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Sample records for degeneration pcd mouse

  1. Mapping of the Sca1 and pcd genes on mouse chromosome 13 provides evidence that they are different genes

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    Servadio, A.; McCall, A.; Zoghbi, H. [Baylor College of Medicine, Houston, TX (United States); Eicher, E.M. [Jackson Laboratory, Bar Harbor, ME (United States)

    1995-10-10

    It is well established that large chromosomal segments have remained intact during the evolution of different mammalian species. Thus, mapping information for a gene in mammalian species facilitates mapping the same gene in another mammalian species. In addition, phenotypically similar diseases that map to linkage conserved regions in two species may be caused by mutations in the same gene. Spinocerebellar ataxia type 1 (SCA1) is a dominantly inherited human disorder characterized by progressive ataxia, dysarthria, and dysmetria. SCA1 maps to the short arm of human chromosome (Chr) 6 in the 6p23-p22 region. SCA1 is caused by the expansion of an unstable CAG repeat located within the coding region of a novel protein, ataxin-1, Purkinje cell degeneration (pcd) is a recessively inherited mouse disorder characterized by a moderate ataxia, usually noted by 3-4 weeks of age. Progressive degeneration of Purkinje cells is the underlying pathogenesis in this disorder. The pcd gene was assigned to mouse Chr 13 because it showed linkage to extra toes (Xt) and pearl (pe). Some doubt about this assignment existed, however, because the calculated genetic distance between pcd and Xt was 32 cM and that between pcd and pe was 18 cM. If pcd is located in Chr 13, its placement relative to Xt and pe suggests that it would be located in the region that shares linkage homology with the region that shares linkage homology with the region of human Chr 6 that contains SCA1. Here, we present data that confirm the assignment of pcd to Chr 13, map the mouse Sca1 gene to Chr 13, and eliminate Sca1 as a candidate gene for pcd. 11 refs., 1 tab.

  2. Lack of Cytosolic Carboxypeptidase 1 Leads to Subfertility due to the Reduced Number of Antral Follicles in pcd3J-/- Females.

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    Ning Song

    Full Text Available Females homozygous for the Purkinje cell degeneration mutation (pcd are fertile, although the success rate is much lower than in the wild type. We performed detailed analysis of reproductive abnormalities of pcd females. The number of oocytes produced following exogenous gonadotropin treatment was much lower in pcd3J-/- females than in pcd3J+/+ females. Furthermore, the estrous cyclicity of pcd3J-/- females according to the appearance of the vagina was almost undetectable comparing to that of the wild type. Histological analyses and follicle counting of 4- and 8-week-old pcd3J-/- ovaries showed an increase in the number of secondary follicles and a decrease in the number of antral follicles, indicating that AGTPBP1/ CCP1 plays an important role in the development of secondary follicles into antral follicles. Consistent with a previous analysis of the pcd cerebellum, pcd3J-/- ovaries also showed a clear increase in the level of polyglutamylation. Gene expression analysis showed that both oocytes and cumulus cells express CCP1. However, Ccp4 and CCP6, which can compensate the function of CCP1, were not expressed in mouse ovaries. Failure of microtubule deglutamylation did not affect the structure and function of the meiotic spindle in properly aligning chromosomes in the center of the nucleus during meiosis in pcd3J-/- females. We also showed that the pituitary-derived growth and reproduction-related endocrine system functions normally in pcd3J-/- mice. The results of this study provide insight into additional functions of CCP1, which cannot be fully explained by the side chain deglutamylation of microtubules alone.

  3. Acute energy restriction triggers Wallerian degeneration in mouse

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    Alvarez, Susana; Moldovan, Mihai; Krarup, Christian

    2008-01-01

    the neurotoxic effect of NO with the effect of the mitochondrial uncoupler 2,4-dinitrophenol (DNP) on electrically active axons of mouse sciatic nerve. The right tibial nerve was stimulated at the ankle. Muscle responses were recorded from plantar muscles and ascending nerve action potentials were recorded form...... the exposed sciatic nerve by means of a hook electrode. The sciatic nerve was focally immersed over a length of 1 cm in either phosphate buffered saline (PBS), a solution of approximately 4 microM NO obtained from 10 mM of the NO-donor DETA NONOate, or a solution of up to 1 mM DNP. Following 3 hours of 200 Hz...

  4. Antioxidants Halt Axonal Degeneration in a Mouse Model of X-Adrenoleukodystrophy

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    López-Erauskin, Jone; Fourcade, Stéphane; Galino, Jorge; Ruiz, Montserrat; Schlüter, Agatha; Naudi, Alba; Jove, Mariona; Portero-Otin, Manuel; Pamplona, Reinald; Ferrer, Isidre; Pujol, Aurora

    2011-01-01

    Objective Axonal degeneration is a main contributor to disability in progressive neurodegenerative diseases in which oxidative stress is often identified as a pathogenic factor. We aim to demonstrate that antioxidants are able to improve axonal degeneration and locomotor deficits in a mouse model of X-adrenoleukodystrophy (X-ALD). Methods X-ALD is a lethal disease caused by loss of function of the ABCD1 peroxisomal transporter of very long chain fatty acids (VLCFA). The mouse model for X-ALD exhibits a late onset neurological phenotype with locomotor disability and axonal degeneration in spinal cord resembling the most common phenotype of the disease, adrenomyeloneuropathy (X-AMN). Recently, we identified oxidative damage as an early event in life, and the excess of VLCFA as a generator of radical oxygen species (ROS) and oxidative damage to proteins in X-ALD. Results Here, we prove the capability of the antioxidants N-acetyl-cysteine, α-lipoic acid, and α-tocopherol to scavenge VLCFA-dependent ROS generation in vitro. Furthermore, in a preclinical setting, the cocktail of the 3 compounds reversed: (1) oxidative stress and lesions to proteins, (2) immunohistological signs of axonal degeneration, and (3) locomotor impairment in bar cross and treadmill tests. Interpretation We have established a direct link between oxidative stress and axonal damage in a mouse model of neurodegenerative disease. This conceptual proof of oxidative stress as a major disease-driving factor in X-AMN warrants translation into clinical trials for X-AMN, and invites assessment of antioxidant strategies in axonopathies in which oxidative damage might be a contributing factor. Ann Neurol 2011; PMID:21786300

  5. Programmed cell death (PCD an essential process of cereal seed development and germination

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    Fernando eDomínguez

    2014-07-01

    Full Text Available The life cycle of cereal seeds can be divided into two phases, development and germination, separated by a quiescent period. Seed development and germination require the growth and differentiation of new tissues, but also the ordered disappearance of cells, which takes place by a process of programmed cell death (PCD. For this reason, cereal seeds have become excellent model systems for the study of developmental PCD in plants. At early stages of seed development, maternal tissues such as the nucellus, the pericarp and the nucellar projections undergo a progressive degeneration by PCD, which allows the remobilization of their cellular contents for nourishing new filial tissues such as the embryo and the endosperm. At a later stage, during seed maturation, the endosperm undergoes PCD, but these cells remain intact in the mature grain and their contents will not be remobilized until germination. Thus, the only tissues that remain alive when seed development is completed are the embryo axis, the scutellum and the aleurone layer. In germinating seeds, both the scutellum and the aleurone layer play essential roles in producing the hydrolytic enzymes for the mobilization of the storage compounds of the starchy endosperm, which serve to support early seedling growth. Once this function is completed, scutellum and aleurone cells undergo PCD; their contents being used to support the growth of the germinated embryo. PCD occurs with tightly controlled spatial-temporal patterns allowing coordinated fluxes of nutrients between the different seed tissues. In this review, we will summarize the current knowledge of the tissues undergoing PCD in developing and germinating cereal seeds, focussing on the biochemical features of the process. The effect of hormones and redox regulation on PCD control will be discussed.

  6. Loss of Ikbkap Causes Slow, Progressive Retinal Degeneration in a Mouse Model of Familial Dysautonomia

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    Ramirez, Grisela

    2016-01-01

    Abstract Familial dysautonomia (FD) is an autosomal recessive congenital neuropathy that is caused by a mutation in the gene for inhibitor of kappa B kinase complex-associated protein (IKBKAP). Although FD patients suffer from multiple neuropathies, a major debilitation that affects their quality of life is progressive blindness. To determine the requirement for Ikbkap in the developing and adult retina, we generated Ikbkap conditional knockout (CKO) mice using a TUBA1a promoter-Cre (Tα1-Cre). In the retina, Tα1-Cre expression is detected predominantly in retinal ganglion cells (RGCs). At 6 months, significant loss of RGCs had occurred in the CKO retinas, with the greatest loss in the temporal retina, which is the same spatial phenotype observed in FD, Leber hereditary optic neuropathy, and dominant optic atrophy. Interestingly, the melanopsin-positive RGCs were resistant to degeneration. By 9 months, signs of photoreceptor degeneration were observed, which later progressed to panretinal degeneration, including RGC and photoreceptor loss, optic nerve thinning, Müller glial activation, and disruption of layers. Taking these results together, we conclude that although Ikbkap is not required for normal development of RGCs, its loss causes a slow, progressive RGC degeneration most severely in the temporal retina, which is later followed by indirect photoreceptor loss and complete retinal disorganization. This mouse model of FD is not only useful for identifying the mechanisms mediating retinal degeneration, but also provides a model system in which to attempt to test therapeutics that may mitigate the loss of vision in FD patients. PMID:27699209

  7. An extracellular proteolytic cascade promotes neuronal degeneration in the mouse hippocampus.

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    Tsirka, S E; Rogove, A D; Bugge, T H; Degen, J L; Strickland, S

    1997-01-15

    Mice lacking the serine protease tissue plasminogen activator (tPA) are resistant to excitotoxin-mediated hippocampal neuronal degeneration. We have used genetic and cellular analyses to study the role of tPA in neuronal cell death. Mice deficient for the zymogen plasminogen, a known substrate for tPA, are also resistant to excitotoxins, implicating an extracellular proteolytic cascade in degeneration. The two known components of this cascade, tPA and plasminogen, are both synthesized in the mouse hippocampus. tPA mRNA and protein are present in neurons and microglia, whereas plasminogen mRNA and protein are found exclusively in neurons. tPA-deficient mice exhibit attenuated microglial activation as a reaction to neuronal injury. In contrast, the microglial response of plasminogen-deficient mice was comparable to that of wild-type mice, suggesting a tPA-mediated, plasminogen-independent pathway for activation of microglia. Infusion of inhibitors of the extracellular tPA/plasmin proteolytic cascade into the hippocampus protects neurons against excitotoxic injury, suggesting a novel strategy for intervening in neuronal degeneration.

  8. Inner retinal change in a novel rd1-FTL mouse model of retinal degeneration

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    Ursula eGreferath

    2015-07-01

    Full Text Available While photoreceptor loss is the most devastating result of inherited retinal degenerations such as retinitis pigmentosa, inner retinal neurons also undergo significant alteration. Detailing these changes has become important as many vision restorative therapies target the remaining neurons. In this study, the rd1-Fos-Tau-LacZ (rd1-FTL mouse model was used to explore inner retinal change at a late stage of retinal degeneration, after the loss of photoreceptor nuclei. The rd1-FTL model carries a mutation in the phosphodiesterase gene, Pde6b, and an axonally targeted transgenic beta galactosidase reporter system under the control of the c-fos promoter. Retinae of transgenic rd1-FTL mice and control FTL animals aged 2 to 12 months were processed for indirect fluorescence immunocytochemistry. At 2 months of age, a time when the majority of photoreceptor nuclei are lost, there was negligible c-fos reporter (FTL expression, however, from 4 months, reporter expression was observed to increase within subpopulations of amacrine and ganglion cells within the central retina. These areas of inner retinal FTL expression coincided with regions that contained aberrant Müller cells. Specifically, these cells exhibited reduced glutamine synthetase and Kir4.1 immunolabelling, whilst showing evidence of proliferative gliosis (increased cyclinD1 and GFAP expression. These changes were limited to distinct regions where cone photoreceptor terminals were absent. Overall, these results highlight that distinct areas of the rd1-FTL central retina undergo significant glial alterations after cone photoreceptor loss. These areas coincide with up-regulation of the c-fos reporter in the inner retina, which may represent a change in neuronal function/plasticity. The rd1-FTL mouse is a useful model system to probe changes that occur in the inner retina at later stages of retinal degeneration.

  9. DNAH6 and Its Interactions with PCD Genes in Heterotaxy and Primary Ciliary Dyskinesia

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    Onuoha, Ezenwa Obi; Damerla, Rama Rao; Francis, Richard; Furutani, Yoshiyuki; Tariq, Muhammad; King, Stephen M.; Hendricks, Gregory; Cui, Cheng; Saydmohammed, Manush; Lee, Dong Min; Zahid, Maliha; Sami, Iman; Leatherbury, Linda; Pazour, Gregory J.; Ware, Stephanie M.; Nakanishi, Toshio; Goldmuntz, Elizabeth; Tsang, Michael; Lo, Cecilia W.

    2016-01-01

    Heterotaxy, a birth defect involving left-right patterning defects, and primary ciliary dyskinesia (PCD), a sinopulmonary disease with dyskinetic/immotile cilia in the airway are seemingly disparate diseases. However, they have an overlapping genetic etiology involving mutations in cilia genes, a reflection of the common requirement for motile cilia in left-right patterning and airway clearance. While PCD is a monogenic recessive disorder, heterotaxy has a more complex, largely non-monogenic etiology. In this study, we show mutations in the novel dynein gene DNAH6 can cause heterotaxy and ciliary dysfunction similar to PCD. We provide the first evidence that trans-heterozygous interactions between DNAH6 and other PCD genes potentially can cause heterotaxy. DNAH6 was initially identified as a candidate heterotaxy/PCD gene by filtering exome-sequencing data from 25 heterotaxy patients stratified by whether they have airway motile cilia defects. dnah6 morpholino knockdown in zebrafish disrupted motile cilia in Kupffer’s vesicle required for left-right patterning and caused heterotaxy with abnormal cardiac/gut looping. Similarly DNAH6 shRNA knockdown disrupted motile cilia in human and mouse respiratory epithelia. Notably a heterotaxy patient harboring heterozygous DNAH6 mutation was identified to also carry a rare heterozygous PCD-causing DNAI1 mutation, suggesting a DNAH6/DNAI1 trans-heterozygous interaction. Furthermore, sequencing of 149 additional heterotaxy patients showed 5 of 6 patients with heterozygous DNAH6 mutations also had heterozygous mutations in DNAH5 or other PCD genes. We functionally assayed for DNAH6/DNAH5 and DNAH6/DNAI1 trans-heterozygous interactions using subthreshold double-morpholino knockdown in zebrafish and showed this caused heterotaxy. Similarly, subthreshold siRNA knockdown of Dnah6 in heterozygous Dnah5 or Dnai1 mutant mouse respiratory epithelia disrupted motile cilia function. Together, these findings support an oligogenic disease

  10. DNAH6 and Its Interactions with PCD Genes in Heterotaxy and Primary Ciliary Dyskinesia.

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    You Li

    2016-02-01

    Full Text Available Heterotaxy, a birth defect involving left-right patterning defects, and primary ciliary dyskinesia (PCD, a sinopulmonary disease with dyskinetic/immotile cilia in the airway are seemingly disparate diseases. However, they have an overlapping genetic etiology involving mutations in cilia genes, a reflection of the common requirement for motile cilia in left-right patterning and airway clearance. While PCD is a monogenic recessive disorder, heterotaxy has a more complex, largely non-monogenic etiology. In this study, we show mutations in the novel dynein gene DNAH6 can cause heterotaxy and ciliary dysfunction similar to PCD. We provide the first evidence that trans-heterozygous interactions between DNAH6 and other PCD genes potentially can cause heterotaxy. DNAH6 was initially identified as a candidate heterotaxy/PCD gene by filtering exome-sequencing data from 25 heterotaxy patients stratified by whether they have airway motile cilia defects. dnah6 morpholino knockdown in zebrafish disrupted motile cilia in Kupffer's vesicle required for left-right patterning and caused heterotaxy with abnormal cardiac/gut looping. Similarly DNAH6 shRNA knockdown disrupted motile cilia in human and mouse respiratory epithelia. Notably a heterotaxy patient harboring heterozygous DNAH6 mutation was identified to also carry a rare heterozygous PCD-causing DNAI1 mutation, suggesting a DNAH6/DNAI1 trans-heterozygous interaction. Furthermore, sequencing of 149 additional heterotaxy patients showed 5 of 6 patients with heterozygous DNAH6 mutations also had heterozygous mutations in DNAH5 or other PCD genes. We functionally assayed for DNAH6/DNAH5 and DNAH6/DNAI1 trans-heterozygous interactions using subthreshold double-morpholino knockdown in zebrafish and showed this caused heterotaxy. Similarly, subthreshold siRNA knockdown of Dnah6 in heterozygous Dnah5 or Dnai1 mutant mouse respiratory epithelia disrupted motile cilia function. Together, these findings support an

  11. 细胞凋亡及p5 3基因的表达在C5 7BL/6N系小鼠腭裂形成中的意义%The significance of PCD and mRNA transcription of p53 gene during development of normal palate and cleft palate in C57BL/6N mouse

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    李鑫; 金岩; 董绍忠; 朱萧玲

    2000-01-01

    Objectives :To observe the difference of programmed cell death (PCD) and the expression of related gene p53 in the development of normal palate and in the formation of cleft palate. Methods:The model of the development of cleft palat was estabished with retinoid acid (80 mg · kg-1 for each pregnant mouse). The palate samples were obtained at GD1314(at 13rd day 14 hours of prenancy) ,1322,148 ,1414,1433 ,158 ,1522 and 168 respectively. PCD was detected with TUNEL staining,while the mRNA transcription of p53 was observed by in situ hybridization. Rssults:In early development of palate process, the positive index of PCD in the cleft palate samples was significantly higher than that in the normal (P<0.01). But no difference was observed in the expression of p53 (P>0.05) between the two groups. Conclusion:The proliferation of mesenchymal cells of the early developmental palate process may be inhibited due to the abnomal PCD in the formation of cleft palate. The mechanism of PCD in this study may be a p53-independed pathway.%目的:探讨细胞程序性死亡和相关基因p53的表达变化在腭裂发生中的意义。方法:利用建立的腭裂模型,采用原位末端转移酶标记法(TUNEL)和基因探针原位杂交法,原位观察了二种阳性信号的表达。结果:实验组小鼠腭突发育的垂直期、上抬期中细胞程序性死亡明显多于对照组(P<0.01)。但两组间p53 mRNA转录水平的变化均无明显差异(P>o.05)。对照组小鼠生长早期p53基因的表达高于同组融合期的腭突。结论:在腭突发育时期出现超出生理范围的细胞程序死亡,影响腭突以后形态、体积的发育,与腭裂形成有密切关系。p53基因在两组中表达无明显变化,提示腭突间充质细胞的程序性死亡,可能是通过非p53依赖途径发生的。

  12. Expression of EFR3A in the mouse cochlea during degeneration of spiral ganglion following hair cell loss.

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    Chen Nie

    Full Text Available Retrograde degeneration of spiral ganglion cells in the cochlea following hair cell loss is similar to dying back in pathology. The EFR3A gene has recently been discovered to be involved in the pathogenesis of dying back. The relationship of EFR3A and spiral ganglion degeneration, however, was rarely investigated. In this study, we destroyed the hair cells of the mouse cochlea by co-administration of kanamycin and furosemide and then investigated the EFR3A expression during the induced spiral ganglion cell degeneration. Our results revealed that co-administration of kanamycin and furosemide quickly induced hair cell loss in the C57BL/6J mice and then resulted in progressive degeneration of the spiral ganglion beginning at day 5 following drug administration. The number of the spiral ganglion cells began to decrease at day 15. The expression of EFR3A increased remarkably in the spiral ganglion at day 5 and then decreased to near normal level within the next 10 days. Our study suggested that the change of EFR3A expression in the spiral ganglion was coincident with the time of the spiral ganglion degeneration, which implied that high expression of EFR3A may be important to prompt initiation of spiral ganglion degeneration following hair cell loss.

  13. Cell degeneration and mitosis in the buccopharyngeal and branchial membranes in the mouse embryo.

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    Poelmann, R E; Dubois, S V; Hermsen, C; Smits-van Prooije, A E; Vermeij-Keers, C

    1985-01-01

    The frequencies of cell degeneration and mitosis were investigated in the rupturing buccopharyngeal membrane (BPM) and in the persistent first branchial membrane (BM). In the BPM, cell degeneration starts many hours before rupture is visible, but mitotic figures are absent. In the BM this situation is reversed: mitotic figures are regularly observed, but a degenerating cell only occasionally. It is concluded that the ratio between the numbers of degenerating and dividing cells regulates the fate of both the BPM and the BM.

  14. Otx2 gene deletion in adult mouse retina induces rapid RPE dystrophy and slow photoreceptor degeneration.

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    Francis Béby

    Full Text Available BACKGROUND: Many developmental genes are still active in specific tissues after development is completed. This is the case for the homeobox gene Otx2, an essential actor of forebrain and head development. In adult mouse, Otx2 is strongly expressed in the retina. Mutations of this gene in humans have been linked to severe ocular malformation and retinal diseases. It is, therefore, important to explore its post-developmental functions. In the mature retina, Otx2 is expressed in three cell types: bipolar and photoreceptor cells that belong to the neural retina and retinal pigment epithelium (RPE, a neighbour structure that forms a tightly interdependent functional unit together with photoreceptor cells. METHODOLOGY/PRINCIPAL FINDINGS: Conditional self-knockout was used to address the late functions of Otx2 gene in adult mice. This strategy is based on the combination of a knock-in CreERT2 allele and a floxed allele at the Otx2 locus. Time-controlled injection of tamoxifen activates the recombinase only in Otx2 expressing cells, resulting in selective ablation of the gene in its entire domain of expression. In the adult retina, loss of Otx2 protein causes slow degeneration of photoreceptor cells. By contrast, dramatic changes of RPE activity rapidly occur, which may represent a primary cause of photoreceptor disease. CONCLUSIONS: Our novel mouse model uncovers new Otx2 functions in adult retina. We show that this transcription factor is necessary for long-term maintenance of photoreceptors, likely through the control of specific activities of the RPE.

  15. Oxidative damage compromises energy metabolism in the axonal degeneration mouse model of X-adrenoleukodystrophy.

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    Galino, Jorge; Ruiz, Montserrat; Fourcade, Stéphane; Schlüter, Agatha; López-Erauskin, Jone; Guilera, Cristina; Jove, Mariona; Naudi, Alba; García-Arumí, Elena; Andreu, Antoni L; Starkov, Anatoly A; Pamplona, Reinald; Ferrer, Isidre; Portero-Otin, Manuel; Pujol, Aurora

    2011-10-15

    Chronic metabolic impairment and oxidative stress are associated with the pathogenesis of axonal dysfunction in a growing number of neurodegenerative conditions. To investigate the intertwining of both noxious factors, we have chosen the mouse model of adrenoleukodystrophy (X-ALD), which exhibits axonal degeneration in spinal cords and motor disability. The disease is caused by loss of function of the ABCD1 transporter, involved in the import and degradation of very long-chain fatty acids (VLCFA) in peroxisomes. Oxidative stress due to VLCFA excess appears early in the neurodegenerative cascade. In this study, we demonstrate by redox proteomics that oxidative damage to proteins specifically affects five key enzymes of glycolysis and TCA (Tricarboxylic acid) cycle in spinal cords of Abcd1(-) mice and pyruvate kinase in human X-ALD fibroblasts. We also show that NADH and ATP levels are significantly diminished in these samples, together with decrease of pyruvate kinase activities and GSH levels, and increase of NADPH. Treating Abcd1(-) mice with the antioxidants N-acetylcysteine and α-lipoic acid (LA) prevents protein oxidation; preserves NADH, NADPH, ATP, and GSH levels; and normalizes pyruvate kinase activity, which implies that oxidative stress provoked by VLCFA results in bioenergetic dysfunction, at a presymptomatic stage. Our results provide mechanistic insight into the beneficial effects of antioxidants and enhance the rationale for translation into clinical trials for X-adrenoleukodystrophy.

  16. Metabolic anatomy of paraneoplastic cerebellar degeneration

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    Anderson, N.E.; Posner, J.B.; Sidtis, J.J.; Moeller, J.R.; Strother, S.C.; Dhawan, V.; Rottenberg, D.A.

    1988-06-01

    Eleven patients with acquired cerebellar degeneration (10 of whom had paraneoplastic cerebellar degeneration (PCD)) were evaluated using neuropsychological tests and /sup 18/F-fluorodeoxyglucose/positron emission tomography to (1) quantify motor, cognitive, and metabolic abnormalities; (2) determine if characteristic alterations in the regional cerebral metabolic rate for glucose (rCMRGlc) are associated with PCD; and (3) correlate behavioral and metabolic measures of disease severity. Eighteen volunteer subjects served as normal controls. Although some PCD neuropsychological test scores were abnormal, these results could not, in general, be dissociated from the effects of dysarthria and ataxia. rCMRGlc was reduced in patients with PCD (versus normal control subjects) in all regions except the brainstem. Analysis of patient and control rCMRGlc data using a mathematical model of regional metabolic interactions revealed two metabolic pattern descriptors, SSF1 and SSF2, which distinguished patients with PCD from normal control subjects; SSF2, which described a metabolic coupling between cerebellum, cuneus, and posterior temporal, lateral frontal, and paracentral cortex, correlated with quantitative indices of cerebellar dysfunction. Our inability to document substantial intellectual impairment in 7 of 10 patients with PCD contrasts with the 50% incidence of dementia in PCD reported by previous investigators. Widespread reductions in PCD rCMRGlc may result from the loss of cerebellar efferents to thalamus and forebrain structures, a reverse cerebellar diaschisis.

  17. Preservation of cone photoreceptors after a rapid yet transient degeneration and remodeling in cone-only Nrl-/- mouse retina.

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    Roger, Jerome E; Ranganath, Keerthi; Zhao, Lian; Cojocaru, Radu I; Brooks, Matthew; Gotoh, Norimoto; Veleri, Shobi; Hiriyanna, Avinash; Rachel, Rivka A; Campos, Maria Mercedes; Fariss, Robert N; Wong, Wai T; Swaroop, Anand

    2012-01-11

    Cone photoreceptors are the primary initiator of visual transduction in the human retina. Dysfunction or death of rod photoreceptors precedes cone loss in many retinal and macular degenerative diseases, suggesting a rod-dependent trophic support for cone survival. Rod differentiation and homeostasis are dependent on the basic motif leucine zipper transcription factor neural retina leucine zipper (NRL). The loss of Nrl (Nrl(-/-)) in mice results in a retina with predominantly S-opsin-containing cones that exhibit molecular and functional characteristics of wild-type cones. Here, we report that Nrl(-/-) retina undergoes a rapid but transient period of degeneration in early adulthood, with cone apoptosis, retinal detachment, alterations in retinal vessel structure, and activation and translocation of retinal microglia. However, cone degeneration stabilizes by 4 months of age, resulting in a thinner but intact outer nuclear layer with residual cones expressing S- and M-opsins and a preserved photopic electroretinogram. At this stage, microglia translocate back to the inner retina and reacquire a quiescent morphology. Gene profiling analysis during the period of transient degeneration reveals misregulation of genes related to stress response and inflammation, implying their involvement in cone death. The Nrl(-/-) mouse illustrates the long-term viability of cones in the absence of rods and retinal pigment epithelium defects in a rodless retina. We propose that Nrl(-/-) retina may serve as a model for elucidating mechanisms of cone homeostasis and degeneration that would be relevant to understanding diseases of the cone-dominant human macula.

  18. Axonal degeneration stimulates the formation of NG2+ cells and oligodendrocytes in the mouse

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    Nielsen, Helle Hvilsted; Ladeby, Rune; Drøjdahl, Nina

    2006-01-01

    the response of the NG2+ cells to the different components of demyelinating pathology, we investigated the response of adult NG2+ cells to axonal degeneration in the absence of primary myelin or oligodendrocyte pathology. Axonal degeneration was induced in the hippocampal dentate gyrus of adult mice...... by transection of the entorhino-dentate perforant path projection. The acutely induced degeneration of axons and terminals resulted in a prompt response of NG2+ cells, consisting of morphological transformation, cellular proliferation, and upregulation of NG2 expression days 2-3 after surgery. This was followed...

  19. Degeneration of axons in spinal white matter in G93A mSOD1 mouse characterized by NFL and α-internexin immunoreactivity.

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    King, Anna E; Blizzard, Catherine A; Southam, Katherine A; Vickers, James C; Dickson, Tracey C

    2012-07-17

    Axonal degeneration is a prominent feature of amyotrophic lateral sclerosis (ALS) both in lower motor nerves as well as descending white matter axons in the spinal cord of human patients. Although the pathology of lower motor axonal degeneration has been described in both human ALS and related transgenic animal models, few studies have examined the pathological features of descending axon degeneration, particularly in mouse models of ALS. We have examined the degeneration of white matter tracts in the G93A mutant superoxide dismutase-1 (mSOD1+) mouse spinal cord white matter from 12 weeks of age to end-stage disease. In a G93A mSOD1 mouse model where green fluorescent protein was expressed in neurons (mSOD1+/GFP+), degeneration of white matter tracts was present from the ventral to dorsolateral funiculi. This pattern of axonal pathology occurred from 16 weeks of age. However, the dorsal funiculus, the site of the major corticospinal tract in mice, showed relatively less degeneration. Immunohistochemical analysis demonstrated that the neurofilament light chain (NFL) and neuronal intermediate filament protein alpha-internexin accumulated in axon swellings in the spinal white matter. Increased levels of alpha-internexin protein, in mSOD1+ mouse spinal cord tissue, were demonstrated by Western blotting. In contrast, degenerating axons did not show obvious accumulations of neurofilament medium and heavy chain proteins (NFM and NFH). These data suggest that white matter degeneration in this mouse model of ALS is widespread and involves a specific molecular signature, particularly the accumulation of NFL and alpha-internexin proteins. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. Spontaneous oscillatory rhythms in the degenerating mouse retina modulate retinal ganglion cell responses to electrical stimulation

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    Yong Sook eGoo

    2016-01-01

    Full Text Available Characterization of the electrical activity of the retina in the animal models of retinal degeneration has been carried out in part to understand the progression of retinal degenerative diseases like age-related macular degeneration (AMD and retinitis pigmentosa (RP, but also to determine optimum stimulus paradigms for use with retinal prosthetic devices. The models most studied in this regard have been the two lines of mice deficient in the β-subunit of phosphodiesterase (rd1 and rd10 mice, where the degenerating retinas exhibit characteristic spontaneous hyperactivity and oscillatory local field potentials (LFPs. Additionally, there is a robust ~10 Hz rhythmic burst of retinal ganglion cell (RGC spikes on the trough of the oscillatory LFP. In rd1 mice, the rhythmic burst of RGC spikes is always phase-locked with the oscillatory LFP and this phase-locking property is preserved regardless of postnatal ages. However, in rd10 mice, the frequency of the oscillatory rhythm changes according to postnatal age, suggesting that this rhythm might be a marker of the stage of degeneration. Furthermore when a biphasic current stimulus is applied to rd10 mice degenerate retina, distinct RGC response patterns that correlate with the stage of degeneration emerge. This review also considers the significance of these response properties.

  1. [Radiation preconditioning of mouse retina results in tolerance to MNU-induced degeneration and stimulates retinal recovery].

    Science.gov (United States)

    Tronov, V A; Vinogradova, Yu V; Poplinskaya, V A; Nekrasova, E I; Ostrovsky, M A

    2015-01-01

    Emerging body of data indicate protecting effect of low level of stress (preconditioning) on retina. Our previous studies have revealed a non-linear dose-response relationship for cytotoxic effect of both ionizing radiation and N-methyl-N-nitrosourea (MNU) on mouse retina. Moreover, non-cytotoxic dose of MNU increased tolerance of retina to following challenge dose of MNU. This result displays protection of retina through mechanism of recovery. In the present study we used the mouse model for MNU-induced retinal degeneration to evaluate the adaptive response of the retina to proton irradiation and implication of glial Muller cells in this response. In this paper, we have shown that the recovery of the retina after exposure to genotoxic agents is associated with an increased efficiency of DNA damage repair and lowered death of retinal photoreceptors.

  2. Gene Therapy Using a miniCEP290 Fragment Delays Photoreceptor Degeneration in a Mouse Model of Leber Congenital Amaurosis.

    Science.gov (United States)

    Zhang, Wei; Li, Linjing; Su, Qin; Gao, Guangping; Khanna, Hemant

    2017-07-05

    Mutations in the cilia-centrosomal protein CEP290 are frequently observed in autosomal recessive childhood blindness disorder Leber congenital amaurosis (LCA). No treatment or cure currently exists for this disorder. The Cep290(rd16) (retinal degeneration 16) mouse (a model of LCA) carries a mutation in the Cep290 gene. This mutation leads to shorter cilia formation and defective photoreceptor structure and function. A roadblock to developing a gene replacement strategy for CEP290 using conventional adeno-associated virus (AAV) vectors is its large size. The identification and characterization is reported of a miniCEP290 gene that is amenable to AAV2/8-mediated delivery and delaying retinal degeneration in the Cep290(rd16) mice. Using the ability of Cep290(rd16) mouse embryonic fibroblasts to from shorter cilia as a platform, a human CEP290 domain encoded by amino acids 580-1180 (miniCEP290(580-1180)) was identified that can recover the cilia length in vitro. Furthermore, subretinal injection of AAV particles carrying the cDNA expressing miniCEP290(580-1180) into neonatal Cep290(rd16) mice resulted in significantly improved photoreceptor survival, morphology, and function compared to control injected mice. These studies show the potential of using a truncated CEP290 to treat this fast progressing and devastating disease.

  3. Axonal degeneration stimulates the formation of NG2+ cells and oligodendrocytes in the mouse

    DEFF Research Database (Denmark)

    Nielsen, Helle Hvilsted; Ladeby, Rune; Drøjdahl, Nina;

    2006-01-01

    Proliferation of the adult NG2-expressing oligodendrocyte precursor cells has traditionally been viewed as a remyelination response ensuing from destruction of myelin and oligodendrocytes, and not to the axonal pathology that is also a characteristic of demyelinating disease. To better understand...... the response of the NG2+ cells to the different components of demyelinating pathology, we investigated the response of adult NG2+ cells to axonal degeneration in the absence of primary myelin or oligodendrocyte pathology. Axonal degeneration was induced in the hippocampal dentate gyrus of adult mice...... by transection of the entorhino-dentate perforant path projection. The acutely induced degeneration of axons and terminals resulted in a prompt response of NG2+ cells, consisting of morphological transformation, cellular proliferation, and upregulation of NG2 expression days 2-3 after surgery. This was followed...

  4. New types of drilling tools fit with PCD elements

    Directory of Open Access Journals (Sweden)

    Koníèek Jiøí

    1997-09-01

    Full Text Available One of the most significant developments in drilling technology over the last years has been the introduction of polycrystalline diamond (PCD as macro-cutting elements in the rotary drill application. This paper gives a summary of core bits and cutter bits, produced by Pramet Šumperk Co., which are fit with these PCD elements. Some results, obtained with these types of cutter bits by drilling in mines of Ostrava-Karviná Basin, are also presented.

  5. Cytological study and PCD assay on pollen development of photoperiod sensitive genic male sterile rice

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    A systematic cytological comparison of the anther development of photoperiod sensitive genic male sterile (PSGMS) rice with its normal fertility counterpart was conducted.The results showed that pollen abortion in PSGMS rice occurred first no later than the pollen mother cell (PMC) stage and continued during the entire process of pollen development till pollen degradation.This abortive process was closely associated with the abnormal behavior of tapetum.Although tapetum degeneration in the PSGMS rice initiated as early as at the PMC stage,it proceeded slowly and did not complete until the breakdown of the pollen,in sharp contrast to the rapid disintegration of the tapetal layer during the late microspore to the bicellular pollen stage in the fertile rice.Such cytological observation was supported by the results of the TUNEL (TdT2 mediated dU TP Nick End Labeling)assay that detects DNA fragmentation resulting from programmed cell death (PCD),indicating that the tapetum degeneration occurs in the process of PCD.

  6. Differential expression of genes involved in the degeneration and regeneration pathways in mouse models for muscular dystrophies.

    Science.gov (United States)

    Onofre-Oliveira, P C G; Santos, A L F; Martins, P M; Ayub-Guerrieri, D; Vainzof, M

    2012-03-01

    The genetically determined muscular dystrophies are caused by mutations in genes coding for muscle proteins. Differences in the phenotypes are mainly the age of onset and velocity of progression. Muscle weakness is the consequence of myofiber degeneration due to an imbalance between successive cycles of degeneration/regeneration. While muscle fibers are lost, a replacement of the degraded muscle fibers by adipose and connective tissues occurs. Major investigation points are to elicit the involved pathophysiological mechanisms to elucidate how each mutation can lead to a specific degenerative process and how the regeneration is stimulated in each case. To answer these questions, we used four mouse models with different mutations causing muscular dystrophies, Dmd (mdx), SJL/J, Large (myd) and Lama2 (dy2J) /J, and compared the histological changes of regeneration and fibrosis to the expression of genes involved in those processes. For regeneration, the MyoD, Myf5 and myogenin genes related to the proliferation and differentiation of satellite cells were studied, while for degeneration, the TGF-β1 and Pro-collagen 1α2 genes, involved in the fibrotic cascade, were analyzed. The result suggests that TGF-β1 gene is activated in the dystrophic process in all the stages of degeneration, while the activation of the expression of the pro-collagen gene possibly occurs in mildest stages of this process. We also observed that each pathophysiological mechanism acted differently in the activation of regeneration, with distinctions in the induction of proliferation of satellite cells, but with no alterations in stimulation to differentiation. Dysfunction of satellite cells can, therefore, be an important additional mechanism of pathogenesis in the dystrophic muscle.

  7. Relative time course of degeneration of different cochlear structures in the CD/1 mouse model of accelerated aging.

    Science.gov (United States)

    Mahendrasingam, Shanthini; Macdonald, Jamie A; Furness, David N

    2011-08-01

    Presbycusis (age-related hearing loss) can result from various cochlear pathologies. We have studied the time course of degeneration in a mouse that shows accelerated presbycusis, the CD/1 mouse, as a possible model to investigate stem-cell strategies to prevent or ameliorate presbycusic changes. CD/1 mice from 0 to 72 weeks old were examined by light and electron microscopy. Early pathological changes were detected in basal turn spiral ligament fibrocytes and spiral ganglion, but the latter was variable as both satellite cells and neurons were normal in some cochleae. Light microscopic counts in the spiral ligament of 20-week-old mice revealed that of the five main types (types I-V), only type V fibrocytes showed no reduction in numbers compared with 3-week-old animals, and type IV showed the greatest losses. However, all types of fibrocyte showed subtle damage when examined using electron microscopy, in the form of swollen mitochondria, as early as 2 weeks. The extent of mitochondrial damage showed a degree of correspondence with the light microscopic pattern of fibrocyte loss in that types III and IV fibrocytes had the most abnormal mitochondria and type V the least, especially at early stages. By 10-15 weeks, ultrastructural features of fibrocyte damage were similar to longer term changes reported in gerbils. Stria vascularis, spiral ganglion and hair cells showed few consistent early signs of damage but became increasingly affected, lagging behind the fibrocyte damage. Our data suggest that fibrocyte pathology may precede other presbycusic changes; breakdown of homeostatic mechanisms to which they contribute may cause the subsequent degeneration of the hair cells. Overall, there were many similarities to presbycusic changes in other rodents and humans. Therefore, the features of accelerated aging in this mouse make it a suitable model for rapidly assessing possible strategies to prevent or ameliorate presbycusic changes.

  8. Characterisation of a C1qtnf5 Ser163Arg knock-in mouse model of late-onset retinal macular degeneration.

    Directory of Open Access Journals (Sweden)

    Xinhua Shu

    Full Text Available A single founder mutation resulting in a Ser163Arg substitution in the C1QTNF5 gene product causes autosomal dominant late-onset retinal macular degeneration (L-ORMD in humans, which has clinical and pathological features resembling age-related macular degeneration. We generated and characterised a mouse "knock-in" model carrying the Ser163Arg mutation in the orthologous murine C1qtnf5 gene by site-directed mutagenesis and homologous recombination into mouse embryonic stem cells. Biochemical, immunological, electron microscopic, fundus autofluorescence, electroretinography and laser photocoagulation analyses were used to characterise the mouse model. Heterozygous and homozygous knock-in mice showed no significant abnormality in any of the above measures at time points up to 2 years. This result contrasts with another C1qtnf5 Ser163Arg knock-in mouse which showed most of the features of L-ORMD but differed in genetic background and targeting construct.

  9. Photodegradation of retinal bisretinoids in mouse models and implications for macular degeneration

    OpenAIRE

    Ueda, Keiko; Zhao, Jin; Kim, Hye Jin; Sparrow, Janet R.

