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101.
102.
Gisela G. Slaats Joshua C. Saldivar Julien Bacal Michelle K. Zeman Andrew C. Kile Ann Marie Hynes Shalabh Srivastava Jekaterina Nazmutdinova Krista den Ouden Miriam S. Zagers Veronica Foletto Marianne C. Verhaar Colin Miles John A. Sayer Karlene A. Cimprich Rachel H. Giles 《The Journal of clinical investigation》2015,125(9):3657-3666
Juvenile ciliopathy syndromes that are associated with renal cysts and premature renal failure are commonly the result of mutations in the gene encoding centrosomal protein CEP290. In addition to centrosomes and the transition zone at the base of the primary cilium, CEP290 also localizes to the nucleus; however, the nuclear function of CEP290 is unknown. Here, we demonstrate that reduction of cellular CEP290 in primary human and mouse kidney cells as well as in zebrafish embryos leads to enhanced DNA damage signaling and accumulation of DNA breaks ex vivo and in vivo. Compared with those from WT mice, primary kidney cells from Cep290-deficient mice exhibited supernumerary centrioles, decreased replication fork velocity, fork asymmetry, and increased levels of cyclin-dependent kinases (CDKs). Treatment of Cep290-deficient cells with CDK inhibitors rescued DNA damage and centriole number. Moreover, the loss of primary cilia that results from CEP290 dysfunction was rescued in 3D cell culture spheroids of primary murine kidney cells after exposure to CDK inhibitors. Together, our results provide a link between CEP290 and DNA replication stress and suggest CDK inhibition as a potential treatment strategy for a wide range of ciliopathy syndromes. 相似文献
103.
Aysheshm Kassahun Jovana Sadlova Vit Dvorak Tatiana Kostalova Iva Rohousova Daniel Frynta Tatiana Aghova Daniel Yasur-Landau Wessenseged Lemma Asrat Hailu Gad Baneth Alon Warburg Petr Volf Jan Votypka 《Acta tropica》2015
Human visceral (VL, also known as Kala-azar) and cutaneous (CL) leishmaniasis are important infectious diseases affecting countries in East Africa that remain endemic in several regions of Ethiopia. The transmission and epidemiology of the disease is complicated due to the complex life cycle of the parasites and the involvement of various Leishmania spp., sand fly vectors, and reservoir animals besides human hosts. Particularly in East Africa, the role of animals as reservoirs for human VL remains unclear. Isolation of Leishmania donovani parasites from naturally infected rodents has been reported in several endemic countries; however, the status of rodents as reservoirs in Ethiopia remains unclear. Here, we demonstrated natural Leishmania infections in rodents. Animals were trapped in 41 localities of endemic and non-endemic areas in eight geographical regions of Ethiopia and DNA was isolated from spleens of 586 rodents belonging to 21 genera and 38 species. Leishmania infection was evaluated by real-time PCR of kinetoplast (k)DNA and confirmed by sequencing of the PCR products. Subsequently, parasite species identification was confirmed by PCR and DNA sequencing of the 18S ribosomal RNA internal transcribed spacer one (ITS1) gene. Out of fifty (8.2%) rodent specimens positive for Leishmania kDNA-PCR and sequencing, 10 were subsequently identified by sequencing of the ITS1 showing that five belonged to the L. donovani complex and five to L. tropica. Forty nine kDNA-positive rodents were found in the endemic localities of southern and eastern Ethiopia while only one was identified from northwestern Ethiopia. Moreover, all the ten ITS1-positive rodents were captured in areas where human leishmaniasis cases have been reported and potential sand fly vectors occur. Our findings suggest the eco-epidemiological importance of rodents in these foci of leishmaniasis and indicate that rodents are likely to play a role in the transmission of leishmaniasis in Ethiopia, possibly as reservoir hosts. 相似文献
104.
Urban O Vitek P Fojtik P Kliment M Janik D Chalupa J Albin A 《Hepato-gastroenterology》2008,55(82-83):351-355
BACKGROUND/AIMS: Laterally spreading tumors (LST) are flat elevated neoplastic lesions with diameters equal to or greater than 10 mm. The treatment results of 138 lesions in 131 patients are presented here as a part of a retrospective analysis. METHODOLOGY: Two gastroenterology centers participated in the study in the period from 1/2002-12/2006. During colonoscopy, each superficial lesion was classified according to the Paris endoscopic classification. Endoscopic mucosal resection (EMR) lift and cut was employed. Treatment was considered successful when both endoscopic and histo-pathological criteria of complete resection were fulfilled. RESULTS: A total of 138 LST in 131 patients were diagnosed. Average LST diameter was 25 mm. A total of 5 (3.6%) lesions in 4 patients were referred for primary surgery. One patient was treated with argon plasma coagulation only. EMR was attempted for 132/138 (95.7%) of all LST and was successful in 125 (90.6%) cases. Complications occured in 16/132 (12.1%) patients. Severe complications, defined as decession, emergency surgery, emergency endoscopy and transfusion of eryhrocyte concentrate occured in 5/132 (3.8%). One (0.7%) 69 year-old-male patient died on the third day following EMR due to complications of acute myocardial infarction. CONCLUSION: LST lesions could be efficiently treated with EMR lift and cut method with a reasonable rate of complications. 相似文献
105.
106.
