl NM Wanjalla C Alexandropoulos K 《Molecular and cellular biology》2005,25(24):11035-11046
Our studies have concentrated on elucidating the role of the signaling protein Sin in T-lymphocyte function. We have previously shown that Sin overexpression inhibits T-lymphocyte development and activation. Here we show that Sin-deficient mice exhibit exaggerated immune responses characterized by enhanced cytokine secretion and T-cell-dependent antibody production. Excessive T-cell responses in young mice correlate with spontaneous development of inflammatory lesions in different organs of aged Sin(-/-) mice, particularly the small intestine. The intestinal inflammation is characterized by T- and B-cell infiltrates in the lamina propria, which correlate with crypt enlargement and marked villus expansion and/or damage. Similar to the human intestinal inflammatory disorder Crohn's disease (CD), and in contrast to most mouse models of mucosal inflammation, inflammatory lesions in the gastrointestinal tract of Sin(-/-) mice are restricted to the small bowel. Taken together, these results suggest that Sin regulates immune system and T-lymphocyte function and that immune system dysfunction in the absence of Sin may underlie the pathogenesis of tissue-specific inflammation and enteropathies such as CD. 相似文献
42.
Jane Bjerg Jensen Andrew C. Lysaght M. Charles Liberman Klaus Qvortrup Konstantina M. Stankovic 《PloS one》2015,10(5)
Moderate acoustic overexposure in adult rodents is known to cause acute loss of synapses on sensory inner hair cells (IHCs) and delayed degeneration of the auditory nerve, despite the completely reversible temporary threshold shift (TTS) and morphologically intact hair cells. Our objective was to determine whether a cochlear synaptopathy followed by neuropathy occurs after noise exposure in pubescence, and to define neuropathic versus non-neuropathic noise levels for pubescent mice. While exposing 6 week old CBA/CaJ mice to 8-16 kHz bandpass noise for 2 hrs, we defined 97 dB sound pressure level (SPL) as the threshold for this particular type of neuropathic exposure associated with TTS, and 94 dB SPL as the highest non-neuropathic noise level associated with TTS. Exposure to 100 dB SPL caused permanent threshold shift although exposure of 16 week old mice to the same noise is reported to cause only TTS. Amplitude of wave I of the auditory brainstem response, which reflects the summed activity of the cochlear nerve, was complemented by synaptic ribbon counts in IHCs using confocal microscopy, and by stereological counts of peripheral axons and cell bodies of the cochlear nerve from 24 hours to 16 months post exposure. Mice exposed to neuropathic noise demonstrated immediate cochlear synaptopathy by 24 hours post exposure, and delayed neurodegeneration characterized by axonal retraction at 8 months, and spiral ganglion cell loss at 8-16 months post exposure. Although the damage was initially limited to the cochlear base, it progressed to also involve the cochlear apex by 8 months post exposure. Our data demonstrate a fine line between neuropathic and non-neuropathic noise levels associated with TTS in the pubescent cochlea. 相似文献
43.