    2016-01-01

    Visual cycle adducts having bisretinoid structures accumulate in retinal pigment epithelial cells as lipofuscin. These light-sensitive compounds are implicated in disease mechanisms leading to visual impairment in some inherited and age-related forms of macular degeneration. The means by which these diretinal adducts impart chronic damage is not fully understood. By studying mice raised under varying levels of intraocular light and by analyzing mice treated with vitamin E, we provide evidence...

  10. Systemic PCD occurs in TMV-tomato interaction

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    In hypersensitive response (HR), programmed cell death (PCD) is reported as a powerful defense mechanism in plant immune responses to pathogen. However, little is known about the PCD in sys-temic acquired resistance (SAR). Using tobacco mosaic virus (TMV) to infect the tomato (Lycopersicon esculentum cv. Jiafen 16) we found that localized TMV-infection could induce cell death in the uninoculated parts of the tomatoes, where the enzyme-linked immunosorbent assay (ELISA) showed no spreading virus. The biological and molecular characterization of this cell death was shown as fol-lowing: chromatin condensed and formed peripheral conglomeration in nuclei; cell nucleus were TUNEL positive labeled; genomic DNA was fragmented and showed DNA laddering; mitochondria and chloroplast were disrupted; tonoplast and plasma membrane were shrunk and degradated. These re-sults suggested that with an absence of TMV spread, the local TMV-infection on certain tomato leaves could induce systemic PCD in the root-tips, stem-apices and uninoculated leaves. The systemic PCD has various initiation and synchronization in such tissues and is distinct in inducement and exhibition from HR-PCD and SAR.

  11. Systemic PCD occurs in TMV-tomato interaction.

    Science.gov (United States)

    Zhou, ShuMin; Liu, WenNa; Kong, LinAn; Wang, Mao

    2008-11-01

    In hypersensitive response (HR), programmed cell death (PCD) is reported as a powerful defense mechanism in plant immune responses to pathogen. However, little is known about the PCD in systemic acquired resistance (SAR). Using tobacco mosaic virus (TMV) to infect the tomato (Lycopersicon esculentum cv. Jiafen 16) we found that localized TMV-infection could induce cell death in the uninoculated parts of the tomatoes, where the enzyme-linked immunosorbent assay (ELISA) showed no spreading virus. The biological and molecular characterization of this cell death was shown as following: chromatin condensed and formed peripheral conglomeration in nuclei; cell nucleus were TUNEL positive labeled; genomic DNA was fragmented and showed DNA laddering; mitochondria and chloroplast were disrupted; tonoplast and plasma membrane were shrunk and degradated. These results suggested that with an absence of TMV spread, the local TMV-infection on certain tomato leaves could induce systemic PCD in the root-tips, stem-apices and uninoculated leaves. The systemic PCD has various initiation and synchronization in such tissues and is distinct in inducement and exhibition from HR-PCD and SAR.

  12. Complement system dysregulation and inflammation in the retinal pigment epithelium of a mouse model for Stargardt macular degeneration.

    Science.gov (United States)

    Radu, Roxana A; Hu, Jane; Yuan, Quan; Welch, Darcy L; Makshanoff, Jacob; Lloyd, Marcia; McMullen, Stephen; Travis, Gabriel H; Bok, Dean

    2011-05-27

    Accumulation of vitamin A-derived lipofuscin fluorophores in the retinal pigment epithelium (RPE) is a pathologic feature of recessive Stargardt macular dystrophy, a blinding disease caused by dysfunction or loss of the ABCA4 transporter in rods and cones. Age-related macular degeneration, a prevalent blinding disease of the elderly, is strongly associated with mutations in the genes for complement regulatory proteins (CRP), causing chronic inflammation of the RPE. Here we explore the possible relationship between lipofuscin accumulation and complement activation in vivo. Using the abca4(-/-) mouse model for recessive Stargardt, we investigated the role of lipofuscin fluorophores (A2E-lipofuscin) on oxidative stress and complement activation. We observed higher expression of oxidative-stress genes and elevated products of lipid peroxidation in eyes from abca4(-/-) versus wild-type mice. We also observed higher levels of complement-activation products in abca4(-/-) RPE cells. Unexpectedly, expression of multiple CRPs, which protect cells from attack by the complement system, were lower in abca4(-/-) versus wild-type RPE. To test whether acute exposure of healthy RPE cells to A2E-lipofuscin affects oxidative stress and expression of CRPs, we fed cultured fetal-derived human RPE cells with rod outer segments from wild-type or abca4(-/-) retinas. In contrast to RPE cells in abca4(-/-) mice, human RPE cells exposed to abca4(-/-) rod outer segments adaptively increased expression of both oxidative-stress and CRP genes. These results suggest that A2E accumulation causes oxidative stress, complement activation, and down-regulation of protective CRP in the Stargardt mouse model. Thus, Stargardt disease and age-related macular degeneration may both be caused by chronic inflammation of the RPE.

  13. Diaphragm degeneration and cardiac structure in mdx mouse: potential clinical implications for Duchenne muscular dystrophy.

    Science.gov (United States)

    Barbin, Isabel Cristina Chagas; Pereira, Juliano Alves; Bersan Rovere, Matheus; de Oliveira Moreira, Drielen; Marques, Maria Julia; Santo Neto, Humberto

    2016-05-01

    We examined the effects of exercise on diaphragm degeneration and cardiomyopathy in dystrophin-deficient mdx mice. Mdx mice (11 months of age) were exercised (swimming) for 2 months to worsen diaphragm degeneration. Control mdx mice were kept sedentary. Morphological evaluation demonstrated increased fibrosis in the diaphragm of exercised mdx mice (33.3 ± 6.0% area of fibrosis) compared with control mdx mice (20.9 ± 1.7% area of fibrosis). Increased (26%) activity of MMP-2, a marker of fibrosis, was detected in the diaphragms from exercised mdx mice. Morphological evaluation of the heart demonstrated a 45% increase in fibrosis in the right ventricle (8.3 ± 0.6% in sedentary vs. 12.0 ± 0.6% of fibrosis in exercised) and in the left ventricle (35% increase) in the exercised mdx mice. The density of inflammatory cells-degenerating cardiomyocytes increased 95% in the right ventricle (2.3 ± 0.6 in sedentary vs. 4.5 ± 0.8 in exercised) and 71% in the left ventricle (1.4 ± 0.6 sedentary vs. 2.4 ± 0.5 exercised). The levels of both active MMP-2 and the pro-fibrotic factor transforming growth factor beta were elevated in the hearts of exercised compared with sedentary mdx mice. The wall thickness to lumen diameter ratio of the pulmonary trunk was significantly increased in the exercised mdx mice (0.11 ± 0.04 in sedentary vs. 0.28 ± 0.12 in exercised), as was the thickness of the right ventricle wall, which suggests the occurrence of pulmonary hypertension in those animals. It is suggested that diaphragm degeneration is a main contributor to right ventricle dystrophic pathology. These findings may be relevant for future interventional studies for Duchenne muscular dystrophy-associated cardiomyopathy.

  14. Macrophage invasion contributes to degeneration of stria vascularis in Pendred syndrome mouse model

    Directory of Open Access Journals (Sweden)

    Everett Lorraine A

    2006-12-01

    Full Text Available Abstract Background Pendred syndrome, an autosomal-recessive disorder characterized by deafness and goiter, is caused by a mutation of SLC26A4, which codes for the anion exchanger pendrin. We investigated the relationship between pendrin expression and deafness using mice that have (Slc26a4+/+ or Slc26a4+/- or lack (Slc26a4-/- a complete Slc26a4 gene. Previously, we reported that stria vascularis of adult Slc26a4-/- mice is hyperpigmented and that marginal cells appear disorganized. Here we determine the time course of hyperpigmentation and marginal cell disorganization, and test the hypothesis that inflammation contributes to this tissue degeneration. Methods Slc26a4-/- and age-matched control (Slc26a4+/+ or Slc26a4+/- mice were studied at four postnatal (P developmental stages: before and after the age that marks the onset of hearing (P10 and P15, respectively, after weaning (P28-41 and adult (P74-170. Degeneration and hyperpigmentation stria vascularis was evaluated by confocal microscopy. Gene expression in stria vascularis was analyzed by microarray and quantitative RT-PCR. In addition, the expression of a select group of genes was quantified in spiral ligament, spleen and liver to evaluate whether expression changes seen in stria vascularis are specific for stria vascularis or systemic in nature. Results Degeneration of stria vascularis defined as hyperpigmentation and marginal cells disorganization was not seen at P10 or P15, but occurred after weaning and was associated with staining for CD68, a marker for macrophages. Marginal cells in Slc26a4-/-, however, had a larger apical surface area at P10 and P15. No difference in the expression of Lyzs, C3 and Cd45 was found in stria vascularis of P15 Slc26a4+/- and Slc26a4-/- mice. However, differences in expression were found after weaning and in adult mice. No difference in the expression of markers for acute inflammation, including Il1a, Il6, Il12a, Nos2 and Nos3 were found at P15, after

  15. Pioglitazone halts axonal degeneration in a mouse model of X-linked adrenoleukodystrophy.

    Science.gov (United States)

    Morató, Laia; Galino, Jorge; Ruiz, Montserrat; Calingasan, Noel Ylagan; Starkov, Anatoly A; Dumont, Magali; Naudí, Alba; Martínez, Juan José; Aubourg, Patrick; Portero-Otín, Manuel; Pamplona, Reinald; Galea, Elena; Beal, M Flint; Ferrer, Isidre; Fourcade, Stéphane; Pujol, Aurora

    2013-08-01

    X-linked adrenoleukodystrophy is a neurometabolic disorder caused by inactivation of the peroxisomal ABCD1 transporter of very long-chain fatty acids. In mice, ABCD1 loss causes late onset axonal degeneration in the spinal cord in association with locomotor disability resembling the most common phenotype in patients, adrenomyeloneuropathy. Increasing evidence indicates that oxidative stress and bioenergetic failure play major roles in the pathogenesis of X-linked adrenoleukodystrophy. In this study, we aimed to evaluate whether mitochondrial biogenesis is affected in X-linked adrenoleukodystrophy. We demonstrated that Abcd1 null mice show reduced mitochondrial DNA concomitant with downregulation of mitochondrial biogenesis pathway driven by PGC-1α/PPARγ and reduced expression of mitochondrial proteins cytochrome c, NDUFB8 and VDAC. Moreover, we show that the oral administration of pioglitazone, an agonist of PPARγ, restored mitochondrial content and expression of master regulators of biogenesis, neutralized oxidative damage to proteins and DNA, and reversed bioenergetic failure in terms of ATP levels, NAD+/NADH ratios, pyruvate kinase and glutathione reductase activities. Most importantly, the treatment halted locomotor disability and axonal damage in X-linked adrenoleukodystrophy mice. These results lend support to the use of pioglitazone in clinical trials with patients with adrenomyeloneuropathy and reveal novel molecular mechanisms of action of pioglitazone in neurodegeneration. Future studies should address the effects of this anti-diabetic drug on other axonopathies in which oxidative stress and mitochondrial dysfunction are contributing factors.

  16. Loss of ATF2 function leads to cranial motoneuron degeneration during embryonic mouse development.

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    Julien Ackermann

    Full Text Available The AP-1 family transcription factor ATF2 is essential for development and tissue maintenance in mammals. In particular, ATF2 is highly expressed and activated in the brain and previous studies using mouse knockouts have confirmed its requirement in the cerebellum as well as in vestibular sense organs. Here we present the analysis of the requirement for ATF2 in CNS development in mouse embryos, specifically in the brainstem. We discovered that neuron-specific inactivation of ATF2 leads to significant loss of motoneurons of the hypoglossal, abducens and facial nuclei. While the generation of ATF2 mutant motoneurons appears normal during early development, they undergo caspase-dependent and independent cell death during later embryonic and foetal stages. The loss of these motoneurons correlates with increased levels of stress activated MAP kinases, JNK and p38, as well as aberrant accumulation of phosphorylated neurofilament proteins, NF-H and NF-M, known substrates for these kinases. This, together with other neuropathological phenotypes, including aberrant vacuolisation and lipid accumulation, indicates that deficiency in ATF2 leads to neurodegeneration of subsets of somatic and visceral motoneurons of the brainstem. It also confirms that ATF2 has a critical role in limiting the activities of stress kinases JNK and p38 which are potent inducers of cell death in the CNS.

  17. Involvement of Autophagic Pathway in the Progression of Retinal Degeneration in a Mouse Model of Diabetes.

    Science.gov (United States)

    Piano, Ilaria; Novelli, Elena; Della Santina, Luca; Strettoi, Enrica; Cervetto, Luigi; Gargini, Claudia

    2016-01-01

    The notion that diabetic retinopathy (DR) is essentially a micro-vascular disease has been recently challenged by studies reporting that vascular changes are preceded by signs of damage and loss of retinal neurons. As to the mode by which neuronal death occurs, the evidence that apoptosis is the main cause of neuronal loss is far from compelling. The objective of this study was to investigate these controversies in a mouse model of streptozotocin (STZ) induced diabetes. Starting from 8 weeks after diabetes induction there was loss of rod but not of cone photoreceptors, together with reduced thickness of the outer and inner synaptic layers. Correspondingly, rhodopsin expression was downregulated and the scotopic electroretinogram (ERG) is suppressed. In contrast, cone opsin expression and photopic ERG response were not affected. Suppression of the scotopic ERG preceded morphological changes as well as any detectable sign of vascular alteration. Only sparse apoptotic figures were detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and glia was not activated. The physiological autophagy flow was altered instead, as seen by increased LC3 immunostaining at the level of outer plexiform layer (OPL) and upregulation of the autophagic proteins Beclin-1 and Atg5. Collectively, our results show that the streptozotocin induced DR in mouse initiates with a functional loss of the rod visual pathway. The pathogenic pathways leading to cell death develop with the initial dysregulation of autophagy well before the appearance of signs of vascular damage and without strong involvement of apoptosis.

  18. Follicle stimulating hormone alleviates radiation-induced degeneration of mouse ovarian follicles

    Energy Technology Data Exchange (ETDEWEB)

    Lee, C.J. [Hanyang Univ., Seoul (Korea, Republic of); Kim, J.K.; Chun, K.J.

    2000-05-01

    The present study was performed to analyze the influences of (FSH) follicle stimulating hormone and {gamma}-radiation on the morphological changes of ovarian follicles and serum concentrations of testosterone, and estradiol-17{beta} in prepubertal mice. Female mice (ICR strain, three weeks old) were irradiated with 8.33 Gy of {gamma}-ray and followed by a 5 IU i.p.-injection of FSH to know the effect of FSH on the ovarian follicles. Left ovaries were collected at 0 h, 1 d, and 2 d after irradiation or saline/ FSH injection. Another group was received 5 IU of FSH 2 hours before irradiation to analyze the changes of ovarian steroidogenic abilities. By the morphometrical analysis, the number of normal or atretic follicles was counted and the ratio of normal to atretic follicle numbers was calculated. The percentage of atretic follicles was significantly reduced by the treatment of FSH. In the case of the FSH-injected group, the cellular debris caused by radiation was engulfed by the immune cells and the neighboring granulosa cells within the follicles. In concurrence with the morphometric analysis, the changes of the serum concentrations (pg/ml) of testosterone (T) and estradiol (E{sub 2}) were determined by radioimmunoassays. The concentration of T was 336.8{+-}61.3 in the control mice. One day after irradiation, the concentration went up to 484.8{+-}80.0 in the irradiated group, and down to 243.5{+-}80.7 in the FSH-treated one. The concentration of E{sub 2} was 174.9{+-}15.0 in the control group. One day after irradiation, however, the concentration was decreased to 94.8{+-}19.8, and 155.9{+-}8.7 in the irradiated and FSH-treated group, respectively. The alleviation of the follicular degeneration by the treatment of FSH is closely related to the elimination of the cellular debris and to the activities of the steroidogenic enzymes. (Author)

  19. Mutation-related differences in exploratory, spatial and depressive-like behavior in pcd and Lurcher cerebellar mutant mice

    Directory of Open Access Journals (Sweden)

    Jan eTuma

    2015-05-01

    Full Text Available The cerebellum is not only essential for motor coordination but is also involved in cognitive and affective processes. These functions of the cerebellum and mechanisms of their disorders in cerebellar injury are not completely understood. There is a wide spectrum of cerebellar mutant mice which are used as models of hereditary cerebellar degenerations. Nevertheless, they differ in pathogenesis of manifestation of the particular mutation and also in the strain background. The aim of this work was to compare spatial navigation, learning and memory in pcd and Lurcher mice, two of the most frequently used cerebellar mutants. The mice were tested in the open field for exploration behavior, in the Morris water maze with visible as well as reversal hidden platform tasks and in the forced swimming test for motivation assessment. Lurcher mice showed different space exploration activity in the open field and a lower tendency to depressive-like behavior in the forced swimming test compared with pcd mice. Severe deficit of spatial navigation was shown in both cerebellar mutants. However, the overall performance of Lurcher mice was better than that of pcd mutants. Lurcher mice showed the ability of visual guidance despite difficulties with the direct swim towards a goal. In the probe trial test, Lurcher mice preferred the visible platform rather than the more recent localization of the hidden goal.

  20. Lack of riluzole efficacy in the progression of the neurodegenerative phenotype in a new conditional mouse model of striatal degeneration

    Directory of Open Access Journals (Sweden)

    Grzegorz Kreiner

    2017-04-01

    Full Text Available Background Huntington’s disease (HD is a rare familial autosomal dominant neurodegenerative disorder characterized by progressive degeneration of medium spiny neurons (MSNs located in the striatum. Currently available treatments of HD are only limited to alleviating symptoms; therefore, high expectations for an effective therapy are associated with potential replacement of lost neurons through stimulation of postnatal neurogenesis. One of the drugs of potential interest for the treatment of HD is riluzole, which may act as a positive modulator of adult neurogenesis, promoting replacement of damaged MSNs. The aim of this study was to evaluate the effects of chronic riluzole treatment on a novel HD-like transgenic mouse model, based on the genetic ablation of the transcription factor TIF-IA. This model is characterized by selective and progressive degeneration of MSNs. Methods Selective ablation of TIF-IA in MSNs (TIF-IAD1RCre mice was achieved by Cre-based recombination driven by the dopamine 1 receptor (D1R promoter in the C57Bl/6N mouse strain. Riluzole was administered for 14 consecutive days (5 mg/kg, i.p.; 1× daily starting at six weeks of age. Behavioral analysis included a motor coordination test performed on 13-week-old animals on an accelerated rotarod (4–40 r.p.m.; 5 min. To visualize the potential effects of riluzole treatment, the striata of the animals were stained by immunohistochemistry (IHC and/or immunofluorescence (IF with Ki67 (marker of proliferating cells, neuronal markers (NeuN, MAP2, DCX, and markers associated with neurodegeneration (GFAP, 8OHdG, FluoroJade C. Additionally, the morphology of dendritic spines of neurons was assessed by a commercially available FD Rapid Golgi Stain™ Kit. Results A comparative analysis of IHC staining patterns with chosen markers for the neurodegeneration process in MSNs did not show an effect of riluzole on delaying the progression of MSN cell death despite an observed enhancement

  1. Systemic PCD occurs in TMV-tomato interaction

    Institute of Scientific and Technical Information of China (English)

    ZHOU ShuMin; LIU WenNa; KONG LinAn; WANG Mao

    2008-01-01

    In hypersensitive response (HR), programmed cell death (POD) is reported as a powerful defense mechanism in plant immune responses to pathogen. However, little is known about the POD in sys-temic acquired resistance (SAR). Using tobacco mosaic virus (TMV) to infect the tomato (Lycopersicon esculentum cv. Jiafen 16) we found that localized TMV-infection could induce cell death in the uninoculated parts of the tomatoes, where the enzyme-linked immunosorbent assay (ELISA) showed no spreading virus. The biological and molecular characterization of this cell death was shown as fol-lowing: chromatin condensed and formed peripheral conglomeration in nuclei; cell nucleus were TUNEL positive labeled; genomic DNA was fragmented and showed DNA laddering; mitochondria and chloroplast were disrupted; tonoplast and plasma membrane were shrunk and degradated. These re-suits suggested that with an absence of TMV spread, the local TMV-infection on certain tomato leaves could induce systemic PCD in the root-tips, stem-apices and uninoculated leaves. The systemic PCD has various initiation and synchronization in such tissues and is distinct in inducement and exhibition from HR-PCD and SAR.

  2. Age-related retinal degeneration (arrd2) in a novel mouse model due to a nonsense mutation in the Mdm1 gene.

    Science.gov (United States)

    Chang, Bo; Mandal, Md Nawajes A; Chavali, Venkata R M; Hawes, Norman L; Khan, Naheed W; Hurd, Ronald E; Smith, Richard S; Davisson, Muriel L; Kopplin, Laura; Klein, Barbara E K; Klein, Ronald; Iyengar, Sudha K; Heckenlively, John R; Ayyagari, Radha

    2008-12-15

    We observed that a naturally occurring mouse strain developed age-related retinal degeneration (arrd2). These mice had normal fundi, electroretinograms (ERGs) and retinal histology at 6 months of age; vessel attenuation, RPE atrophy and pigmentary abnormalities at 14 months, which progressed to complete loss of photoreceptors and extinguished ERG by 22 months. Genetic analysis revealed that the retinal degeneration in arrd2 segregates in an autosomal recessive manner and the disease gene localizes to mouse chromosome 10. A positional candidate cloning approach detected a nonsense mutation in the mouse double minute-1 gene (Mdm1), which results in the truncation of the putative protein from 718 amino acids to 398. We have identified a novel transcript of the Mdm1 gene, which is the predominant transcript in the retina. The Mdm1 transcript is localized to the nuclear layers of neural retina. Expression of Mdm1 in the retina increases steadily from post-natal day 30 to 1 year, and a high level of Mdm1 are subsequently maintained. The Mdm1 transcript was found to be significantly depleted in the retina of arrd2 mice and the transcript was observed to degrade by nonsense-mediated decay. These results indicate that the depletion of the Mdm1 transcript may underlie the mechanism leading to late-onset progressive retinal degeneration in arrd2 mice. Analysis of a cohort of patients with age-related macular degeneration (AMD) wherein the susceptibility locus maps to chromosome 12q, a region bearing the human ortholog to MDM1, did not reveal association between human MDM1 and AMD.

  3. Network oscillations drive correlated spiking of ON and OFF ganglion cells in the rd1 mouse model of retinal degeneration.

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    David J Margolis

    Full Text Available Following photoreceptor degeneration, ON and OFF retinal ganglion cells (RGCs in the rd-1/rd-1 mouse receive rhythmic synaptic input that elicits bursts of action potentials at ∼ 10 Hz. To characterize the properties of this activity, RGCs were targeted for paired recording and morphological classification as either ON alpha, OFF alpha or non-alpha RGCs using two-photon imaging. Identified cell types exhibited rhythmic spike activity. Cross-correlation of spike trains recorded simultaneously from pairs of RGCs revealed that activity was correlated more strongly between alpha RGCs than between alpha and non-alpha cell pairs. Bursts of action potentials in alpha RGC pairs of the same type, i.e. two ON or two OFF cells, were in phase, while bursts in dissimilar alpha cell types, i.e. an ON and an OFF RGC, were 180 degrees out of phase. This result is consistent with RGC activity being driven by an input that provides correlated excitation to ON cells and inhibition to OFF cells. A2 amacrine cells were investigated as a candidate cellular mechanism and found to display 10 Hz oscillations in membrane voltage and current that persisted in the presence of antagonists of fast synaptic transmission and were eliminated by tetrodotoxin. Results support the conclusion that the rhythmic RGC activity originates in a presynaptic network of electrically coupled cells including A2s via a Na(+-channel dependent mechanism. Network activity drives out of phase oscillations in ON and OFF cone bipolar cells, entraining similar frequency fluctuations in RGC spike activity over an area of retina that migrates with changes in the spatial locus of the cellular oscillator.

  4. miR-126 Regulation of Angiogenesis in Age-Related Macular Degeneration in CNV Mouse Model

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    Lei Wang

    2016-06-01

    Full Text Available miR-126 has recently been implicated in modulating angiogenic factors in vascular development. Understandings its biological significance might enable development of therapeutic interventions for diseases like age-related macular degeneration (AMD. We aimed to determine the role of miR-126 in AMD using a laser-induced choroidal neovascularization (CNV mouse model. CNV was induced by laser photocoagulation in C57BL/6 mice. The CNV mice were transfected with scrambled miR or miR-126 mimic. The expression of miR-126, vascular endothelial growth factor-A (VEGF-A, Kinase insert domain receptor (KDR and Sprouty-related EVH1 domain-containing protein 1 (SPRED-1 in ocular tissues were analyzed by qPCR and Western blot. The overexpression effects of miR-126 were also proven on human microvascular endothelial cells (HMECs. miR-126 showed a significant decrease in CNV mice (p < 0.05. Both mRNA and protein levels of VEGF-A, KDR and SPRED-1 were upregulated with CNV; these changes were ameliorated by restoration of miR-126 (p < 0.05. CNV was reduced after miR-126 transfection. Transfection of miR-126 reduced the HMECs 2D-capillary-like tube formation (p < 0.01 and migration (p < 0.01. miR-126 has been shown to be a negative modulator of angiogenesis in the eye. All together these results high lights the therapeutic potential of miR-126 suggests that it may contribute as a putative therapeutic target for AMD in humans.

  5. Preservation of cone photoreceptors after a rapid yet transient degeneration and remodeling in cone-only Nrl−/− mouse retina

    Science.gov (United States)

    Roger, Jerome E; Ranganath, Keerthi; Zhao, Lian; Cojocaru, Radu I; Brooks, Matthew; Gotoh, Norimoto; Veleri, Shobi; Hiriyanna, Avinash; Rachel, Rivka A; Campos, Maria Mercedes; Fariss, Robert N; Wong, Wai T; Swaroop, Anand

    2012-01-01

    Cone photoreceptors are the primary initiator of visual transduction in the human retina. Dysfunction or death of rod photoreceptors precedes cone loss in many retinal and macular degenerative diseases, suggesting a rod-dependent trophic support for cone survival. Rod differentiation and homeostasis are dependent on the basic motif leucine zipper transcription factor NRL. The loss of Nrl (Nrl−/−) in mice results in a retina with predominantly S-opsin containing cones that exhibit molecular and functional characteristics of WT cones. Here we report that Nrl−/− retina undergoes a rapid but transient period of degeneration in early adulthood, with cone apoptosis, retinal detachment, alterations in retinal vessel structure, and activation and translocation of retinal microglia. However, cone degeneration stabilizes by four months of age, resulting in a thinner but intact outer nuclear layer with residual cones expressing S- and M-opsins and a preserved photopic ERG. At this stage, microglia translocate back to the inner retina and reacquire a quiescent morphology. Gene profiling analysis during the period of transient degeneration reveals misregulation of genes related to stress response and inflammation, implying their involvement in cone death. The Nrl−/− mouse illustrates the long-term viability of cones in the absence of rods and RPE defects in a rodless retina. We propose that Nrl−/− retina may serve as a model for elucidating mechanisms of cone homeostasis and degeneration that would be relevant to understanding diseases of the cone-dominant human macula. PMID:22238088

  6. Early cytoskeletal protein modifications precede overt structural degeneration in the DBA/2J mouse model of glaucoma

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    Gina Nicole Wilson

    2016-11-01

    Full Text Available Axonal transport deficits precede structural loss in glaucoma and other neurodegenerations. Impairments in structural support, including modified cytoskeletal proteins and microtubule-destabilizing elements, could be initiating factors in glaucoma pathogenesis. We investigated the time course of changes in protein levels and post-translational modifications in the DBA/2J mouse model of glaucoma. Using anterograde tract tracing of the retinal projection, we assessed major cytoskeletal and transported elements as a function of transport integrity in different stages of pathological progression. Using capillary-based electrophoresis, single- and multiplex immunosorbent assays, and immunofluorescence, we quantified hyperphosphorylated neurofilament-heavy chain, phosphorylated tau (ptau, calpain-mediated spectrin breakdown product (145/150kDa, β –tubulin, and amyloid-β42 proteins based on age and transport outcome to the superior colliculus (SC, the main retinal target in mice. Phosphorylated neurofilament-heavy chain (pNF-H was elevated within the optic nerve (ON and SC of 8-10 month-old DBA/2J mice, but was not evident in the retina until 12-15 months, suggesting that cytoskeletal modifications first appear in the distal retinal projection. As expected, higher pNF-H levels in the SC and retina were correlated with axonal transport deficits. Elevations in hyperphosphorylated tau (ptau occurred in ON and SC between 3-8 month of age while retinal ptau accumulations occurred at 12-15 months in DBA/2J mice. In vitro co-immunoprecipitation experiments suggested increased affinity of ptau for the retrograde motor complex protein, dynactin. We observed a transport-related decrease of β-tubulin in ON of 10-12 month-old DBA/2J mice, suggesting destabilized microtubule array. Elevations in calpain-mediated spectrin breakdown product were seen in ON and SC at the earliest age examined, well before axonal transport loss is evident. Finally, transport

  7. Application of the comet assay in studies of programmed cell death (PCD) in plants

    OpenAIRE

    2014-01-01

    Programmed cell death (PCD) in plants is an intensively investigated process. One of the main characteristics of PCD in both animal and plant organisms is the non-random, internucleosomal fragmentation of nuclear DNA, usually analysed using total DNA gel electrophoresis or TUNEL method. In this paper we present application of the "comet assay" (Single Cell Gel Electrophoresis) for detection of nDNA degradation in studies of PCD during plant life cycle. We analyzed three types of tissue: anthe...

  8. Mitochondrial alterations and oxidative stress in an acute transient mouse model of muscle degeneration: implications for muscular dystrophy and related muscle pathologies.

    Science.gov (United States)

    Ramadasan-Nair, Renjini; Gayathri, Narayanappa; Mishra, Sudha; Sunitha, Balaraju; Mythri, Rajeswara Babu; Nalini, Atchayaram; Subbannayya, Yashwanth; Harsha, Hindalahalli Chandregowda; Kolthur-Seetharam, Ullas; Srinivas Bharath, Muchukunte Mukunda

    2014-01-03

    Muscular dystrophies (MDs) and inflammatory myopathies (IMs) are debilitating skeletal muscle disorders characterized by common pathological events including myodegeneration and inflammation. However, an experimental model representing both muscle pathologies and displaying most of the distinctive markers has not been characterized. We investigated the cardiotoxin (CTX)-mediated transient acute mouse model of muscle degeneration and compared the cardinal features with human MDs and IMs. The CTX model displayed degeneration, apoptosis, inflammation, loss of sarcolemmal complexes, sarcolemmal disruption, and ultrastructural changes characteristic of human MDs and IMs. Cell death caused by CTX involved calcium influx and mitochondrial damage both in murine C2C12 muscle cells and in mice. Mitochondrial proteomic analysis at the initial phase of degeneration in the model detected lowered expression of 80 mitochondrial proteins including subunits of respiratory complexes, ATP machinery, fatty acid metabolism, and Krebs cycle, which further decreased in expression during the peak degenerative phase. The mass spectrometry (MS) data were supported by enzyme assays, Western blot, and histochemistry. The CTX model also displayed markers of oxidative stress and a lowered glutathione reduced/oxidized ratio (GSH/GSSG) similar to MDs, human myopathies, and neurogenic atrophies. MS analysis identified 6 unique oxidized proteins from Duchenne muscular dystrophy samples (n = 6) (versus controls; n = 6), including two mitochondrial proteins. Interestingly, these mitochondrial proteins were down-regulated in the CTX model thereby linking oxidative stress and mitochondrial dysfunction. We conclude that mitochondrial alterations and oxidative damage significantly contribute to CTX-mediated muscle pathology with implications for human muscle diseases.

  9. Muscle spindles exhibit core lesions and extensive degeneration of intrafusal fibers in the Ryr1{sup I4895T/wt} mouse model of core myopathy

    Energy Technology Data Exchange (ETDEWEB)

    Zvaritch, Elena; MacLennan, David H., E-mail: david.maclennan@utoronto.ca

    2015-04-24

    Muscle spindles from the hind limb muscles of adult Ryr1{sup I4895T/wt} (IT/+) mice exhibit severe structural abnormalities. Up to 85% of the spindles are separated from skeletal muscle fascicles by a thick layer of connective tissue. Many intrafusal fibers exhibit degeneration, with Z-line streaming, compaction and collapse of myofibrillar bundles, mitochondrial clumping, nuclear shrinkage and pyknosis. The lesions resemble cores observed in the extrafusal myofibers of this animal model and of core myopathy patients. Spindle abnormalities precede those in extrafusal fibers, indicating that they are a primary pathological feature in this murine Ryr1-related core myopathy. Muscle spindle involvement, if confirmed for human core myopathy patients, would provide an explanation for an array of devastating clinical features characteristic of these diseases and provide novel insights into the pathology of RYR1-related myopathies. - Highlights: • Muscle spindles exhibit structural abnormalities in a mouse model of core myopathy. • Myofibrillar collapse and mitochondrial clumping is observed in intrafusal fibers. • Myofibrillar degeneration follows a pattern similar to core formation in extrafusal myofibers. • Muscle spindle abnormalities are a part of the pathological phenotype in the mouse model of core myopathy. • Direct involvement of muscle spindles in the pathology of human RYR1-related myopathies is proposed.

  10. Loss of the E3 ubiquitin ligase LRSAM1 sensitizes peripheral axons to degeneration in a mouse model of Charcot-Marie-Tooth disease

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    Laurent P. Bogdanik

    2013-05-01

    Charcot-Marie-Tooth disease (CMT is a clinically and genetically heterogeneous condition characterized by peripheral axon degeneration with subsequent motor and sensory deficits. Several CMT gene products function in endosomal sorting and trafficking to the lysosome, suggesting that defects in this cellular pathway might present a common pathogenic mechanism for these conditions. LRSAM1 is an E3 ubiquitin ligase that is implicated in this process, and mutations in LRSAM1 have recently been shown to cause CMT. We have generated mouse mutations in Lrsam1 to create an animal model of this form of CMT (CMT2P. Mouse Lrsam1 is abundantly expressed in the motor and sensory neurons of the peripheral nervous system. Both homozygous and heterozygous mice have largely normal neuromuscular performance and only a very mild neuropathy phenotype with age. However, Lrsam1 mutant mice are more sensitive to challenge with acrylamide, a neurotoxic agent that causes axon degeneration, indicating that the axons in the mutant mice are indeed compromised. In transfected cells, LRSAM1 primarily localizes in a perinuclear compartment immediately beyond the Golgi and shows little colocalization with components of the endosome to lysosome trafficking pathway, suggesting that other cellular mechanisms also merit consideration.

  11. The international primary ciliary dyskinesia cohort (iPCD Cohort): methods and first results

    Science.gov (United States)

    Goutaki, Myrofora; Maurer, Elisabeth; Halbeisen, Florian S.; Amirav, Israel; Barbato, Angelo; Behan, Laura; Boon, Mieke; Casaulta, Carmen; Clement, Annick; Crowley, Suzanne; Haarman, Eric; Hogg, Claire; Karadag, Bulent; Koerner-Rettberg, Cordula; Leigh, Margaret W.; Loebinger, Michael R.; Mazurek, Henryk; Morgan, Lucy; Nielsen, Kim G.; Omran, Heymut; Schwerk, Nicolaus; Scigliano, Sergio; Werner, Claudius; Yiallouros, Panayiotis; Zivkovic, Zorica; Lucas, Jane S.

    2017-01-01

    Data on primary ciliary dyskinesia (PCD) epidemiology is scarce and published studies are characterised by low numbers. In the framework of the European Union project BESTCILIA we aimed to combine all available datasets in a retrospective international PCD cohort (iPCD Cohort). We identified eligible datasets by performing a systematic review of published studies containing clinical information on PCD, and by contacting members of past and current European Respiratory Society Task Forces on PCD. We compared the contents of the datasets, clarified definitions and pooled them in a standardised format. As of April 2016 the iPCD Cohort includes data on 3013 patients from 18 countries. It includes data on diagnostic evaluations, symptoms, lung function, growth and treatments. Longitudinal data are currently available for 542 patients. The extent of clinical details per patient varies between centres. More than 50% of patients have a definite PCD diagnosis based on recent guidelines. Children aged 10–19 years are the largest age group, followed by younger children (≤9 years) and young adults (20–29 years). This is the largest observational PCD dataset available to date. It will allow us to answer pertinent questions on clinical phenotype, disease severity, prognosis and effect of treatments, and to investigate genotype–phenotype correlations. PMID:28052956

  12. Morphological characteristics of motor neurons do not determine their relative susceptibility to degeneration in a mouse model of severe spinal muscular atrophy.

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    Sophie R Thomson

    Full Text Available Spinal muscular atrophy (SMA is a leading genetic cause of infant mortality, resulting primarily from the degeneration and loss of lower motor neurons. Studies using mouse models of SMA have revealed widespread heterogeneity in the susceptibility of individual motor neurons to neurodegeneration, but the underlying reasons remain unclear. Data from related motor neuron diseases, such as amyotrophic lateral sclerosis (ALS, suggest that morphological properties of motor neurons may regulate susceptibility: in ALS larger motor units innervating fast-twitch muscles degenerate first. We therefore set out to determine whether intrinsic morphological characteristics of motor neurons influenced their relative vulnerability to SMA. Motor neuron vulnerability was mapped across 10 muscle groups in SMA mice. Neither the position of the muscle in the body, nor the fibre type of the muscle innervated, influenced susceptibility. Morphological properties of vulnerable and disease-resistant motor neurons were then determined from single motor units reconstructed in Thy.1-YFP-H mice. None of the parameters we investigated in healthy young adult mice - including motor unit size, motor unit arbor length, branching patterns, motor endplate size, developmental pruning and numbers of terminal Schwann cells at neuromuscular junctions - correlated with vulnerability. We conclude that morphological characteristics of motor neurons are not a major determinant of disease-susceptibility in SMA, in stark contrast to related forms of motor neuron disease such as ALS. This suggests that subtle molecular differences between motor neurons, or extrinsic factors arising from other cell types, are more likely to determine relative susceptibility in SMA.

  13. Systemic administration of Abeta mAb reduces retinal deposition of Abeta and activated complement C3 in age-related macular degeneration mouse model.

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    Ian Catchpole

    Full Text Available Age-related macular degeneration (AMD is a leading cause of legal blindness in the Western world. There are effective treatments for the vascular complications of neo-vascular AMD, but no effective therapies are available for the dry/atrophic form of the disease. A previously described transgenic CFH-gene deficient mouse model, (cfh-/-, shows hallmarks of early AMD. The ocular phenotype has been further analysed to demonstrate amyloid beta (Aβ rich basement membrane deposits associated with activated complement C3. Cfh-/- mice were treated systemically in both prophylactic and therapeutic regimes with an anti-Aβ monoclonal antibody (mAb, 6F6, to determine the effect on the cfh-/- retinal phenotype. Prophylactic treatment with 6F6 demonstrated a dose dependent reduction in the accumulation of both Aβ and activated C3 deposition. A similar reduction in the retinal endpoints could be seen after therapeutic treatment. Serum Aβ levels after systemic administration of 6F6 show accumulation of Aβ in the periphery suggestive of a peripheral sink mechanism. In summary, anti-Aβ mAb treatment can partially prevent or reverse ocular phenotypes of the cfh-/- mouse. The data support this therapeutic approach in humans potentially modulating two key elements in the pathogenesis of AMD - Aβ and activated, complement C3.

  14. Fast cortical oscillation after thalamic degeneration: pivotal role of NMDA receptor.

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    Kyuhou, Shin-ichi; Gemba, Hisae

    2007-04-27

    We examined electrophysiological and molecular changes of the thalamocortical system after thalamic degeneration in Purkinje cell degeneration (pcd) mice. In pcd mice, neurons in specific thalamic nuclei including the ventral medial geniculate nucleus began to degenerate around postnatal day 50, whereas the visual thalamic nucleus and nonspecific thalamic nuclei remained almost intact. In association with the morphological changes, auditory evoked potentials in the primary auditory cortex (AC) began to decrease gradually. Fast Fourier transform analysis of spontaneous cortical field potentials revealed that fast oscillation (FO) around 25 Hz occurred in the AC but not in the visual cortex. Quantitative mRNA analysis demonstrated that expression of the N-methyl-D-aspartate (NMDA) receptor was up-regulated in the AC but not in the visual cortex. Systemic administration of an NMDA antagonist abolished the FO in the AC. These results indicate that increased NMDA activity may cause the FO in the AC of pcd mice.

