排序方式: 共有122条查询结果,搜索用时 15 毫秒
21.
Kerstin Hahn Cecilia Rohdin Vidhya Jagannathan Peter Wohlsein Wolfgang Baumg?rtner Frauke Seehusen Ingo Spitzbarth Rodrigo Grandon Cord Dr?gemüller Karin Hultin J?derlund 《PloS one》2015,10(11)
Clinical, pathological and genetic examination revealed an as yet uncharacterized juvenile-onset neuroaxonal dystrophy (NAD) in Spanish water dogs. Affected dogs presented with various neurological deficits including gait abnormalities and behavioral deficits. Histopathology demonstrated spheroid formation accentuated in the grey matter of the cerebral hemispheres, the cerebellum, the brain stem and in the sensory pathways of the spinal cord. Iron accumulation was absent. Ultrastructurally spheroids contained predominantly closely packed vesicles with a double-layered membrane, which were characterized as autophagosomes using immunohistochemistry. The family history of the four affected dogs suggested an autosomal recessive inheritance. SNP genotyping showed a single genomic region of extended homozygosity of 4.5 Mb in the four cases on CFA 8. Linkage analysis revealed a maximal parametric LOD score of 2.5 at this region. By whole genome re-sequencing of one affected dog, a perfectly associated, single, non-synonymous coding variant in the canine tectonin beta-propeller repeat-containing protein 2 (TECPR2) gene affecting a highly conserved region was detected (c.4009C>T or p.R1337W). This canine NAD form displays etiologic parallels to an inherited TECPR2 associated type of human hereditary spastic paraparesis (HSP). In contrast to the canine NAD, the spinal cord lesions in most types of human HSP involve the sensory and the motor pathways. Furthermore, the canine NAD form reveals similarities to cases of human NAD defined by widespread spheroid formation without iron accumulation in the basal ganglia. Thus TECPR2 should also be considered as candidate gene for human NAD. Immunohistochemistry and the ultrastructural findings further support the assumption, that TECPR2 regulates autophagosome accumulation in the autophagic pathways. Consequently, this report provides the first genetic characterization of juvenile canine NAD, describes the histopathological features associated with the TECPR2 mutation and provides evidence to emphasize the association between failure of autophagy and neurodegeneration. 相似文献
22.
Vidhya V. Iyer P. Yoga Priya Jeipreeti Kangeyavelu 《Molecular and cellular biochemistry》2018,446(1-2):91-103
We investigated the eplerenone-induced, PI3K/Akt- and GSK-3β-mediated cardioprotection against ischemia/reperfusion (I/R) injury in diabetic rats. The study groups comprising diabetic rats were treated for 14 days with 150 mg/kg/day eplerenone orally and 1 mg/kg wortmannin (PI3K/Akt antagonist) intraperitoneally with eplerenone. On the 15th day, the rats were exposed to I/R injury by 20-min occlusion of the left anterior descending coronary artery followed by 30 min of reperfusion. The hearts were processed for biochemical, molecular, and histological investigations. The I/R injury in diabetic rats inflicted a significant rise in the oxidative stress and apoptosis along with a decrease in the arterial and ventricular function and the expressions of PI3K/Akt and GSK-3β proteins. Eplerenone pretreatment reduced the arterial pressure, cardiac inotropy, and lusitropy. It significantly reduced apoptosis and cardiac injury markers. The histology revealed cardioprotection in eplerenone-treated rats. Eplerenone up-regulated the PI3K/Akt and reduced the GSK-3β expression. The group receiving wortmannin with eplerenone was deprived eplerenone-induced cardioprotection. Our results reveal the eplerenone-induced cardioprotection against I/R injury in diabetic rats and substantiate the involvement of PI3K/Akt and GSK-3β pathways in its efficacy. 相似文献
23.
24.
Marjo K. Hyt?nen Meharji Arumilli Anu K. Lappalainen Marta Owczarek-Lipska Vidhya Jagannathan Sruthi Hundi Elina Salmela Patrick Venta Eva Sarkiala Tarja Jokinen Daniela Gorgas Juha Kere Pekka Nieminen Cord Dr?gemüller Hannes Lohi 《PLoS genetics》2016,12(5)
One to two percent of all children are born with a developmental disorder requiring pediatric hospital admissions. For many such syndromes, the molecular pathogenesis remains poorly characterized. Parallel developmental disorders in other species could provide complementary models for human rare diseases by uncovering new candidate genes, improving the understanding of the molecular mechanisms and opening possibilities for therapeutic trials. We performed various experiments, e.g. combined genome-wide association and next generation sequencing, to investigate the clinico-pathological features and genetic causes of three developmental syndromes in dogs, including craniomandibular osteopathy (CMO), a previously undescribed skeletal syndrome, and dental hypomineralization, for which we identified pathogenic variants in the canine SLC37A2 (truncating splicing enhancer variant), SCARF2 (truncating 2-bp deletion) and FAM20C (missense variant) genes, respectively. CMO is a clinical equivalent to an infantile cortical hyperostosis (Caffey disease), for which SLC37A2 is a new candidate gene. SLC37A2 is a poorly characterized member of a glucose-phosphate transporter family without previous disease associations. It is expressed in many tissues, including cells of the macrophage lineage, e.g. osteoclasts, and suggests a disease mechanism, in which an impaired glucose homeostasis in osteoclasts compromises their function in the developing bone, leading to hyperostosis. Mutations in SCARF2 and FAM20C have been associated with the human van den Ende-Gupta and Raine syndromes that include numerous features similar to the affected dogs. Given the growing interest in the molecular characterization and treatment of human rare diseases, our study presents three novel physiologically relevant models for further research and therapy approaches, while providing the molecular identity for the canine conditions. 相似文献
25.