Juan Carlos Lopez-Delgado Francisco Esteve Rafael Manez Herminia Torrado Maria L. Carrio David Rodríguez-Castro Elisabet Farrero Casimiro Javierre Konstantina Skaltsa Josep L. Ventura 《PloS one》2015,10(3)
Purpose
Obesity influences risk stratification in cardiac surgery in everyday practice. However, some studies have reported better outcomes in patients with a high body mass index (BMI): this is known as the obesity paradox. The aim of this study was to quantify the effect of diverse degrees of high BMI on clinical outcomes after cardiac surgery, and to assess the existence of an obesity paradox in our patients.Methods
A total of 2,499 consecutive patients requiring all types of cardiac surgery with cardiopulmonary bypass between January 2004 and February 2009 were prospectively studied at our institution. Patients were divided into four groups based on BMI: normal weight (18.5–24.9 kg∙m−2; n = 523; 21.4%), overweight (25–29.9kg∙m−2; n = 1150; 47%), obese (≥30–≤34.9kg∙m−2; n = 624; 25.5%) and morbidly obese (≥35kg∙m−2; n = 152; 6.2%). Follow-up was performed in 2,379 patients during the first year.Results
After adjusting for confounding factors, patients with higher BMI presented worse oxygenation and better nutritional status, reflected by lower PaO2/FiO2 at 24h and higher albumin levels 48h after admission respectively. Obese patients showed a higher risk for Perioperative Myocardial Infarction (OR: 1.768; 95% CI: 1.035–3.022; p = 0.037) and septicaemia (OR: 1.489; 95% CI: 1.282–1.997; p = 0.005). In-hospital mortality was 4.8% (n = 118) and 1-year mortality was 10.1% (n = 252). No differences were found regarding in-hospital mortality between BMI groups. The overweight group showed better 1-year survival than normal weight patients (91.2% vs. 87.6%; Log Rank: p = 0.029. HR: 1.496; 95% CI: 1.062–2.108; p = 0.021).Conclusions
In our population, obesity increases Perioperative Myocardial Infarction and septicaemia after cardiac surgery, but does not influence in-hospital mortality. Although we found better 1-year survival in overweight patients, our results do not support any protective effect of obesity in patients undergoing cardiac surgery. 相似文献44.
Zagris N Gilipathi K Soulintzi N Konstantopoulos K 《The International journal of developmental biology》2011,55(6):633-639
Decorin, a proteoglycan, interacts with extracellular matrix proteins, growth factors and receptors. Decorin expression and spatio-temporal distribution were studied by RT-PCR and immunofluorescence, while decorin function was examined by blocking antibodies in the early chick embryo. Decorin was first detectable at stage XIII (late blastula). During gastrulation (stage HH3-4), decorin fluorescence was intense in epiblast cells immediately adjacent to the streak, and in migrating cells. Decorin fluorescence was intense in endoderm and strong at mesoderm-neural plate surfaces at stage HH5-6 (neurula). At stage HH10-11 (12 somites), decorin fluorescence was intense in myelencephalon and then showed distinct expression patterns along the myelencephalon axes by stage HH17. Decorin fluorescence was intense in neural crest cells, dorsal aorta, heart, somite and neuroepithelial cells apposing the somite, nephrotome, gut and in pancreatic and liver primordia. Antibody-mediated inhibition of decorin function affected the head-to-tail embryonic axis extension, indicating that decorin is essential for convergent extension cell movements during avian gastrulation. Decorin was also essential for retinal progenitor cell polarization, neural crest migration, somite boundary formation and cell polarization, mesenchymal cell polarization and primary endoderm displacement to the embryo periphery. The embryonic blood vessels were deformed, the dorsal mesocardium was thinned and the cardiac jelly was abnormally thickened in the heart. Decorin is known to modulate collagen fibrillogenesis, a key mechanism of matrix assembly, and cell proliferation. Decorin also appears to be essential for the coordination of cell and tissue polarization, which is an important feature in organ patterning of the embryo. 相似文献
45.
Kouyanou-Koutsoukou S Baier A Kolaitis RM Maniatopoulou E Thanopoulou K Szyszka R 《Molecular and cellular biochemistry》2011,356(1-2):261-267
The Mediterranean fruit fly Ceratitis capitata is an insect capable of wreaking extensive damage to a wide range of fruit crops. Protein kinase CK2 is a ubiquitous Ser/Thr kinase that is highly conserved among eukaryotes; it is a heterotetramer composed of two catalytic (α) and a dimer of regulatory (β) subunits. We present here the construction of the cDNA molecules of the CK2α and CK2β subunits from the medfly C. capitata by the 5'/3' RACE and RT-PCR methods, respectively. CcCK2α catalytic subunit presents the characteristic and conserved features of a typical protein kinase, similar to the regulatory CcCK2β subunit, that also possess the conserved features of regulatory CK2β subunits, as revealed by comparison of their predicted amino acid sequences with other eukaryotic species. The recombinant CcCK2α and CcCK2β proteins were purified by affinity chromatography to homogeneity, after overexpression in Escherichia coli. CcCK2α is capable to utilize GTP and its activity and is inhibited by polyanions and stimulated by polycations in phosphorylation assays, using purified acidic ribosomal protein P1 as a substrate. 相似文献
46.