  15. Emergence of endoplasmic reticulum stress and activated microglia in Purkinje cell degeneration mice.

    Science.gov (United States)

    Kyuhou, Shin-ichi; Kato, Nobuo; Gemba, Hisae

    2006-03-27

    In the current studies, we characterized the molecular and cellular mechanism of cell death in Purkinje cell degeneration (pcd) mice using real-time quantitative PCR, immunohistochemistry, and Western blotting. It appears that endoplasmic reticulum (ER) stress is involved in this degeneration of Purkinje cells because ER stress-related substrates, such as CHOP and caspase 12, were strongly activated in Purkinje cells of pcd mice during the third postnatal (P) week. A significant increase in the expression of the ER-specific chaperone BiP suggested that unfolded protein responses were induced. We also found that Purkinje cells underwent apoptosis via the activation of caspase 3 and subsequent fragmentation of DNA. In addition to the activation of apoptosis in Purkinje cells, many activated microglial cells are found to be present in the molecular layer of the cerebellar cortex. In the later phase of degeneration, there was conspicuous expression of inducible nitric oxide synthase (iNOS), and some Purkinje cells were strongly labeled with an antibody to nitrotyrosine, suggesting that Purkinje cells in pcd mice are damaged by nitric oxide released from microglial cells. Administration of minocycline, which may inhibit iNOS expression, delayed the death of Purkinje cells in pcd mice and mildly improved their motor abilities. These findings suggest that ER stress participates in the degeneration of Purkinje cells and that activation of microglia accelerates Purkinje cell death in pcd mice.

  16. Impaired mitochondrial biogenesis, defective axonal transport of mitochondria, abnormal mitochondrial dynamics and synaptic degeneration in a mouse model of Alzheimer's disease.

    Science.gov (United States)

    Calkins, Marcus J; Manczak, Maria; Mao, Peizhong; Shirendeb, Ulziibat; Reddy, P Hemachandra

    2011-12-01

    Increasing evidence suggests that the accumulation of amyloid beta (Aβ) in synapses and synaptic mitochondria causes synaptic mitochondrial failure and synaptic degeneration in Alzheimer's disease (AD). The purpose of this study was to better understand the effects of Aβ in mitochondrial activity and synaptic alterations in neurons from a mouse model of AD. Using primary neurons from a well-characterized Aβ precursor protein transgenic (AβPP) mouse model (Tg2576 mouse line), for the first time, we studied mitochondrial activity, including axonal transport of mitochondria, mitochondrial dynamics, morphology and function. Further, we also studied the nature of Aβ-induced synaptic alterations, and cell death in primary neurons from Tg2576 mice, and we sought to determine whether the mitochondria-targeted antioxidant SS31 could mitigate the effects of oligomeric Aβ. We found significantly decreased anterograde mitochondrial movement, increased mitochondrial fission and decreased fusion, abnormal mitochondrial and synaptic proteins and defective mitochondrial function in primary neurons from AβPP mice compared with wild-type (WT) neurons. Transmission electron microscopy revealed a large number of small mitochondria and structurally damaged mitochondria, with broken cristae in AβPP primary neurons. We also found an increased accumulation of oligomeric Aβ and increased apoptotic neuronal death in the primary neurons from the AβPP mice relative to the WT neurons. Our results revealed an accumulation of intraneuronal oligomeric Aβ, leading to mitochondrial and synaptic deficiencies, and ultimately causing neurodegeneration in AβPP cultures. However, we found that the mitochondria-targeted antioxidant SS31 restored mitochondrial transport and synaptic viability, and decreased the percentage of defective mitochondria, indicating that SS31 protects mitochondria and synapses from Aβ toxicity.

  17. Bacterial evolution in PCD and CF patients follows the same mutational steps

    DEFF Research Database (Denmark)

    Madsen Sommer, Lea Mette; Alanin, Mikkel Christian; Marvig, Rasmus L.

    2016-01-01

    Infections with Pseudomonas aeruginosa increase morbidity in primary ciliary dyskinesia (PCD) and cystic fibrosis (CF) patients. Both diseases are associated with a defect of the mucociliary clearance; in PCD caused by non-functional cilia, in CF by changed mucus. Whole genome sequencing of P...... isolates from 12 PCD patients were whole genome sequenced and phenotypically characterised. Ten out of 12 PCD patients were infected with persisting clone types. We identified convergent evolution in eight genes, which are also important for persistent infections in CF airways: genes related to antibiotic...... resistance, quorum sensing, motility, type III secretion and mucoidity. We document phenotypic and genotypic parallelism in the evolution of P. aeruginosa across infected patients with different genetic disorders. The parallel changes and convergent adaptation and evolution may be caused by similar selective...

  18. Progressive retinal degeneration and glial activation in the CLN6 (nclf mouse model of neuronal ceroid lipofuscinosis: a beneficial effect of DHA and curcumin supplementation.

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    Myriam Mirza

    Full Text Available Neuronal ceroid lipofuscinosis (NCL is a group of neurodegenerative lysosomal storage disorders characterized by vision loss, mental and motor deficits, and spontaneous seizures. Neuropathological analyses of autopsy material from NCL patients and animal models revealed brain atrophy closely associated with glial activity. Earlier reports also noticed loss of retinal cells and reactive gliosis in some forms of NCL. To study this phenomenon in detail, we analyzed the ocular phenotype of CLN6 (nclf mice, an established mouse model for variant-late infantile NCL. Retinal morphometry, immunohistochemistry, optokinetic tracking, electroretinography, and mRNA expression were used to characterize retinal morphology and function as well as the responses of Müller cells and microglia. Our histological data showed a severe and progressive degeneration in the CLN6 (nclf retina co-inciding with reactive Müller glia. Furthermore, a prominent phenotypic transformation of ramified microglia to phagocytic, bloated, and mislocalized microglial cells was identified in CLN6 (nclf retinas. These events overlapped with a rapid loss of visual perception and retinal function. Based on the strong microglia reactivity we hypothesized that dietary supplementation with immuno-regulatory compounds, curcumin and docosahexaenoic acid (DHA, could ameliorate microgliosis and reduce retinal degeneration. Our analyses showed that treatment of three-week-old CLN6 (nclf mice with either 5% DHA or 0.6% curcumin for 30 weeks resulted in a reduced number of amoeboid reactive microglia and partially improved retinal function. DHA-treatment also improved the morphology of CLN6 (nclf retinas with a preserved thickness of the photoreceptor layer in most regions of the retina. Our results suggest that microglial reactivity closely accompanies disease progression in the CLN6 (nclf retina and both processes can be attenuated with dietary supplemented immuno-modulating compounds.

  19. The excimer lamp induces cutaneous nerve degeneration and reduces scratching in a dry-skin mouse model.

    Science.gov (United States)

    Kamo, Atsuko; Tominaga, Mitsutoshi; Kamata, Yayoi; Kaneda, Kazuyuki; Ko, Kyi C; Matsuda, Hironori; Kimura, Utako; Ogawa, Hideoki; Takamori, Kenji

    2014-12-01

    Epidermal hyperinnervation, which is thought to underlie intractable pruritus, has been observed in patients with atopic dermatitis (AD). The epidermal expression of axonal guidance molecules has been reported to regulate epidermal hyperinnervation. Previously, we showed that the excimer lamp has antihyperinnervative effects in nonpruritic dry-skin model mice, although epidermal expression of axonal guidance molecules was unchanged. Therefore, we investigated the antipruritic effects of excimer lamp irradiation and its mechanism of action. A single irradiation of AD model mice significantly inhibited itch-related behavior 1 day later, following improvement in the dermatitis score. In addition, irradiation of nerve fibers formed by cultured dorsal root ganglion neurons increased bleb formation and decreased nerve fiber expression of nicotinamide mononucleotide adenylyl transferase 2, suggesting degenerative changes in these fibers. We also analyzed whether attaching a cutoff excimer filter (COF) to the lamp, thus decreasing cytotoxic wavelengths, altered hyperinnervation and the production of cyclobutane pyrimidine dimer (CPD), a DNA damage marker, in dry-skin model mice. Irradiation with COF decreased CPD production in keratinocytes, as well as having an antihyperinnervative effect, indicating that the antipruritic effects of excimer lamp irradiation with COF are due to induction of epidermal nerve degeneration and reduced DNA damage.

  20. 17-DMAG ameliorates polyglutamine-mediated motor neuron degeneration through well-preserved proteasome function in an SBMA model mouse.

    Science.gov (United States)

    Tokui, Keisuke; Adachi, Hiroaki; Waza, Masahiro; Katsuno, Masahisa; Minamiyama, Makoto; Doi, Hideki; Tanaka, Keiji; Hamazaki, Jun; Murata, Shigeo; Tanaka, Fumiaki; Sobue, Gen

    2009-03-01

    The ubiquitin-proteasome system (UPS) is the principal protein degradation system that tags and targets short-lived proteins, as well as damaged or misfolded proteins, for destruction. In spinal and bulbar muscular atrophy (SBMA), the androgen receptor (AR), an Hsp90 client protein, is such a misfolded protein that tends to aggregate in neurons. Hsp90 inhibitors promote the degradation of Hsp90 client proteins via the UPS. In a transgenic mouse model of SBMA, we examined whether a functioning UPS is preserved, if it was capable of degrading polyglutamine-expanded mutant AR, and what might be the therapeutic effects of 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG), an oral Hsp90 inhibitor. Ubiquitin-proteasomal function was well preserved in SBMA mice and was even increased during advanced stages when the mice developed severe phenotypes. Administration of 17-DMAG markedly ameliorated motor impairments in SBMA mice without detectable toxicity and reduced amounts of monomeric and nuclear-accumulated mutant AR. Mutant AR was preferentially degraded in the presence of 17-DMAG in both SBMA cell and mouse models when compared with wild-type AR. 17-DMAG also significantly induced Hsp70 and Hsp40. Thus, 17-DMAG would exert a therapeutic effect on SBMA via preserved proteasome function.

  1. Degeneration of retinal on bipolar cells induced by serum including autoantibody against TRPM1 in mouse model of paraneoplastic retinopathy.

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    Shinji Ueno

    Full Text Available The paraneoplastic retinopathies (PRs are a group of eye diseases characterized by a sudden and progressive dysfunction of the retina caused by an antibody against a protein in a neoplasm. Evidence has been obtained that the transient receptor potential melastatin 1 (TRPM1 protein was one of the antigens for the autoantibody against the ON bipolar cells in PR patients. However, it has not been determined how the autoantibody causes the dysfunction of the ON bipolar cells. We hypothesized that the antibody against TRPM1 in the serum of patients with PR causes a degeneration of retinal ON bipolar cells. To test this hypothesis, we injected the serum from the PR patient, previously shown to contain anti-TRPM1 antibodies by westerblot, intravitreally into mice and examined the effects on the retina. We found that the electroretinograms (ERGs of the mice were altered acutely after the injection, and the shape of the ERGs resembled that of the patient with PR. Immunohistochemical analysis of the eyes injected with the serum showed immunoreactivity against bipolar cells only in wild-type animals and not in TRPM1 knockout mice,consistent with the serum containing anti-TRPM1 antibodies. Histology also showed that some of the bipolar cells were apoptotic by 5 hours after the injection in wild type mice, but no bipolar cell death was found in TRPM1 knockout mice, . At 3 months, the inner nuclear layer was thinner and the amplitudes of the ERGs were still reduced. These results indicate that the serum of a patient with PR contained an antibody against TRPM1 caused an acute death of retinal ON bipolar cells of mice.

  2. Malfunctioning DNA damage response (DDR) leads to the degeneration of nigro-striatal pathway in mouse brain.

    Science.gov (United States)

    Kirshner, Michal; Galron, Ronit; Frenkel, Dan; Mandelbaum, Gil; Shiloh, Yosef; Wang, Zhao-Qi; Barzilai, Ari

    2012-03-01

    Pronounced neuropathology is a feature of ataxia-telangiectasia (A-T) and Nijmegen breakage syndrome (NBS), which are both genomic instability syndromes. The Nbs1 protein, which is defective in NBS, is a component of the Mre11/RAD50/NBS1 (MRN) complex. This complex plays a major role in the early phase of the cellular response to double strand breaks (DSBs) in the DNA. Among others, MRN is required for timely activation of the protein kinase ATM (A-T mutated), which is disrupted in patients with A-T. Earlier reports show that Atm-deficient mice exhibit severe degeneration of tyrosine hydroxylase (TH)-positive dopaminergic nigro-striatal neurons and their terminals in the striatum. This cell loss is accompanied by a large reduction in immunoreactivity for the dopamine transporter protein (DAT) in the striatum. To test whether Nbs1 inactivation also affects the integrity of the nigro-striatal pathway, we examined this pathway in a murine model with conditional inactivation of the Nbs1 gene in central nervous system (Nbs1-CNS-Δ). We report that this model has a reduction in TH-positive cells in the substantia nigra. This phenomenon was seen at very early age, while Atm-/- mice showed a progressive age-dependent reduction. Furthermore, we observed an age-dependent increase in the level of TH in the striatum of Atm-/- and Nbs1-CNS-Δ mice. In addition to the altered expression of TH, we also found a reduction of DAT in the striatum of both Atm-/- and Nbs1-CNS-Δ mice at 60 days of age. Finally, microglial recruitment and alterations in the levels of various neurotrophic factors were also observed. These results indicate that malfunctioning DNA damage response severely affects the integrity of the nigro-striatal pathway and suggest a new neurodegenerative pathway in Parkinsonian syndromes.

  3. Macroautophagy occurs in distal TMV-uninfected root tip tissue of tomato taking place systemic PCD.

    Science.gov (United States)

    Zhou, Shumin; Hong, Qiang; Li, Yang; Li, Qi; Li, Ruisha; Zhang, Hongli; Wang, Mao; Yuan, Xiaojun

    2017-05-27

    Autophagy is an important mechanism for recycling cell materials upon encountering stress conditions. Our previous studies had shown that TMV infection could lead to systemic PCD in the distal uninfected tissues, including root tip and shoot tip tissues. But it is not clear whether there is autophagy in the distal apical meristem of TMV-induced plants. To better understand the autophagy process during systemic PCD, here we investigated the formation and type of autophagy in the root meristem cells occurring PCD. Transmission electron microscopy assay revealed that the autophagic structures formed by the fusion of vesicles, containing the sequestered cytoplasm, multilamellar bodies, and degraded mitochondria. In the PCD progress, many mitochondria appeared degradation with blurred inner membrane structure. And the endoplasmic reticulum was broke into small fragments. Finally, the damaged mitochodria were engulfed and degraded by the autophagosomes. These results indicated that during the systemic PCD process of root tip cells, the classical macroautophagy occurred, and the cell contents and damaged organelles (mitochondria) would be self-digested by autophagy.

  4. Application of the comet assay in studies of programmed cell death (PCD in plants

    Directory of Open Access Journals (Sweden)

    Maria Charzyńska

    2014-01-01

    Full Text Available Programmed cell death (PCD in plants is an intensively investigated process. One of the main characteristics of PCD in both animal and plant organisms is the non-random, internucleosomal fragmentation of nuclear DNA, usually analysed using total DNA gel electrophoresis or TUNEL method. In this paper we present application of the "comet assay" (Single Cell Gel Electrophoresis for detection of nDNA degradation in studies of PCD during plant life cycle. We analyzed three types of tissue: anther tapetum, endosperm and mesophyll which were prepared in different ways to obtain a suspension of viable cells (without cell walls. The comet assay gives a possibility of examination of the nDNA degradation in individual cell. This method is significant for studies of the plant tissue differentiation and senescence especially in the cases when it is not possible to isolate large number of cells at the same developmental stage.

  5. Unveiling interactions among mitochondria, caspase-like proteases, and the actin cytoskeleton during plant programmed cell death (PCD.

    Directory of Open Access Journals (Sweden)

    Christina E N Lord

    Full Text Available Aponogeton madagascariensis produces perforations over its leaf surface via programmed cell death (PCD. PCD begins between longitudinal and transverse veins at the center of spaces regarded as areoles, and continues outward, stopping several cells from these veins. The gradient of PCD that exists within a single areole of leaves in an early stage of development was used as a model to investigate cellular dynamics during PCD. Mitochondria have interactions with a family of proteases known as caspases, and the actin cytoskeleton during metazoan PCD; less is known regarding these interactions during plant PCD. This study employed the actin stain Alexa Fluor 488 phalloidin, the actin depolymerizer Latrunculin B (Lat B, a synthetic caspase peptide substrate and corresponding specific inhibitors, as well as the mitochondrial pore inhibitor cyclosporine A (CsA to analyze the role of these cellular constituents during PCD. Results depicted that YVADase (caspase-1 activity is higher during the very early stages of perforation formation, followed by the bundling and subsequent breakdown of actin. Actin depolymerization using Lat B caused no change in YVADase activity. In vivo inhibition of YVADase activity prevented PCD and actin breakdown, therefore substantiating actin as a likely substrate for caspase-like proteases (CLPs. The mitochondrial pore inhibitor CsA significantly decreased YVADase activity, and prevented both PCD and actin breakdown; therefore suggesting the mitochondria as a possible trigger for CLPs during PCD in the lace plant. To our knowledge, this is the first in vivo study using either caspase-1 inhibitor (Ac-YVAD-CMK or CsA, following which the actin cytoskeleton was examined. Overall, our findings suggest the mitochondria as a possible upstream activator of YVADase activity and implicate these proteases as potential initiators of actin breakdown during perforation formation via PCD in the lace plant.

  6. Flavonoids and darkness lower PCD in senescing Vitis vinifera suspension cell cultures.

    Science.gov (United States)

    Bertolini, Alberto; Petrussa, Elisa; Patui, Sonia; Zancani, Marco; Peresson, Carlo; Casolo, Valentino; Vianello, Angelo; Braidot, Enrico

    2016-10-26

    Senescence is a key developmental process occurring during the life cycle of plants that can be induced also by environmental conditions, such as starvation and/or darkness. During senescence, strict control of genes regulates ordered degradation and dismantling events, the most remarkable of which are genetically programmed cell death (PCD) and, in most cases, an upregulation of flavonoid biosynthesis in the presence of light. Flavonoids are secondary metabolites that play multiple essential roles in development, reproduction and defence of plants, partly due to their well-known antioxidant properties, which could affect also the same cell death machinery. To understand further the effect of endogenously-produced flavonoids and their interplay with different environment (light or dark) conditions, two portions (red and green) of a senescing grapevine callus were used to obtain suspension cell cultures. Red Suspension cell Cultures (RSC) and Green Suspension cell Cultures (GSC) were finally grown under either dark or light conditions for 6 days. Darkness enhanced cell death (mainly necrosis) in suspension cell culture, when compared to those grown under light condition. Furthermore, RSC with high flavonoid content showed a higher viability compared to GSC and were more protected toward PCD, in accordance to their high content in flavonoids, which might quench ROS, thus limiting the relative signalling cascade. Conversely, PCD was mainly occurring in GSC and further increased by light, as it was shown by cytochrome c release and TUNEL assays. Endogenous flavonoids were shown to be good candidates for exploiting an efficient protection against oxidative stress and PCD induction. Light seemed to be an important environmental factor able to induce PCD, especially in GSC, which lacking of flavonoids were not capable of preventing oxidative damage and signalling leading to senescence.

  7. EST analysis of Prorocentrum donghaiense with emphasis on genes involved in PCD

    Institute of Scientific and Technical Information of China (English)

    Zhang Xiufang; Liu Yongjian; Yang Guanpin; Zhu Mingyuan; Li Ruixiang

    2009-01-01

    Prorocentrum donghaiense has caused large-scale red tides off the Chinese coast in recent years. Expressed sequence tag (EST) analysis was carried out for this dinoflagellate in order to identify the functional genes involved in its biological processes. A cDNA library was constructed for P. donghaiense at exponential growth phase, and 565 usable sequencing reads were obtained from 700 clones selected randomly. Messenger RNA corresponding reads were clustered into 36 contigs and 272 singletons (EST groups). Twenty-two EST groups were found to tag the genes involved in diverse biological processes including programmed cell death (PCD). Two EST groups showed significant homologies with the encoding genes of cysteine protease (caspase) and proliferating cell nuclear antigen, respectively, two key proteins involved in PCD.

  8. Machinability of Al-SiC metal matrix composites using WC, PCD and MCD inserts

    Energy Technology Data Exchange (ETDEWEB)

    Beristain, J.; Gonzalo, O.; Sanda, A.

    2014-04-01

    The aim of this work is the study of the machinability of aluminium-silicon carbide Metal Matrix Composites (MMC) in turning operations. The cutting tools used were hard metal (WC) with and without coating, different grades and geometries of Poly-Crystalline Diamond (PCD) and Mono-Crystalline Diamond (MCD). The work piece material was AMC225xe, composed of aluminium-copper alloy AA 2124 and 25% wt of SiC, being the size of the SiC particles around 3 {mu}m. Experiments were conducted at various cutting speeds and cutting parameters in facing finishing operations, measuring the surface roughness, cutting forces and tool wear. The worn surface of the cutting tool was examined by Scanning Electron Microscope (SEM). It was observed that the Built Up Edge (BUE) and stuck material is higher in the MCD tools than in the PCD tools. The BUE acts as a protective layer against abrasive wear of the tool. (Author)

  9. Comparison Between Cemented Carbide and PCD Tools on Machinability of a High Silicon Aluminum Alloy

    Science.gov (United States)

    Soares, R. B.; de Jesus, A. M. P.; Neto, R. J. L.; Chirita, B.; Rosa, P. A. R.; Reis, A.

    2017-08-01

    The high content of silicon of aluminum casting alloys challenges the tool life of conventional cemented carbide inserts, and polycrystalline diamond (PCD) tools appear as an interesting material to machine these alloys because they improve substantially the durability of cutting tools and consequently the productivity of machining. However, the surface roughness, cutting forces and chip morphology are equally important factors in machining evaluation. Therefore, an experimental study is performed aiming at comparing the performance of cemented carbide and PCD tools taking into account cutting forces, surface roughness and chip morphology, under dry longitudinal turning, performed for the AlSi9Cu3 alloy produced by permanent mold casting process. Different chip breaker geometries were also considered, and their influence on the referred parameters was also investigated. Analysis of variance was employed to study the different contributions of inserts, cutting speed, feed rate, depth of cut and their interactions in machinability performance. The results show low cutting forces and better results for surface roughness for uncoated cemented carbide tools, with simpler chip breakers and flat rake face PCD tool, but an efficient chip control was obtained for inserts with small grooves with high cutting forces and power consumption. Nevertheless, the feed rate and depth of cut have the highest influence on the machinability performance of the alloy under investigation.

  10. Transcriptional adaptation of Mycosphaerella graminicola to programmed cell death (PCD) of its susceptible wheat host.

    Science.gov (United States)

    Keon, John; Antoniw, John; Carzaniga, Raffaella; Deller, Siân; Ward, Jane L; Baker, John M; Beale, Michael H; Hammond-Kosack, Kim; Rudd, Jason J

    2007-02-01

    Many important fungal pathogens of plants spend long periods (days to weeks) of their infection cycle in symptomless association with living host tissue, followed by a sudden transition to necrotrophic feeding as host tissue death occurs. Little is known about either the host responses associated with this sudden transition or the specific adaptations made by the pathogen to invoke or tolerate it. We are studying a major host-specific fungal pathogen of cultivated wheat, Septoria tritici (teleomorph Mycosphaerella graminicola). Here, we describe the host responses of wheat leaves infected with M. graminicola during the development of disease symptoms and use microarray transcription profiling to identify adaptive responses of the fungus to its changing environment. We show that symptom development on a susceptible host genotype has features reminiscent of the hypersensitive response, a rapid and strictly localized form of host programmed cell death (PCD) more commonly associated with disease-resistance mechanisms. The initiation and advancement of this host response is associated with a loss of cell-membrane integrity and dramatic increases in apoplastic metabolites and the rate of fungal growth. Microarray analysis of the fungal genes differentially expressed before and after the onset of host PCD supports a transition to more rapid growth. Specific physiological adaptation of the fungus is also revealed with respect to membrane transport, chemical and oxidative stress mechanisms, and metabolism. Our data support the hypothesis that host plant PCD plays an important role in susceptibility towards fungal pathogens with necrotrophic lifestyles.

  11. Q344ter mutation causes mislocalization of rhodopsin molecules that are catalytically active: a mouse model of Q344ter-induced retinal degeneration.

    Directory of Open Access Journals (Sweden)

    Francis Concepcion

    Full Text Available Q344ter is a naturally occurring rhodopsin mutation in humans that causes autosomal dominant retinal degeneration through mechanisms that are not fully understood, but are thought to involve an early termination that removed the trafficking signal, QVAPA, leading to its mislocalization in the rod photoreceptor cell. To better understand the disease mechanism(s, transgenic mice that express Q344ter were generated and crossed with rhodopsin knockout mice. Dark-reared Q344ter(rho+/- mice exhibited retinal degeneration, demonstrating that rhodopsin mislocalization caused photoreceptor cell death. This degeneration is exacerbated by light-exposure and is correlated with the activation of transducin as well as other G-protein signaling pathways. We observed numerous sub-micrometer sized vesicles in the inter-photoreceptor space of Q344ter(rho+/- and Q344ter(rho-/- retinas, similar to that seen in another rhodopsin mutant, P347S. Whereas light microscopy failed to reveal outer segment structures in Q344ter(rho-/- rods, shortened and disorganized rod outer segment structures were visible using electron microscopy. Thus, some Q344ter molecules trafficked to the outer segment and formed disc structures, albeit inefficiently, in the absence of full length wildtype rhodopsin. These findings helped to establish the in vivo role of the QVAPA domain as well as the pathways leading to Q344ter-induced retinal degeneration.

  12. Multiple quantitative trait loci modify cochlear hair cell degeneration in the Beethoven (Tmc1Bth) mouse model of progressive hearing loss DFNA36.

    Science.gov (United States)

    Noguchi, Yoshihiro; Kurima, Kiyoto; Makishima, Tomoko; de Angelis, Martin Hrabé; Fuchs, Helmut; Frolenkov, Gregory; Kitamura, Ken; Griffith, Andrew J

    2006-08-01

    Dominant mutations of transmembrane channel-like gene 1 (TMC1) cause progressive sensorineural hearing loss in humans and Beethoven (Tmc1Bth/+) mice. Here we show that Tmc1Bth/+ mice on a C3HeB/FeJ strain background have selective degeneration of inner hair cells while outer hair cells remain structurally and functionally intact. Inner hair cells primarily function as afferent sensory cells, whereas outer hair cells are electromotile amplifiers of auditory stimuli that can be functionally assessed by distortion product otoacoustic emission (DPOAE) analysis. When C3H-Tmc1Bth/Bth is crossed with either C57BL/6J or DBA/2J wild-type mice, F1 hybrid Tmc1Bth/+ progeny have increased hearing loss associated with increased degeneration of outer hair cells and diminution of DPOAE amplitudes but no difference in degeneration of inner hair cells. We mapped at least one quantitative trait locus (QTL), Tmc1m1, for DPOAE amplitude on chromosome 2 in [(C/B)F1xC]N2-Tmc1Bth/+ backcross progeny, and three other QTL on chromosomes 11 (Tmc1m2), 12 (Tmc1m3), and 5 (Tmc1m4) in [(C/D)F1xC]N2-Tmc1Bth/+ progeny. The polygenic basis of outer hair cell degeneration in Beethoven mice provides a model system for the dissection of common, complex hearing loss phenotypes, such as presbycusis, that involve outer hair cell degeneration in humans.

  13. Machinability of Al-SiC metal matrix composites using WC, PCD and MCD inserts

    Directory of Open Access Journals (Sweden)

    Beristain, Jokin

    2014-03-01

    Full Text Available The aim of this work is the study of the machinability of aluminium-silicon carbide Metal Matrix Composites (MMC in turning operations. The cutting tools used were hard metal (WC with and without coating, different grades and geometries of Poly-Crystalline Diamond (PCD and Mono-Crystalline Diamond (MCD. The work piece material was AMC225xe, composed of aluminium-copper alloy AA 2124 and 25% wt of SiC, being the size of the SiC particles around 3 μm. Experiments were conducted at various cutting speeds and cutting parameters in facing finishing operations, measuring the surface roughness, cutting forces and tool wear. The worn surface of the cutting tool was examined by Scanning Electron Microscope (SEM. It was observed that the Built Up Edge (BUE and stuck material is higher in the MCD tools than in the PCD tools. The BUE acts as a protective layer against abrasive wear of the tool.El objetivo de este trabajo es el estudio de la maquinabilidad del material compuesto de matriz metálica aluminio-carburo de silicio en operaciones de torneado. Las herramientas de corte utilizadas han sido de metal duro con y sin recubrimiento, diferentes grados de diamante policristalino (PCD y diamante monocristalino (MCD. El material mecanizado ha sido AMC225xe, compuesto de la aleación de aluminio AA 2124 con un 25% en peso de partículas de SiC con un tamaño medio de 3 μm. Los experimentos se han realizado con diferentes velocidades de corte en una operación de refrentado, midiendo la rugosidad superficial, las fuerzas y el desgaste de la herramienta. La superficie desgastada de la herramienta ha sido examinada en el microscopio electrónico (SEM. Se ha observado que el filo recrecido y el material adherido son mayores en el caso de las herramientas de MCD que en las de PCD. El filo recrecido actúa como una capa protectora contra la abrasión.

  14. Arquitectura y salud: arquitectura para PcD (personas con discapacidad).

    OpenAIRE

    Jochims Backes, Rosane; Oliveira Roveda, Patricia; Ribas Moraes, Jorge André; Pedro Roos, Nestor; Kuhn, Eduarda

    2012-01-01

    Exposición oral presentada en la sesión dedicada a Ámbitos, Innovación y Calidad, en las IV Jornadas Internacionales sobre Investigación en Arquitectura y Urbanismo. El proyecto de extensión Arquitectura y Salud: arquitectura para PcD integra áreas de la arquitectura y de la salud, más específicamente, los cursos de Arquitectura y Urbanismo, Ingeniería de la Producción, Fisioterapia y de Enfermería de la Universidad de Santa Cruz do Sul con el objetivo de conocer, fomentar e integrar la Pe...

  15. Retinal degeneration slow (rds) in mouse results from simple insertion of a t haplotype-specific element into protein-coding exon II

    Energy Technology Data Exchange (ETDEWEB)

    Ma, J.; Norton, J.C.; Allen, A.C.; Burns, J.L.; Travis, G.H. [Univ. of Texas Southwestern Medical Center, Dallas, TX (United States)] [and others

    1995-07-20

    Retinal degeneration slow (rds) is a semidominant mutation of mice that causes dysplasia and degeneration of rod and cone photoreceptors. Mutations in RDS, the human ortholog of the rds gene, are responsible for several inherited retinal dystrophies including a subset of retinitis pigmentosa. The normal rds locus encodes rds/peripherin, an integral membrane glycoprotein present in outer segment discs. Genomic libraries form wildtype and rds/rds mice were screened with an rds cDNA, and phage {lambda} clones that span the normal and mutant loci were mapped. We show that in mice, rds is caused by the insertion into exon II of a 9.2-kb repetitive genomic element that is very similar to the t haplotype-specific element in the H-2 complex. The entire element is included in the RNA products of the mutant locus. We present evidence that rds in mice represents a null allele. 40 refs., 4 figs.

  16. Ionomycin-induced calcium influx induces neurite degeneration in mouse neuroblastoma cells: analysis of a time-lapse live cell imaging system.

    Science.gov (United States)

    Nakamura, Saki; Nakanishi, Ayumi; Takazawa, Minami; Okihiro, Shunsuke; Urano, Shiro; Fukui, Koji

    2016-01-01

    Reactive oxygen species induce neuronal cell death. However, the detailed mechanisms of cell death have not yet been elucidated. Previously, we reported neurite degeneration before the induction of cell death. Here, we attempted to elucidate the mechanisms of neurite degeneration before the induction of cell death using the neuroblastoma N1E-115 cell line and a time-lapse live cell imaging system. Treatment with the calcium ionophore ionomycin induced cell death and neurite degeneration in a concentration- and time-dependent manner. Treatment with a low concentration of ionomycin immediately produced a significant calcium influx into the intracellular region in N1E-115 cells. After 1-h incubation with ionomycin, the fluorescence emission of MitoSOX(TM) increased significantly compared to the control. Finally, analysis using a new mitochondrial specific fluorescence dye, MitoPeDPP, indicated that treatment with ionomycin significantly increased the mitochondrial lipid hydroperoxide production in N1E-115 cells. The fluorescence emissions of Fluo-4 AM and MitoPeDPP were detected in the cell soma and neurite regions in ionomycin-treated N1E-115 cells. However, the emissions of neurites were much lower than those of the cell soma. TBARS values of ionomycin-treated cells significantly increased compared to the control. These results indicate that ionomycin induces calcium influx into the intracellular region and reactive oxygen species production in N1E-115 cells. Lipid hydroperoxide production was induced in ionomycin-treated N1E-115 cells. Calcium influx into the intracellular region is a possible activator of neurite degeneration.

  17. Tool Life and Surface Integrity in High-speed Milling of Titanium Alloy TA15 with PCD/PCBN Tools

    Institute of Scientific and Technical Information of China (English)

    SU Honghua; LIU Peng; FU Yucan; XU Jiuhua

    2012-01-01

    Titanium alloys are widely used in aeronautics that demand a good combination of high strength,good corrosion resistance and low mass.The mechanical properties lead to challenges in machining operations such as high process temperature as well as rapidly increasing tool wear.The conventional tool materials are not able to maintain their hardness and other mechanical properties at higher cutting temperatures encountered in high speed machining.In this work,the new material tools,which are polycrystalline diamond (PCD) and polycrystalline cubic boron nitride (PCBN) tools,are used in high-speed milling of Ti-6.5Al-2Zr-1Mo-1V (TA15) alloy.The performance and wear mechanism of the tools are investigated.Compared to PCBN tool,PCD tool has a much longer tool life,especially at higher cutting speeds.Analyses based on the SEM and EDX suggest that attrition,adhesion and diffusion are the main wear mechanisms of PCD and PCBN tools in high-speed milling of TA15.Oxidation wear is also observed at PCBN tool/workpiece interface.Roughness,defects,micro-hardness and microstructure of the machined surface are investigated.The recorded surface roughness values with PCD/PCBN tools are bellow 0.3μm at initial and steady cutting stage.Micro-hardness analysis shows that the machined surface hardening depth with PCD and PCBN tools is small.There is no evidence of sub-surface defects with PCD and PCBN tools.It is concluded that for TA15 alloy,high-speed milling can be carried out with PCD/PCBN tools.

  18. Microglial reactivity correlates to the density and the myelination of the anterogradely degenerating axons and terminals following perforant path denervation of the mouse fascia dentata

    DEFF Research Database (Denmark)

    Jensen, M B; Hegelund, I V; Rom Poulsen, Frantz

    1999-01-01

    Transection of the entorhino-dentate perforant path is a well known model for lesion-induced axonal sprouting and glial reactions in the rat. In this study, we have characterized the microglial reaction in the dentate molecular layer of the SJL/J and C57Bl/6 mouse. The morphological transformation...

  19. Microglial reactivity correlates to the density and the myelination of the anterogradely degenerating axons and terminals following perforant path denervation of the mouse fascia dentata

    DEFF Research Database (Denmark)

    Jensen, M B; Hegelund, I V; Rom Poulsen, Frantz

    1999-01-01

    Transection of the entorhino-dentate perforant path is a well known model for lesion-induced axonal sprouting and glial reactions in the rat. In this study, we have characterized the microglial reaction in the dentate molecular layer of the SJL/J and C57Bl/6 mouse. The morphological transformatio...

  20. Muscle spindles exhibit core lesions and extensive degeneration of intrafusal fibers in the Ryr1(I4895T/wt) mouse model of core myopathy.

    Science.gov (United States)

    Zvaritch, Elena; MacLennan, David H

    2015-04-24

    Muscle spindles from the hind limb muscles of adult Ryr1(I4895T/wt) (IT/+) mice exhibit severe structural abnormalities. Up to 85% of the spindles are separated from skeletal muscle fascicles by a thick layer of connective tissue. Many intrafusal fibers exhibit degeneration, with Z-line streaming, compaction and collapse of myofibrillar bundles, mitochondrial clumping, nuclear shrinkage and pyknosis. The lesions resemble cores observed in the extrafusal myofibers of this animal model and of core myopathy patients. Spindle abnormalities precede those in extrafusal fibers, indicating that they are a primary pathological feature in this murine Ryr1-related core myopathy. Muscle spindle involvement, if confirmed for human core myopathy patients, would provide an explanation for an array of devastating clinical features characteristic of these diseases and provide novel insights into the pathology of RYR1-related myopathies.

  1. MPACVD growth of single crystalline diamond substrates with PCD rimless and expanding surfaces

    Science.gov (United States)

    Nad, Shreya; Charris, Amanda; Asmussen, Jes

    2016-10-01

    Single crystal diamond (SCD) growth was performed in optimized pocket substrate holders at a high pressure (240 Torr) and a high power density (˜1000 W/cm3). In an effort to overcome the challenges of growing large area SCD substrates without a corresponding polycrystalline diamond (PCD) rim, a growth recipe using these pocket holders was developed. This growth recipe controls the substrate temperature (Ts) and the incident microwave power (Pinc) in a prescribed function of growth time. Through this process, the feasibility to enlarge the SCD substrate in situ, i.e., during the growth itself is shown. By allowing the temperature to increase from ˜980 °C to 1040 °C, then reducing the temperature, and then allowing it to drift up again, the deposition process alternates between the fast growth of the different crystal directions (i.e., , , and ) and a slow growth to smoothen the top surface. This leads to an increased lateral SCD growth. The slow growth of the crystal faces in turn leads to a smooth and enlarged top surface. Certain strategies such as the termination of the growth process at the appropriate time are critical in obtaining flat and smooth SCD surfaces without the formation of any PCD rim. The SCD substrates grown via this method have been analyzed by optical and scanning electron microscopies. The lateral SCD surface area increased between 1.7 and 2 times greater than the initial seed surface area during one continuous run. The deposited SCDs have high growth rates of ˜30 μm/h resulting in smooth, flat and rimless substrates, hence indicating the improvement in the quality and morphology of the deposited substrates.

  2. Sanguinarine-induced oxidative stress and apoptosis-like programmed cell death(AL-PCD) in root meristem cells of Allium cepa.

    Science.gov (United States)

    Żabka, Aneta; Winnicki, Konrad; Polit, Justyna Teresa; Maszewski, Janusz

    2017-03-01

    A vast number of studies on plant cell systems clearly indicate that various biotic and abiotic stresses give rise to the uncontrolled increase in the level of reactive oxygen species (ROS). Excess concentrations of ROS result in damage to proteins, lipids, carbohydrates, and DNA, which may lead, in consequence, to the apoptotic cell death. The current study investigates the effects of sanguinarine (SAN), a natural alkaloid derived from the roots of Sanguinaria canadensis, on root apical meristem cells of Allium cepa. It is shown that SAN treatment generated large amounts of hydrogen peroxide (H2O2) and superoxide anion (O2·-). Oxidative stress induced in SAN-treated cells was correlated with DNA fragmentation, formation of micronuclei (MN), altered and 'degenerated' chromatin structures characteristic of apoptosis-like programmed cell death (AL-PCD). The experiments with SAN + MG132 (a proteasome inhibitor engaged in Topo II-mediated formation of cleavable complexes) and SAN + ascorbic acid (AA; H2O2 scavenger) seem to suggest, however, that the high level of H2O2 is not the only factor responsible for changes observed at the chromatin level and for the consequent cell death. Our findings imply that Topo II-DNA covalent complexes and 26S proteasomes are also involved in SAN-induced DNA damage. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  3. Analysis of premature centromere division (PCD) of the X chromosome in Alzheimer patients through the cell cycle.

    Science.gov (United States)

    Spremo-Potparevic, Biljana; Zivkovic, Lada; Djelic, Ninoslav; Bajic, Vladan

    2004-05-01

    Cytogenetic analysis of the X chromosome in phytohaemagglutinin stimulated peripheral blood lymphocytes was evaluated in 12 sporadic Alzheimer disease (AD) patients and in 11 healthy subjects. For chromosome analysis two methods were used: (1) standard analysis of G-banded metaphase chromosomes and; (2) fluorescent in situ hybridization (FISH) for the detection of the X chromosome centromeric region in interphase nuclei. Cytogenetic analysis revealed that the X chromosome expresses premature centromere division (PCD) in AD females in 10.53% of metaphase cells and in 15.22% of interphase nuclei. In AD men the percentages were 3.98 and 6.06%, respectively. X chromosome PCD in the female control group showed a percentage of 7.46% in metaphase cells and 9.35% in interphase nuclei and in male controls the percentages were 2.84% in metaphases and 5.54% in interphase nuclei. The results of FISH analysis showed that PCD could occur much earlier than metaphase of mitosis, i.e. in interphase of the cell cycle, immediately after replication. The FISH method can be used for PCD verification in all phases of the cell cycle in various disorders including AD.