Vidhya Hindu S. Chandrasekaran Natarajan Mukherjee Amitava Thomas John 《Probiotics and antimicrobial proteins》2018,10(2):356-366
Probiotics and Antimicrobial Proteins - The aim of the present work was to isolate probiotic bacteria from the intestinal tract of healthy freshwater prawn Macrobrachium rosenbergii and to examine... 相似文献
26.
27.
Matthias Christen Sandra Hgler Miriam Kleiter Michael Leschnik Corinna Weber Denise Thaller Vidhya Jagannathan Tosso Leeb 《PLoS genetics》2021,17(8)
We investigated a hereditary cerebellar ataxia in Belgian Shepherd dogs. Affected dogs developed uncoordinated movements and intention tremor at two weeks of age. The severity of clinical signs was highly variable. Histopathology demonstrated atrophy of the CNS, particularly in the cerebellum. Combined linkage and homozygosity mapping in a family with four affected puppies delineated a 52 Mb critical interval. The comparison of whole genome sequence data of one affected dog to 735 control genomes revealed a private homozygous structural variant in the critical interval, Chr4:66,946,539_66,963,863del17,325. This deletion includes the entire protein coding sequence of SELENOP and is predicted to result in complete absence of the encoded selenoprotein P required for selenium transport into the CNS. Genotypes at the deletion showed the expected co-segregation with the phenotype in the investigated family. Total selenium levels in the blood of homozygous mutant puppies of the investigated litter were reduced to about 30% of the value of a homozygous wildtype littermate. Genotyping >600 Belgian Shepherd dogs revealed an additional homozygous mutant dog. This dog also suffered from pronounced ataxia, but reached an age of 10 years. Selenop-/- knock-out mice were reported to develop ataxia, but their histopathological changes were less severe than in the investigated dogs. Our results demonstrate that deletion of the SELENOP gene in dogs cause a defect in selenium transport associated with CNS atrophy and cerebellar ataxia (CACA). The affected dogs represent a valuable spontaneous animal model to gain further insights into the pathophysiological consequences of CNS selenium deficiency. 相似文献
28.
Neelakandan Vidhya Lakshmi Prakasam Thirumurugan K.M. Noorulla Paramasivan.T. Perumal 《Bioorganic & medicinal chemistry letters》2010,20(17):5054-5061
A simple and convenient method for the one-pot three-component synthesis of 3-pyranyl indoles has been accomplished by tandem Knoevenagel–Michael reaction of 3-cyanoacetyl indole, various aromatic aldehydes and malononitrile catalyzed by InCl3 in ethanol under reflux conditions. The newly synthesized 3-pyranyl indoles were evaluated for anti-microbial, antioxidant, and anticancer activities. Some of the compounds showed good anticancer activity against MCF-7 breast cancer cell lines on comparison with of standard drug. 相似文献
29.
Brooks DM Hernández-Guzmán G Kloek AP Alarcón-Chaidez F Sreedharan A Rangaswamy V Peñaloza-Vázquez A Bender CL Kunkel BN 《Molecular plant-microbe interactions : MPMI》2004,17(2):162-174
To identify Pseudomonas syringae pv. tomato genes involved in pathogenesis, we carried out a screen for Tn5 mutants of P. syringae pv. tomato DC3000 with reduced virulence on Arabidopsis thaliana. Several mutants defining both known and novel virulence loci were identified. Six mutants contained insertions in biosynthetic genes for the phytotoxin coronatine (COR). The P. syringae pv. tomato DC3000 COR genes are chromosomally encoded and are arranged in two separate clusters, which encode enzymes responsible for the synthesis of coronafacic acid (CFA) or coronamic acid (CMA), the two defined intermediates in COR biosynthesis. High-performance liquid chromatography fractionation and exogenous feeding studies confirmed that Tn5 insertions in the cfa and cma genes disrupt CFA and CMA biosynthesis, respectively. All six COR biosynthetic mutants were significantly impaired in their ability to multiply to high levels and to elicit disease symptoms on A. thaliana plants. To assess the relative contributions of CFA, CMA, and COR in virulence, we constructed and characterized cfa6 cmaA double mutant strains. These exhibited virulence phenotypes on A. thalliana identical to those observed for the cmaA or cfa6 single mutants, suggesting that reduced virulence of these mutants on A. thaliana is caused by the absence of the intact COR toxin. This is the first study to use biochemically and genetically defined COR mutants to address the role of COR in pathogenesis. 相似文献
30.
Joseph B Srinivasan A Soumittra N Vidhya A Shetty NS Uthra S Kumaramanickavel G 《Journal of genetics》2002,81(1):19-23
We used multiplex PCR followed by sequencing to screen for mutations in the 14 exons of theRPE65 gene in early-hildhood-onset autosomal recessive retinitis pigmentosa (arRP) and Leber’s congenital amaurosis (LCA) patients.
The RPE65 protein is believed to play an important role in the metabolism of vitamin A in the visual cycle and mutations identified
in the gene could have implications for vitamin A-based therapeutic intervention. We were able to identify a homozygous mutation
(AAT → AAG) in exon 9 in an arRP patient and a heterozygous missense transversion (AAT → AAG) also in exon 9 of an LCA patient.
We also identified a polymorphism in exon 10 (GAG → GAA) in an arRP as well as an LCA patient. Mutation screening would be
greatly facilitated by multiplex PCR which could cut down costs, labour and time involved. The nucleotide changes observed
in this study could bede novo. Though a larger study has been undertaken, from the preliminary results it appears that in India theRPE65 gene seems to be less involved in causation of LCA. 相似文献