Paulidou A Giastas P Mourtzis N Yannakopoulou K Mavridis IM 《Carbohydrate research》2007,342(11):1519-1524
Octakis(6-bromo-6-deoxy)cyclomaltooctaose, perbrominated gamma-cyclodextrin at the primary side, crystallises from methanol in a very unique manner. The macrocycles are quite distorted in contrast to their beta-cyclodextrin analogue, heptakis(6-bromo-6-deoxy)cyclomaltoheptaose. The two monomers, arranged head-to-head, form a completely new kind of dimer by mutually entering into each other, both at the primary and the secondary sides. At the primary, hydrophobic side, they interact by Br...Br interactions and at the secondary, hydrophilic side, by direct H-bonds between hydroxylic groups. The short contacts of the Br atoms contribute to the macrocycle's distortion, which is considerable compared to the few available structures of gamma-CDs persubstituted at the primary side with bulkier and in some occasions charged substituents. Water and methanol molecules are entrapped in the cyclodextrin cavity, mostly in the area of the secondary hydroxylic groups connecting the macrocycles by indirect H-bonds. Thus the solvent molecules strengthen the association of the two monomers and contribute to the stabilisation of the cavity. The monomers stack along the a-axis and form columns that align in parallel lines along the same axis resulting in the formation of alternating hydrophobic and hydrophilic layers perpendicular to the a-axis resembling in this respect, the structure of the analogous perbrominated beta-cyclodextrin. 相似文献
47.
Konstantina Zografou Vassiliki Kati Andrea Grill Robert J. Wilson Elli Tzirkalli Lazaros N. Pamperis John M. Halley 《PloS one》2014,9(1)
The European protected-area network will cease to be efficient for biodiversity conservation, particularly in the Mediterranean region, if species are driven out of protected areas by climate warming. Yet, no empirical evidence of how climate change influences ecological communities in Mediterranean nature reserves really exists. Here, we examine long-term (1998–2011/2012) and short-term (2011–2012) changes in the butterfly fauna of Dadia National Park (Greece) by revisiting 21 and 18 transects in 2011 and 2012 respectively, that were initially surveyed in 1998. We evaluate the temperature trend for the study area for a 22-year-period (1990–2012) in which all three butterfly surveys are included. We also assess changes in community composition and species richness in butterfly communities using information on (a) species’ elevational distributions in Greece and (b) Community Temperature Index (calculated from the average temperature of species'' geographical ranges in Europe, weighted by species'' abundance per transect and year). Despite the protected status of Dadia NP and the subsequent stability of land use regimes, we found a marked change in butterfly community composition over a 13 year period, concomitant with an increase of annual average temperature of 0.95°C. Our analysis gave no evidence of significant year-to-year (2011–2012) variability in butterfly community composition, suggesting that the community composition change we recorded is likely the consequence of long-term environmental change, such as climate warming. We observe an increased abundance of low-elevation species whereas species mainly occurring at higher elevations in the region declined. The Community Temperature Index was found to increase in all habitats except agricultural areas. If equivalent changes occur in other protected areas and taxonomic groups across Mediterranean Europe, new conservation options and approaches for increasing species’ resilience may have to be devised. 相似文献
48.