  4. Neuroprotective changes in degeneration-related gene expression in the substantia nigra following acupuncture in an MPTP mouse model of Parkinsonism: Microarray analysis

    Directory of Open Access Journals (Sweden)

    Sujung Yeo

    2015-03-01

    Full Text Available Parkinson’s disease (PD is a neurodegenerative disorder characterized by the death of dopamine-generating cells in the substantia nigra (SN. Acupuncture stimulation results in an enhanced survival of dopaminergic neurons in the SN in Parkinsonism animal models. The present study investigated changes in gene expression profiles measured using whole transcript array in the SN region related to the inhibitory effects of acupuncture in a chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP Parkinsonism model. In this model, acupuncture stimulation at GB34 and LR3 attenuated the decrease in tyrosine hydroxylase in the SN region; stimulation at non-acupoints did not suppress this decrease. Gene array analysis revealed that 22 (10 annotated genes: Cdh1, Itih2, Mpzl2, Rdh9, Serping1, Slc6a13, Slc6a20a, Slc6a4, Tph2, and Ucma probes that were up-regulated in MPTP animals relative to controls were exclusively down-regulated by acupuncture stimulation. In addition, 17 (two annotated genes: 4921530L21Rik and Gm13931 probes that were down-regulated in MPTP animals compared to controls were exclusively up-regulated by acupuncture stimulation. These findings indicate that the 39 probes (12 annotated genes affected by MPTP and acupuncture may be responsible for the inhibitory effects of acupuncture on degeneration-related gene expression in the SN following damage induced by MPTP intoxication.

  5. Neuroprotective changes in degeneration-related gene expression in the substantia nigra following acupuncture in an MPTP mouse model of Parkinsonism: Microarray analysis.

    Science.gov (United States)

    Yeo, Sujung; An, Keon Sang; Hong, Yeon-Mi; Choi, Yeong-Gon; Rosen, Bruce; Kim, Sung-Hoon; Lim, Sabina

    2015-03-01

    Parkinson's disease (PD) is a neurodegenerative disorder characterized by the death of dopamine-generating cells in the substantia nigra (SN). Acupuncture stimulation results in an enhanced survival of dopaminergic neurons in the SN in Parkinsonism animal models. The present study investigated changes in gene expression profiles measured using whole transcript array in the SN region related to the inhibitory effects of acupuncture in a chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) Parkinsonism model. In this model, acupuncture stimulation at GB34 and LR3 attenuated the decrease in tyrosine hydroxylase in the SN region; stimulation at non-acupoints did not suppress this decrease. Gene array analysis revealed that 22 (10 annotated genes: Cdh1, Itih2, Mpzl2, Rdh9, Serping1, Slc6a13, Slc6a20a, Slc6a4, Tph2, and Ucma) probes that were up-regulated in MPTP animals relative to controls were exclusively down-regulated by acupuncture stimulation. In addition, 17 (two annotated genes: 4921530L21Rik and Gm13931) probes that were down-regulated in MPTP animals compared to controls were exclusively up-regulated by acupuncture stimulation. These findings indicate that the 39 probes (12 annotated genes) affected by MPTP and acupuncture may be responsible for the inhibitory effects of acupuncture on degeneration-related gene expression in the SN following damage induced by MPTP intoxication.

  6. Postsynaptic degeneration as revealed by PSD-95 reduction occurs after advanced Aβ and tau pathology in transgenic mouse models of Alzheimer's disease.

    Science.gov (United States)

    Shao, Charles Y; Mirra, Suzanne S; Sait, Hameetha B R; Sacktor, Todd C; Sigurdsson, Einar M

    2011-09-01

    Impairment of synaptic plasticity underlies memory dysfunction in Alzheimer's disease (AD). Molecules involved in this plasticity such as PSD-95, a major postsynaptic scaffold protein at excitatory synapses, may play an important role in AD pathogenesis. We examined the distribution of PSD-95 in transgenic mice of amyloidopathy (5XFAD) and tauopathy (JNPL3) as well as in AD brains using double-labeling immunofluorescence and confocal microscopy. In wild type control mice, PSD-95 primarily labeled neuropil with distinct distribution in hippocampal apical dendrites. In 3-month-old 5XFAD mice, PSD-95 distribution was similar to that of wild type mice despite significant Aβ deposition. However, in 6-month-old 5XFAD mice, PSD-95 immunoreactivity in apical dendrites markedly decreased and prominent immunoreactivity was noted in neuronal soma in CA1 neurons. Similarly, PSD-95 immunoreactivity disappeared from apical dendrites and accumulated in neuronal soma in 14-month-old, but not in 3-month-old, JNPL3 mice. In AD brains, PSD-95 accumulated in Hirano bodies in hippocampal neurons. Our findings support the notion that either Aβ or tau can induce reduction of PSD-95 in excitatory synapses in hippocampus. Furthermore, this PSD-95 reduction is not an early event but occurs as the pathologies advance. Thus, the time-dependent PSD-95 reduction from synapses and accumulation in neuronal soma in transgenic mice and Hirano bodies in AD may mark postsynaptic degeneration that underlies long-term functional deficits.

  7. Hsp70 gene transfer by adeno-associated virus inhibits MPTP-induced nigrostriatal degeneration in the mouse model of Parkinson disease.

    Science.gov (United States)

    Dong, Zhizhong; Wolfer, David P; Lipp, Hans-Peter; Büeler, Hansruedi

    2005-01-01

    Mitochondrial dysfunction and oxidative stress have been implicated in Parkinson disease (PD). In addition, genetic evidence points to an important role of protein misfolding, aggregation, and failure in the proteasomal degradation of specific neuronal proteins in the pathogenesis of PD. The chaperone heat-shock protein 70 (Hsp70) reduces protein misfolding and aggregation and protects cells against a variety of adverse conditions, including oxidative stress. Moreover, Hsp70 exerts antiapoptotic activity by blocking the function of several key proapoptotic factors. Recently, Hsp70 was shown to inhibit alpha-synuclein toxicity in a Drosophila model of inherited PD. Here we tested the potential of Hsp70 (approved gene symbol HSPA1A) for gene therapy in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of idiopathic PD. We show that Hsp70 gene transfer to dopamine neurons by a recombinant adeno-associated virus significantly protects the mouse dopaminergic system against MPTP-induced dopamine neuron loss and the associated decline in striatal dopamine levels and tyrosine hydroxylase-positive fibers. Hsp70 reduced MPTP-induced apoptosis in the substantia nigra, and unilateral protection of the dopaminergic system by Hsp70 was associated with increased amphetamine-induced turning toward the uninjected side. Collectively, these results suggest that increasing chaperone activity may be beneficial for the treatment of idiopathic PD.

  8. Paraneoplastic cerebellar degeneration with anti-Yo antibodies - a review.

    Science.gov (United States)

    Venkatraman, Anand; Opal, Puneet

    2016-08-01

    The ataxic syndrome associated with Anti-Yo antibody, or Purkinje cell cytoplasmic antibody type 1 (PCA1), is the most common variant of paraneoplastic cerebellar degeneration (PCD). The typical presentation involves the subacute development of pancerebellar deficits with a clinical plateau within 6 months. The vast majority of cases have been reported in women with pelvic or breast tumors. Magnetic resonance imaging of the brain is often normal in the early stages, with cerebellar atrophy seen later. The underlying mechanism is believed to be an immunological reaction to cerebellar degeneration-related protein 2 (CDR2), a protein usually found in the cerebellum that is ectopically produced by tumor cells. Although both B- and T-cell abnormalities are seen, there is debate about the relative importance of the autoantibodies and cytotoxic T lymphocytes in the neuronal loss. Cerebrospinal fluid abnormalities, primarily elevated protein, lymphocytic pleocytosis, and oligoclonal bands, are common in the early stages. The low prevalence of this condition has not allowed for large-scale randomized controlled trials. Immunotherapies, such as steroids, intravenous immune globulins, and plasma exchange, have been extensively used in managing this condition, with limited success. Although some reports indicate benefit from antitumor therapies like surgery and chemotherapy, this has not been consistently observed. The prognosis for anti-Yo PCD is almost uniformly poor, with most patients left bedridden. Further studies are required to clarify the pathophysiology and provide evidence-based treatment options.

  9. [Hepatolenticular degeneration].

    Science.gov (United States)

    Zudenigo, D; Relja, M

    1990-01-01

    Hepatolenticular degeneration (Wilson's disease) is a hereditary disease in which metabolic disorder of copper leads to its accumulation in the liver, brain, cornea and kidneys with consequent pathologic changes in those organs. Hereditary mechanism of the disease is autosomal recessive with prevalence of 30-100 per 1,000,000 inhabitants. Etiology of this disease is not yet explained. There are two hypotheses. The first one is that it is the disorder of ceruloplasmine metabolism caused by insufficient synthesis of normal ceruloplasmine, or synthesis of functionally abnormal ceruloplasmine. The second one is: the block of copper biliar excretion which is the consequence of the liver lysosomes functional defect. Pathogenetic mechanism of disease is firstly long-term accumulation of copper in the liver, and later, when the liver depo is full, its releasing in circulation and accumulation in the brain, cornea, kidneys and bones, which causes adequate pathologic changes. Toxic activity of copper is the consequence of its activity on enzymes, particularly on those with -SH group. There are two basic clinical forms of the disease: liver disease or neurologic disease. Before puberty the liver damage is more frequent, while in adolescents and young adults neurologic form of the disease is usual. The liver disease is nonspecific and characterized by symptoms of cirrhosis and chronic aggressive hepatitis. The only specificity is hemolytic anemia which, in combination with previous symptoms, is important for diagnosis of the disease. Neurologic symptoms are the most frequent consequence of pathologic changes in the basal ganglia. In our patients the most frequent symptoms were tremor (63%); dysarthria, choreoathetosis and rigor (38%); ataxia and mental disorders (31%); dysphagia and dystonia (12%), diplopia, hypersalivation, nystagmus and Babinski's sign (6%). Among pathologic changes in other tissues and organs the most important is the finding of Kayser-Fleischer ring in the

  10. ILDR1 deficiency causes degeneration of cochlear outer hair cells and disrupts the structure of the organ of Corti: a mouse model for human DFNB42

    Directory of Open Access Journals (Sweden)

    Qing Sang

    2015-03-01

    Full Text Available Immunoglobulin-like domain containing receptor 1 (ILDR1 is a poorly characterized gene that was first identified in lymphoma cells. Mutations in ILDR1 are responsible for DFNB42, but the pathogenesis of hearing loss caused by ILDR1 mutations remains to be elucidated. To explore the role of ILDR1 in hearing, we created Ildr1 knockout mice. In heterozygous mice, ILDR1 expression was found in outer hair cells (OHCs and inner hair cells (IHCs of the organ of Corti. ILDR1-deficient mice are profoundly deaf by postnatal day 21 (P21. No significant difference was observed in the supporting cells and IHCs of ILDR1-deficient mice, but progressive degeneration of OHCs occurred at P15 and disruption of the tunnel running through the organ of Corti was noticeable at P21. By P28, there were no OHCs visible in any of the turns of the organ of Corti, and the tunnel of the organ of Corti was entirely destroyed. ILDR1 deficiency affects expression of tricellulin in vivo, and this provides a possible explanation to hearing loss. To further elucidate the mechanism of deafness related to ILDR1 deficiency, we pursued a differential proteomic approach to comprehensively assess differential protein expression in the cochleae of Ildr1+/− and Ildr1−/− mice at P21. Altogether, 708 proteins were up-regulated (fold change >1.5 and 114 proteins were down-regulated (fold change <0.5 in the Ildr1−/− mice compared with Ildr1+/− mice. Gene ontology classification indicated that a number of differentially expressed proteins are involved in cell adhesion, protein and vesicle-mediated transport, cell death, membrane organization, and cellular homeostasis. A few of these proteins are closely related to hearing development. Taken together, our data suggest that ILDR1 is important for the survival of OHCs and provide novel insights into the pathogenesis of human deafness DFNB42 deafness.

  11. Short-term salinity stress in tobacco plants leads to the onset of animal-like PCD hallmarks in planta in contrast to long-term stress.

    Science.gov (United States)

    Andronis, Efthimios A; Roubelakis-Angelakis, Kalliopi A

    2010-01-01

    Recent results have identified mitochondria as centers of stress-induced generation of reactive oxygen species in plants. Depolarization of plant mitochondrial membrane during stress results the release of programmed cell death (PCD)-inducing factors in the cytosol in a fashion similar to the onset of animal-like PCD. Herein, we report significant similarities of animal-like PCD and salinity stress-induced plant PCD. Short-term salinity stress (3 h) led to depolarization of the mitochondrial membrane, release of cytochrome c (CYT-c), which was visualized using a contemporary molecular technique, activation of caspase-3 type proteases and the onset of PCD in wild type tobacco plants, Nicotiana tabacum cv. Petit Havana. However, PCD was not manifested during long-term salinity stress (24 h). Interestingly long-term salinity stress led to necrotic-like features, which were accompanied by collapse of respiration, reduction of key components of the respiratory chain, such as CYT-c and alternative oxidase, ATP depletion and high proteolytic activity. The results suggest that salinity stress of tobacco plants in planta leads to the onset of animal-like PCD only during the early stages post-stress, while long-term stress leads to necrotic-like features.

  12. A randomised trial to compare Truview PCD(®), C-MAC(®) and Macintosh laryngoscopes in paediatric airway management.

    Science.gov (United States)

    Singh, Ranju; Kumar, Nishant; Jain, Aruna

    2017-06-01

    To evaluate and compare the Truview PCD and C-MAC laryngoscopes to the standard Macintosh laryngoscope in paediatric patients. One hundred and fifty ASA I-II patients in the age group of 1-6 years (10-20 kg) scheduled for elective surgery were randomised into three equal groups for laryngoscopy and intubation with either Truview PCD (Group T), C-MAC (Group C) or Macintosh (Group M) laryngoscopes under general anaesthesia. Percentage of glottic opening (POGO) score, application of external laryngeal manoeuvre, time to intubation, number of attempts at intubation, failed intubations, episodes of desaturation and trauma caused were recorded and statistically analysed. A p value of MAC and Macintosh laryngoscopes (94.7 ± 12.9/82 ± 25.0/85.1 ± 17.1; p < 0.01). There were no failed attempts, episodes of desaturation or trauma in any of the patients. The mean intubation time taken was 19.2 s in group T, 12.3 s in group C and 10.7 s in group M, respectively. There is a statistically significant difference among groups (p < 0.01). Eight patients in group T, 21 out of 50 patients in group C and 19 out of 50 patients in group M needed OELM, respectively. There is significant difference among the groups (p < 0.01) CONCLUSION: Using Truview PCD to assist intubation offers excellent view field of glottic opening after OLEM and the mean time taken is less than 20 s. The Truview PCD tool is suitable for paediatric patients. Copyright © 2017. Published by Elsevier B.V.

  13. Finite Element Simulations of Micro Turning of Ti-6Al-4V using PCD and Coated Carbide tools

    Science.gov (United States)

    Jagadesh, Thangavel; Samuel, G. L.

    2016-07-01

    The demand for manufacturing axi-symmetric Ti-6Al-4V implants is increasing in biomedical applications and it involves micro turning process. To understand the micro turning process, in this work, a 3D finite element model has been developed for predicting the tool chip interface temperature, cutting, thrust and axial forces. Strain gradient effect has been included in the Johnson-Cook material model to represent the flow stress of the work material. To verify the simulation results, experiments have been conducted at four different feed rates and at three different cutting speeds. Since titanium alloy has low Young's modulus, spring back effect is predominant for higher edge radius coated carbide tool which leads to the increase in the forces. Whereas, polycrystalline diamond (PCD) tool has smaller edge radius that leads to lesser forces and decrease in tool chip interface temperature due to high thermal conductivity. Tool chip interface temperature increases by increasing the cutting speed, however the increase is less for PCD tool as compared to the coated carbide tool. When uncut chip thickness decreases, there is an increase in specific cutting energy due to material strengthening effects. Surface roughness is higher for coated carbide tool due to ploughing effect when compared with PCD tool. The average prediction error of finite element model for cutting and thrust forces are 11.45 and 14.87 % respectively.

  14. Finite Element Simulations of Micro Turning of Ti-6Al-4V using PCD and Coated Carbide tools

    Science.gov (United States)

    Jagadesh, Thangavel; Samuel, G. L.

    2017-02-01

    The demand for manufacturing axi-symmetric Ti-6Al-4V implants is increasing in biomedical applications and it involves micro turning process. To understand the micro turning process, in this work, a 3D finite element model has been developed for predicting the tool chip interface temperature, cutting, thrust and axial forces. Strain gradient effect has been included in the Johnson-Cook material model to represent the flow stress of the work material. To verify the simulation results, experiments have been conducted at four different feed rates and at three different cutting speeds. Since titanium alloy has low Young's modulus, spring back effect is predominant for higher edge radius coated carbide tool which leads to the increase in the forces. Whereas, polycrystalline diamond (PCD) tool has smaller edge radius that leads to lesser forces and decrease in tool chip interface temperature due to high thermal conductivity. Tool chip interface temperature increases by increasing the cutting speed, however the increase is less for PCD tool as compared to the coated carbide tool. When uncut chip thickness decreases, there is an increase in specific cutting energy due to material strengthening effects. Surface roughness is higher for coated carbide tool due to ploughing effect when compared with PCD tool. The average prediction error of finite element model for cutting and thrust forces are 11.45 and 14.87 % respectively.

  15. Endosperm degradation during seed development of Echinocystis lobata (Cucurbitaceae) as a manifestation of programmed cell death (PCD) in plants.

    Science.gov (United States)

    Wojciechowska, Marzena; Olszewska, Maria J

    2003-01-01

    Programmed cell death (PCD) is an active, genetically controlled process that ultimately leads to elimination of unnecessary or damaged cells from multicellular organism. It occurs during normal growth and development or in response to a variety of environmental triggers and is indispensable for survival of the organism. In Echinocystis lobata the endosperm, an ephemeral tissue in angiosperm plants, undergoes distinct cytological, physiological and molecular changes during seed development and maturation. As a result, mature seeds are deprived of this tissue. The endosperm was analyzed at the consecutive stages of seed development. The morphological changes of cells were studied at light and electron microscope levels. In this paper we report that endosperm cells undergo morphological and biochemical changes characteristic of apoptosis, a particular type of PCD, i.e. cell shrinkage, chromatin condensation, nuclear fragmentation, and cytoplasm degradation, while the ultrastructure of mitochondria seems to be less changed. Furthermore, the progression of DNA degradation has been shown by agarose gel electrophoresis (ladder pattern of DNA fragmentseparation), TUNEL and comet assay. It isconcluded that during seed maturation, endosperm degradation process is accompanied by typical PCD-related changes of cell morphology and internucleosomal DNA cleavage.

  16. Wet Macular Degeneration

    Science.gov (United States)

    ... macular degeneration Overview By Mayo Clinic Staff Wet macular degeneration is a chronic eye disease that causes blurred vision or a blind spot in your visual field. It's generally caused by abnormal blood vessels that leak fluid or blood into ... macular degeneration is one of two types of age-related ...

  17. Degenerate Euler zeta function

    OpenAIRE

    Kim, Taekyun

    2015-01-01

    Recently, T. Kim considered Euler zeta function which interpolates Euler polynomials at negative integer (see [3]). In this paper, we study degenerate Euler zeta function which is holomorphic function on complex s-plane associated with degenerate Euler polynomials at negative integers.

  18. Characterization of the Lactobacillus plantarum plasmid pCD033 and generation of the plasmid free strain L. plantarum 3NSH.

    Science.gov (United States)

    Heiss, Silvia; Grabherr, Reingard; Heinl, Stefan

    2015-09-01

    Lactobacillus plantarum CD033, a strain isolated from grass silage in Austria, harbors a 7.9 kb plasmid designated pCD033. Sequence analysis identified 14 open reading frames and 8 of these were supposed to be putative coding sequences. Gene annotation revealed no putative essential genes being plasmid encoded, but a plasmid addiction system based on a PemI/PemK-like toxin-antitoxin system, able to stabilize plasmid maintenance. Absence of a replication initiation protein, a double strand origin as well as a single strand origin on plasmid pCD033 suggests replication via a new type of theta mechanism, whereby plasmid replication is potentially initiated and regulated by non-coding RNA. Detailed examination of segregational stability of plasmid vectors consisting of pCD033-fragments, combined with a selection marker, resulted in definition of a stably maintained minimal replicon. A gene encoding a RepB/OrfX-like protein was found to be not essential for plasmid replication. Alignment of the amino acid sequence of this protein with related proteins unveiled a highly conserved amino acid motif (LLDQQQ). L. plantarum CD033 was cured of pCD033 resulting in the novel plasmid free strain L. plantarum 3NSH. Plasmid curing demonstrated that no essential features are provided by pCD033 under laboratory conditions.

  19. Anti-Yo Mediated Paraneoplastic Cerebellar Degeneration Associated with Pseudobulbar Affect in a Patient with Breast Cancer

    Science.gov (United States)

    Martin, Allison N.; Jones, David E.; Brenin, David R.; Lapides, David A.

    2017-01-01

    Paraneoplastic cerebellar degeneration (PCD) is a rare anti-Yo mediated paraneoplastic syndromes rarely that is infrequently associated with breast cancer. We present a case of a 52-year-old female presenting with diplopia, gait instability, dysarthria, dysphagia, nystagmus, and, most notably, new onset paroxysmal episodes of uncontrollable crying concerning for pseudobulbar affect (PBA). Serologic testing showed anti-Yo antibodies. The patient was found to have stage IIIA breast cancer as the inciting cause of the paraneoplastic syndrome. The patient was treated with neoadjuvant chemotherapy, modified radical mastectomy, adjuvant Herceptin, and pertuzumab. She was given IVIG for paraneoplastic syndrome, antidepressants, and dextromethorphan-quinidine (Nuedexta), the first FDA-approved therapy for PBA. With multimodality therapy, she demonstrated significant improvement in neurologic and mood symptoms associated with PCD and PBA. PMID:28377827

  20. Anti-Yo Mediated Paraneoplastic Cerebellar Degeneration Associated with Pseudobulbar Affect in a Patient with Breast Cancer

    Directory of Open Access Journals (Sweden)

    Allison N. Martin

    2017-01-01

    Full Text Available Paraneoplastic cerebellar degeneration (PCD is a rare anti-Yo mediated paraneoplastic syndromes rarely that is infrequently associated with breast cancer. We present a case of a 52-year-old female presenting with diplopia, gait instability, dysarthria, dysphagia, nystagmus, and, most notably, new onset paroxysmal episodes of uncontrollable crying concerning for pseudobulbar affect (PBA. Serologic testing showed anti-Yo antibodies. The patient was found to have stage IIIA breast cancer as the inciting cause of the paraneoplastic syndrome. The patient was treated with neoadjuvant chemotherapy, modified radical mastectomy, adjuvant Herceptin, and pertuzumab. She was given IVIG for paraneoplastic syndrome, antidepressants, and dextromethorphan-quinidine (Nuedexta, the first FDA-approved therapy for PBA. With multimodality therapy, she demonstrated significant improvement in neurologic and mood symptoms associated with PCD and PBA.

  1. The Development of Open Water-lubricated Polycrystalline Diamond (PCD) Thrust Bearings for Use in Marine Hydrokinetic (MHK) Energy Machines

    Energy Technology Data Exchange (ETDEWEB)

    Cooley, Craig, H.; Khonsari, Michael,, M; Lingwall, Brent

    2012-11-28

    Polycrstalline diamond (PCD) bearings were designed, fabricated and tested for marine-hydro-kinetic (MHK) application. Bearing efficiency and life were evaluated using the US Synthetic bearing test facility. Three iterations of design, build and test were conducted to arrive at the best bearing design. In addition life testing that simulated the starting and stopping and the loading of real MHK applications were performed. Results showed polycrystalline diamond bearings are well suited for MHK applications and that diamond bearing technology is TRL4 ready. Based on life tests results bearing life is estimated to be at least 11.5 years. A calculation method for evaluating the performance of diamond bearings of round geometry was also investigated and developed. Finally, as part of this effort test bearings were supplied free of charge to the University of Alaska for further evaluation. The University of Alaska test program will subject the diamond bearings to sediment laden lubricating fluid.

  2. Sarm1-Mediated Axon Degeneration Requires Both SAM and TIR Interactions

    OpenAIRE

    Gerdts, Josiah; Summers, Daniel W; Sasaki, Yo; DiAntonio, Aaron; Milbrandt, Jeffrey

    2013-01-01

    Axon degeneration is an evolutionarily conserved pathway that eliminates damaged or unneeded axons. Manipulation of this poorly understood pathway may allow treatment of a wide range of neurological disorders. In an RNAi-based screen performed in cultured mouse DRG neurons, we observed strong suppression of injury-induced axon degeneration upon knockdown of Sarm1 [SARM (sterile α-motif-containing and armadillo-motif containing protein)]. We find that a SARM-dependent degeneration program is e...

  3. Tool Wear, Surface Integrity and Dimensional Accuracy in Turning Al2124SiCp (45%wt Metal Matrix Composite using CBN and PCD Tools

    Directory of Open Access Journals (Sweden)

    Muguthu Joseph Njuguna

    2013-12-01

    Full Text Available The focus of this study is the turning of Al2124SiCp (45% wt Metal Matrix Composite using PCD, CBN-coated and CBN-uncoated tools. The machinability of Al2124SiCp (45% wt Metal Matrix Composite is evaluated by measurement of tool wear, surface finish and dimensional accuracy of the work-piece. Wear mechanisms and patterns of tools in turning of Al2124SiCp (45% wt Metal Matrix Composite are discussed. The experimental setup involved turning Al2124SiCp (45% wt 78.0 mm long and 31.8 mm diameter on a precision lathe at fixed feed rate, different depth of cut and cutting speed using PCD, CBN-coated and CBN-uncoated tools. The reinforcement of the matrix consists of SiC 5-8 µm in diameter. Experimental results reveal that abrasion and adhesion presented the most prevalent mode of wear among all the tools. Fracture was observed among CBN tools while chipping on PCD tools. Flank and crater wear were observed in all tools with flank wear more prevalent in both CBN-coated and CBN-uncoated. Wear among PCD tools was low as compared to CBN tools. Further analysis reveal that the outer layer of the CBN-coated tools wear off fast creating a good platform for adhesion of matrix material on to the tool. This further increases wear of the tool due to adhesive wear as the built-up edge breaks off from the tool. PCD tool presented better surface finish than CBN tools with CBN-coated performing better than CBN-uncoated. Due to high SiC content, discontinuous chips are formed which are also curled due to increase in temperature at cutting zone causing bimetallic effect on the chip. On dimensional accuracy it was observed that PCD tool produced lowest diameter error followed by CBN-uncoated and finally CBN-Coated. It is concluded that in machining Al2124SiCp (45% wt Metal Matrix Composite PCD tools are the best followed by CBN-coated and lastly CBN-uncoated.

  4. Degenerate Density Perturbation Theory

    CERN Document Server

    Palenik, Mark C

    2016-01-01

    Fractional occupation numbers can be used in density functional theory to create a symmetric Kohn-Sham potential, resulting in orbitals with degenerate eigenvalues. We develop the corresponding perturbation theory and apply it to a system of $N_d$ degenerate electrons in a harmonic oscillator potential. The order-by-order expansions of both the fractional occupation numbers and unitary transformations within the degenerate subspace are determined by the requirement that a differentiable map exists connecting the initial and perturbed states. Using the X$\\alpha$ exchange-correlation (XC) functional, we find an analytic solution for the first-order density and first through third-order energies as a function of $\\alpha$, with and without a self-interaction correction. The fact that the XC Hessian is not positive definite plays an important role in the behavior of the occupation numbers.

  5. Degenerate density perturbation theory

    Science.gov (United States)

    Palenik, Mark C.; Dunlap, Brett I.

    2016-09-01

    Fractional occupation numbers can be used in density functional theory to create a symmetric Kohn-Sham potential, resulting in orbitals with degenerate eigenvalues. We develop the corresponding perturbation theory and apply it to a system of Nd degenerate electrons in a harmonic oscillator potential. The order-by-order expansions of both the fractional occupation numbers and unitary transformations within the degenerate subspace are determined by the requirement that a differentiable map exists connecting the initial and perturbed states. Using the X α exchange-correlation (XC) functional, we find an analytic solution for the first-order density and first- through third-order energies as a function of α , with and without a self-interaction correction. The fact that the XC Hessian is not positive definite plays an important role in the behavior of the occupation numbers.

  6. Vortices as degenerate metrics

    CERN Document Server

    Baptista, J M

    2012-01-01

    We note that the Bogomolny equation for abelian vortices is precisely the condition for invariance of the Hermitian-Einstein equation under a degenerate conformal transformation. This leads to a natural interpretation of vortices as degenerate hermitian metrics that satisfy a certain curvature equation. Using this viewpoint, we rephrase standard results about vortices and make some new observations. We note the existence of a conceptually simple, non-linear rule for superposing vortex solutions, and we describe the natural behaviour of the L^2-metric on the moduli space upon certain restrictions.

  7. Kraepelin and degeneration theory.

    Science.gov (United States)

    Hoff, Paul

    2008-06-01

    Emil Kraepelin's contribution to the clinical and scientific field of psychiatry is recognized world-wide. In recent years, however, there have been a number of critical remarks on his acceptance of degeneration theory in particular and on his political opinion in general, which was said to have carried "overtones of proto-fascism" by Michael Shepherd [28]. The present paper discusses the theoretical cornerstones of Kraepelinian psychiatry with regard to their relevance for Kraepelin's attitude towards degeneration theory. This theory had gained wide influence not only in scientific, but also in philosophical and political circles in the last decades of the nineteenth century. There is no doubt that Kraepelin, on the one hand, accepted and implemented degeneration theory into the debate on etiology and pathogenesis of mental disorders. On the other hand, it is not appropriate to draw a simple and direct line from early versions of degeneration theory to the crimes of psychiatrists and politicians during the rule of national socialism. What we need, is a differentiated view, since this will be the only scientific one. Much research needs to be done here in the future, and such research will surely have a significant impact not only on the historical field, but also on the continuous debate about psychiatry, neuroscience and neurophilosophy.

  8. X-82 to Treat Age-related Macular Degeneration

    Science.gov (United States)

    2017-01-12

    Age-Related Macular Degeneration (AMD); Macular Degeneration; Exudative Age-related Macular Degeneration; AMD; Macular Degeneration, Age-related, 10; Eye Diseases; Retinal Degeneration; Retinal Diseases

  9. On Degenerate Partial Differential Equations

    OpenAIRE

    Chen, Gui-Qiang G.

    2010-01-01

    Some of recent developments, including recent results, ideas, techniques, and approaches, in the study of degenerate partial differential equations are surveyed and analyzed. Several examples of nonlinear degenerate, even mixed, partial differential equations, are presented, which arise naturally in some longstanding, fundamental problems in fluid mechanics and differential geometry. The solution to these fundamental problems greatly requires a deep understanding of nonlinear degenerate parti...

  10. Laenderyggens degeneration og radiologi

    DEFF Research Database (Denmark)

    Jacobsen, Steffen; Gosvig, Kasper Kjaerulf; Sonne-Holm, Stig

    2006-01-01

    Low back pain (LBP) is one of the most common conditions, and at the same time one of the most complex nosological entities. The lifetime prevalence is approximately 80%, and radiological features of lumbar degeneration are almost universal in adults. The individual risk factors for LBP and signi......Low back pain (LBP) is one of the most common conditions, and at the same time one of the most complex nosological entities. The lifetime prevalence is approximately 80%, and radiological features of lumbar degeneration are almost universal in adults. The individual risk factors for LBP...... and significant relationships between radiological findings and subjective symptoms have both been notoriously difficult to identify. The lack of consensus on clinical criteria and radiological definitions has hampered the undertaking of properly executed epidemiological studies. The natural history of LBP...

  11. Quantum degenerate systems

    Energy Technology Data Exchange (ETDEWEB)

    Micheli, Fiorenza de [Centro de Estudios Cientificos, Arturo Prat 514, Valdivia (Chile); Instituto de Fisica, Pontificia Universidad Catolica de Valparaiso, Casilla 4059, Valparaiso (Chile); Zanelli, Jorge [Centro de Estudios Cientificos, Arturo Prat 514, Valdivia (Chile); Universidad Andres Bello, Av. Republica 440, Santiago (Chile)

    2012-10-15

    A degenerate dynamical system is characterized by a symplectic structure whose rank is not constant throughout phase space. Its phase space is divided into causally disconnected, nonoverlapping regions in each of which the rank of the symplectic matrix is constant, and there are no classical orbits connecting two different regions. Here the question of whether this classical disconnectedness survives quantization is addressed. Our conclusion is that in irreducible degenerate systems-in which the degeneracy cannot be eliminated by redefining variables in the action-the disconnectedness is maintained in the quantum theory: there is no quantum tunnelling across degeneracy surfaces. This shows that the degeneracy surfaces are boundaries separating distinct physical systems, not only classically, but in the quantum realm as well. The relevance of this feature for gravitation and Chern-Simons theories in higher dimensions cannot be overstated.

  12. Cataracts and macular degeneration.

    Science.gov (United States)

    Shoch, D

    1979-09-01

    The intraocular lens restores general vision and some degree of independence and mobility to patients with dense cataracts and macular degeneration. The patient, however, must be repeatedly warned that fine central vision, particularly reading, will not be possible after the surgery. An aphakic spectacle leaves such patients a narrow band of vision when superimposed over the macular lesion, and contact lenses are too small for the patient to manage insertion without help.

  13. Discrete dislocation dynamic simulation for PCD indentation behavior%聚晶金刚石压痕行为的离散位错动力学仿真分析

    Institute of Scientific and Technical Information of China (English)

    白清顺; 白锦轩; 泽华; 姜丽辉; 梁迎春

    2014-01-01

    According to dislocation theory,PCD indentation simulation model was established by coupling discrete dislocation dynamics and finite element model.Through the discrete dislocation simulation,we got the PCD dislocation cloud under the action of micro indentation,obtained the influence law of PCD indentation characteristic which was caused by various granularities and diamond volume fractions,and analyzed PCD dislocation evolution mechanism and failure behavior.Result showed that the PCD dislocation movement could be accurately described by discrete dislocation dynamic analysis method,that the crystal dislocation slip degree increased with enlarging granularities, and that the dislocation nucleation density increased as the diamond volume fractions increased.Such changes would lead to the decline of fracture strength finally.This paper introduced discrete dislocation theory into the analysis of PCD dislocation evolution behavior,and it provided a theoretical basis for the study on materials failure behavior of PCD cutting tool in engineering application.%依据位错理论,建立了聚晶金刚石(polycrystalline diamond,PCD)离散位错动力学-有限元耦合的压痕仿真模型。通过离散位错动力学仿真,获得了在微压痕作用下 PCD 的位错云图,揭示了金刚石微粉颗粒尺寸及颗粒体积分数对聚晶金刚石压痕特性的影响规律,并分析了聚晶金刚石的位错演化机制及其失效行为。研究结果表明:采用离散位错动力学分析方法能够准确描述 PCD 的位错运动过程,PCD 微粉颗粒尺寸增加会增大晶体位错滑移程度,金刚石颗粒体积分数增加则导致位错形核密度增加,最终将引起聚晶金刚石材料断裂强度下降。将离散位错理论引入到为分析聚晶金刚石位错演化的行为中,将为研究 PCD 在切削刀具等工程应用中材料的失效行为提供理论基础。

  14. Geometric phases for non-degenerate and degenerate mixed states

    CERN Document Server

    Singh, K; Basu, K; Chen, J L; Du Jiang Feng

    2003-01-01

    This paper focuses on the geometric phase of general mixed states under unitary evolution. Here we analyze both non-degenerate as well as degenerate states. Starting with the non-degenerate case, we show that the usual procedure of subtracting the dynamical phase from the total phase to yield the geometric phase for pure states, does not hold for mixed states. To this end, we furnish an expression for the geometric phase that is gauge invariant. The parallelity conditions are shown to be easily derivable from this expression. We also extend our formalism to states that exhibit degeneracies. Here with the holonomy taking on a non-abelian character, we provide an expression for the geometric phase that is manifestly gauge invariant. As in the case of the non-degenerate case, the form also displays the parallelity conditions clearly. Finally, we furnish explicit examples of the geometric phases for both the non-degenerate as well as degenerate mixed states.

  15. Premature tapetum degeneration: a major cause of abortive pollen development in photoperiod sensitive genic male sterility in rice.

    Science.gov (United States)

    Shi, Yinlian; Zhao, Sha; Yao, Jialing

    2009-08-01

    Photoperiod-sensitive genic male-sterile (PSGMS) rice (Oryza sativa L.), a natural mutant found in the rice cultivar Nongken 58, is very useful for the development of hybrid rice cultivars. Despite its widespread use in breeding programs, the initial stage of the abortive development of PSGMS rice and the possible cytological mechanisms of pollen abortion have not been determined. In the present study, a systematic cytological comparison of the anther development of PSGMS rice with its normal fertile counterpart is conducted. The results show that pollen abortion in PSGMS rice first occurs before the pollen mother cell (PMC) stage, and continues during the entire process of pollen development until pollen degradation. The abortive process was closely associated with the abnormal behavior of the tapetum. Although tapetum degeneration in PSGMS rice initiates already at the PMC stage, it proceeds slowly and does not complete until the breakdown of the pollen. Such cytological observations were supported by the results of the TUNEL (TdT-mediated dUTP Nick End Labeling) assay, which detects DNA fragmentation resulting from programmed cell death (PCD), indicating that the premature tapetum degeneration is in the process of PCD.

  16. Premature Tapetum Degeneration: a Major Cause of Abortive Pollen Development in Photoperiod Sensitive Genic Male Sterility in Rice

    Institute of Scientific and Technical Information of China (English)

    Yinlian Shi; Sha Zhao; Jialing Yao

    2009-01-01

    Photoperiod-sensitive genic male-sterile (PSGMS) rice (Oryza sativa L.), a natural mutant found in the rice cultivar Nongken 58, is very useful for the development of hybrid rice cultivars. Despite its widespread use in breeding programs, the initial stage of the abortive development of PSGMS rice and the possible cytological mechanisms of pollen abortion have not been determined. In the present study, a systematic cytological comparison of the anther development of PSGMS rice with its normal fertile counterpart is conducted. The results show that pollen abortion in PSGMS rice first occurs before the pollen mother cell (PMC) stage, and continues during the entire process of pollen development until pollen degradation. The abortive process was closely associated with the abnormal behavior of the tapetum. Although tapetum degeneration in PSGMS rice initiates already at the PMC stage, it proceeds slowly and does not complete until the breakdown of the pollen. Such cytological observations were supported by the results of the TUNEL (TdT-mediated dUTP Nick End Labeling) assay, which detects DNA fragmentation resulting from programmed cell death (PCD), indicating that the premature tapetum degeneration is in the process of PCD.

  17. The wobbler mouse, an ALS animal model

    DEFF Research Database (Denmark)

    Moser, Jakob Maximilian; Bigini, Paolo; Schmitt-John, Thomas

    2013-01-01

    This review article is focused on the research progress made utilizing the wobbler mouse as animal model for human motor neuron diseases, especially the amyotrophic lateral sclerosis (ALS). The wobbler mouse develops progressive degeneration of upper and lower motor neurons and shows striking...

  18. Intervertebral disc degeneration in dogs

    NARCIS (Netherlands)

    Bergknut, Niklas

    2011-01-01

    Back pain is common in both dogs and humans, and is often associated with intervertebral disc (IVD) degeneration. The IVDs are essential structures of the spine and degeneration can ultimately result in diseases such as IVD herniation or spinal instability. In order to design new treatments halting

  19. Double Degenerate Stars

    Institute of Scientific and Technical Information of China (English)

    LUO Xin-Lian; BAI Hua; ZHAO Lei

    2008-01-01

    Regardless of the formation mechanism, an exotic object, the double degenerate star (DDS), is introduced and investigated, which is composed of baryonic matter and some unknown fermion dark matter. Different from the simple white dwarfs (WDs), there is additional gravitational force provided by the unknown fermion component inside DDSs, which may strongly affect the structure and the stability of such kind of objects. Many possible and strange observational phenomena connecting with them are concisely discussed. Similar to the normal WD, this object can also experience thermonuclear explosion as type Ia supernova explosion when DDS's mass exceeds the maximum mass that can be supported by electron degeneracy pressure. However, since the total mass of baryonic matter can be much lower than that of WD at Chandrasekhar mass limit, the peak luminosity should be much dimmer than what we expect before, which may throw a slight shadow on the standard candle of SN Ia in the research of cosmology.

  20. Molecular and enzymatic characterization of two enzymes BmPCD and BmDHPR involving in the regeneration pathway of tetrahydrobiopterin from the silkworm Bombyx mori.