Goure J Broz P Attree O Cornelis GR Attree I 《The Journal of infectious diseases》2005,192(2):218-225
Pathogenic Yersinia species and Pseudomonas aeruginosa share a similar type III secretion/translocation system. The translocation system consists of 3 secreted proteins, YopB/PopB, YopD/PopD, and LcrV/PcrV; the latter is known to be a protective antigen. In an in vitro assay, the translocation system causes the lysis of erythrocytes infected with wild-type (wt) P. aeruginosa. wt Y. enterocolitica is not hemolytic, but a multiknockout mutant deprived of all the effectors and of YopN ( Delta HOPEMN) is hemolytic. In the presence of antibodies against PcrV and Y. pestis LcrV, the hemolytic activity of P. aeruginosa was inhibited. Similarly, the hemolytic activity of Delta HOPEMN was inhibited in the presence of anti-LcrV antibodies. The assembly of the translocon, composed of PopB/D and YopB/D proteins, was disturbed in immunoprotected erythrocyte membranes, mimicking the phenotypes of V knockout mutants. Thus, protective antibodies against the V antigens of Yersinia species and P. aeruginosa act at the level of the formation of the translocon pore in membranes of infected host cells by blocking the function of LcrV/PcrV. The hemolysis assay could be adapted for high-throughput screening of anti-infectious compounds that specifically target the type III translocon. 相似文献
107.
Alan Bulava Petr Heinc Martin Hutyra Milan Kaminek Malvina Krivankova Marek Richter Jan Lukl 《Journal of interventional cardiac electrophysiology》2006,16(2):117-122
A sixty-year-old man with previous history of coronary artery disease was admitted due to progressive worsening of dyspnoea at exertion (NYHA III functional class) and no angina. Coronary angiography confirmed occlusion of the right coronary artery which was naturally bypassed by homocollaterals with TIMI 3 flow to the peripheral branches. The lesion was not technically suitable for percutaneous angioplasty. The left coronary artery was without stenosis. On echocardiography, both the left ventricle and the left atrium were dilated and hemodynamically significant mitral regurgitation was present. Surface ECG showed a left bundle branch block with repeated runs of monomorphic ventricular ectopic beats (PVC). Radiofrequency catheter ablation of the focus in the posteroseptal region of the left ventricle underneath the mitral valve was performed using electroanatomical mapping system. After the procedure, mitral regurgitation decreased and reverse remodeling of the left ventricle and the left atrium occurred with concomitant significant clinical improvement of the patient. The authors discuss several treatment strategies: mitral valve repair surgery combined with revascularization, implantation of a biventricular ICD system or elimination of the focus of monomorphic VT runs by radiofrequency catheter ablation as a possible causal approach in the treatment of PVC-induced cardiomyopathy. 相似文献
108.
Gurpreet Singh Dhillon Shohreh Honarbakhsh Antonio Di Monaco Ann Elizabeth Coling Kernerov Lenka Francesca Pizzamiglio Ross J. Hunter Rodney Horton Moussa Mansour Andrea Natale Vivek Reddy Massimo Grimaldi Petr Neuzil Claudio Tondo Richard J. Schilling 《Journal of cardiovascular electrophysiology》2020,31(6):1259-1269
109.
Arnot Vespalec Josef Novk Alena Kohoutkov Petr Vosynek Jan Podrouek David karoupka Tom Zikmund Josef Kaiser David Palouek 《Materials》2020,13(22)
3D concrete printing technology (3DCP) is a relatively new technology that was first established in the 1990s. The main weakness of the technology is the interface strength between the extruded layers, which are deposited at different time intervals. Consequently, the interface strength is assumed to vary in relation to the time of concrete casting. The proposed experimental study investigated the behavior of a hardened concrete mixture containing coarse aggregates that were up to 8 mm in size, which is rather unusual for 3DCP technology. The resulting direct tensile strength at the layer interface was investigated for various time intervals of deposition from the initial mixing of concrete components. To better understand the material behavior at the layer interface area, computed tomography (CT) scanning was conducted, where the volumetric and area analysis enabled validation of the pore size and count distribution in accordance with the layer deposition process. The analyzed CT data related the macroscopic anisotropy and the resulting crack pattern to the temporal and spatial variability that is inherent to the additive manufacturing process at construction scales while providing additional insights into the porosity formation during the extrusion of the cementitious composite. The observed results contribute to previous investigations in this field by demonstrating the causal relationships, namely, how the interface strength development is determined by time, deposition process, and pore size distribution. Moreover, in regard to the printability of the proposed coarse aggregate mixture, the specific time interval is presented and its interplay with interface roughness and porosity is discussed. 相似文献
110.
New-generation oxide dispersion-strengthened (ODS) alloys with a high volume fraction of nano-oxides of 5% are intended to become the leading creep- and oxidation-resistant alloys for applications at 1100–1300 °C. Hot consolidation of mechanically alloyed powders by intensive plastic deformation followed by heat treatment of the alloys are the key aspects for achieving top creep properties, typically ensured by a coarse-grained microstructure strengthened with homogeneously dispersed, very stable yttrium nano-oxides. The rotary swaging method proves to be favourable for hot consolidation of the new-generation ODS alloy presented. Compared to specimens consolidated by hot rolling, consolidation by hot rotary swaging predetermines the formation of coarse grains with a very high aspect ratio during subsequent secondary recrystallization. Such a grain morphology increases the creep strength of the new-generation ODS alloy considerably. 相似文献