Tzetis M Stefanaki K Syrmou A Kosma K Leze E Giannikou K Oikonomakis V Sofocleous C Choulakis M Kolialexi A Makrythanasis P Kitsiou-Tzeli S 《Birth defects research. Part A, Clinical and molecular teratology》2012,94(7):561-566
BACKGROUND Cat-Eye syndrome (CES) with teratoma has not been previously reported. We present the clinical and molecular findings of a 9-month-old girl with features of CES and also a palpable midline neck mass proved to be an extragonadal mature teratoma, additionally characterized by array comparative genomic hybridization (aCGH). RESULTS High resolution oligonucleotide-based aCGH confirmed that the supernumerary marker chromosome (SMC) derived from chromosome 22, as was indicated by molecular cytogenetic analysis with fluorescence in situ hybridization (FISH). Additionally, aCGH clarified the size, breakpoints, and gene content of the duplication (dup 22q11.1q11.21; size:1.6 Mb; breakpoints: 15,438,946-17,041,773; hg18). The teratoma tissue was also tested with aCGH, in which the CES duplication was not found, but the analysis revealed three aberrations: del Xp22.3 (108,864-2788,689; 2.7 Mb hg18), dup Yp11.2 (6688,491-7340,982; 0.65 Mb, hg18), and dup Yq11.2q11.23 (12,570,853-27,177,133; 14.61 Mb, hg18). These results indicated 46 XY (male) karyotype of the teratoma tissue, making this the second report of mature extragonadal teratoma in a female neonate, probably deriving from an included dizygotic twin of opposite sex (fetus in fetu). CONCLUSIONS Our findings extend the phenotypic spectrum of CES syndrome, a disorder with clinical variability, pointing out specific dosage-sensitive genes that might contribute to specific phenotypic features. 相似文献
49.
Vassiliki Kati Konstantina Zografou Elli Tzirkalli Theodoros Chitos Luc Willemse 《Journal of Insect Conservation》2012,16(6):807-818
The present paper studies butterfly, grasshopper and vascular plant communities in ten seasonally flooded grasslands with different anthropogenic disturbance regimes (NW Greece). Disturbance intensity was assessed on the basis of disturbance frequency and type (grazing, mowing, trampling, constructions). The distribution patterns of butterflies are regulated by humidity and elevation (Redundancy Analysis). Elevation, flower-heads abundance, low disturbance intensity and plant species richness predict grasshopper species richness well, while the latter together with humidity predict plant species richness (Generalized Linear Models). Chorthippus lacustris, a critically endangered endemic grasshopper species, is positively associated with humid microhabitats with high flower-heads abundance. An indicator value procedure reveals four butterfly species as being typical species for habitats with a pronounced character of hedgerows and tree lines. Conservation management of grassland butterflies should focus on the maintenance of the humid character of the humid grasslands as well as on the maintenance of hedgerows and tree lines. The reduction of human-induced disturbance towards occasional grazing and mowing seems to benefit both butterfly and grasshopper communities. Finally, we suggest the use of grasshoppers as surrogates for vascular plants and vice versa, given their congruent species richness patterns. 相似文献
50.
K Giannikou H Fryssira V Oikonomakis A Syrmou K Kosma M Tzetis S Kitsiou-Tzeli E Kanavakis 《Gene》2012,506(2):360-368
High resolution oligonucleotide array Comparative Genome Hybridization technology (array-CGH) has greatly assisted the recognition of the 1p36 contiguous gene deletion syndrome. The 1p36 deletion syndrome is considered to be one of the most common subtelomeric microdeletion syndromes and has an incidence of ~1 in 5000 live births, while respectively the "pure" 1p36 microduplication has not been reported so far. We present seven new patients who were referred for genetic evaluation due to Developmental Delay (DD), Mental Retardation (MR), and distinct dysmorphic features. They all had a wide phenotypic spectrum. In all cases previous standard karyotypes were negative. Array-CGH analysis revealed five patients with interstitial 1p36 microdeletion (four de novo and one maternal) and two patients with de novo reciprocal duplication of different sizes. These were the first reported "pure" 1p36 microduplication cases so far. Three of our patients carrying the 1p36 microdeletion syndrome were also found to have additional pathogenetic aberrations. These findings (del 3q27.1; del 4q21.22-q22.1; del 16p13.3; dup 21q21.2-q21.3; del Xp22.12) might contribute to the patients' severe phenotype, acting as additional modifiers of their clinical manifestations. We review and compare the clinical and array-CGH findings of our patients to previously reported cases with the aim of clearly delineating more accurate genotype-phenotype correlations for the 1p36 syndrome that could allow for a more precise prognosis. 相似文献