    Science.gov (United States)

    Li, Wentian; Gong, Meixia; Shu, Rui; Li, Xin; Gao, Junshan; Meng, Yan

    2015-08-01

    Tetrahydrobiopterin (BH4) is an essential cofactor of aromatic amino acid hydroxylases and nitric oxide synthase so that BH4 plays a key role in many biological processes. BH4 deficiency is associated with numerous metabolic syndromes and neuropsychological disorders. BH4 concentration in mammals is maintained through a de novo synthesis pathway and a regeneration pathway. Previous studies showed that the de novo pathway of BH4 is similar between insects and mammals. However, knowledge about the regeneration pathway of BH4 (RPB) is very limited in insects. Several mutants in the silkworm Bombyx mori have been approved to be associated with BH4 deficiency, which are good models to research on the RPB in insects. In this study, homologous genes encoding two enzymes, pterin-4a-carbinolamine dehydratase (PCD) and dihydropteridine reductase (DHPR) involving in RPB have been cloned and identified from B. mori. Enzymatic activity of DHPR was found in the fat body of wild type silkworm larvae. Together with the transcription profiles, it was indicated that BmPcd and BmDhpr might normally act in the RPB of B. mori and the expression of BmDhpr was activated in the brain and sexual glands while BmPcd was expressed in a wider special pattern when the de novo pathway of BH4 was lacked in lemon. Biochemical analyses showed that the recombinant BmDHPR exhibited high enzymatic activity and more suitable parameters to the coenzyme of NADH in vitro. The results in this report give new information about the RPB in B. mori and help in better understanding insect BH4 biosynthetic networks.

  1. Facts about Age-Related Macular Degeneration

    Science.gov (United States)

    ... Degeneration (AMD) > Facts About Age-Related Macular Degeneration Facts About Age-Related Macular Degeneration This information was ... an Eye Care Professional Last Reviewed: September 2015 Fact Sheet Blurb The National Eye Institute (NEI) is ...

  2. Monitoring peripheral nerve degeneration in ALS by label-free stimulated Raman scattering imaging

    Science.gov (United States)

    Tian, Feng; Yang, Wenlong; Mordes, Daniel A.; Wang, Jin-Yuan; Salameh, Johnny S.; Mok, Joanie; Chew, Jeannie; Sharma, Aarti; Leno-Duran, Ester; Suzuki-Uematsu, Satomi; Suzuki, Naoki; Han, Steve S.; Lu, Fa-Ke; Ji, Minbiao; Zhang, Rosanna; Liu, Yue; Strominger, Jack; Shneider, Neil A.; Petrucelli, Leonard; Xie, X. Sunney; Eggan, Kevin

    2016-10-01

    The study of amyotrophic lateral sclerosis (ALS) and potential interventions would be facilitated if motor axon degeneration could be more readily visualized. Here we demonstrate that stimulated Raman scattering (SRS) microscopy could be used to sensitively monitor peripheral nerve degeneration in ALS mouse models and ALS autopsy materials. Three-dimensional imaging of pre-symptomatic SOD1 mouse models and data processing by a correlation-based algorithm revealed that significant degeneration of peripheral nerves could be detected coincidentally with the earliest detectable signs of muscle denervation and preceded physiologically measurable motor function decline. We also found that peripheral degeneration was an early event in FUS as well as C9ORF72 repeat expansion models of ALS, and that serial imaging allowed long-term observation of disease progression and drug effects in living animals. Our study demonstrates that SRS imaging is a sensitive and quantitative means of measuring disease progression, greatly facilitating future studies of disease mechanisms and candidate therapeutics.

  3. Neer Award 2016: reduced muscle degeneration and decreased fatty infiltration after rotator cuff tear in a poly(ADP-ribose) polymerase 1 (PARP-1) knock-out mouse model.

    Science.gov (United States)

    Kuenzler, Michael B; Nuss, Katja; Karol, Agnieszka; Schär, Michael O; Hottiger, Michael; Raniga, Sumit; Kenkel, David; von Rechenberg, Brigitte; Zumstein, Matthias A

    2017-05-01

    Disturbed muscular architecture, atrophy, and fatty infiltration remain irreversible in chronic rotator cuff tears even after repair. Poly (adenosine 5'-diphosphate-ribose) polymerase 1 (PARP-1) is a key regulator of inflammation, apoptosis, muscle atrophy, muscle regeneration, and adipocyte development. We hypothesized that the absence of PARP-1 would lead to a reduction in damage to the muscle subsequent to combined tenotomy and neurectomy in a PARP-1 knockout (KO) mouse model. PARP-1 KO and wild-type C57BL/6 (WT group) mice were analyzed at 1, 6, and 12 weeks (total n = 84). In all mice, the supraspinatus and infraspinatus muscles of the left shoulder were detached and denervated. Macroscopic analysis, magnetic resonance imaging, gene expression analysis, immunohistochemistry, and histology were used to assess the differences in PARP-1 KO and WT mice. The muscles in the PARP-1 KO group had significantly less retraction, atrophy, and fatty infiltration after 12 weeks than in the WT group. Gene expression of inflammatory, apoptotic, adipogenic, and muscular atrophy genes was significantly decreased in PARP-1 KO mice in the first 6 weeks. Absence of PARP-1 leads to a reduction in muscular architectural damage, early inflammation, apoptosis, atrophy, and fatty infiltration after combined tenotomy and neurectomy of the rotator cuff muscle. Although the macroscopic reaction to injury is similar in the first 6 weeks, the ability of the muscles to regenerate was much greater in the PARP-1 KO group, leading to a near-normalization of the muscle after 12 weeks. Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

  4. [Age related macular degeneration].

    Science.gov (United States)

    Sayen, Alexandra; Hubert, Isabelle; Berrod, Jean-Paul

    2011-02-01

    Age-related macular degeneration (ARMD) is a multifactorial disease caused by a combination of genetic and environmental factors. It is the first cause of blindness in patients over 50 in the western world. The disease has been traditionally classified into early and late stages with dry (atrophic) and wet (neovascular) forms: neovascular form is characterized by new blood vessels development under the macula (choroidal neovascularisation) which lead to a rapid decline of vision associated with metamorphopsia and requiring an urgent ophtalmological examination. Optical coherence tomography is now one of the most important part of the examination for diagnosis and treatment. Patient with age related maculopathy should consider taking a dietary supplement such that used in AREDS. The treatment of the wet ARMD has largely beneficied since year 2006 of anti-VEGF (vascular endothelial growth factor) molecules such as ranibizumab or bevacizumab given as repeated intravitreal injections. A systematic follow up each 4 to 8 week in required for several years. There is no effective treatment at the moment for dry AMD. For patients with binocular visual acuity under 60/200 rehabilitation includes low vision specialist, vision aids and psychological support.

  5. Degenerate pseudo-Riemannian metrics

    CERN Document Server

    Hervik, Sigbjorn; Yamamoto, Kei

    2014-01-01

    In this paper we study pseudo-Riemannian spaces with a degenerate curvature structure i.e. there exists a continuous family of metrics having identical polynomial curvature invariants. We approach this problem by utilising an idea coming from invariant theory. This involves the existence of a boost, the existence of this boost is assumed to extend to a neighbourhood. This approach proves to be very fruitful: It produces a class of metrics containing all known examples of degenerate metrics. To date, only Kundt and Walker metrics have been given, however, our study gives a plethora of examples showing that degenerate metrics extend beyond the Kundt and Walker examples. The approach also gives a useful criterion for a metric to be degenerate. Specifically, we use this to study the subclass of VSI and CSI metrics (i.e., spaces where polynomial curvature invariants are all vanishing or constants, respectively).

  6. Age-Related Macular Degeneration

    Science.gov (United States)

    ... version of this page please turn Javascript on. Age-related Macular Degeneration About AMD Click for more ... a leading cause of vision loss among people age 60 and older. It causes damage to the ...

  7. On the degenerate phase boundaries

    CERN Document Server

    Ma, Y; Kuang, Z; Ma, Yongge; Liang, Canbin; Kuang, Zhiquan

    1999-01-01

    The structure of the phase boundary between degenerate and non-degenerate regions in Ashtekar's gravity has been studied by Bengtsson and Jacobson who conjectured that the "phase boundary" should always be null. In this paper, we reformulate the reparametrization procedure in the mapping language and distinguish a phase boundary from its image. It is shown that the image has to be null, while the nullness of the phase boundary requries more suitable criterion.

  8. Wilson's disease (hepatolenticular degeneration).

    Science.gov (United States)

    Herron, B E

    1976-01-01

    Wilson's disease, or hepatolenticular degeneration, is a rare inherited disorder of copper metabolism which usually affects young people. Excess copper accumulates in the tissues, primarily in the liver, brain, and cornea. This copper deposition results in a wide range of hepatic and neurological symptoms, and may produce psychiatric illness. Hepatic involvement often occurs in childhood, while neurological deficits generally are detected at a later age. The disease is inherited in an autosomal recessive fashion. Ocular findings are of particular importance because the corneal copper deposition, forming the Kayser-Fleischer ring,is the only pathognomonic sign of the disease. The structure of the ring and the presence of copper have been well established. An anterior capsular deposition of copper in the lens results in a characteristic sunflower cataract in some of these patients. Other ocular abnormalities have been described but are much less common. The pathogenesis of the disease and the basic genetic defect remain obscure. It is clear that there is excess copper in the tissues, but the mechanism of its deposition is unknown. It is in some way associated with a failure to synthesize the serum copper protein ceruloplasmin normally. Another theory suggests that an abnormal protein with a high affinity for copper may bind the metal in the tissues. The diagnosis may be suggested by the clinical manifestations and confirmed by the presence of a Kayser-Fleischer ring. In the absence of these findings biochemical determinations are necessary. The most important of these are the serum ceruloplasmin, the urinary copper, and the hepatic copper concentration on biopsy. Treatment consists in the administration of the copper chelating agent, penicillamine, and the avoidance of a high copper intake. This usually results in marked clinical improvement if irreversible tissue damage has not occurred. Maintenance therapy for life is necessary in order to continue the negative

  9. 4-Nitrocatecholato iron(III) complexes of 2-aminomethyl pyridine-based bis(phenol) amine as structural models for catechol-bound 3,4-PCD

    Science.gov (United States)

    Safaei, Elham; Heidari, Sima; Wojtczak, Andrzej; Cotič, Patricia; Kozakiewicz, Anna

    2016-02-01

    Two nitrocatecholato(HNC) iron(III) complexes, [FeLAMPX(H-NC)]. NEt3, of the tetradendate ligand (2-aminomethylpyridine)bis(2-pyridylmethyl)amine (H2LAMPX) were synthesized and structurally characterized. These structural models for catechol-bound 3,4-PCD were characterized by IR, UV-vis, elemental analysis and magnetic measurements. X-ray crystallography studies revealed that in both complexes the iron(III) centers are distorted octahedral and coordinated by two phenolate oxygen's, two amine nitrogen's of the ligand and mono anionic nitrocatecholate group (HNC). The variable-temperature magnetic susceptibility studies revealed paramagnetic properties of the reported complexes. The effective magnetic moments for the complexes lie between 5.3 and 5.4 BM correspond to the reported values for high spin Fe(III) center. The ligand-centered oxidation and metal-centered reduction of complexes was studies using cyclic voltammetry (CV) technique.

  10. Selection of metal cups used to synthesize PCD and PCBN compacts%合成PCD和PCBN复合片用金属屏蔽杯的选择

    Institute of Scientific and Technical Information of China (English)

    林高安

    2014-01-01

    Some selection principles of metal cups used to fabricate poly-crystal diamond (PCD) and poly-crystal cubic boron nitride (PCBN) compacts have been summarized according to the actual production. The selection principle are as follow, 1)higher melting point;2) higher plasticity, transformation equality and no breaking at high pressure;3) there is the purification function on cavity body; 4) simple technology. The effects of some common metal cup materials and some assembly modes on the ultra-high pressure-high temperature sintering process have been analyzed in detail in the present paper. Some assistances can be provided to the production of superhard materials.%结合聚晶金刚石(PCD)和聚晶立方氮化硼(PCBN)复合片的生产实际,总结 PCD和PCBN 复合片制备过程中使用的金属屏蔽杯材料的选择原则为:(1)具有较高熔点;(2)具备良好的塑性,高压下变形均匀且不发生开裂;(3)对合成腔体具有一定的净化功能;(4)制造方法简单。并详细分析了常用金属杯材料及其组装方式在超高压高温烧结过程中的作用。以期能为超硬材料生产提供有益的帮助与指导。

  11. Systematic design of mouse Vh gene family-specific oligonucleotides

    NARCIS (Netherlands)

    Seijen, AM; Seijen, HG; Bos, NA

    2001-01-01

    Kabat's database has often been used to design mouse Vh gene-specific 5 ' primers. The emphasis was mostly on constructing a universal (degenerate) 5 ' primer or 5 ' primer set, which would be able to match every mouse Vh gene. We were interested in finding oligonucleotides that could be used as pri

  12. Systematic design of mouse Vh gene family-specific oligonucleotides

    NARCIS (Netherlands)

    Seijen, AM; Seijen, HG; Bos, NA

    2001-01-01

    Kabat's database has often been used to design mouse Vh gene-specific 5 ' primers. The emphasis was mostly on constructing a universal (degenerate) 5 ' primer or 5 ' primer set, which would be able to match every mouse Vh gene. We were interested in finding oligonucleotides that could be used as pri

  13. Genetics Home Reference: age-related macular degeneration

    Science.gov (United States)

    ... Resources (3 links) BrightFocus Foundation: Macular Degeneration Treatment Macular Degeneration Partnership: Low Vision Rehabilitation Prevent Blindness America: Age-Related Macular Degeneration (AMD) ...

  14. Gribov ambiguity and degenerate systems

    CERN Document Server

    Canfora, Fabrizio; Salgado-Rebolledo, Patricio; Zanelli, Jorge

    2014-01-01

    The relation between Gribov ambiguity and degeneracies in the symplectic structure of physical systems is analyzed. It is shown that, in finite-dimensional systems, the presence of Gribov ambiguities in regular constrained systems (those where the constraints are functionally independent) always leads to a degenerate symplectic structure upon Dirac reduction. The implications for the Gribov-Zwanziger approach to QCD are discussed.

  15. Ccdc66 null mutation causes retinal degeneration and dysfunction.

    Science.gov (United States)

    Gerding, Wanda M; Schreiber, Sabrina; Schulte-Middelmann, Tobias; de Castro Marques, Andreia; Atorf, Jenny; Akkad, Denis A; Dekomien, Gabriele; Kremers, Jan; Dermietzel, Rolf; Gal, Andreas; Rülicke, Thomas; Ibrahim, Saleh; Epplen, Jörg T; Petrasch-Parwez, Elisabeth

    2011-09-15

    Retinitis pigmentosa (RP) is a group of human retinal disorders, with more than 100 genes involved in retinal degeneration. Canine and murine models are useful for investigating human RP based on known, naturally occurring mutations. In Schapendoes dogs, for example, a mutation in the CCDC66 gene has been shown to cause autosomal recessively inherited, generalized progressive retinal atrophy (gPRA), the canine counterpart to RP. Here, a novel mouse model with a disrupted Ccdc66 gene was investigated to reveal the function of protein CCDC66 and the pathogenesis of this form of gPRA. Homozygous Ccdc66 mutant mice lack retinal Ccdc66 RNA and protein expression. Light and electron microscopy reveal an initial degeneration of photoreceptors already at 13 days of age, followed by a slow, progressive retinal degeneration over months. Retinal dysfunction causes reduced scotopic a-wave amplitudes, declining from 1 to 7 months of age as well as an early reduction of the photopic b-wave at 1 month, improving slightly at 7 months, as evidenced by electroretinography. In the retina of the wild-type (WT) mouse, protein CCDC66 is present at highest levels after birth, followed by a decline until adulthood, suggesting a crucial role in early development. Protein CCDC66 is expressed predominantly in the developing rod outer segments as confirmed by subcellular analyses. These findings illustrate that the lack of protein CCDC66 causes early, slow progressive rod-cone dysplasia in the novel Ccdc66 mutant mouse model, thus providing a sound foundation for the development of therapeutic strategies.

  16. Spheroidal Degeneration of the Cornea

    Directory of Open Access Journals (Sweden)

    Erdem Dinç

    2011-08-01

    Full Text Available A thirty-one-year-old male patient presented with bilateral epiphora and stinging sensation in the cornea. Detailed history revealed that a bilateral corneal scraping had been made regarding the initial diagnosis of fungal keratitis. His bestcorrected visual acuities were 20/20 and 20/30 in right and left eyes, respectively. Biomicroscopy showed bilateral amber colored spherules in the anterior stroma of the central cornea. The diagnosis of spheroidal corneal degeneration was established and symptomatic therapy with artificial tear drops was prescribed. Ultraviolet light is widely accepted to be the main etiological factor in the pathogenesis of spheroidal degeneration. Because of difficulties in the early stages of the diagnostic process of the disease, incorrect diagnoses can be made with inappropriate interventions. (Turk J Ophthalmol 2011; 41: 264-6

  17. Radial keratotomy associated endothelial degeneration

    Directory of Open Access Journals (Sweden)

    Moshirfar M

    2012-02-01

    Full Text Available Majid Moshirfar, Andrew Ollerton, Rodmehr T Semnani, Maylon HsuJohn A Moran Eye Center, Department of Ophthalmology and Visual Sciences, University of Utah, Salt Lake City, UT, USAPurpose: To describe the presentation and clinical course of eyes with a history of radial keratotomy (RK and varying degrees of endothelial degeneration.Methods: Retrospective case series were used.Results: Thirteen eyes (seven patients were identified with clinical findings of significant guttata and a prior history of RK. The mean age of presentation for cornea evaluation was 54.3 years (range: 38–72 years, averaging 18.7 years (range: 11–33 years after RK. The presentation of guttata varied in degree from moderate to severe. Best corrected visual acuity (BCVA ranged from 20/25 to 20/80. All patients had a history of bilateral RK, except one patient who did not develop any guttata in the eye without prior RK. No patients reported a family history of Fuch’s Dystrophy. One patient underwent a penetrating keratoplasty in one eye and a Descemet’s stripping automated endothelial keratoplasty (DSAEK in the other eye.Conclusions: RK may induce a spectrum of endothelial degeneration. In elderly patients, the findings of guttata may signify comorbid Fuch’s dystrophy in which RK incisions could potentially hasten endothelial decomposition. In these select patients with stable cornea topography and prior RK, DSAEK may successfully treat RK endothelial degeneration.Keywords: radial keratotomy, RK, Descemet’s stripping automated endothelial keratoplasty, DSAEK, guttata, endothelial degeneration, Fuch’s dystrophy

  18. Degenerating the elliptic Schlesinger system

    Science.gov (United States)

    Aminov, G. A.; Artamonov, S. B.

    2013-01-01

    We study various ways of degenerating the Schlesinger system on the elliptic curve with R marked points. We construct a limit procedure based on an infinite shift of the elliptic curve parameter and on shifts of the marked points. We show that using this procedure allows obtaining a nonautonomous Hamiltonian system describing the Toda chain with additional spin sl(N, ℂ) degrees of freedom.

  19. Radial keratotomy associated endothelial degeneration.

    Science.gov (United States)

    Moshirfar, Majid; Ollerton, Andrew; Semnani, Rodmehr T; Hsu, Maylon

    2012-01-01

    To describe the presentation and clinical course of eyes with a history of radial keratotomy (RK) and varying degrees of endothelial degeneration. Retrospective case series were used. Thirteen eyes (seven patients) were identified with clinical findings of significant guttata and a prior history of RK. The mean age of presentation for cornea evaluation was 54.3 years (range: 38-72 years), averaging 18.7 years (range: 11-33 years) after RK. The presentation of guttata varied in degree from moderate to severe. Best corrected visual acuity (BCVA) ranged from 20/25 to 20/80. All patients had a history of bilateral RK, except one patient who did not develop any guttata in the eye without prior RK. No patients reported a family history of Fuch's Dystrophy. One patient underwent a penetrating keratoplasty in one eye and a Descemet's stripping automated endothelial keratoplasty (DSAEK) in the other eye. RK may induce a spectrum of endothelial degeneration. In elderly patients, the findings of guttata may signify comorbid Fuch's dystrophy in which RK incisions could potentially hasten endothelial decomposition. In these select patients with stable cornea topography and prior RK, DSAEK may successfully treat RK endothelial degeneration.

  20. Focal degeneration of astrocytes in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Rossi, D; Brambilla, L; Valori, C F; Roncoroni, C; Crugnola, A; Yokota, T; Bredesen, D E; Volterra, A

    2008-11-01

    Astrocytes emerge as key players in motor neuron degeneration in Amyotrophic Lateral Sclerosis (ALS). Whether astrocytes cause direct damage by releasing toxic factors or contribute indirectly through the loss of physiological functions is unclear. Here we identify in the hSOD1(G93A) transgenic mouse model of ALS a degenerative process of the astrocytes, restricted to those directly surrounding spinal motor neurons. This phenomenon manifests with an early onset and becomes significant concomitant with the loss of motor cells and the appearance of clinical symptoms. Contrary to wild-type astrocytes, mutant hSOD1-expressing astrocytes are highly vulnerable to glutamate and undergo cell death mediated by the metabotropic type-5 receptor (mGluR5). Blocking mGluR5 in vivo slows down astrocytic degeneration, delays the onset of the disease and slightly extends survival in hSOD1(G93A) transgenic mice. We propose that excitotoxicity in ALS affects both motor neurons and astrocytes, favouring their local interactive degeneration. This new mechanistic hypothesis has implications for therapeutic interventions.

  1. Changes in ganglion cell physiology during retinal degeneration influence excitability by prosthetic electrodes

    Science.gov (United States)

    Cho, Alice; Ratliff, Charles; Sampath, Alapakkam; Weiland, James

    2016-01-01

    Objective Here we investigate ganglion cell physiology in healthy and degenerating retina to test its influence on threshold to electrical stimulation. Approach Age-related Macular Degeneration and Retinitis Pigmentosa cause blindness via outer retinal degeneration. Inner retinal pathways that transmit visual information to the central brain remain intact, so direct electrical stimulation from prosthetic devices offers the possibility for visual restoration. Since inner retinal physiology changes during degeneration, we characterize physiological properties and responses to electrical stimulation in retinal ganglion cells of both wild type mice and the rd10 mouse model of retinal degeneration. Main results Our aggregate results support previous observations that elevated thresholds characterize diseased retinas. However, a physiology-driven classification scheme reveals distinct sub-populations of ganglion cells with thresholds either normal or strongly elevated compared to wild-type. When these populations are combined, only a weakly elevated threshold with large variance is observed. The cells with normal threshold are more depolarized at rest and exhibit periodic oscillations. Significance During degeneration, physiological changes in retinal ganglion cells affect the threshold stimulation currents required to evoke action potentials. PMID:26905177

  2. Disc degeneration: current surgical options

    Directory of Open Access Journals (Sweden)

    C Schizas

    2010-10-01

    Full Text Available Chronic low back pain attributed to lumbar disc degeneration poses a serious challenge to physicians. Surgery may be indicated in selected cases following failure of appropriate conservative treatment. For decades, the only surgical option has been spinal fusion, but its results have been inconsistent. Some prospective trials show superiority over usual conservative measures while others fail to demonstrate its advantages. In an effort to improve results of fusion and to decrease the incidence of adjacent segment degeneration, total disc replacement techniques have been introduced and studied extensively. Short-term results have shown superiority over some fusion techniques. Mid-term results however tend to show that this approach yields results equivalent to those of spinal fusion. Nucleus replacement has gained some popularity initially, but evidence on its efficacy is scarce. Dynamic stabilisation, a technique involving less rigid implants than in spinal fusion and performed without the need for bone grafting, represents another surgical option. Evidence again is lacking on its superiority over other surgical strategies and conservative measures. Insertion of interspinous devices posteriorly, aiming at redistributing loads and relieving pain, has been used as an adjunct to disc removal surgery for disc herniation. To date however, there is no clear evidence on their efficacy. Minimally invasive intradiscal thermocoagulation techniques have also been tried, but evidence of their effectiveness is questioned. Surgery using novel biological solutions may be the future of discogenic pain treatment. Collaboration between clinicians and basic scientists in this multidisciplinary field will undoubtedly shape the future of treating symptomatic disc degeneration.

  3. Regularized degenerate multi-solitons

    CERN Document Server

    Correa, Francisco

    2016-01-01

    We report complex PT-symmetric multi-soliton solutions to the Korteweg de-Vries equation that asymptotically contain one-soliton solutions, with each of them possessing the same amount of finite real energy. We demonstrate how these solutions originate from degenerate energy solutions of the Schroedinger equation. Technically this is achieved by the application of Darboux-Crum transformations involving Jordan states with suitable regularizing shifts. Alternatively they may be constructed from a limiting process within the context Hirota's direct method or on a nonlinear superposition obtained from multiple Baecklund transformations. The proposed procedure is completely generic and also applicable to other types of nonlinear integrable systems.

  4. Degenerate Neutrinos and CP Violation

    CERN Document Server

    Ioannisian, A N

    2003-01-01

    We have studied mixing and masses of three left handed Majorana neutrinos in the model, which assumes exactly degenerate neutrino masses at some "neutrino unification" scale. Such a simple theoretical ansatz naturally leads to quasidegenerate neutrinos. The neutrino mass splittings induced by renormalization effects. In the model we found that the parameters of the neutrino physics (neutrino mass spectrum, mixing angles and CP violation phases) are strongly intercorrelated to each other. From these correlations we got strong bounds on the parameters which could be checked in the oscillation experiments.

  5. Radiative seesaw and degenerate neutrinos

    CERN Document Server

    Bajc, B; Bajc, Borut; Senjanovic, Goran

    2005-01-01

    The radiative see-saw mechanism of Witten generates the right-handed neutrino masses in SO(10) with the spinorial 16_H Higgs field. We study here analytically the 2nd and 3rd generations for the minimal Yukawa structure containing 10_H and 120_H Higgs representations. In the approximation of small 2nd generation masses and gauge loop domination we find the following results : (1) b-tau unification, (2) natural coexistence between large theta_l and small theta_q, (3) degenerate neutrinos.

  6. Macular Degeneration Prevention and Risk Factors

    Science.gov (United States)

    ... Grant Terms & Conditions Patent & Intellectual Property Policy For Current Awardees FAQs Our Funding Philosophy ... Alzheimer’s Disease Research Macular Degeneration Research National Glaucoma Research ...

  7. [Pathogenesis of age-related macular degeneration].

    Science.gov (United States)

    Kaarniranta, Kai; Seitsonen, Sanna; Paimela, Tuomas; Meri, Seppo; Immonen, Ilkka

    2009-01-01

    Age-related macular degeneration is a multiform disease of the macula, the region responsible for detailed central vision. In recent years, plenty of new knowledge of the pathogenesis of this disease has been obtained, and the treatment of exudative macular degeneration has greatly progressed. The number of patients with age-related macular degeneration will multiply in the following decades, because knowledge of mechanisms of development of macular degeneration that could be subject to therapeutic measures is insufficient. Central underlying factors are genetic inheritance, exposure of the retina to chronic oxidative stress and accumulation of inflammation-inducing harmful proteins into or outside of retinal cells.

  8. Structure of Degenerate Block Algebras

    Institute of Scientific and Technical Information of China (English)

    Linsheng Zhu; Daoji Meng

    2003-01-01

    Given a non-trivial torsion-free abelian group (A,+,0), a field F of characteristic 0, and a non-degenerate bi-additive skew-symmetric map φ :A × A → F, we define a Lie algebra ∑ = ∑(A, φ) over F with basis {ex | x ∈ A\\{0}}and Lie product [ex, ey] = φ(x, y)ex+y. We show that ∑ is endowed uniquely with a non-degenerate symmetric invariant bilinear form and the derivation algebra Der ∑ of ∑ is a complete Lie algebra. We describe the double extension D(∑, T) of ∑ by T, where T is spanned by the locally finite derivations of ∑, and determine the second cohomology group H2(D(∑,T),F) using anti-derivations related to the form on D(∑, T). Finally, we compute the second Leibniz cohomology groups HL2(∑, F) and HL2(D(∑, T), F).

  9. Tapetum Degeneration Retardation is Critical for Aliphatic Metabolism and Gene Regulation during Rice Pollen Development

    Institute of Scientific and Technical Information of China (English)

    Da-Sheng Zhang; Wan-Qi Liang; Zheng Yuan; Na Li; Jing Shi; Jue Wang; Yu-Min Liu; Wen-Juan Yu; Da-Bing Zhang

    2008-01-01

    As a complex wall system in flowering plants,the pollen outer wall mainly contains aliphatic sporopollenin;however,the mechanism for synthesizing these lipidic precursors during pollen development remains less well under-stood.Here,we report on the function of the rice tapetum-expressing TDR(Tapetum Degeneration Retardation)gene in aliphatic metabolism and its regulatory role during rice pollen development.The observations of transmission electron microscopy (TEM) and scanning electron microscopy(SEM)analyses suggested that pollen wall formation was significantly altered in the tdr mutant.The contents of aliphatic compositions of anther were greatly changed in the tdr mutant revealed by GC-MS(gas chromatography-mass spectrometry)testing,particularly less accumulated in fatty acids, primary alcohols,alkanes and alkenes,and an abnormal increase in secondary alcohols with carbon Iengths from C29 to C35 in tdr.Microarray data revealed that a group of genes putatively involved in lipid transport and metabolism were significantly altered in the tdr mutant,indicating the critical role of TDR in the formation of the pollen wall.Also,a wide range of genes tween wild-type and tdr.In addition to its function in promoting tapetum PCD,TDR possibly plays crucial regulatory roles in several basic biological processes during rice pollen development.

  10. Cav1.4 L-Type Calcium Channels Contribute to Calpain Activation in Degenerating Photoreceptors of rd1 Mice.

    Directory of Open Access Journals (Sweden)

    Christian Schön

    Full Text Available Retinitis pigmentosa is an inherited blinding disorder characterized by progressive degeneration and loss of photoreceptors. The exact mechanism of degeneration and cell death of photoreceptors is not known, but is thought to involve disturbed Ca2+-signaling. Ca2+ can enter the photoreceptor cell via outer segment cyclic nucleotide-gated (CNG channels or synaptic Cav1.4 L-type voltage-gated calcium channels (VGCC. Previously, we have shown that genetic ablation of the Cngb1 gene encoding the B subunit of the rod CNG channel delays the fast progressing degeneration in the rd1 mutant mouse model of retinitis pigmentosa. In this study, we crossbred rd1 mice with the Cacna1f-deficient mouse lacking the Cav1.4 α1 subunit of the L-type VGCC. Longitudinal in vivo examinations of photoreceptor layer thickness by optical coherence tomography revealed a significant, but not sustained delay of retinal degeneration in Cacna1f x rd1 double mutant mice compared to rd1 mice. This was accompanied by a reduction of TUNEL positive cells in the early phase of rod degeneration. Remarkably, Cacna1f x rd1 double mutant mice displayed a strong decrease in the activation of the Ca2+-dependent protease calpain during photoreceptor loss. Our results show that genetic deletion of the synaptic Cav1.4 L-type VGCCs impairs calpain activation and leads to a short-term preservation of photoreceptors in the rd1 mouse.

  11. Excitotoxin-induced neuronal degeneration and seizure are mediated by tissue plasminogen activator.

    Science.gov (United States)

    Tsirka, S E; Gualandris, A; Amaral, D G; Strickland, S

    1995-09-28

    Neuronal degeneration in the hippocampus, a region of the brain important for acquisition of memory in humans, occurs in various pathological conditions, including Alzheimer's disease, brain ischaemia and epilepsy. When neuronal activity is stimulated in the adult rat and mouse hippocampus, tissue plasminogen activator (tPA), a serine protease that converts inactive plasminogen to the active protease plasmin, is transcriptionally induced. The activity of tPA in neural tissue is correlated with neurite outgrowth, regeneration and migration, suggesting that it might be involved in neuronal plasticity. Here we show that tPA is produced primarily by microglia in the hippocampus. Using excitotoxins to induce neuronal cell loss, we demonstrate that tPA-deficient mice are resistant to neuronal degeneration. These mice are also less susceptible to pharmacologically induced seizures than wild-type mice. These findings identify a role for tPA in neuronal degeneration and seizure.

  12. Nrl knockdown by AAV-delivered CRISPR/Cas9 prevents retinal degeneration in mice.

    Science.gov (United States)

    Yu, Wenhan; Mookherjee, Suddhasil; Chaitankar, Vijender; Hiriyanna, Suja; Kim, Jung-Woong; Brooks, Matthew; Ataeijannati, Yasaman; Sun, Xun; Dong, Lijin; Li, Tiansen; Swaroop, Anand; Wu, Zhijian

    2017-03-14

    In retinitis pigmentosa, loss of cone photoreceptors leads to blindness, and preservation of cone function is a major therapeutic goal. However, cone loss is thought to occur as a secondary event resulting from degeneration of rod photoreceptors. Here we report a genome editing approach in which adeno-associated virus (AAV)-mediated CRISPR/Cas9 delivery to postmitotic photoreceptors is used to target the Nrl gene, encoding for Neural retina-specific leucine zipper protein, a rod fate determinant during photoreceptor development. Following Nrl disruption, rods gain partial features of cones and present with improved survival in the presence of mutations in rod-specific genes, consequently preventing secondary cone degeneration. In three different mouse models of retinal degeneration, the treatment substantially improves rod survival and preserves cone function. Our data suggest that CRISPR/Cas9-mediated NRL disruption in rods may be a promising treatment option for patients with retinitis pigmentosa.

  13. Dwarfism and age-associated spinal degeneration of heterozygote cmd mice defective in aggrecan

    Science.gov (United States)

    Watanabe, Hideto; Nakata, Ken; Kimata, Koji; Nakanishi, Isao; Yamada, Yoshihiko

    1997-01-01

    Mouse cartilage matrix deficiency (cmd) is an autosomal recessive disorder caused by a genetic defect of aggrecan, a large chondroitin sulfate proteoglycan in cartilage. The homozygotes (−/−) are characterized by cleft palate and short limbs, tail, and snout. They die just after birth because of respiratory failure, and the heterozygotes (+/−) appear normal at birth. Here we report that the heterozygotes show dwarfism and develop spinal misalignment with age. Within 19 months of age, they exhibit spastic gait caused by misalignment of the cervical spine and die because of starvation. Histological examination revealed a high incidence of herniation and degeneration of vertebral discs. Electron microscopy showed a degeneration of disc chondrocytes in the heterozygotes. These findings may facilitate the identification of mutations in humans predisposed to spinal degeneration. PMID:9192671

  14. A comparison of some organizational characteristics of the mouse central retina and the human macula.

    Science.gov (United States)

    Volland, Stefanie; Esteve-Rudd, Julian; Hoo, Juyea; Yee, Claudine; Williams, David S

    2015-01-01

    Mouse models have greatly assisted our understanding of retinal degenerations. However, the mouse retina does not have a macula, leading to the question of whether the mouse is a relevant model for macular degeneration. In the present study, a quantitative comparison between the organization of the central mouse retina and the human macula was made, focusing on some structural characteristics that have been suggested to be important in predisposing the macula to stresses leading to degeneration: photoreceptor density, phagocytic load on the RPE, and the relative thinness of Bruch's membrane. Light and electron microscopy measurements from retinas of two strains of mice, together with published data on human retinas, were used for calculations and subsequent comparisons. As in the human retina, the central region of the mouse retina possesses a higher photoreceptor cell density and a thinner Bruch's membrane than in the periphery; however, the magnitudes of these periphery to center gradients are larger in the human. Of potentially greater relevance is the actual photoreceptor cell density, which is much greater in the mouse central retina than in the human macula, underlying a higher phagocytic load for the mouse RPE. Moreover, at eccentricities that correspond to the peripheral half of the human macula, the rod to cone ratio is similar between mouse and human. Hence, with respect to photoreceptor density and phagocytic load of the RPE, the central mouse retina models at least the more peripheral part of the macula, where macular degeneration is often first evident.

  15. Genetic association studies in lumbar disc degeneration

    DEFF Research Database (Denmark)

    Eskola, Pasi J; Lemmelä, Susanna; Kjaer, Per

    2012-01-01

    Low back pain is associated with lumbar disc degeneration, which is mainly due to genetic predisposition. The objective of this study was to perform a systematic review to evaluate genetic association studies in lumbar disc degeneration as defined on magnetic resonance imaging (MRI) in humans....

  16. Degenerated differential pair with controllable transconductance

    NARCIS (Netherlands)

    Mensink, Clemens; Mensink, Clemens H.J.; Nauta, Bram

    1998-01-01

    A differential pair with input transistors and provided with a variable degeneration resistor. The degeneration resistor comprises a series arrangement of two branches of coupled resistors which are shunted in mutually corresponding points by respective control transistors whose gates are interconne

  17. Regularized degenerate multi-solitons

    Science.gov (United States)

    Correa, Francisco; Fring, Andreas

    2016-09-01

    We report complex {P}{T} -symmetric multi-soliton solutions to the Korteweg de-Vries equation that asymptotically contain one-soliton solutions, with each of them possessing the same amount of finite real energy. We demonstrate how these solutions originate from degenerate energy solutions of the Schrödinger equation. Technically this is achieved by the application of Darboux-Crum transformations involving Jordan states with suitable regularizing shifts. Alternatively they may be constructed from a limiting process within the context Hirota's direct method or on a nonlinear superposition obtained from multiple Bäcklund transformations. The proposed procedure is completely generic and also applicable to other types of nonlinear integrable systems.

  18. Naturalness of nearly degenerate neutrinos

    CERN Document Server

    Casas, J A; Ibarra, Alejandro; Navarro, I

    1999-01-01

    If neutrinos are to play a relevant cosmological role, they must be essentially degenerate. We study whether radiative corrections can or cannot be responsible for the small mass splittings, in agreement with all the available experimental data. We perform an exhaustive exploration of the bimaximal mixing scenario, finding that (i) the vacuum oscillations solution to the solar neutrino problem is always excluded; (ii) if the mass matrix is produced by a see-saw mechanism, there are large regions of the parameter space consistent with the large angle MSW solution, providing a natural origin for the Delta m^2_{sol} << Delta m^2_{atm} hierarchy; (iii) the bimaximal structure becomes then stable under radiative corrections. We also provide analytical expressions for the mass splittings and mixing angles and present a particularly simple see-saw ansatz consistent with all the observations.

  19. Degenerate doping of metallic anodes

    Science.gov (United States)

    Friesen, Cody A; Zeller, Robert A; Johnson, Paul B; Switzer, Elise E

    2015-05-12

    Embodiments of the invention relate to an electrochemical cell comprising: (i) a fuel electrode comprising a metal fuel, (ii) a positive electrode, (iii) an ionically conductive medium, and (iv) a dopant; the electrodes being operable in a discharge mode wherein the metal fuel is oxidized at the fuel electrode and the dopant increases the conductivity of the metal fuel oxidation product. In an embodiment, the oxidation product comprises an oxide of the metal fuel which is doped degenerately. In an embodiment, the positive electrode is an air electrode that absorbs gaseous oxygen, wherein during discharge mode, oxygen is reduced at the air electrode. Embodiments of the invention also relate to methods of producing an electrode comprising a metal and a doped metal oxidation product.

  20. Combining comparative proteomics and molecular genetics uncovers regulators of synaptic and axonal stability and degeneration in vivo.

    Directory of Open Access Journals (Sweden)

    Thomas M Wishart

    Full Text Available Degeneration of synaptic and axonal compartments of neurons is an early event contributing to the pathogenesis of many neurodegenerative diseases, but the underlying molecular mechanisms remain unclear. Here, we demonstrate the effectiveness of a novel "top-down" approach for identifying proteins and functional pathways regulating neurodegeneration in distal compartments of neurons. A series of comparative quantitative proteomic screens on synapse-enriched fractions isolated from the mouse brain following injury identified dynamic perturbations occurring within the proteome during both initiation and onset phases of degeneration. In silico analyses highlighted significant clustering of proteins contributing to functional pathways regulating synaptic transmission and neurite development. Molecular markers of degeneration were conserved in injury and disease, with comparable responses observed in synapse-enriched fractions isolated from mouse models of Huntington's disease (HD and spinocerebellar ataxia type 5. An initial screen targeting thirteen degeneration-associated proteins using mutant Drosophila lines revealed six potential regulators of synaptic and axonal degeneration in vivo. Mutations in CALB2, ROCK2, DNAJC5/CSP, and HIBCH partially delayed injury-induced neurodegeneration. Conversely, mutations in DNAJC6 and ALDHA1 led to spontaneous degeneration of distal axons and synapses. A more detailed genetic analysis of DNAJC5/CSP mutants confirmed that loss of DNAJC5/CSP was neuroprotective, robustly delaying degeneration in axonal and synaptic compartments. Our study has identified conserved molecular responses occurring within synapse-enriched fractions of the mouse brain during the early stages of neurodegeneration, focused on functional networks modulating synaptic transmission and incorporating molecular chaperones, cytoskeletal modifiers, and calcium-binding proteins. We propose that the proteins and functional pathways identified in

  1. Combining comparative proteomics and molecular genetics uncovers regulators of synaptic and axonal stability and degeneration in vivo.

    Directory of Open Access Journals (Sweden)

    Thomas M Wishart

    Full Text Available Degeneration of synaptic and axonal compartments of neurons is an early event contributing to the pathogenesis of many neurodegenerative diseases, but the underlying molecular mechanisms remain unclear. Here, we demonstrate the effectiveness of a novel "top-down" approach for identifying proteins and functional pathways regulating neurodegeneration in distal compartments of neurons. A series of comparative quantitative proteomic screens on synapse-enriched fractions isolated from the mouse brain following injury identified dynamic perturbations occurring within the proteome during both initiation and onset phases of degeneration. In silico analyses highlighted significant clustering of proteins contributing to functional pathways regulating synaptic transmission and neurite development. Molecular markers of degeneration were conserved in injury and disease, with comparable responses observed in synapse-enriched fractions isolated from mouse models of Huntington's disease (HD and spinocerebellar ataxia type 5. An initial screen targeting thirteen degeneration-associated proteins using mutant Drosophila lines revealed six potential regulators of synaptic and axonal degeneration in vivo. Mutations in CALB2, ROCK2, DNAJC5/CSP, and HIBCH partially delayed injury-induced neurodegeneration. Conversely, mutations in DNAJC6 and ALDHA1 led to spontaneous degeneration of distal axons and synapses. A more detailed genetic analysis of DNAJC5/CSP mutants confirmed that loss of DNAJC5/CSP was neuroprotective, robustly delaying degeneration in axonal and synaptic compartments. Our study has identified conserved molecular responses occurring within synapse-enriched fractions of the mouse brain during the early stages of neurodegeneration, focused on functional networks modulating synaptic transmission and incorporating molecular chaperones, cytoskeletal modifiers, and calcium-binding proteins. We propose that the proteins and functional pathways identified in

  2. The Highwire ubiquitin ligase promotes axonal degeneration by tuning levels of Nmnat protein.

    Directory of Open Access Journals (Sweden)

    Xin Xiong

    Full Text Available Axonal degeneration is a hallmark of many neuropathies, neurodegenerative diseases, and injuries. Here, using a Drosophila injury model, we have identified a highly conserved E3 ubiquitin ligase, Highwire (Hiw, as an important regulator of axonal and synaptic degeneration. Mutations in hiw strongly inhibit Wallerian degeneration in multiple neuron types and developmental stages. This new phenotype is mediated by a new downstream target of Hiw: the NAD+ biosynthetic enzyme nicotinamide mononucleotide adenyltransferase (Nmnat, which acts in parallel to a previously known target of Hiw, the Wallenda dileucine zipper kinase (Wnd/DLK MAPKKK. Hiw promotes a rapid disappearance of Nmnat protein in the distal stump after injury. An increased level of Nmnat protein in hiw mutants is both required and sufficient to inhibit degeneration. Ectopically expressed mouse Nmnat2 is also subject to regulation by Hiw in distal axons and synapses. These findings implicate an important role for endogenous Nmnat and its regulation, via a conserved mechanism, in the initiation of axonal degeneration. Through independent regulation of Wnd/DLK, whose function is required for proximal axons to regenerate, Hiw plays a central role in coordinating both regenerative and degenerative responses to axonal injury.

  3. Sarm1-mediated axon degeneration requires both SAM and TIR interactions.

    Science.gov (United States)

    Gerdts, Josiah; Summers, Daniel W; Sasaki, Yo; DiAntonio, Aaron; Milbrandt, Jeffrey

    2013-08-14

    Axon degeneration is an evolutionarily conserved pathway that eliminates damaged or unneeded axons. Manipulation of this poorly understood pathway may allow treatment of a wide range of neurological disorders. In an RNAi-based screen performed in cultured mouse DRG neurons, we observed strong suppression of injury-induced axon degeneration upon knockdown of Sarm1 [SARM (sterile α-motif-containing and armadillo-motif containing protein)]. We find that a SARM-dependent degeneration program is engaged by disparate neuronal insults: SARM ablation blocks axon degeneration induced by axotomy or vincristine treatment, while SARM acts in parallel with a soma-derived caspase-dependent pathway following trophic withdrawal. SARM is a multidomain protein that associates with neuronal mitochondria. Deletion of the N-terminal mitochondrial localization sequence disrupts SARM mitochondrial localization in neurons but does not alter its ability to promote axon degeneration. In contrast, mutation of either the SAM (sterile α motif) or TIR (Toll-interleukin-1 receptor) domains abolishes the ability of SARM to promote axonal degeneration, while a SARM mutant containing only these domains elicits axon degeneration and nonapoptotic neuronal death even in the absence of injury. Protein-protein interaction studies demonstrate that the SAM domains are necessary and sufficient to mediate SARM-SARM binding. SARM mutants lacking a TIR domain bind full-length SARM and exhibit strong dominant-negative activity. These results indicate that SARM plays an integral role in the dismantling of injured axons and support a model in which SAM-mediated multimerization is necessary for TIR-dependent engagement of a downstream destruction pathway. These findings suggest that inhibitors of SAM and TIR interactions represent therapeutic candidates for blocking pathological axon loss and neuronal cell death.

  4. Lack of Acid Sphingomyelinase Induces Age-Related Retinal Degeneration.

    Directory of Open Access Journals (Sweden)

    Bill X Wu

    Full Text Available Mutations of acid sphingomyelinase (ASMase cause Niemann-Pick diseases type A and B, which are fatal inherited lipid lysosomal storage diseases, characterized with visceral organ abnormalities and neurodegeneration. However, the effects of suppressing retinal ASMase expression are not understood. The goal of this study was to determine if the disruption of ASMase expression impacts the retinal structure and function in the mouse, and begin to investigate the mechanisms underlying these abnormalities.Acid sphingomyelinase knockout (ASMase KO mice were utilized to study the roles of this sphingolipid metabolizing enzyme in the retina. Electroretinogram and morphometric analysis were used to assess the retinal function and structure at various ages. Sphingolipid profile was determined by liquid chromatography-mass spectrometry. Western blots evaluated the level of the autophagy marker LC3-II.When compared to control animals, ASMase KO mice exhibited significant age-dependent reduction in ERG a- and b-wave amplitudes. Associated with these functional deficits, morphometric analysis revealed progressive thinning of retinal layers; however, the most prominent degeneration was observed in the photoreceptor and outer nuclear layer. Additional analyses of ASMase KO mice revealed early reduction in ERG c-wave amplitudes and increased lipofuscin accumulation in the retinal pigment epithelium (RPE. Sphingolipid analyses showed abnormal accumulation of sphingomyelin and sphingosine in ASMase KO retinas. Western blot analyses showed a higher level of the autophagosome marker LC3-II.These studies demonstrate that ASMase is necessary for the maintenance of normal retinal structure and function. The early outer retinal dysfunction, outer segment degeneration, accumulation of lipofuscin and autophagosome markers provide evidence that disruption of lysosomal function contributes to the age-dependent retinal degeneration exhibited by ASMase KO mice.

  5. Arap1 Deficiency Causes Photoreceptor Degeneration in Mice

    Science.gov (United States)

    Moshiri, Ala; Humpal, Devin; Leonard, Brian C.; Imai, Denise M.; Tham, Addy; Bower, Lynette; Clary, Dave; Glaser, Thomas M.; Lloyd, K. C. Kent; Murphy, Christopher J.

    2017-01-01

    Purpose Small guanosine triphosphatase (GTPase) ADP-ribosylation factors (Arfs) regulate membrane traffic and actin reorganization under the control of GTPase-activating proteins (GAPs). Arap1 is an Arf-directed GAP that inhibits the trafficking of epidermal growth factor receptor (EGFR) to the early endosome, but the diversity of its functions is incompletely understood. The aim of this study was to determine the role of Arap1 in the mammalian retina. Methods Genetically engineered Arap1 knockout mice were screened for ocular abnormalities in the National Institutes of Health Knockout Mouse Production and Phenotyping (KOMP2) Project. Arap1 knockout and wild-type eyes were imaged using optical coherence tomography and fundus photography, and analyzed by immunohistochemistry. Results Arap1−/− mice develop a normal appearing retina, but undergo photoreceptor degeneration starting at 4 weeks postnatal age. The fundus appearance of mutants is notable for pigmentary changes, optic nerve pallor, vascular attenuation, and outer retinal thinning, reminiscent of retinitis pigmentosa in humans. Immunohistochemical studies suggest the cell death is predominantly in the outer nuclear layer. Functional evaluation of the retina by electroretinography reveals amplitudes are reduced. Arap1 is detected most notably in Müller glia, and not in photoreceptors, implicating a role for Müller glia in photoreceptor survival. Conclusions Arap1 is necessary for normal photoreceptor survival in mice, and may be a novel gene relevant to human retinal degenerative processes, although its mechanism is unknown. Further studies in this mouse model of retinal degeneration will give insights into the cellular functions and signaling pathways in which Arap1 participates. PMID:28324111

  6. Modified gravitational instability of degenerate and non-degenerate dusty plasma

    Science.gov (United States)

    Jain, Shweta; Sharma, Prerana

    2016-09-01

    The gravitational instability of strongly coupled dusty plasma (SCDP) is studied considering degenerate and non-degenerate dusty plasma situations. The SCDP system is assumed to be composed of the electrons, ions, neutrals, and strongly coupled dust grains. First, in the high density regime, due to small interparticle distance, the electrons are considered degenerate, whereas the neutrals, dust grains, and ions are treated non-degenerate. In this case, the dynamics of inertialess electrons are managed by Fermi pressure and Bohm potential, while the inertialess ions are by only thermal pressure. Second, in the non-degenerate regime, both the electrons and ions are governed by the thermal pressure. The generalized hydrodynamic model and the normal mode analysis technique are employed to examine the low frequency waves and gravitational instability in both degenerate and non-degenerate cases. The general dispersion relation is discussed for a characteristic timescale which provides two regimes of frequency, i.e., hydrodynamic regime and kinetic regime. Analytical solutions reveal that the collisions reduce the growth rate and have a strong impact on structure formation in both degenerate and non-degenerate circumstances. Numerical estimation on the basis of observed parameters for the degenerate and non-degenerate cases is presented to show the effects of dust-neutral collisions and dust effective velocity in the presence of polarization force. The values of Jeans length and Jeans mass have been estimated for degenerate white dwarfs as Jeans length L J = 1.3 × 10 5 cm and Jeans mass M J = 0.75 × 10 - 3 M⊙ and for non-degenerate laboratory plasma Jeans length L J = 6.86 × 10 16 cm and Jeans mass M J = 0.68 × 10 10 M⊙. The stability of the SCDP system is discussed using the Routh-Hurwitz criterion.

  7. A Monte Carlo algorithm for degenerate plasmas

    Energy Technology Data Exchange (ETDEWEB)

    Turrell, A.E., E-mail: a.turrell09@imperial.ac.uk; Sherlock, M.; Rose, S.J.

    2013-09-15

    A procedure for performing Monte Carlo calculations of plasmas with an arbitrary level of degeneracy is outlined. It has possible applications in inertial confinement fusion and astrophysics. Degenerate particles are initialised according to the Fermi–Dirac distribution function, and scattering is via a Pauli blocked binary collision approximation. The algorithm is tested against degenerate electron–ion equilibration, and the degenerate resistivity transport coefficient from unmagnetised first order transport theory. The code is applied to the cold fuel shell and alpha particle equilibration problem of inertial confinement fusion.

  8. Horizon Supertranslation and Degenerate Black Hole Solution

    CERN Document Server

    Cai, Rong-Gen; Zhang, Yun-Long

    2016-01-01

    In this note we first review the degenerate vacua arising from the BMS symmetries. According to the discussion in [1] one can define BMS-analogous supertranslation and superrotation for spacetime with black hole in Gaussian null coordinates. In the leading and subleading orders of near horizon approximation, the infinitely degenerate black hole solutions are derived by considering Einstein equations with or without cosmological constant, and they are related to each other by the diffeomorphism generated by horizon supertranslation. Higher order results and degenerate Rindler horizon solutions also are given in appendices.

  9. Genetics of frontotemporal lobar degeneration

    Directory of Open Access Journals (Sweden)

    Aswathy P

    2010-10-01

    Full Text Available Frontotemporal lobar degeneration (FTLD is a highly heterogenous group of progressive neurodegenerative disorders characterized by atrophy of prefrontal and anterior temporal cortices. Recently, the research in the field of FTLD has gained increased attention due to the clinical, neuropathological, and genetic heterogeneity and has increased our understanding of the disease pathogenesis. FTLD is a genetically complex disorder. It has a strong genetic basis and 50% of patients show a positive family history for FTLD. Linkage studies have revealed seven chromosomal loci and a number of genes including MAPT, PGRN, VCP, and CHMB-2B are associated with the disease. Neuropathologically, FTLD is classified into tauopathies and ubiquitinopathies. The vast majority of FTLD cases are characterized by pathological accumulation of tau or TDP-43 positive inclusions, each as an outcome of mutations in MAPT or PGRN, respectively. Identification of novel proteins involved in the pathophysiology of the disease, such as progranulin and TDP-43, may prove to be excellent biomarkers of disease progression and thereby lead to the development of better therapeutic options through pharmacogenomics. However, much more dissections into the causative pathways are needed to get a full picture of the etiology. Over the past decade, advances in research on the genetics of FTLD have revealed many pathogenic mutations leading to different clinical manifestations of the disease. This review discusses the current concepts and recent advances in our understanding of the genetics of FTLD.

  10. Vitelliform macular degeneration associated with mitochondrial myopathy.

    OpenAIRE

    Modi, G; Heckman, J M; Saffer, D

    1992-01-01

    A patient with mitochondrial myopathy is described. Examination of his fundus revealed bilateral vitelliform degeneration of the maculae. This lesion is a focal abnormality of the retinal pigment epithelium and may be a manifestation of the underlying mitochondrial disease.

  11. Magnetic resonance imaging of intervertebral disc degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Maeda, Hiroshi; Noguchi, Masao (Kitakyushu City Yahata Hospital, Fukuoka (Japan)); Kira, Hideaki; Fujiki, Hiroshi; Shimokawa, Isao; Hinoue, Kaichi

    1993-02-01

    The aim of this study was to correlate the degree of lumbar intervertebral disc degeneration with findings of magnetic resonance imaging (MRI). Seventeen autopsied (from 7 patients) and 21 surgical (from 20 patients) intervertebral discs were used as specimens for histopathological examination. In addition, 21 intervertebral discs were examined on T2-weighted images. Histopathological findings from both autopsied and surgical specimens were well correlated with MRI findings. In particular, T2-weighted images reflected increased collagen fibers and rupture within the fibrous ring accurately. However, when severely degenerated intervertebral discs and hernia protruding the posterior longitudinal ligament existed, histological findings were not concordant well with T2-weighted images. Morphological appearances of autopsy specimens, divided into four on T2-weighted images, were well consistent with histological degeneration. This morphological classification, as shown on T2-weighted images, could also be used in the evaluation of intervertebral disc degeneration. (N.K.).

  12. Degenerate primer design for highly variable genomes.

    Science.gov (United States)

    Li, Kelvin; Shrivastava, Susmita; Stockwell, Timothy B

    2015-01-01

    The application of degenerate PCR primers towards target amplification and sequencing is a useful technique when a population of organisms under investigation is evolving rapidly, or is highly diverse. Degenerate bases in these primers are specified with ambiguity codes that represent alternative nucleotide configurations. Degenerate PCR primers allow the simultaneous amplification of a heterogeneous population by providing a mixture of PCR primers each of which anneal to an alternative genotype found in the isolated sample. However, as the number of degenerate bases specified in a pair of primers rises, the likelihood of amplifying unwanted alternative products also increases. These alternative products may confound downstream data analyses if their levels begin to obfuscate the desired PCR products. This chapter describes a set of computational methodologies that may be used to minimize the degeneracy of designed primers, while still maximizing the proportion of genotypes assayed in the targeted population.

  13. Degenerate second order mean field games systems

    OpenAIRE

    Tonon, Daniela; Cardaliaguet, Pierre; Graber, Philip,; Poretta, Alessio

    2014-01-01

    Parallel session; International audience; We consider degenerate second order mean field games systems with a local coupling. The starting point is the idea that mean field games systems can be understood as an optimality condition for optimal control of PDEs. Developing this strategy for the degenerate second order case, we discuss the existence and uniqueness of a weak solution as well as its stability (vanishing viscosity limit). Speaker: Daniela TONON

  14. The nature of apraxia in corticobasal degeneration.

    OpenAIRE

    Leiguarda, R; Lees, A J; Merello, M; STARKSTEIN, S; Marsden, C D

    1994-01-01

    Although apraxia is one of the most frequent signs in corticobasal degeneration, the phenomenology of this disorder has not been formally examined. Hence 10 patients with corticobasal degeneration were studied with a standardised evaluation for different types of apraxia. To minimise the confounding effects of the primary motor disorder, apraxia was assessed in the least affected limb. Whereas none of the patients showed buccofacial apraxia, seven showed deficits on tests of ideomotor apraxia...

  15. Retinal Cell Degeneration in Animal Models

    OpenAIRE

    Masayuki Niwa; Hitomi Aoki; Akihiro Hirata; Hiroyuki Tomita; Green, Paul G.; Akira Hara

    2016-01-01

    The aim of this review is to provide an overview of various retinal cell degeneration models in animal induced by chemicals (N-methyl-d-aspartate- and CoCl2-induced), autoimmune (experimental autoimmune encephalomyelitis), mechanical stress (optic nerve crush-induced, light-induced) and ischemia (transient retinal ischemia-induced). The target regions, pathology and proposed mechanism of each model are described in a comparative fashion. Animal models of retinal cell degeneration provide insi...

  16. Splitting deformations of degenerations of complex curves towards the classification of atoms of degenerations

    CERN Document Server

    2006-01-01

    The author develops a deformation theory for degenerations of complex curves; specifically, he treats deformations which induce splittings of the singular fiber of a degeneration. He constructs a deformation of the degeneration in such a way that a subdivisor is "barked" (peeled) off from the singular fiber. These "barking deformations" are related to deformations of surface singularities (in particular, cyclic quotient singularities) as well as the mapping class groups of Riemann surfaces (complex curves) via monodromies. Important applications, such as the classification of atomic degenerations, are also explained.

  17. 针对EMV Level1 Analog Test认证的金融支付PCD设计与调试%Design and Debugging of PCD for EMV Level 1 Analog Test

    Institute of Scientific and Technical Information of China (English)

    刘丽丽; 王丰; 余秋芳; 王西国

    2015-01-01

    文章针对最新版EMV Level 1标准,对PCD的EMV Level 1 Analog test认证的检测环境及检测项目进行总结,对实际测试中可能遇到的问题进行分析,总结出其技术难点。针对这些难点提出PCD设计中需要重点关注的方面以及设计技巧,进一步给出调试中使用怎样的方法达到系统的最优配置,成功通过EMV Level1 Analog test的检测。%According to the newest EMV Level 1 protocol, EMV Level 1 Analog test environment and PCD test cases are analyzed. The problems that may be encounted in real testing are analyzeed and the technological difficulties are concluded. The aspects that need to be concerned and the design skills are proposed for the PCD design, aand the method to be adopted in the debugging is given to achieve optimum system configuration,.Then passing the PCD’s EMV Level1 Analog test is expected.

  18. Mouse phenotyping.

    Science.gov (United States)

    Fuchs, Helmut; Gailus-Durner, Valérie; Adler, Thure; Aguilar-Pimentel, Juan Antonio; Becker, Lore; Calzada-Wack, Julia; Da Silva-Buttkus, Patricia; Neff, Frauke; Götz, Alexander; Hans, Wolfgang; Hölter, Sabine M; Horsch, Marion; Kastenmüller, Gabi; Kemter, Elisabeth; Lengger, Christoph; Maier, Holger; Matloka, Mikolaj; Möller, Gabriele; Naton, Beatrix; Prehn, Cornelia; Puk, Oliver; Rácz, Ildikó; Rathkolb, Birgit; Römisch-Margl, Werner; Rozman, Jan; Wang-Sattler, Rui; Schrewe, Anja; Stöger, Claudia; Tost, Monica; Adamski, Jerzy; Aigner, Bernhard; Beckers, Johannes; Behrendt, Heidrun; Busch, Dirk H; Esposito, Irene; Graw, Jochen; Illig, Thomas; Ivandic, Boris; Klingenspor, Martin; Klopstock, Thomas; Kremmer, Elisabeth; Mempel, Martin; Neschen, Susanne; Ollert, Markus; Schulz, Holger; Suhre, Karsten; Wolf, Eckhard; Wurst, Wolfgang; Zimmer, Andreas; Hrabě de Angelis, Martin

    2011-02-01

    Model organisms like the mouse are important tools to learn more about gene function in man. Within the last 20 years many mutant mouse lines have been generated by different methods such as ENU mutagenesis, constitutive and conditional knock-out approaches, knock-down, introduction of human genes, and knock-in techniques, thus creating models which mimic human conditions. Due to pleiotropic effects, one gene may have different functions in different organ systems or time points during development. Therefore mutant mouse lines have to be phenotyped comprehensively in a highly standardized manner to enable the detection of phenotypes which might otherwise remain hidden. The German Mouse Clinic (GMC) has been established at the Helmholtz Zentrum München as a phenotyping platform with open access to the scientific community (www.mousclinic.de; [1]). The GMC is a member of the EUMODIC consortium which created the European standard workflow EMPReSSslim for the systemic phenotyping of mouse models (http://www.eumodic.org/[2]). Copyright © 2010 Elsevier Inc. All rights reserved.

  19. Prospectives for gene therapy of retinal degenerations.

    Science.gov (United States)

    Thumann, Gabriele

    2012-08-01

    Retinal degenerations encompass a large number of diseases in which the retina and associated retinal pigment epithelial (RPE) cells progressively degenerate leading to severe visual disorders or blindness. Retinal degenerations can be divided into two groups, a group in which the defect has been linked to a specific gene and a second group that has a complex etiology that includes environmental and genetic influences. The first group encompasses a number of relatively rare diseases with the most prevalent being Retinitis pigmentosa that affects approximately 1 million individuals worldwide. Attempts have been made to correct the defective gene by transfecting the appropriate cells with the wild-type gene and while these attempts have been successful in animal models, human gene therapy for these inherited retinal degenerations has only begun recently and the results are promising. To the second group belong glaucoma, age-related macular degeneration (AMD) and diabetic retinopathy (DR). These retinal degenerations have a genetic component since they occur more often in families with affected probands but they are also linked to environmental factors, specifically elevated intraocular pressure, age and high blood sugar levels respectively. The economic and medical impact of these three diseases can be assessed by the number of individuals affected; AMD affects over 30 million, DR over 40 million and glaucoma over 65 million individuals worldwide. The basic defect in these diseases appears to be the relative lack of a neurogenic environment; the neovascularization that often accompanies these diseases has suggested that a decrease in pigment epithelium-derived factor (PEDF), at least in part, may be responsible for the neurodegeneration since PEDF is not only an effective neurogenic and neuroprotective agent but also a potent inhibitor of neovascularization. In the last few years inhibitors of vascularization, especially antibodies against vascular endothelial cell

  20. PGC-1α regulation of mitochondrial degeneration in experimental diabetic neuropathy.

    Science.gov (United States)

    Choi, Joungil; Chandrasekaran, Krish; Inoue, Tatsuya; Muragundla, Anjaneyulu; Russell, James W

    2014-04-01

    Mitochondrial degeneration is considered to play an important role in the development of diabetic peripheral neuropathy in humans. Mitochondrial degeneration and the corresponding protein regulation associated with the degeneration were studied in an animal model of diabetic neuropathy. PGC-1α and its-regulated transcription factors including TFAM and NRF1, which are master regulators of mitochondrial biogenesis, are significantly downregulated in streptozotocin diabetic dorsal root ganglion (DRG) neurons. Diabetic mice develop peripheral neuropathy, loss of mitochondria, decreased mitochondrial DNA content and increased protein oxidation. Importantly, this phenotype is exacerbated in PGC-1α (-/-) diabetic mice, which develop a more severe neuropathy with reduced mitochondrial DNA and a further increase in protein oxidation. PGC-1α (-/-) diabetic mice develop an increase in total cholesterol and triglycerides, and a decrease in TFAM and NRF1 protein levels. Loss of PGC-1α causes severe mitochondrial degeneration with vacuolization in DRG neurons, coupled with reduced state 3 and 4 respiration, reduced expression of oxidative stress response genes and an increase in protein oxidation. In contrast, overexpression of PGC-1α in cultured adult mouse neurons prevents oxidative stress associated with increased glucose levels. The study provides new insights into the role of PGC-1α in mitochondrial regeneration in peripheral neurons and suggests that therapeutic modulation of PGC-1α function may be an attractive approach for treatment of diabetic neuropathy.

  1. Optic pathway degeneration in Japanese black cattle.

    Science.gov (United States)

    Chiba, Shiori; Funato, Shingo; Horiuchi, Noriyuki; Matsumoto, Kotaro; Inokuma, Hisashi; Furuoka, Hidefumi; Kobayashi, Yoshiyasu

    2015-02-01

    Degeneration of the optic pathway has been reported in various animal species including cattle. We experienced a case of bilateral optic tract degeneration characterized by severe gliosis in a Japanese black cattle without any obvious visual defects. To evaluate the significance, pathological nature and pathogenesis of the lesions, we examined the optic pathway in 60 cattle (41 Japanese black, 13 Holstein and 6 crossbreed) with or without ocular abnormalities. None of these animals had optic canal stenosis. Degenerative changes with severe gliosis in the optic pathway, which includes the optic nerve, optic chiasm and optic tract, were only observed in 8 Japanese black cattle with or without ocular abnormalities. Furthermore, strong immunoreactivity of glial fibrillary acidic protein was observed in the retinal stratum opticum and ganglion cell layer in all 5 cattle in which the optic pathway lesions could be examined. As etiological research, we also examined whether the concentrations of vitamin A and vitamin B12 or bovine viral diarrhea virus (BVDV) infection was associated with optic pathway degeneration. However, our results suggested that the observed optic pathway degeneration was probably not caused by these factors. These facts indicate the presence of optic pathway degeneration characterized by severe gliosis that has never been reported in cattle without bilateral compressive lesions in the optic pathway or bilateral severe retinal atrophy.

  2. Ultrastructure of Campylobacter jejuni in gamma-irradiated mouse jejunum

    Energy Technology Data Exchange (ETDEWEB)

    Sosula, L.; Nicholls, E.M.; Skeen, M.

    1988-04-01

    This paper describes the ultrastructure of intracellular elongated, transitional and coccoid forms of Campylobacter jejuni, in irradiated mouse jejunum infected both in vitro and in vivo and in cultured human skin fibroblasts. Jejunum of irradiated mouse incubated for 1 hour under conditions favorable to the organisms showed minimal tissue degeneration. The intracellular organisms in this material were free cytoplasmic forms showing inner membrane degeneration, loss of cytoplasmic granules, and absence of flagella. The diameter of the coccoids was up to four times that of the elongated forms, as in plate cultures. Intracellular organisms were not found in challenged unirradiated controls, indicating that irradiation of mouse cells may be required for intracellular infection with human strains of C jejuni. In contrast, challenged human fibroblasts contained typical elongated organisms in cytoplasmic vacuoles. These findings are discussed with reference to Campylobacter strain, host resistance, and natural animal and human Campylobacter infections.

  3. Phase space methods for degenerate quantum gases

    CERN Document Server

    Dalton, Bryan J; Barnett, Stephen M

    2015-01-01

    Recent experimental progress has enabled cold atomic gases to be studied at nano-kelvin temperatures, creating new states of matter where quantum degeneracy occurs - Bose-Einstein condensates and degenerate Fermi gases. Such quantum states are of macroscopic dimensions. This book presents the phase space theory approach for treating the physics of degenerate quantum gases, an approach already widely used in quantum optics. However, degenerate quantum gases involve massive bosonic and fermionic atoms, not massless photons. The book begins with a review of Fock states for systems of identical atoms, where large numbers of atoms occupy the various single particle states or modes. First, separate modes are considered, and here the quantum density operator is represented by a phase space distribution function of phase space variables which replace mode annihilation, creation operators, the dynamical equation for the density operator determines a Fokker-Planck equation for the distribution function, and measurable...

  4. The cell stress machinery and retinal degeneration.

    Science.gov (United States)

    Athanasiou, Dimitra; Aguilà, Monica; Bevilacqua, Dalila; Novoselov, Sergey S; Parfitt, David A; Cheetham, Michael E

    2013-06-27

    Retinal degenerations are a group of clinically and genetically heterogeneous disorders characterised by progressive loss of vision due to neurodegeneration. The retina is a highly specialised tissue with a unique architecture and maintaining homeostasis in all the different retinal cell types is crucial for healthy vision. The retina can be exposed to a variety of environmental insults and stress, including light-induced damage, oxidative stress and inherited mutations that can lead to protein misfolding. Within retinal cells there are different mechanisms to cope with disturbances in proteostasis, such as the heat shock response, the unfolded protein response and autophagy. In this review, we discuss the multiple responses of the retina to different types of stress involved in retinal degenerations, such as retinitis pigmentosa, age-related macular degeneration and glaucoma. Understanding the mechanisms that maintain and re-establish proteostasis in the retina is important for developing new therapeutic approaches to fight blindness.

  5. Families and degenerations of conformal field theories

    Energy Technology Data Exchange (ETDEWEB)

    Roggenkamp, D.

    2004-09-01

    In this work, moduli spaces of conformal field theories are investigated. In the first part, moduli spaces corresponding to current-current deformation of conformal field theories are constructed explicitly. For WZW models, they are described in detail, and sigma model realizations of the deformed WZW models are presented. The second part is devoted to the study of boundaries of moduli spaces of conformal field theories. For this purpose a notion of convergence of families of conformal field theories is introduced, which admits certain degenerated conformal field theories to occur as limits. To such a degeneration of conformal field theories, a degeneration of metric spaces together with additional geometric structures can be associated, which give rise to a geometric interpretation. Boundaries of moduli spaces of toroidal conformal field theories, orbifolds thereof and WZW models are analyzed. Furthermore, also the limit of the discrete family of Virasoro minimal models is investigated. (orig.)

  6. 临床药师对乳腺癌合并副肿瘤性小脑变性患者的药学监护%Pharmaceutical Care for Patients with Breast Cancer Combined with Paraneoplastic Cerebellar Degeneration

    Institute of Scientific and Technical Information of China (English)

    魏筱; 全香花; 苏风云; 张婷

    2016-01-01

    OBJECTIVE:To probe into the pharmaceutical care for patients with breast cancer combined with paraneoplastic cerebellar degeneration( PCD) in drug treatment by the clinical pharmacists.METHODS: The clinical pharmacists participated into the whole process of drug treatment of patients with breast cancer combined with PCD and provided pharmaceutical care.RESULTS:The clinical pharmacists discussed the entry point of pharmaceutical care for patients with breast cancer combined with PCD, analyzed the drug treatment difference of patients with two chemotherapy under the intervention and provided rational individualized treatment recommendations for the clinicians. CONCLUSIONS:The characteristics of pharmaceutical care for patients with PCD are different from general tumor patients, therefore, the immune-enhancing drugs should be prohibited.Besides, the clinical pharmacists should provide education of drug-use and follow up visit for patients.The clinical pharmacists bring their specialty into full play and reflect their own value.%目的:探讨临床药师参与乳腺癌合并副肿瘤性小脑变性( paraneoplastic cerebellar degeneration,PCD)患者药物治疗、提供药学服务的实践。方法:临床药师参与1例乳腺癌合并PCD患者药物治疗的全过程,给予药学监护。结果:临床药师初步探讨了PCD患者药学监护的切入点,分析了在其干预下患者2次入院化疗期间用药情况的不同,为临床医师提供了合理的个体化治疗建议。结论:PCD患者的监护特点与普通肿瘤患者不同,应避免使用免疫增强药;此外,结合PCD患者出院带药多的特点,临床药师应做好用药教育及随访工作。通过对该患者的药学实践,临床药师发挥了专业特长,体现了自身价值。

  7. [New aspects in age related macular degeneration].

    Science.gov (United States)

    Turlea, C

    2012-01-01

    Being the leading cause of blindness in modern world Age Related Macular Degeneration has beneficiated in the last decade of important progress in diagnosis, classification and the discovery of diverse factors who contribute to the etiology of this disease. Treatments have arised who can postpone the irreversible evolution of the disease and thus preserve vision. Recent findings have identified predisposing genetic factors and also inflamatory and imunological parameters that can be modified trough a good and adequate prevention and therapy This articole reviews new aspects of patology of Age Related Macular Degeneration like the role of complement in maintaining inflamation and the role of oxidative stress on different structures of the retina.

  8. Intracavity frequency-doubled degenerate laser

    CERN Document Server

    Liew, Seng Fatt; Weiler, Sascha; Monjardin-Lopez, Jesus Fernando; Ramme, Mark; Redding, Brandon; Choma, Michael A; Cao, Hui

    2016-01-01

    We develop a green light source with low spatial coherence via intracavity frequency doubling of a solid-state degenerate laser. The second harmonic emission supports many more transverse modes than the fundamental emission, and exhibit lower spatial coherence. A strong suppression of speckle formation is demonstrated for both fundamental and second harmonic beams. Using the green emission for fluorescence excitation, we show the coherent artifacts are removed from the full-field fluorescence images. The high power, low spatial coherence and good directionality makes the green degenerate laser an attractive illumination source for parallel imaging and projection display.

  9. Angels and Degenerates: Artistic Virtuosity and Degeneration Theory in Fin de Siècle Fiction

    OpenAIRE

    2015-01-01

    The aim in "Angels and Degenerates: Artistic Virtuosity and Degeneration Theory in Fin de Siècle Fiction" is to complicate the popular image of the fin de siècle as uniformly pessimistic by examining the continuities between a range of novelists, as well as other late nineteenth century writers from such disparate fields as psychology and cultural criticism, as they critique degeneration theory. Some of these writers, like Thomas Hardy, H.G. Wells, and Sarah Grand, are typically read as promo...

  10. Motor axon excitability during Wallerian degeneration

    DEFF Research Database (Denmark)

    Moldovan, Mihai; Alvarez, Susana; Krarup, Christian

    2008-01-01

    , action potential propagation and structural integrity of the distal segment are maintained. The aim of this study was to investigate in vivo the changes in membrane function of motor axons during the 'latent' phase of Wallerian degeneration. Multiple indices of axonal excitability of the tibial nerve...

  11. MR findings of degenerating parenchymal neurocysticercosis

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Yul; Chung, Eun A; Yang, Ik; Park, Hae Jung; Chung, Soo Young [Hallym Univ. Kangnam Sungshim Hospital, Seoul (Korea, Republic of)

    1996-06-01

    To evaluate MR imaging findings of degenerating parenchymal neurocysticercosis and to determine the characteristics which distinguish it from other brain diseases. MR imagings of 19 patients (56 lesions) of degenerating parenchymal neurocysticercosis were retrospectively evaluated, focusing on the size and location of lesions signal intensity patterns of cyst fluid and wall, the extent of the surrounding edema and features of contrast enhancement. Degenerating parenchymal neurocysticercosis was located in gray or subcortical while matter in 89.3% of 56 lesions (50/56) ; most of these (98.2%) were smaller than 2 cm in diameter. Cyst fluid signal was hyperintense relative to CSF on T1 and proton density weighted images (92.9%). A hypointense signal rim of the cyst wall was noted in the lesions on proton density (92.9%) and T2 weighted (98.2%) images, Surrounding edema was mostly mild. Peripheral rim enhancement was noted in all lesions, and this was frequently irregular and lobulated (67.9%) with a focal defect in the enhancing rim(41.1%). Findings which could be helpful in distinguishing degenerating parencymal neurocysticercosis from other brain diseases are as follows : small, superficial lesions ; hyperintense signal of the cyst fluid on T1 and proton density weighted images ; hypointense signal of the cyst wall on proton density and T2 weighted images ; relatively mild extent of surrounding edema, and peripheral rim enhancement which is frequently irregular and lobulated with a focal defect in the enhancing rim.

  12. Single Degenerate Progenitors of Type Ia Supernovae

    Science.gov (United States)

    Bours, Madelon; Toonen, Silvia; Nelemans, Gijs

    2013-01-01

    There is a general agreement that Type Ia supernovae correspond to the thermonuclear runaway of a white dwarf (WD) in a compact binary. The details of these progenitor systems are still unclear. Using the population synthesis code SeBa and several assumption for the WD retention efficiency, we estimate the delay times and supernova rates for the single degenerate scenario.

  13. Driving and Age-Related Macular Degeneration

    Science.gov (United States)

    Owsley, Cynthia; McGwin, Gerald, Jr.

    2008-01-01

    This article reviews the research literature on driving and age-related macular degeneration, which is motivated by the link between driving and the quality of life of older adults and their increased collision rate. It addresses the risk of crashes, driving performance, driving difficulty, self-regulation, and interventions to enhance, safety,…

  14. The nature of apraxia in corticobasal degeneration.

    Science.gov (United States)

    Leiguarda, R; Lees, A J; Merello, M; Starkstein, S; Marsden, C D

    1994-01-01

    Although apraxia is one of the most frequent signs in corticobasal degeneration, the phenomenology of this disorder has not been formally examined. Hence 10 patients with corticobasal degeneration were studied with a standardised evaluation for different types of apraxia. To minimise the confounding effects of the primary motor disorder, apraxia was assessed in the least affected limb. Whereas none of the patients showed buccofacial apraxia, seven showed deficits on tests of ideomotor apraxia and movement imitation, four on tests of sequential arm movements (all of whom had ideomotor apraxia), and three on tests of ideational apraxia (all of whom had ideomotor apraxia). Ideomotor apraxia significantly correlated with deficit in both the mini mental state examination and in a task sensitive to frontal lobe dysfunction (picture arrangement). Two of the three patients with ideomotor apraxia and ideational apraxia showed severe cognitive impairments. The alien limb behaviour was present only in patients with ideomotor apraxia. In conclusion, ideomotor apraxia is the most frequent type of apraxia in corticobasal degeneration, and may be due to dysfunction of the supplementary motor area. There is a subgroup of patients with corticobasal degeneration who have a severe apraxia (ideomotor and ideational apraxia), which correlates with global cognitive impairment, and may result from additional parietal or diffuse cortical damage. PMID:8163995

  15. Specific heats of degenerate ideal gases

    OpenAIRE

    Caruso, Francisco; Oguri, Vitor; Silveira, Felipe

    2017-01-01

    From arguments based on Heisenberg's uncertainty principle and Pauli's exclusion principle, the molar specific heats of degenerate ideal gases at low temperatures are estimated, giving rise to values consistent with the Nerst-Planck Principle (third law of Thermodynamics). The Bose-Einstein condensation phenomenon based on the behavior of specific heat of massive and non-relativistic boson gases is also presented.

  16. Transversal heteroclinic orbits in general degenerate cases

    Institute of Scientific and Technical Information of China (English)

    朱德明

    1996-01-01

    A geometrical method using the exponential dichotomy and the invariant manifold thoery is given to set up the criteria for the existence of transversal and tangential heterodinic orbits under the most general degenerate cases. Conclusions given here extend and contain the relevant known results.

  17. Depression in Age-Related Macular Degeneration

    Science.gov (United States)

    Casten, Robin; Rovner, Barry

    2008-01-01

    Age-related macular degeneration (AMD) is a major cause of disability in the elderly, substantially degrades the quality of their lives, and is a risk factor for depression. Rates of depression in AMD are substantially greater than those found in the general population of older people, and are on par with those of other chronic and disabling…

  18. DNA sequencing by synthesis with degenerate primers

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The degenerate primer-based sequencing Was developed by a synthesis method(DP-SBS)for high-throughput DNA sequencing,in which a set of degenerate primers are hybridized on the arrayed DNA templates and extended by DNA polymerase on microarrays.In this method,adifferent set of degenerate primers containing a give nnumber(n)of degenerate nucleotides at the 3'-ends were annealed to the sequenced templates that were immobilized on the solid surface.The nucleotides(n+1)on the template sequences were determined by detecting the incorporation of fluorescent labeled nucleotides.The fluorescent labeled nucleotide was incorporated into the primer in a base-specific manner after the enzymatic primer extension reactions and nine-base length were read out accurately.The main advanmge of the DP-SBS is that the method only uses very conventional biochemical reagents and avoids the complicated special chemical reagents for removing the labeled nucleotides and reactivating the primer for further extension.From the present study,it is found that the DP-SBS method is reliable,simple,and cost-effective for laboratory-sequencing a large amount of short DNA fragments.

  19. Nonunital Spectral Triples Associated to Degenerate Metrics

    Science.gov (United States)

    Rennie, A.

    We show that one can define (p,∞)-summable spectral triples using degenerate metrics on smooth manifolds. Furthermore, these triples satisfy Connes-Moscovici's discrete and finite dimension spectrum hypothesis, allowing one to use the Local Index Theorem [1] to compute the pairing with K-theory. We demonstrate this with a concrete example.

  20. Retinal Degeneration Triggers the Activation of YAP/TEAD in Reactive Müller Cells.

    Science.gov (United States)

    Hamon, Annaïg; Masson, Christel; Bitard, Juliette; Gieser, Linn; Roger, Jérôme E; Perron, Muriel

    2017-04-01

    During retinal degeneration, Müller glia cells respond to photoreceptor loss by undergoing reactive gliosis, with both detrimental and beneficial effects. Increasing our knowledge of the complex molecular response of Müller cells to retinal degeneration is thus essential for the development of new therapeutic strategies. The purpose of this work was to identify new factors involved in Müller cell response to photoreceptor cell death. Whole transcriptome sequencing was performed from wild-type and degenerating rd10 mouse retinas at P30. The changes in mRNA abundance for several differentially expressed genes were assessed by quantitative RT-PCR (RT-qPCR). Protein expression level and retinal cellular localization were determined by western blot and immunohistochemistry, respectively. Pathway-level analysis from whole transcriptomic data revealed the Hippo/YAP pathway as one of the main signaling pathways altered in response to photoreceptor degeneration in rd10 retinas. We found that downstream effectors of this pathway, YAP and TEAD1, are specifically expressed in Müller cells and that their expression, at both the mRNA and protein levels, is increased in rd10 reactive Müller glia after the onset of photoreceptor degeneration. The expression of Ctgf and Cyr61, two target genes of the transcriptional YAP/TEAD complex, is also upregulated following photoreceptor loss. This work reveals for the first time that YAP and TEAD1, key downstream effectors of the Hippo pathway, are specifically expressed in Müller cells. We also uncovered a deregulation of the expression and activity of Hippo/YAP pathway components in reactive Müller cells under pathologic conditions.

  1. On Doubly Degenerate Quasilinear Parabolic Equations of Higher Order

    Institute of Scientific and Technical Information of China (English)

    Zhen Hai LIU

    2005-01-01

    We deal with the existence of periodic solutions for doubly degenerate quasilinear parabolic equations of higher order, which can degenerate, on a part of the boundary, on a segment in the interior of the domain and in time.

  2. Quasiconformal mappings and degenerate elliptic and parabolic equations

    Directory of Open Access Journals (Sweden)

    Filippo Chiarenza

    1987-11-01

    Full Text Available In this paper two Harnak inequalities are proved concerning a degenerate elliptic and a degenerate parabolic equation. In both cases the weight giving the degeneracy is a power of the jacobian of a quasiconformal mapping.

  3. Degenerate solutions obtained from several variants of factor analysis

    NARCIS (Netherlands)

    Zijlstra, Bonne J.H.; Kiers, Henk A.L.

    2002-01-01

    Considerable research has been performed concerning degenerate solutions from the Parafac model. However, degenerate solutions have also been reported to occur with the shifted multiplicative model and a model for component analysis of multitrait multimethod matrices. Furthermore, we obtained

  4. NMNAT1 inhibits axon degeneration via blockade of SARM1-mediated NAD+ depletion

    Science.gov (United States)

    Sasaki, Yo; Nakagawa, Takashi; Mao, Xianrong; DiAntonio, Aaron; Milbrandt, Jeffrey

    2016-01-01

    Overexpression of the NAD+ biosynthetic enzyme NMNAT1 leads to preservation of injured axons. While increased NAD+ or decreased NMN levels are thought to be critical to this process, the mechanism(s) of this axon protection remain obscure. Using steady-state and flux analysis of NAD+ metabolites in healthy and injured mouse dorsal root ganglion axons, we find that rather than altering NAD+ synthesis, NMNAT1 instead blocks the injury-induced, SARM1-dependent NAD+ consumption that is central to axon degeneration. DOI: http://dx.doi.org/10.7554/eLife.19749.001 PMID:27735788

  5. Synaptopathy in the noise-exposed and aging cochlea: Primary neural degeneration in acquired sensorineural hearing loss.

    Science.gov (United States)

    Kujawa, Sharon G; Liberman, M Charles

    2015-12-01

    The classic view of sensorineural hearing loss (SNHL) is that the "primary" targets are hair cells, and that cochlear-nerve loss is "secondary" to hair cell degeneration. Our recent work in mouse and guinea pig has challenged that view. In noise-induced hearing loss, exposures causing only reversible threshold shifts (and no hair cell loss) nevertheless cause permanent loss of >50% of cochlear-nerve/hair-cell synapses. Similarly, in age-related hearing loss, degeneration of cochlear synapses precedes both hair cell loss and threshold elevation. This primary neural degeneration has remained hidden for three reasons: 1) the spiral ganglion cells, the cochlear neural elements commonly assessed in studies of SNHL, survive for years despite loss of synaptic connection with hair cells, 2) the synaptic terminals of cochlear nerve fibers are unmyelinated and difficult to see in the light microscope, and 3) the degeneration is selective for cochlear-nerve fibers with high thresholds. Although not required for threshold detection in quiet (e.g. threshold audiometry or auditory brainstem response threshold), these high-threshold fibers are critical for hearing in noisy environments. Our research suggests that 1) primary neural degeneration is an important contributor to the perceptual handicap in SNHL, and 2) in cases where the hair cells survive, neurotrophin therapies can elicit neurite outgrowth from spiral ganglion neurons and re-establishment of their peripheral synapses. This article is part of a Special Issue entitled .

  6. Prox 1 in eye degeneration and sensory organ compensation during development and evolution of the cavefish Astyanax.

    Science.gov (United States)

    Jeffery, W; Strickler, A; Guiney, S; Heyser, D; Tomarev, S

    2000-05-01

    We have investigated expression of the homeobox gene Prox 1 during eye degeneration and sensory organ compensation in cavefish embryos. The teleost Astyanax mexicanus consists of sighted surface-dwelling forms (surface fish) and several populations of blind cave-dwelling forms (cavefish), which have evolved independently. Eye formation is initiated during cavefish development, but the lens vesicle undergoes apoptosis, and the eye subsequently arrests and degenerates. The requirement of Prox 1 for lens fiber differentiation and gamma-crystallin expression in the mouse suggests that changes in the expression of this gene could be involved in cavefish eye degeneration. Surface fish and cavefish embryos stained with a Prox 1 antibody showed Prox 1 expression in the lens, neuroretina, myotomes, heart, hindbrain, and gut, as reported in other vertebrates. We found that Prox 1 expression is not altered during cavefish lens development. Prox 1 protein was detected in the lens vesicle as soon as it formed and persisted until the time of lens degeneration in each cavefish population. The cavefish lens vesicle was also shown to express a gamma-crystallin gene, suggesting that Prox 1 is functional in cavefish lens development. In addition to the tissues described above, Prox 1 is expressed in developing taste buds and neuromasts in cavefish, which are enhanced to compensate for blindness. It is concluded that the Prox 1 gene is not involved in lens degeneration, but that expansion of the Prox 1 expression domain occurs during taste bud and neuromast development in cavefish.

  7. Yersinia pestis subverts the dermal neutrophil response in a mouse model of bubonic plague.

    Science.gov (United States)

    Shannon, Jeffrey G; Hasenkrug, Aaron M; Dorward, David W; Nair, Vinod; Carmody, Aaron B; Hinnebusch, B Joseph

    2013-08-27

    The majority of human Yersinia pestis infections result from introduction of bacteria into the skin by the bite of an infected flea. Once in the dermis, Y. pestis can evade the host's innate immune response and subsequently disseminate to the draining lymph node (dLN). There, the pathogen replicates to large numbers, causing the pathognomonic bubo of bubonic plague. In this study, several cytometric and microscopic techniques were used to characterize the early host response to intradermal (i.d.) Y. pestis infection. Mice were infected i.d. with fully virulent or attenuated strains of dsRed-expressing Y. pestis, and tissues were analyzed by flow cytometry. By 4 h postinfection, there were large numbers of neutrophils in the infected dermis and the majority of cell-associated bacteria were associated with neutrophils. We observed a significant effect of the virulence plasmid (pCD1) on bacterial survival and neutrophil activation in the dermis. Intravital microscopy of i.d. Y. pestis infection revealed dynamic interactions between recruited neutrophils and bacteria. In contrast, very few bacteria interacted with dendritic cells (DCs), indicating that this cell type may not play a major role early in Y. pestis infection. Experiments using neutrophil depletion and a CCR7 knockout mouse suggest that dissemination of Y. pestis from the dermis to the dLN is not dependent on neutrophils or DCs. Taken together, the results of this study show a very rapid, robust neutrophil response to Y. pestis in the dermis and that the virulence plasmid pCD1 is important for the evasion of this response. Yersinia pestis remains a public health concern today because of sporadic plague outbreaks that occur throughout the world and the potential for its illegitimate use as a bioterrorism weapon. Since bubonic plague pathogenesis is initiated by the introduction of Y. pestis into the skin, we sought to characterize the response of the host's innate immune cells to bacteria early after

  8. Ultracompact quantum splitter of degenerate photon pairs

    CERN Document Server

    He, Jiakun; Casas-Bedoya, Alvaro; Zhang, Yanbing; Xiong, Chunle; Eggleton, Benjamin J

    2015-01-01

    Integrated sources of indistinguishable photons have attracted a lot of attention because of their applications in quantum communication and optical quantum computing. Here, we demonstrate an ultra-compact quantum splitter for degenerate single photons based on a monolithic chip incorporating Sagnac loop and a micro-ring resonator with a footprint of 0.011 mm2, generating and deterministically splitting indistinguishable photon pairs using time-reversed Hong-Ou-Mandel interference. The ring resonator provides enhanced photon generation rate, and the Sagnac loop ensures the photons travel through equal path lengths and interfere with the correct phase to enable the reversed HOM effect to take place. In the experiment, we observed a HOM dip visibility of 94.5 +- 3.3 %, indicating the photons generated by the degenerate single photon source are in a suitable state for further integration with other components for quantum applications, such as controlled-NOT gates.

  9. Acquired hepatocerebral degeneration: A case report

    Institute of Scientific and Technical Information of China (English)

    Wei-Xing Chen; Ping Wang; Sen-Xiang Yan; You-Ming Li; Chao-Hui Yu; Ling-Ling Jiang

    2005-01-01

    AIM: Acquired hepatocerebral degeneration (AHD) is an exceptional type of hepatic encephalopathies (HE). It is characterized by neuropsychiatric and extrapyramidal symptomathology similar to that seen in hepatolenticular degeneration (Wilson's disease). In this paper, we report a case of AHD with unusual presenting features.METHODS: A 28-year-old man with AHD was described and the literature was reviewed.RESULTS: The man had a history of HBV-related liver cirrhosis. He was admitted to our hospital with apathy,dysarthria, mild consciousness impairment and extrapyramidal symptoms after hematemesis. By review of the literature,cases with AHD often did not present consciousness impairment. So our case was once diagnosed incorrectly as Wilson's disease.CONCLUSION: AHD is a rare syndrome and its variable clinical manifestations make it difficult to be diagnosed.But we believe that extensive examination and thorough understanding of the disease are beneficial to a correct diagnosis. Moreover, biocoene is effective in treating the case.

  10. Small automorphic representations and degenerate Whittaker vectors

    CERN Document Server

    Gustafsson, Henrik P A; Persson, Daniel

    2014-01-01

    We investigate Fourier coefficients of automorphic forms on split simply-laced Lie groups G. We show that for automorphic representations of small Gelfand-Kirillov dimension the Fourier coefficients are completely determined by certain degenerate Whittaker vectors on G. Although we expect our results to hold for arbitrary simply-laced groups, we give complete proofs only for G=SL(3) and G=SL(4). This is based on a method of Ginzburg that associates Fourier coefficients of automorphic forms with nilpotent orbits of G. Our results complement and extend recent results of Miller and Sahi. We also use our formalism to calculate various local (real and p-adic) spherical vectors of minimal representations of the exceptional groups E_6, E_7, E_8 using global (adelic) degenerate Whittaker vectors, correctly reproducing existing results for such spherical vectors obtained by very different methods.

  11. Dichromatic Langmuir waves in degenerate quantum plasma

    Science.gov (United States)

    Dubinov, A. E.; Kitayev, I. N.

    2015-06-01

    Langmuir waves in fully degenerate quantum plasma are considered. It is shown that, in the linear approximation, Langmuir waves are always dichromatic. The low-frequency component of the waves corresponds to classical Langmuir waves, while the high-frequency component, to free-electron quantum oscillations. The nonlinear problem on the profile of dichromatic Langmuir waves is solved. Solutions in the form of a superposition of waves and in the form of beatings of its components are obtained.

  12. Immunology of age related macular degeneration

    Institute of Scientific and Technical Information of China (English)

    Kijlstra Aize; Yang Peizeng

    2011-01-01

    @@ Age-related macular degeneration(AMD)is the most important cause of blindness in persons over 55 years of age in the Western world.In view of the increasing life expectancy we can assume that the problem will increase dramatically over the coming decades unless preventive or therapeutic measures are developed.Towards this goal many groups all over the world have performed epidemiological studies to identify potential risk factors for AMD.

  13. Degenerate spacetimes in first order gravity

    CERN Document Server

    Kaul, Romesh K

    2016-01-01

    We present a systematic framework to obtain the most general solutions of the equations of motion in first order gravity theory with degenerate tetrads. There are many possible solutions. Generically, these exhibit non-vanishing torsion even in the absence of any matter coupling. These solutions are shown to contain a special set of eight configurations which are associated with the homogeneous model three-geometries of Thurston.

  14. Degenerate RFID Channel Modeling for Positioning Applications

    Directory of Open Access Journals (Sweden)

    A. Povalac

    2012-12-01

    Full Text Available This paper introduces the theory of channel modeling for positioning applications in UHF RFID. It explains basic parameters for channel characterization from both the narrowband and wideband point of view. More details are given about ranging and direction finding. Finally, several positioning scenarios are analyzed with developed channel models. All the described models use a degenerate channel, i.e. combined signal propagation from the transmitter to the tag and from the tag to the receiver.

  15. Biomechanical study of intervertebral disc degeneration

    OpenAIRE

    González Guitiérrez, Ramiro Arturo

    2012-01-01

    Degeneration and age affect the biomechanics of the intervertebral disc, by reducing its stiffness, flexibility and shock absorption capacities against daily movement and spinal load. The biomechanical characterization of intervertebral discs is achieved by conducting mechanical testing to vertebra-disc-vertebra segments and applying axial, shear, bend and torsion loads, statically or dynamically, with load magnitudes corresponding to the physiological range. However, traditional testing does...

  16. Biomechanical study of intervertebral disc degeneration

    OpenAIRE

    González Guitiérrez, Ramiro Arturo

    2012-01-01

    Degeneration and age affect the biomechanics of the intervertebral disc, by reducing its stiffness, flexibility and shock absorption capacities against daily movement and spinal load. The biomechanical characterization of intervertebral discs is achieved by conducting mechanical testing to vertebra-disc-vertebra segments and applying axial, shear, bend and torsion loads, statically or dynamically, with load magnitudes corresponding to the physiological range. However, traditional testing does...

  17. Depression in Age-Related Macular Degeneration

    OpenAIRE

    Casten,Robin; Rovner,Barry

    2008-01-01

    Age-related macular degeneration (AMD) is a major cause of disability in the elderly, substantially degrades the quality of their lives, and is a risk factor for depression. Rates of depression in AMD are substantially greater than those found in the general population of older people, and are on par with those of other chronic and disabling diseases. This article discusses the effect of depression on vision-related disability in patients with AMD, suggests methods for screening for depressio...

  18. Stem cell horizons in intervertebral disc degeneration

    Directory of Open Access Journals (Sweden)

    Joseph Ciacci

    2009-01-01

    Full Text Available Joseph Ciacci1, Allen Ho1,2, Christopher P Ames3, Rahul Jandial41Division of Neurosurgery, University of California, San Diego, La Jolla, California, USA; 2Del E Webb Neurosciences, Aging and Stem Cell Research Center, The Burnham Institute for Medical Research, La Jolla, California, USA; 3Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA; 4Division of Neurosurgery, Department of Surgery, City of Hope Cancer Center, Duarte, CA, USAAbstract: Intervertebral disc degeneration remains a pervasive and intractable disease arising from a combination of aging and stress on the back and spine. The growing field of regenerative medicine brings the promise of stem cells in the treatment of disc disease. Scientists and physicians hope to employ stem cells not only to stop, but also reverse degeneration. However, there are many important outstanding issues, including the hostile avascular, apoptotic physiological environment of the intervertebral disc, and the difficulty of obtaining mesenchymal stem cells, and directing them towards chondrocytic differentiation and integration within the nucleus pulposus of the disc. Given the recent advances in minimally invasive spine surgery, and developing body of work on stem cell manipulation and transplantation, stem cells are uniquely poised to bring about large-scale improvements in treatment and outcomes for degenerative disc disease. In this review we will first discuss the cellular and molecular factors influencing degeneration, and then examine the efficacy and difficulties of stem cell transplantation.Keywords: intervertebral disc degeneration, stem cells, disc disease, mesenchymal stem cells, stem cell transplantation

  19. Rehabilitation Approaches in Macular Degeneration Patients

    OpenAIRE

    Maniglia, Marcello; Benoit R Cottereau; Soler, Vincent; Trotter, Yves

    2016-01-01

    Age related macular degeneration (AMD) is a visual disease that affects elderly population. It entails a progressive loss of central vision whose consequences are dramatic for the patient’s quality of life. Current rehabilitation programs are restricted to technical aids based on visual devices. They only temporarily improve specific visual functions such as reading skills. Considering the rapid increase of the aging population worldwide, it is crucial to intensify clinical research on AMD in...

  20. Controllability of nonlinear degenerate parabolic cascade systems

    Directory of Open Access Journals (Sweden)

    Mamadou Birba

    2016-08-01

    Full Text Available This article studies of null controllability property of nonlinear coupled one dimensional degenerate parabolic equations. These equations form a cascade system, that is, the solution of the first equation acts as a control in the second equation and the control function acts only directly on the first equation. We prove positive null controllability results when the control and a coupling set have nonempty intersection.

  1. Animal models of age related macular degeneration

    OpenAIRE

    Pennesi, Mark E.; Neuringer, Martha; Courtney, Robert J.

    2012-01-01

    Age related macular degeneration (AMD) is the leading cause of vision loss of those over the age of 65 in the industrialized world. The prevalence and need to develop effective treatments for AMD has lead to the development of multiple animal models. AMD is a complex and heterogeneous disease that involves the interaction of both genetic and environmental factors with the unique anatomy of the human macula. Models in mice, rats, rabbits, pigs and non-human primates have recreated many of the ...

  2. Conceptual foundations of schizophrenia: I. Degeneration.

    Science.gov (United States)

    Barrett, R J

    1998-10-01

    This is the first of two papers that aim to identify some of the institutional processes of 19th century European psychiatry, and some prevailing cultural themes of that era that played a role in shaping the development of schizophrenia as a disease concept. Three areas of psychiatric history are examined: the first is concerned with the key figures who coined the concept of dementia praecox; the second with the rise of the asylum; and the third is to do with the ideology of 19th century psychiatric science and its relationship to a broader intellectual milieu. These three literatures are examined for common themes. The theme of degeneration is evident in all three literatures, and denotes both a biological process (neuro-degeneration) and a moral state (degeneracy). The idea of degeneration, a pervasive cultural theme of the 19th century, dominated psychiatric thinking long before schizophrenia was developed as a diagnostic category. It contributed to the ideational form-work that gave foundation, structure and shape to the concept of schizophrenia.

  3. Propagation of Disturbances in Degenerate Quantum Systems

    CERN Document Server

    Chancellor, Nicholas

    2011-01-01

    Disturbances in gapless quantum many-body models are known to travel an unlimited distance throughout the system. Here, we explore this phenomenon in finite clusters with degenerate ground states. The specific model studied here is the one-dimensional J1-J2 Heisenberg Hamiltonian at and close to the Majumdar-Ghosh point. Both open and periodic boundary conditions are considered. Quenches are performed using a local magnetic field. The degenerate Majumdar-Ghosh ground state allows disturbances which carry quantum entanglement to propagate throughout the system, and thus dephase the entire system within the degenerate subspace. These disturbances can also carry polarization, but not energy, as all energy is stored locally. The local evolution of the part of the system where energy is stored drives the rest of the system through long-range entanglement. We also examine approximations for the ground state of this Hamiltonian in the strong field limit, and study how couplings away from the Majumdar-Ghosh point aff...

  4. Visual hallucinations in patients with macular degeneration.

    Science.gov (United States)

    Holroyd, S; Rabins, P V; Finkelstein, D; Nicholson, M C; Chase, G A; Wisniewski, S C

    1992-12-01

    This study was undertaken to determine the prevalence of visual hallucinations in patients with macular degeneration, describe such hallucinations phenomenologically, and possibly determine factors predisposing to their development. Using a case-control design, the authors screened 100 consecutive patients with age-related macular degeneration for visual hallucinations. Each patient with visual hallucinations was matched to the next three patients without hallucinations. The patients and comparison subjects were compared in terms of scores on the Beck Depression Inventory, Eysenck Personality Questionnaire, Telephone Interview for Cognitive Status, and a structured questionnaire including demographic characteristics, family history, and medical and psychiatric history. Ophthalmologic data were obtained by chart review. Of the 100 patients, 13 experienced visual hallucinations. Four variables were significantly associated with having hallucinations: living alone, lower cognition score, history of stroke, and bilaterally worse visual acuity. Hallucinations were not associated with family or personal history of psychiatric disorder or with personality traits. In 11 (84.6%) of the 13 patients, the hallucinations had begun in association with an acute change in vision. These results indicate that visual hallucinations are prevalent among patients with macular degeneration. They appear unrelated to primary psychiatric disorder. The predisposing factors of bilaterally worse vision and living alone support an association with sensory deprivation, while history of stroke and worse cognition support a decreased cortical inhibition theory.

  5. Non-aggregating tau phosphorylation by cyclin-dependent kinase 5 contributes to motor neuron degeneration in spinal muscular atrophy.

    Science.gov (United States)

    Miller, Nimrod; Feng, Zhihua; Edens, Brittany M; Yang, Ben; Shi, Han; Sze, Christie C; Hong, Benjamin Taige; Su, Susan C; Cantu, Jorge A; Topczewski, Jacek; Crawford, Thomas O; Ko, Chien-Ping; Sumner, Charlotte J; Ma, Long; Ma, Yong-Chao

    2015-04-15

    Mechanisms underlying motor neuron degeneration in spinal muscular atrophy (SMA), the leading inherited cause of infant mortality, remain largely unknown. Many studies have established the importance of hyperphosphorylation of the microtubule-associated protein tau in various neurodegenerative disorders, including Alzheimer's and Parkinson's diseases. However, tau phosphorylation in SMA pathogenesis has yet to be investigated. Here we show that tau phosphorylation on serine 202 (S202) and threonine 205 (T205) is increased significantly in SMA motor neurons using two SMA mouse models and human SMA patient spinal cord samples. Interestingly, phosphorylated tau does not form aggregates in motor neurons or neuromuscular junctions (NMJs), even at late stages of SMA disease, distinguishing it from other tauopathies. Hyperphosphorylation of tau on S202 and T205 is mediated by cyclin-dependent kinase 5 (Cdk5) in SMA disease condition, because tau phosphorylation at these sites is significantly reduced in Cdk5 knock-out mice; genetic knock-out of Cdk5 activating subunit p35 in an SMA mouse model also leads to reduced tau phosphorylation on S202 and T205 in the SMA;p35(-/-) compound mutant mice. In addition, expression of the phosphorylation-deficient tauS202A,T205A mutant alleviates motor neuron defects in a zebrafish SMA model in vivo and mouse motor neuron degeneration in culture, whereas expression of phosphorylation-mimetic tauS202E,T205E promotes motor neuron defects. More importantly, genetic knock-out of tau in SMA mice rescues synapse stripping on motor neurons, NMJ denervation, and motor neuron degeneration in vivo. Altogether, our findings suggest a novel mechanism for SMA pathogenesis in which hyperphosphorylation of non-aggregating tau by Cdk5 contributes to motor neuron degeneration.

  6. [New drug therapy for retinal degeneration].

    Science.gov (United States)

    Ohguro, Hiroshi

    2008-01-01

    Retinitis pigmentosa (RP) is an inherited retinal degeneration characterized by nyctalopia, ring scotoma, and bone-spicule pigmentation of the retina. So far, no effective therapy has been found for RP. As a possible molecular etiology of RP, retina-specific gene deficits are most likely involved, but little has been identified in terms of intracellular mechanisms leading to retinal photoreceptor cell death at post-translational levels. In order to find an effective therapy for RP, we must look for underlying common mechanisms that are responsible for the development of RP, instead of designing a specific therapy for each of the RP types with different causes. Therefore, in the present study, several animal models with different causes of RP were studied, including (1)Royal College of Surgeons (RCS) rats with a deficit of retinal pigment epithelium (RPE) function caused by rhodopsin mutation; (2) P23H rats, (3) S334ter rats, (4) photo stress rats, (5) retinal degeneration (rd) mice with a deficit of phosphodiesterase(PDE) function; and (6) cancer-associated retinopathy (CAR) model rats with a deficit of recoverin-dependent photoreceptor adaptation function. In each of these models, the following assessments were made in order to elucidate common pathological mechanisms among the models: (1) retinal function assessed by electroretinogram (ERG), (2) retinal morphology, (3) retinoid analysis, (4) rhodopsin regeneration, (5) rhodopsin phosphorylation and dephosphorylation, and (6) cytosolic cGMP levels. We found that unregulated photoreceptor adaptation processes caused by an imbalance of rhodopsin phosphorylation and dephosphorylation caused retinal dysfunction leading to photoreceptor cell death. As possible candidate drugs for normalizing these retinal dysfunctions and stopping further retinal degeneration, nilvadipine, a Ca channel blocker, retinoid derivatives, and anthocyanine were chosen and tested to determine their effect on the above animal models with

  7. A Taenia crassiceps metacestode factor enhances ovarian follicle atresia and oocyte degeneration in female mice.

    Science.gov (United States)

    Solano, S; Zepeda, N; Copitin, N; Fernandez, A M; Tato, P; Molinari, J L

    2015-01-01

    The histopathological effects of Taenia crassiceps infection or T. crassiceps metacestode factor inoculation on the mouse ovary were determined using six female mice in three groups: infected mice, mice inoculated with the metacestode factor and control mice. The control group was subcutaneously inoculated with healthy peritoneal fluid. The infected group was intraperitoneally inoculated with 40 T. crassiceps metacestodes, and the metacestode factor group was subcutaneously inoculated with T. crassiceps metacestode factor (MF). Light and electron microscopy and TUNEL (terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labelling) assays revealed a significant increase in ovarian follicular atresia (predominantly in antral/preovulatory stages of development), oocyte degeneration (P< 0.05), and a decrease in the amount of corpus luteum in follicles of mice infected and inoculated with MF compared with the control group. Significant abnormalities of the granulosa cells and oocytes of the primordial, primary and secondary ovarian follicles occurred in both treated mouse groups (P< 0.05) compared with no degeneration in the control group. These pathological changes in female mice either infected with T. crassiceps metacestodes or inoculated with T. crassiceps MF may have consequences for ovulation and fertility.

  8. Analysis of the RPE sheet in the rd10 retinal degeneration model

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Yi [Los Alamos National Laboratory

    2011-01-04

    The normal RPE sheet in the C57Bl/6J mouse is subclassified into two major tiling patterns: A regular generally hexagonal array covering most of the surface and a 'soft network' near the ciliary body made of irregularly shaped cells. Physics models predict these two patterns based on contractility and elasticity of the RPE cell, and strength of cellular adhesion between cells. We hypothesized and identified major changes in RPE regular hexagonal tiling pattern in rdl0 compared to C57BL/6J mice. RPE sheet damage was extensive but occurred in rd10 later than expected, after most retinal degeneration. RPE sheet changes occur in zones with a bullseye pattern. In the posterior zone around the optic nerve RPE cells take on larger irregular and varied shapes to form an intact monolayer. In mid periphery, there is a higher than normal density of cells that progress into involuted layers of RPE under the retina. The periphery remains mostly normal until late stages of degeneration. The number of neighboring cells varies widely depending on zone and progression. RPE morphology continues to deteriorate long after the photoreceptors have degenerated. The RPE cells are bystanders to the rd10 degeneration within photo receptors, and the collateral damage to the RPE sheet resembles stimulation of migration or chemotaxis. Quantitative measures of the tiling patterns and histopathology detected here, scripted in a pipeline written in Perl and Cell Profiler (an open source Matlab plugin), are directly applicable to RPE sheet images from noninvasive fundus autofluorescence (FAF), adaptive optics confocal scanning laser ophthalmoscope (AO-cSLO), and spectral domain optical coherence tomography (SD-OCT) of patients with early stage AMD or RP.

  9. Effects of vacuolization in aleurone layers on PCD during germinating rice seeds%水稻糊粉层液泡化进程对种子萌发过程细胞程序性死亡的影响

    Institute of Scientific and Technical Information of China (English)

    郑岩; 陈惠萍

    2015-01-01

    以水稻(Oryza sativa L.)品种Ⅱ优128种子为材料,利用激光扫描共聚焦显微技术及荧光标记等手段,解析萌发水稻种子糊粉层细胞程序性死亡(Programmed Cell Death,PCD)中液泡的形态变化,揭示液泡化对PCD进程的影响.结果表明:糊粉层细胞PCD过程液泡的形态结构会发生一系列变化,由最初较小的蛋白贮藏液泡,逐渐相互融合成为大的液泡,之后液泡破裂消失;液泡化现象是糊粉层PCD的显著特征,且其进程会直接影响到糊粉层PCD的进程;抑制液泡融合阻缓了糊粉层PCD进程,从而影响水稻种子的萌发.

  10. Degenerate Neutrinos in Left Right Symmetric Theory

    OpenAIRE

    Joshipura, Anjan S.

    1994-01-01

    Various hints on the neutrino masses namely, ({\\em i}) the solar neutrino deficit ({\\em ii}) the atmospheric neutrino deficit ({\\em iii}) the need for the dark matter and/or ({\\em iv}) the non-zero neutrinoless double beta decay collectively imply that all the three neutrinos must be nearlty degenerate. This feature can be understood in the left right symmetric theory. We present a model based on the group $SU(2)_{L}\\times SU(2)_R\\times U(1)_{B-L}\\times SU(2)_H$ which can explain the required...

  11. REITERATED HOMOGENIZATION OF DEGENERATE NONLINEAR ELLIPTIC EQUATIONS

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The authors study homogenization of some nonlinear partial differential equations of the form -div (a (hx,h2x,Duh)) = f,where a is periodic in the first two arguments and monotone in the third.In particular the case where a satisfies degenerated structure conditions is studied.It is proved that uh converges weakly in Wo1.1 (Ω) to the unique solution of a limit problem as h →∞.Moreover,explicit expressions for the limit problem are obtained.

  12. Length spectra and degeneration of flat metrics

    CERN Document Server

    Duchin, Moon; Rafi, Kasra

    2009-01-01

    In this paper we consider flat metrics (semi-translation structures) on surfaces of finite type. There are two main results. The first is a complete description of when a set of simple closed curves is spectrally rigid, that is, when the length vector determines a metric among the class of flat metrics. Secondly, we give an embedding into the space of geodesic currents and use this to get a boundary for the space of flat metrics. The geometric interpretation is that flat metrics degenerate to "mixed structures" on the surface: part flat metric and part measured foliation.

  13. Aneutronic Fusion in a Degenerate Plasma

    Energy Technology Data Exchange (ETDEWEB)

    S. Son; N.J. Fisch

    2004-09-03

    In a Fermi-degenerate plasma, the electronic stopping of a slow ion is smaller than that given by the classical formula, because some transitions between the electron states are forbidden. The bremsstrahlung losses are then smaller, so that the nuclear burning of an aneutronic fuel is more efficient. Consequently, there occurs a parameter regime in which self-burning is possible. Practical obstacles in this regime that must be overcome before net energy can be realized include the compression of the fuel to an ultra dense state and the creation of a hot spot.

  14. [Age-related macular degeneration (AMD)].

    Science.gov (United States)

    Michels, Stephan; Kurz-Levin, Malaika

    2009-03-01

    Today age-related macular degeneration (AMD) is the most frequent cause for legal blindness in western industrialized countries. The prevalence of this disease rises with increasing age. A multifactorial pathogenesis of AMD is postulated including genetic predisposition and environmental risk factors. The most relevant modifiable risk factor is smoking. Up to today there is no cure of this chronic disease. Prophylaxis, including a healthy diet and antioxidants as nutrional supplements for selected patients, aims to slow down the disease progression. Significant progress has been made in the treatment of the neovascular form of the disease using inhibitors of the vascular endothelial growth factor (VEGF).

  15. Was Maurice Ravel's illness a corticobasal degeneration?

    Science.gov (United States)

    Baeck, E

    1996-02-01

    The French composer Maurice Ravel (1875-1937) was struck down at the peak of his career by an aphasia and apraxia that destroyed his artistic realization but preserved his musical sensibility and judgment. He died after craniotomy. Multiple hypotheses have been formulated to explain the exact nature of his illness, probably corticobasal degeneration. However, in the absence of a post-mortem examination, the diagnosis must remain speculative despite the accurate descriptions of the symptoms in numerous biographies, the neuro-psychological notes of Théophile Alajouanine and the operative findings of Clovis Vincent.

  16. Precursors of age-related macular degeneration

    DEFF Research Database (Denmark)

    Munch, Inger Christine; Toft, Ulla; Linneberg, Allan;

    2016-01-01

    PURPOSE: To investigate associations of very early age-related macular degeneration (AMD) with daily intake of vitamin A, beta-carotene, vitamin E, vitamin C, zinc and copper and interactions with AMD-associated polymorphisms in complement factor H (CFHY402H) and ARMS2/LOC387715. METHODS: Cross......: In this cross-sectional study, a higher intake of vitamin A increased the risk of macular drusen >63 μm in subjects with CFHY402H. The study supports that vitamin A may be a risk factor for early AMD....

  17. Affine and degenerate affine BMW algebras: The center

    CERN Document Server

    Daugherty, Zajj; Virk, Rahbar

    2011-01-01

    The degenerate affine and affine BMW algebras arise naturally in the context of Schur-Weyl duality for orthogonal and symplectic Lie algebras and quantum groups, respectively. Cyclotomic BMW algebras, affine Hecke algebras, cyclotomic Hecke algebras, and their degenerate versions are quotients. In this paper the theory is unified by treating the orthogonal and symplectic cases simultaneously; we make an exact parallel between the degenerate affine and affine cases via a new algebra which takes the role of the affine braid group for the degenerate setting. A main result of this paper is an identification of the centers of the affine and degenerate affine BMW algebras in terms of rings of symmetric functions which satisfy a "cancellation property" or "wheel condition" (in the degenerate case, a reformulation of a result of Nazarov). Miraculously, these same rings also arise in Schubert calculus, as the cohomology and K-theory of isotropic Grassmanians and symplectic loop Grassmanians. We also establish new inte...

  18. Affine and degenerate affine BMW algebras: Actions on tensor space

    CERN Document Server

    Daugherty, Zajj; Virk, Rahbar

    2012-01-01

    The affine and degenerate affine Birman-Murakami-Wenzl (BMW) algebras arise naturally in the context of Schur-Weyl duality for orthogonal and symplectic quantum groups and Lie algebras, respectively. Cyclotomic BMW algebras, affine and cyclotomic Hecke algebras, and their degenerate versions are quotients. In this paper we explain how the affine and degenerate affine BMW algebras are tantalizers (tensor power centralizer algebras) by defining actions of the affine braid group and the degenerate affine braid algebra on tensor space and showing that, in important cases, these actions induce actions of the affine and degenerate affine BMW algebras. We then exploit the connection to quantum groups and Lie algebras to determine universal parameters for the affine and degenerate affine BMW algebras. Finally, we show that the universal parameters are central elements--the higher Casimir elements for orthogonal and symplectic enveloping algebras and quantum groups.

  19. Degenerations and limit Frobenius structures in rigid cohomology

    OpenAIRE

    Lauder, Alan G. B.

    2011-01-01

    We introduce a "limiting Frobenius structure" attached to any degeneration of projective varieties over a finite field of characteristic p which satisfies a p-adic lifting assumption. Our limiting Frobenius structure is shown to be effectively computable in an appropriate sense for a degeneration of projective hypersurfaces. We conjecture that the limiting Frobenius structure relates to the rigid cohomology of a semistable limit of the degeneration through an analogue of the Clemens-Schmidt e...

  20. SARM1 activation triggers axon degeneration locally via NAD+ destruction

    OpenAIRE

    Gerdts, Josiah; Brace, E. J.; Sasaki, Yo; DiAntonio, Aaron; Milbrandt, Jeffrey

    2015-01-01

    Axon degeneration is an intrinsic self-destruction program that underlies axon loss during injury and disease. Sterile alpha and TIR motif containing 1 (SARM1) protein is an essential mediator of axon degeneration. We report that SARM1 initiates a local destruction program involving rapid breakdown of NAD+ after injury. We used an engineered protease-sensitized SARM1 to demonstrate that SARM1 activity is required after axon injury to induce axon degeneration. Dimerization of the Toll-Interleu...

  1. Mechanisms of axon degeneration: from development to disease.

    Science.gov (United States)

    Saxena, Smita; Caroni, Pico

    2007-10-01

    Axon degeneration is an active, tightly controlled and versatile process of axon segment self-destruction. Although not involving cell death, it resembles apoptosis in its logics. It involves three distinct steps: induction of competence in specific neurons, triggering of degeneration at defined axon segments of competent neurons, and rapid fragmentation and removal of the segments. The mechanisms that initiate degeneration are specific to individual settings, but the final pathway of pruning is shared; it involves microtubule disassembly, axon swellings, axon fragmentation, and removal of the remnants by locally recruited phagocytes. The tight regulatory properties of axon degeneration distinguish it from passive loss phenomena, and confer significance to processes that involve it. Axon degeneration has prominent roles in development, upon lesions and in disease. In development, it couples the progressive specification of neurons and circuits to the removal of defined axon branches. Competence might involve transcriptional switches, and local triggering can involve axon guidance molecules and synaptic activity patterns. Lesion-induced Wallerian degeneration is inhibited in the presence of Wld(S) fusion protein in neurons; it involves early local, and later, distal degeneration. It has recently become clear that like in other settings, axon degeneration in disease is a rapid and specific process, which should not be confused with a variety of disease-related pathologies. Elucidating the specific mechanisms that initiate axon degeneration should open up new avenues to investigate principles of circuit assembly and plasticity, to uncover mechanisms of disease progression, and to identify ways of protecting synapses and axons in disease.

  2. Integrable systems, toric degenerations and Okounkov bodies

    CERN Document Server

    Harada, Megumi

    2012-01-01

    Let X be a smooth projective variety of dimension n over C equipped with a very ample line bundle L. Using the theory of Okounkov bodies and an associated toric degeneration, we construct -- under a mild technical hypothesis on X -- an integrable system on X in the sense of symplectic geometry. More precisely, we construct a collection of real-valued functions {H_1, ..., H_n} on X which are continuous on all of X, smooth on an open dense subset U of X, and pairwise Poisson-commute on U. Here the symplectic structure on X is the pullback of the Fubini-Study form on P(H^0(X, L)^*) via the Kodaira embedding. The image of the `moment map' (H_1, ..., H_n): X to R^n is precisely the Okounkov body \\Delta = \\Delta(R, v) associated to the homogeneous coordinate ring R of X, and an appropriate choice of valuation v on R. Our main technical tools come from algebraic geometry, differential (Kaehler) geometry, and analysis. Specifically, we use: a toric degeneration of X to a (not necessarily normal) toric variety X_0, th...

  3. MR imaging findings of hypertrophic olivary degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Do Joong; Jeon, Pyung; Kim, Dong Ik [Yonsei Univ. College of Medicine, Seoul (Korea, Republic of)

    1997-06-01

    To describe the magnetic resonance (MR) imaging findings of hypertrophic olivary degeneration (HOD) MR images of seven patients with HOD were retrospectively reviewed. Two were women and five were men, and they were aged between 48 and 65 (mean 58) years. Imaging examinations were performed with a 1.5-T unit, and the findings were used to evaluate the size and signal intensity of olivary lesions. The time interval from hemorrhagic ictus to MR imaging was between two and 30 months. Follow-up examinations were performed in two patients. All four patients with hemorrhages involving the central tegmental tract in the pons or midbrain showed ipsilateral HOD. Among these four, bilateral HOD was seen in one patient with hemorrhage involving the bilateral central tegmental tract, and in another with tegmental hemorrhage extending to the ipsilateral superior cerebellar peduncle. One patient with cerebellar hemorrhage involving the dentate nucleus had contralateral HOD. Two patients with multiple hemorrhages involving both the pons and cerebellum showed bilateral HOD. Axial MR images showed mild enlargement of the involved olivary mucleus, with high signal intensity on both proton density and T2 weighted images. There was no apparent enhancement on postcontrast T1-weighted images. MR imaging can clearly distinguish secondary olivary degeneration from underlying pathology involving the central tegmental tract in the pons or midbrain and cerebellum. These olivary abnormalities should not, however, be mistaken for primary medullary lesions.

  4. On the degenerated Arnold-Givental conjecture

    CERN Document Server

    Lu, Guangcun

    2008-01-01

    Let $(M, \\omega, \\tau)$ be a real symplectic manifold with nonempty and compact real part $L={\\rm Fix}(\\tau)$. We study the following degenerated version of the Arnold-Givental conjecture: $\\sharp(L\\cap\\phi(L))\\ge{\\rm Cuplength}_{\\F}(L)$ for any Hamiltonian diffeomorphism $\\phi:M\\to M$ and $\\F=\\Z, \\Z_2$. Suppose that $(M, \\omega)$ is geometrical bounded for some $J\\in{\\cal J}(M, \\omega)$ with $\\tau^\\ast J=-J$. We prove $\\sharp(L\\cap\\phi(L))\\ge {\\rm Cuplength}_{\\F}(L)$ for $\\F=\\Z_2$, and $\\F=\\Z_2, \\Z$ if $L$ is orientable, and for every Hamiltonian diffeomorphism $\\phi$ generated by a compactly supported Hamiltonian function whose Hofer norm is less than the minimal area of all nonconstant $J$-holomorphic spheres in $M$. In particular, this implies that the above degenerated Arnold-Givental conjecture holds on the K3-surfaces and closed negative monotone real symplectic manifolds of dimension $2n$ with either $n\\le 3$ or minimal Chern number $N\\ge n-2$. As consequences we get that every Hamiltonian diffeomorph...

  5. Progranulin in frontotemporal lobar degeneration and neuroinflammation

    Directory of Open Access Journals (Sweden)

    Hutton Michael L

    2007-02-01

    Full Text Available Abstract Progranulin (PGRN is a pleiotropic protein that has gained the attention of the neuroscience community with recent discoveries of mutations in the gene for PGRN that cause frontotemporal lobar degeneration (FTLD. Pathogenic mutations in PGRN result in null alleles, and the disease is likely the result of haploinsufficiency. Little is known about the normal function of PGRN in the central nervous system apart from a role in brain development. It is expressed by microglia and neurons. In the periphery, PGRN is involved in wound repair and inflammation. High PGRN expression has been associated with more aggressive growth of various tumors. The properties of full length PGRN are distinct from those of proteolytically derived peptides, referred to as granulins (GRNs. While PGRN has trophic properties, GRNs are more akin to inflammatory mediators such as cytokines. Loss of the neurotrophic properties of PGRN may play a role in selective neuronal degeneration in FTLD, but neuroinflammation may also be important. Gene expression studies suggest that PGRN is up-regulated in a variety of neuroinflammatory conditions, and increased PGRN expression by microglia may play a pivotal role in the response to brain injury, neuroinflammation and neurodegeneration.

  6. SIRT3 Reverses Aging-Associated Degeneration

    Directory of Open Access Journals (Sweden)

    Katharine Brown

    2013-02-01

    Full Text Available Despite recent controversy about their function in some organisms, sirtuins are thought to play evolutionarily conserved roles in lifespan extension. Whether sirtuins can reverse aging-associated degeneration is unknown. Tissue-specific stem cells persist throughout the entire lifespan to repair and maintain tissues, but their self-renewal and differentiation potential become dysregulated with aging. We show that SIRT3, a mammalian sirtuin that regulates the global acetylation landscape of mitochondrial proteins and reduces oxidative stress, is highly enriched in hematopoietic stem cells (HSCs where it regulates a stress response. SIRT3 is dispensable for HSC maintenance and tissue homeostasis at a young age under homeostatic conditions but is essential under stress or at an old age. Importantly, SIRT3 is suppressed with aging, and SIRT3 upregulation in aged HSCs improves their regenerative capacity. Our study illuminates the plasticity of mitochondrial homeostasis controlling stem cell and tissue maintenance during the aging process and shows that aging-associated degeneration can be reversed by a sirtuin.

  7. Hyaline cartilage degenerates after autologous osteochondral transplantation.

    Science.gov (United States)

    Tibesku, C O; Szuwart, T; Kleffner, T O; Schlegel, P M; Jahn, U R; Van Aken, H; Fuchs, S

    2004-11-01

    Autologous osteochondral grafting is a well-established clinical procedure to treat focal cartilage defects in patients, although basic research on this topic remains sparse. The aim of the current study was to evaluate (1) histological changes of transplanted hyaline cartilage of osteochondral grafts and (2) the tissue that connects the transplanted cartilage with the adjacent cartilage in a sheep model. Both knee joints of four sheep were opened surgically and osteochondral grafts were harvested and simultaneously transplanted to the contralateral femoral condyle. The animals were sacrificed after three months and the received knee joints were evaluated histologically. Histological evaluation showed a complete ingrowth of the osseous part of the osteochondral grafts. A healing or ingrowth at the level of the cartilage could not be observed. Histological evaluation of the transplanted grafts according to Mankin revealed significantly more and more severe signs of degeneration than the adjacent cartilage, such as cloning of chondrocytes and irregularities of the articular surface. We found no connecting tissue between the transplanted and the adjacent cartilage and histological signs of degeneration of the transplanted hyaline cartilage. In the light of these findings, long-term results of autologous osteochondral grafts in human beings have to be followed critically.

  8. Disc degeneration-related clinical phenotypes.

    Science.gov (United States)

    Battié, Michele C; Lazáry, Aron; Fairbank, Jeremy; Eisenstein, Stephen; Heywood, Chris; Brayda-Bruno, Marco; Varga, Péter Pál; McCall, Iain

    2014-06-01

    The phenotype, or observable trait of interest, is at the core of studies identifying associated genetic variants and their functional pathways, as well as diagnostics. Yet, despite remarkable technological developments in genotyping and progress in genetic research, relatively little attention has been paid to the equally important issue of phenotype. This is especially true for disc degeneration-related disorders, and the concept of degenerative disc disease, in particular, where there is little consensus or uniformity of definition. Greater attention and rigour are clearly needed in the development of disc degeneration-related clinical phenotypes if we are to see more rapid advancements in knowledge of this area. When selecting phenotypes, a basic decision is whether to focus directly on the complex clinical phenotype (e.g. the clinical syndrome of spinal stenosis), which is ultimately of interest, or an intermediate phenotype (e.g. dural sac cross-sectional area). While both have advantages, it cannot be assumed that associated gene variants will be similarly relevant to both. Among other considerations are factors influencing phenotype identification, comorbidities that are often present, and measurement issues. Genodisc, the European research consortium project on disc-related clinical pathologies has adopted a strategy that will allow for the careful characterisation and examination of both the complex clinical phenotypes of interest and their components.

  9. Degenerate parametric oscillation in quantum membrane optomechanics

    Science.gov (United States)

    Benito, Mónica; Sánchez Muñoz, Carlos; Navarrete-Benlloch, Carlos

    2016-02-01

    The promise of innovative applications has triggered the development of many modern technologies capable of exploiting quantum effects. But in addition to future applications, such quantum technologies have already provided us with the possibility of accessing quantum-mechanical scenarios that seemed unreachable just a few decades ago. With this spirit, in this work we show that modern optomechanical setups are mature enough to implement one of the most elusive models in the field of open system dynamics: degenerate parametric oscillation. Introduced in the eighties and motivated by its alleged implementability in nonlinear optical resonators, it rapidly became a paradigm for the study of dissipative phase transitions whose corresponding spontaneously broken symmetry is discrete. However, it was found that the intrinsic multimode nature of optical cavities makes it impossible to experimentally study the model all the way through its phase transition. In contrast, here we show that this long-awaited model can be implemented in the motion of a mechanical object dispersively coupled to the light contained in a cavity, when the latter is properly driven with multichromatic laser light. We focus on membranes as the mechanical element, showing that the main signatures of the degenerate parametric oscillation model can be studied in state-of-the-art setups, thus opening the possibility of analyzing spontaneous symmetry breaking and enhanced metrology in one of the cleanest dissipative phase transitions. In addition, the ideas put forward in this work would allow for the dissipative preparation of squeezed mechanical states.

  10. Quasi-degenerate neutrinos in SO(10)

    CERN Document Server

    Joshipura, Anjan S

    2010-01-01

    Quark lepton universality inherent in grand unified theories based on $SO(10)$ gauge group generically leads to hierarchical neutrino masses. We propose a specific ansatz for the structure of Yukawa matrices in $SO(10)$ models which differ from this generic expectations and lead to quasi degenerate neutrinos through the type-I seesaw mechanism. Consistency of this ansatz is demonstrated through a detailed fits to fermion masses and mixing angles all of which can be explained with reasonable accuracy in a model which uses the Higgs fields transforming as $10,120$ and $\\overline{126}$ representations of $SO(10)$. The proposed ansatz is shown to follow from an extended model based on the three generations of the vector like fermions and an $O(3)$ flavour symmetry. Successful numerical fits are also discussed in earlier proposed models which used combination of the type-I and type-II seesaw mechanisms for obtaining quasi degenerate neutrinos. Large neutrino mixing angles emerge as a consequence of neutrino mass d...

  11. Ccl2, Cx3cr1 and Ccl2/Cx3cr1 chemokine deficiencies are not sufficient to cause age-related retinal degeneration.

    Science.gov (United States)

    Luhmann, Ulrich F O; Carvalho, Livia S; Robbie, Scott J; Cowing, Jill A; Duran, Yanai; Munro, Peter M G; Bainbridge, James W B; Ali, Robin R

    2013-02-01

    Monocytes, macrophages, dendritic cells and microglia play critical roles in the local immune response to acute and chronic tissue injury and have been implicated in the pathogenesis of age-related macular degeneration. Defects in Ccl2-Ccr2 and Cx3cl1-Cx3cr1 chemokine signalling cause enhanced accumulation of bloated subretinal microglia/macrophages in senescent mice and this phenomenon is reported to result in the acceleration of age-related retinal degeneration. The purpose of this study was to determine whether defects in CCL2-CCR2 and CX3CL1-CX3CR1 signalling pathways, alone or in combination, cause age-dependent retinal degeneration. We tested whether three chemokine knockout mouse lines, Ccl2(-/-), Cx3cr1(-/-) and Ccl2(-/-)/Cx3cr1(-/-), in comparison to age-matched C57Bl/6 control mice show differences in subretinal macrophage accumulation and loss of adjacent photoreceptor cells at 12-14 months of age. All mouse lines are derived from common parental strains and do not carry the homozygous rd8 mutation in the Crb1 gene that has been a major confounding factor in previous reports. We quantified subretinal macrophages by counting autofluorescent lesions in fundus images obtained by scanning laser ophthalmoscopy (AF-SLO) and by immunohistochemistry for Iba1 positive cells. The accumulation of subretinal macrophages was enhanced in Ccl2(-/-), but not in Cx3cr1(-/-) or Ccl2(-/-)/Cx3cr1(-/-) mice. We identified no evidence of retinal degeneration in any of these mouse lines by TUNEL staining or semithin histology. In conclusion, CCL2-CCR2 and/or CX3CL1-CX3CR1 signalling defects may differentially affect the trafficking of microglia and macrophages in the retina during ageing, but do not appear to cause age-related retinal degeneration in mice.

  12. New treatment strategies for canine intervertebral disc degeneration

    NARCIS (Netherlands)

    Smolders, L.A.

    2013-01-01

    Degeneration of the intervertebral disc (IVD) is a common problem in dogs and humans. IVD degeneration can lead to herniation of the IVD with subsequent compression of neural structures and various clinical signs, including back pain. Current treatment of IVD disease is conservative or surgical. How

  13. Impulse Observability and Impulse Controllability of Regular Degenerate Evolution Systems

    Institute of Scientific and Technical Information of China (English)

    GE Zhaoqiang

    2016-01-01

    Impulse observability and impulse controllability of regular degenerate evolution systems are discussed by using functional analysis and operator theory in Banach space.Necessary and sufficient conditions for the impulse observability and impulse controllability of the system are obtained.This research is theoretically important for studying the design of the degenerate evolution system.

  14. Non-autonomous Degenerate KdV Systems

    OpenAIRE

    Turhan, Refik

    2002-01-01

    Non-autonomous degenerate KdV systems in (1+1) dimensions are considered for integrability classification. Integrability of the systems is associated with the existence of a recursion operator. Some new non-autonomous degenerate two-component KdV systems are found.

  15. Delivery systems for the treatment of degenerated intervertebral discs

    NARCIS (Netherlands)

    Blanquer, S.B.G.; Grijpma, D.W.; Poot, A.A.

    2015-01-01

    The intervertebral disc (IVD) is the most avascular and acellular tissue in the body and therefore prone to degeneration. During IVD degeneration, the balance between anabolic and catabolic processes in the disc is deregulated, amongst others leading to alteration of extracellular matrix production,

  16. Demonstration of Degenerate Vector Phase-Sensitive Amplification

    OpenAIRE

    Riesgo, A.L.; Karlsson, M.; Lundstrm, C.; Andrekson, P. A.

    2013-01-01

    The performance of a degenerate vector (dual cross-polarized pump) phase-sensitive amplifier (PSA) is characterized and compared to a degenerate scalar (dual co-polarized pump) PSA. In both schemes, we assess the gain as a function of the signal state of polarization, verifying its compliance with theory, and the phase transfer function. PSOPA

  17. Long-term Analysis of Degenerate Parabolic Equations in RN

    Institute of Scientific and Technical Information of China (English)

    Gao Cheng YUE; Cheng Kui ZHONG

    2015-01-01

    Longtime behavior of degenerate equations with the nonlinearity of polynomial growth of arbitrary order on the whole space RN is considered. By using ?-trajectories methods, we proved that weak solutions generated by degenerate equations possess an (L2U (RN ), L2loc(RN ))-global attractor. Moreover, the upper bounds of the Kolmogorovε-entropy for such global attractor are also obtained.

  18. 9 CFR 311.35 - Muscular inflammation, degeneration, or infiltration.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Muscular inflammation, degeneration, or infiltration. 311.35 Section 311.35 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE... PARTS § 311.35 Muscular inflammation, degeneration, or infiltration. (a) If muscular lesions are...

  19. Delivery systems for the treatment of degenerated intervertebral discs

    NARCIS (Netherlands)

    Blanquer, S. B. G.; Grijpma, D. W.; Poot, A. A.

    2015-01-01

    The intervertebral disc (ND) is the most avascular and acellular tissue in the body and therefore prone to degeneration. During IVD degeneration, the balance between anabolic and catabolic processes in the disc is deregulated, amongst others leading to alteration of extracellular matrix production,

  20. Prevalence of age-related macular degeneration in elderly Caucasians

    DEFF Research Database (Denmark)

    Erke, Maja G; Bertelsen, Geir; Peto, Tunde;

    2012-01-01

    To describe the sex- and age-specific prevalence of drusen, geographic atrophy, and neovascular age-related macular degeneration (AMD).......To describe the sex- and age-specific prevalence of drusen, geographic atrophy, and neovascular age-related macular degeneration (AMD)....

  1. Conjunctival spheroid degeneration. Recurrence after excision.

    Science.gov (United States)

    Norn, M S

    1982-06-01

    After excision of part of the conjunctiva in 15 eyes (14 subjects) due to spheroid degeneration, the author noticed only fairly small, varying numbers of autofluorescent and colourless spheroids-after an observation period of 18 months, only 6% of autofluorescent and 13% of colourless bodies were observed compared to the number before biopsy. Around the biopsy site only a few spheroids were seen, with a non-significant tendency to increase in number of the colourless bodies. In the cornea the band-shaped keratopathy had aggravated, with the formation of a small number of large, autofluorescent spheroids. A pinguecula recurred in a mild degree only in 3 out of 13 cases within 18 months.

  2. Degenerate Neutrinos in Left Right Symmetric Theory

    CERN Document Server

    Joshipura, A S

    1995-01-01

    Various hints on the neutrino masses namely, ({\\em i}) the solar neutrino deficit ({\\em ii}) the atmospheric neutrino deficit ({\\em iii}) the need for the dark matter and/or ({\\em iv}) the non-zero neutrinoless double beta decay collectively imply that all the three neutrinos must be nearlty degenerate. This feature can be understood in the left right symmetric theory. We present a model based on the group $SU(2)_{L}\\times SU(2)_R\\times U(1)_{B-L}\\times SU(2)_H$ which can explain the required departures from degeneracy in neutrino masses and large mixing among them without assuming any of the mixing in the quark or charged lepton sector to be large as would be expected in a typical $SO(10)$ model.

  3. Frequency metrology in quantum degenerate helium

    Directory of Open Access Journals (Sweden)

    Vassen Wim

    2013-08-01

    Full Text Available We have measured the absolute frequency of the 1557-nm doubly forbidden transition between the two metastable states of helium, 2 3S1 (lifetime 8000 s and 2 1S0 (lifetime 20 ms, with 1 kHz precision. With an Einstein coefficient of 10−7 s−1 this is one of weakest optical transitions ever measured. The measurement was performed in a Bose-Einstein condensate of 4He* as well as in a Degenerate Fermi Gas of 3He*, trapped in a crossed dipole trap. From the isotope shift we deduced the nuclear charge radius difference between the α-particle and the helion. Our value differs by 4σ with a very recent result obtained on the 2 3S → 2 3P transition.

  4. [Climate, brain, and degeneration in Cabanis].

    Science.gov (United States)

    Caponi, Sandra

    2009-01-01

    This analysis of the arguments defended by Cabanis in "Rapports du physique et du moral de l'homme" takes as its point of departure his eighth and ninth Memoirs, which focus on analyzing the influences of regime and climate. These writings afford a new reading of the arguments Cabanis used to explain the relation between the physical traits and moral habits of individuals and races. The article analyzes his debts to natural history, especially Buffon's theory of degeneration; to the Hippocratic tradition, above all the humor theory; and to studies of brain anatomy and pathology. Lastly, it examines the role that the human and moral sciences of medicine and hygiene play in the regeneration of the human species.

  5. Bmi-1 absence causes premature brain degeneration.

    Directory of Open Access Journals (Sweden)

    Guangliang Cao

    Full Text Available Bmi-1, a polycomb transcriptional repressor, is implicated in cell cycle regulation and cell senescence. Its absence results in generalized astrogliosis and epilepsy during the postnatal development, but the underlying mechanisms are poorly understood. Here, we demonstrate the occurrence of oxidative stress in the brain of four-week-old Bmi-1 null mice. The mice showed various hallmarks of neurodegeneration including synaptic loss, axonal demyelination, reactive gliosis and brain mitochondrial damage. Moreover, astroglial glutamate transporters and glutamine synthetase decreased in the Bmi-1 null hippocampus, which might contribute to the sporadic epileptic-like seizures in these mice. These results indicate that Bmi-1 is required for maintaining endogenous antioxidant defenses in the brain, and its absence subsequently causes premature brain degeneration.

  6. A computational model of motor neuron degeneration.

    Science.gov (United States)

    Le Masson, Gwendal; Przedborski, Serge; Abbott, L F

    2014-08-20

    To explore the link between bioenergetics and motor neuron degeneration, we used a computational model in which detailed morphology and ion conductance are paired with intracellular ATP production and consumption. We found that reduced ATP availability increases the metabolic cost of a single action potential and disrupts K+/Na+ homeostasis, resulting in a chronic depolarization. The magnitude of the ATP shortage at which this ionic instability occurs depends on the morphology and intrinsic conductance characteristic of the neuron. If ATP shortage is confined to the distal part of the axon, the ensuing local ionic instability eventually spreads to the whole neuron and involves fasciculation-like spiking events. A shortage of ATP also causes a rise in intracellular calcium. Our modeling work supports the notion that mitochondrial dysfunction can account for salient features of the paralytic disorder amyotrophic lateral sclerosis, including motor neuron hyperexcitability, fasciculation, and differential vulnerability of motor neuron subpopulations.

  7. LOCKING-FREE DEGENERATED ISOPARAMETRIC SHELL ELEMENT

    Institute of Scientific and Technical Information of China (English)

    章向明; 王安稳; 何汉林

    2001-01-01

    An 8-noded locking-free degenerated isoparametric shell element is presented.A revised interpolation for shear strain terms was constructed in natural co-ordinate system such that all necessary modes ( translation, rotation and constant curvature ) are preserved,which can be used to eliminate shear locking. A revised interpolation for membrane strains was produced in the local Cartesian co-ordinate system to overcome membrane locking behavior. The new 8-noded element has the proper rank, with the requisite number of zero eigenvalues each associated with a rigid mode. The element does not exhibit membrane or shear locking for large span-thickness ratio. The element does not form element mechanisms or extra spurious zero energy modes. Therefore, it can be used for both thin and thick shells.

  8. Neuropathology of frontotemporal lobar degeneration: A review

    Directory of Open Access Journals (Sweden)

    Valéria Santoro Bahia

    Full Text Available ABSTRACT Frontotemporal lobar degeneration (FTLD is the second most common cause of presenile dementia. Three main clinical variants are widely recognized within the FTLD spectrum: the behavioural variant of frontotemporal dementia (bvFTD, semantic dementia (SD and progressive non-fluent aphasia (PNFA. FTLD represents a highly heterogeneous group of neurodegenerative disorders which are best classified according to the main protein component of pathological neuronal and glial inclusions. The most common pathological class of FTLD is associated with the TDP-43 protein (FTLD-TDP, while FTLD-Tau is considered slightly less common while the FTLD-FUS (Fused in sarcoma protein pathology is rare. In this review, these three major pathological types of FTLD are discussed.

  9. Output radiation from a degenerate parametric oscillator

    CERN Document Server

    Tesfa, S

    2007-01-01

    We study the squeezing as well as the statistical properties of the output radiation from a degenerate parametric oscillator coupled to a squeezed vacuum reservoir employing the stochastic differential equations associated with the normal ordering. It is found that the degree of squeezing of the output radiation is less than the corresponding cavity radiation. However, for output radiation the correlation of the quadrature operators evaluated at different times also exhibits squeezing, which is the reason for quenching of the overall noise in one of the quadrature components of the squeezing spectrum even when the oscillator is coupled to a vacuum reservoir. Moreover, coupling the oscillator to the squeezed vacuum reservoir enhances the squeezing exponentially and it also increases the mean photon number.

  10. Nearly degenerate neutrinos, Supersymmetry and radiative corrections

    CERN Document Server

    Casas, J A; Ibarra, Alejandro; Navarro, I

    2000-01-01

    If neutrinos are to play a relevant cosmological role, they must be essentially degenerate with a mass matrix of the bimaximal mixing type. We study this scenario in the MSSM framework, finding that if neutrino masses are produced by a see-saw mechanism, the radiative corrections give rise to mass splittings and mixing angles that can accommodate the atmospheric and the (large angle MSW) solar neutrino oscillations. This provides a natural origin for the $\\Delta m^2_{sol} << \\Delta m^2_{atm}$ hierarchy. On the other hand, the vacuum oscillation solution to the solar neutrino problem is always excluded. We discuss also in the SUSY scenario other possible effects of radiative corrections involving the new neutrino Yukawa couplings, including implications for triviality limits on the Majorana mass, the infrared fixed point value of the top Yukawa coupling, and gauge coupling and bottom-tau unification.

  11. Conjunctival intraepithelial neoplasia with corneal furrow degeneration

    Directory of Open Access Journals (Sweden)

    Pukhraj Rishi

    2014-01-01

    Full Text Available A 68-year-old man presented with redness of left eye since six months. Examination revealed bilateral corneal furrow degeneration. Left eye lesion was suggestive of conjunctival squamous cell carcinoma, encroaching on to cornea. Anterior segment optical coherence tomography (AS-OCT confirmed peripheral corneal thinning. Fluorescein angiography confirmed intrinsic vascularity of lesion. Patient was managed with "no touch" surgical excision, dry keratectomy without alcohol, cryotherapy, and primary closure. Pathologic examination of removed tissue confirmed clinical diagnosis. Management of this particular case required modification of standard treatment protocol. Unlike the alcohol-assisted technique of tumor dissection described, ethyl alcohol was not used for risk of corneal perforation due to underlying peripheral corneal thinning. Likewise, topical steroids were withheld in the post-operative period. Three weeks post-operatively, left eye was healing well. Hence, per-operative usage of absolute alcohol and post-operative use of topical steroids may be best avoided in such eyes.

  12. CEMAsuite: open source degenerate PCR primer design.

    Science.gov (United States)

    Lane, Courtney E; Hulgan, Daniel; O'Quinn, Kelly; Benton, Michael G

    2015-11-15

    The codon-equivalent multiple alignment suite begins conservational analysis for polymerase chain reaction primer design at the protein level, allowing the user to design consensus primers capable of detecting homologous coding sequences even when low-to-moderate sequence information is available. This package also condenses the wealth of information associated with multiple sequence alignments and presents them in an intuitive manner, allowing the user to quickly and effectively address degenerate primer design considerations. https://sourceforge.net/projects/cemasuite/. benton@lsu.edu or cemasuite@gmail.com Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  13. Progression of Fatty Muscle Degeneration in Atraumatic Rotator Cuff Tears.

    Science.gov (United States)

    Hebert-Davies, Jonah; Teefey, Sharlene A; Steger-May, Karen; Chamberlain, Aaron M; Middleton, William; Robinson, Kathryn; Yamaguchi, Ken; Keener, Jay D

    2017-05-17

    The purpose of this prospective study was to examine the progression of fatty muscle degeneration over time in asymptomatic shoulders with degenerative rotator cuff tears. Subjects with an asymptomatic rotator cuff tear in 1 shoulder and pain due to rotator cuff disease in the contralateral shoulder were enrolled in a prospective cohort. Subjects were followed annually with shoulder ultrasonography, which evaluated tear size, location, and fatty muscle degeneration. Tears that were either full-thickness at enrollment or progressed to a full-thickness defect during follow-up were examined. A minimum follow-up of 2 years was necessary for eligibility. One hundred and fifty-six shoulders with full-thickness rotator cuff tears were potentially eligible. Seventy shoulders had measurable fatty muscle degeneration of at least 1 rotator cuff muscle at some time point. Patients with fatty muscle degeneration in the shoulder were older than those without degeneration (mean, 65.8 years [95% confidence interval (CI), 64.0 to 67.6 years] compared with 61.0 years [95% CI, 59.1 to 62.9 years]; p tears at baseline was larger in shoulders with degeneration than in shoulders that did not develop degeneration (13 and 10 mm wide, respectively, and 13 and 10 mm long; p Tears with fatty muscle degeneration were more likely to have enlarged during follow-up than were tears that never developed muscle degeneration (79% compared with 58%; odds ratio, 2.64 [95% CI, 1.29 to 5.39]; p muscle degeneration occurred more frequently in shoulders with tears that had enlarged (43%; 45 of 105) than in shoulders with tears that had not enlarged (20%; 10 of 51; p tears with enlargement and progression of muscle degeneration were more likely to extend into the anterior supraspinatus than were those without progression (53% and 17%, respectively; p tear size (p = 0.56). The median time from tear enlargement to progression of fatty muscle degeneration was 1.0 year (range, -2.0 to 6.9 years) for the

  14. Expression of human complement factor H prevents age-related macular degeneration-like retina damage and kidney abnormalities in aged Cfh knockout mice.

    Science.gov (United States)

    Ding, Jin-Dong; Kelly, Una; Landowski, Michael; Toomey, Christopher B; Groelle, Marybeth; Miller, Chelsey; Smith, Stephanie G; Klingeborn, Mikael; Singhapricha, Terry; Jiang, Haixiang; Frank, Michael M; Bowes Rickman, Catherine

    2015-01-01

    Complement factor H (CFH) is an important regulatory protein in the alternative pathway of the complement system, and CFH polymorphisms increase the genetic risk of age-related macular degeneration dramatically. These same human CFH variants have also been associated with dense deposit disease. To mechanistically study the function of CFH in the pathogenesis of these diseases, we created transgenic mouse lines using human CFH bacterial artificial chromosomes expressing full-length human CFH variants and crossed these to Cfh knockout (Cfh(-/-)) mice. Human CFH protein inhibited cleavage of mouse complement component 3 and factor B in plasma and in retinal pigment epithelium/choroid/sclera, establishing that human CFH regulates activation of the mouse alternative pathway. One of the mouse lines, which express relatively higher levels of CFH, demonstrated functional and structural protection of the retina owing to the Cfh deletion. Impaired visual function, detected as a deficit in the scotopic electroretinographic response, was improved in this transgenic mouse line compared with Cfh(-/-) mice, and transgenics had a thicker outer nuclear layer and less sub-retinal pigment epithelium deposit accumulation. In addition, expression of human CFH also completely protected the mice from developing kidney abnormalities associated with loss of CFH. These humanized CFH mice present a valuable model for study of the molecular mechanisms of age-related macular degeneration and dense deposit disease and for testing therapeutic targets.

  15. CONTROLLABILITY OF DELAY DEGENERATE CONTROL SYSTEMS WITH INDEPENDENT SUBSYSTEMS

    Institute of Scientific and Technical Information of China (English)

    蒋威

    2003-01-01

    The controllability of delay degenerate differential control systems is discussed. Firstly, delay degenerate differential control system was transformed to be canonical form, and the connected terms were gotten rid of, had delay degenerate differential control systems with independent subsystems. For the general delay degenerate differnetial control systems, it was gotten that the necessary and sufficient condition of that they are controllable is that their reachable set is equal to the whole space For the delay degenerate differential control systems with independent subsystems, it was gotten that the necessary and sufficient conditions of that they are controllable are that their reachable sets are equal to their corresponding subspaces. Then some algebra criteria were gotten. Finally, an example was given to illustrate the main results.

  16. Formation of Degenerate Band Gaps in Layered Systems

    Directory of Open Access Journals (Sweden)

    Alexey P. Vinogradov

    2012-06-01

    Full Text Available In the review, peculiarities of spectra of one-dimensional photonic crystals made of anisotropic and/or magnetooptic materials are considered. The attention is focused on band gaps of a special type—the so called degenerate band gaps which are degenerate with respect to polarization. Mechanisms of formation and properties of these band gaps are analyzed. Peculiarities of spectra of photonic crystals that arise due to the linkage between band gaps are discussed. Particularly, it is shown that formation of a frozen mode is caused by linkage between Brillouin and degenerate band gaps. Also, existence of the optical Borrmann effect at the boundaries of degenerate band gaps and optical Tamm states at the frequencies of degenerate band gaps are analyzed.

  17. Hoelder Continuity for Solutions of Degenerate Parabolic Equation with Two Degenerate Points

    Institute of Scientific and Technical Information of China (English)

    刘建中; 李育生; 等

    1993-01-01

    In this paper we discuss the quasilinear parabolic equation Ut=△↓(uα(1-u)β.△↓u)+B(x,t,u)△↓u+C(x,t,u)which is degenerate at u=0 and u=1.Let u(x,t)be a weak solution of the equation satisfying 0

  18. Fibrosis and inflammation are greater in muscles of beta-sarcoglycan-null mouse than mdx mouse.

    Science.gov (United States)

    Gibertini, Sara; Zanotti, Simona; Savadori, Paolo; Curcio, Maurizio; Saredi, Simona; Salerno, Franco; Andreetta, Francesca; Bernasconi, Pia; Mantegazza, Renato; Mora, Marina

    2014-05-01

    The Sgcb-null mouse, with knocked-down β-sarcoglycan, develops severe muscular dystrophy as in type 2E human limb girdle muscular dystrophy. The mdx mouse, lacking dystrophin, is the most used model for Duchenne muscular dystrophy (DMD). Unlike DMD, the mdx mouse has mild clinical features and shows little fibrosis in limb muscles. To characterize ECM protein deposition and the progression of muscle fibrosis, we evaluated protein and transcript levels of collagens I, III and VI, decorin, and TGF-β1, in quadriceps and diaphragm, at 2, 4, 8, 12, 26, and 52 weeks in Sgcb-null mice, and protein levels at 12, 26, and 52 weeks in mdx mice. In Sgcb-null mice, severe morphological disruption was present from 4 weeks in both quadriceps and diaphragm, and included conspicuous deposition of extracellular matrix components. Histopathological features of Sgcb-null mouse muscles were similar to those of age-matched mdx muscles at all ages examined, but, in the Sgcb-null mouse, the extent of connective tissue deposition was generally greater than mdx. Furthermore, in the Sgcb-null mouse, the amount of all three collagen isoforms increased steadily, while, in the mdx, they remained stable. We also found that, at 12 weeks, macrophages were significantly more numerous in mildly inflamed areas of Sgcb-null quadriceps compared to mdx quadriceps (but not in highly inflamed regions), while, in the diaphragm, macrophages did not differ significantly between the two models, in either region. Osteopontin mRNA was also significantly greater at 12 weeks in laser-dissected highly inflamed areas of the Sgcb-null quadriceps compared to the mdx quadriceps. TGF-β1 was present in areas of degeneration-regeneration, but levels were highly variable and in general did not differ significantly between the two models and controls. The roles of the various subtypes of macrophages in muscle repair and fibrosis in the two models require further study. The Sgcb-null mouse, which develops early fibrosis

  19. Aberrant Schwann cell lipid metabolism linked to mitochondrial deficits leads to axon degeneration and neuropathy.

    Science.gov (United States)

    Viader, Andreu; Sasaki, Yo; Kim, Sungsu; Strickland, Amy; Workman, Cayce S; Yang, Kui; Gross, Richard W; Milbrandt, Jeffrey

    2013-03-06

    Mitochondrial dysfunction is a common cause of peripheral neuropathy. Much effort has been devoted to examining the role played by neuronal/axonal mitochondria, but how mitochondrial deficits in peripheral nerve glia (Schwann cells [SCs]) contribute to peripheral nerve diseases remains unclear. Here, we investigate a mouse model of peripheral neuropathy secondary to SC mitochondrial dysfunction (Tfam-SCKOs). We show that disruption of SC mitochondria activates a maladaptive integrated stress response (ISR) through the actions of heme-regulated inhibitor (HRI) kinase, and causes a shift in lipid metabolism away from fatty acid synthesis toward oxidation. These alterations in SC lipid metabolism result in depletion of important myelin lipid components as well as in accumulation of acylcarnitines (ACs), an intermediate of fatty acid β-oxidation. Importantly, we show that ACs are released from SCs and induce axonal degeneration. A maladaptive ISR as well as altered SC lipid metabolism are thus underlying pathological mechanisms in mitochondria-related peripheral neuropathies.

  20. Fluorescently labeled peptide increases identification of degenerated facial nerve branches during surgery and improves functional outcome.

    Directory of Open Access Journals (Sweden)

    Timon Hussain

    Full Text Available Nerve degeneration after transection injury decreases intraoperative visibility under white light (WL, complicating surgical repair. We show here that the use of fluorescently labeled nerve binding probe (F-NP41 can improve intraoperative visualization of chronically (up to 9 months denervated nerves. In a mouse model for the repair of chronically denervated facial nerves, the intraoperative use of fluorescent labeling decreased time to nerve identification by 40% compared to surgeries performed under WL alone. Cumulative functional post-operative recovery was also significantly improved in the fluorescence guided group as determined by quantitatively tracking of the recovery of whisker movement at time intervals for 6 weeks post-repair. To our knowledge, this is the first description of an injectable probe that increases visibility of chronically denervated nerves during surgical repair in live animals. Future translation of this probe may improve functional outcome for patients with chronic denervation undergoing surgical repair.

  1. Recent advances in early-onset severe retinal degeneration: more than just basic research?

    DEFF Research Database (Denmark)

    Preising, M. N.; Heegaard, S.

    2004-01-01

    ophthalmology, Leber's congenital amaurosis, phenotype, gene therapy, retina, degeneration, rewiew......ophthalmology, Leber's congenital amaurosis, phenotype, gene therapy, retina, degeneration, rewiew...

  2. Gaze beats mouse

    DEFF Research Database (Denmark)

    Mateo, Julio C.; San Agustin, Javier; Hansen, John Paulin

    2008-01-01

    Facial EMG for selection is fast, easy and, combined with gaze pointing, it can provide completely hands-free interaction. In this pilot study, 5 participants performed a simple point-and-select task using mouse or gaze for pointing and a mouse button or a facial-EMG switch for selection. Gaze...... pointing was faster than mouse pointing, while maintaining a similar error rate. EMG and mouse-button selection had a comparable performance. From analyses of completion time, throughput and error rates, we concluded that the combination of gaze and facial EMG holds potential for outperforming the mouse....

  3. Age related macular degeneration and visual disability.

    Science.gov (United States)

    Christoforidis, John B; Tecce, Nicola; Dell'Omo, Roberto; Mastropasqua, Rodolfo; Verolino, Marco; Costagliola, Ciro

    2011-02-01

    Age-related macular degeneration (AMD) is the leading cause of central blindness or low vision among the elderly in industrialized countries. AMD is caused by a combination of genetic and environmental factors. Among modifiable environmental risk factors, cigarette smoking has been associated with both the dry and wet forms of AMD and may increase the likelihood of worsening pre-existing AMD. Despite advances, the treatment of AMD has limitations and affected patients are often referred for low vision rehabilitation to help them cope with their remaining eyesight. The characteristic visual impairment for both forms of AMD is loss of central vision (central scotoma). This loss results in severe difficulties with reading that may be only partly compensated by magnifying glasses or screen-projection devices. The loss of central vision associated with the disease has a profound impact on patient quality of life. With progressive central visual loss, patients lose their ability to perform the more complex activities of daily living. Common vision aids include low vision filters, magnifiers, telescopes and electronic aids. Low vision rehabilitation (LVR) is a new subspecialty emerging from the traditional fields of ophthalmology, optometry, occupational therapy, and sociology, with an ever-increasing impact on the usual concepts of research, education, and services for visually impaired patients. Relatively few ophthalmologists practise LVR and fewer still routinely use prismatic image relocation (IR) in AMD patients. IR is a method of stabilizing oculomotor functions with the purpose of promoting better function of preferred retinal loci (PRLs). The aim of vision rehabilitation therapy consists in the achievement of techniques designed to improve PRL usage. The use of PRLs to compensate for diseased foveae has offered hope to these patients in regaining some function. However, in a recently published meta-analysis, prism spectacles were found to be unlikely to be of

  4. Hyperhomocysteinemia disrupts retinal pigment epithelial structure and function with features of age-related macular degeneration.

    Science.gov (United States)

    Ibrahim, Ahmed S; Mander, Suchreet; Hussein, Khaled A; Elsherbiny, Nehal M; Smith, Sylvia B; Al-Shabrawey, Mohamed; Tawfik, Amany

    2016-02-23

    The disruption of retinal pigment epithelial (RPE) function and the degeneration of photoreceptors are cardinal features of age related macular degeneration (AMD); however there are still gaps in our understanding of underlying biological processes. Excess homocysteine (Hcy) has been reported to be elevated in plasma of patients with AMD. This study aimed to evaluate the direct effect of hyperhomocysteinemia (HHcy) on structure and function of RPE. Initial studies in a mouse model of HHcy, in which cystathionine-β-synthase (cbs) was deficient, revealed abnormal RPE cell morphology with features similar to that of AMD upon optical coherence tomography (OCT), fluorescein angiography (FA), histological, and electron microscopic examinations. These features include atrophy, vacuolization, hypopigmentation, thickened basal laminar membrane, hyporeflective lucency, choroidal neovascularization (CNV), and disturbed RPE-photoreceptor relationship. Furthermore, intravitreal injection of Hcy per se in normal wild type (WT) mice resulted in diffuse hyper-fluorescence, albumin leakage, and CNV in the area of RPE. In vitro experiments on ARPE-19 showed that Hcy dose-dependently reduced tight junction protein expression, increased FITC dextran leakage, decreased transcellular electrical resistance, and impaired phagocytic activity. Collectively, our results demonstrated unreported effects of excess Hcy levels on RPE structure and function that lead to the development of AMD-like features.

  5. Altered glial gene expression, density, and architecture in the visual cortex upon retinal degeneration.

    Science.gov (United States)

    Cornett, Ashley; Sucic, Joseph F; Hillsburg, Dylan; Cyr, Lindsay; Johnson, Catherine; Polanco, Anthony; Figuereo, Joe; Cabine, Kenneth; Russo, Nickole; Sturtevant, Ann; Jarvinen, Michael K

    2011-11-08

    Genes encoding the proteins of cytoskeletal intermediate filaments (IF) are tightly regulated, and they are important for establishing neural connections. However, it remains uncertain to what extent neurological disease alters IF gene expression or impacts cells that express IFs. In this study, we determined the onset of visual deficits in a mouse model of progressive retinal degeneration (Pde6b(-) mice; Pde6b(+) mice have normal vision) by observing murine responses to a visual task throughout development, from postnatal day (PND) 21 to adult (N=174 reliable observations). Using Q-PCR, we evaluated whether expression of the genes encoding two Type III IF proteins, glial fibrillary acidic protein (GFAP) and vimentin was altered in the visual cortex before, during, and after the onset of visual deficits. Using immunohistochemical techniques, we investigated the impact of vision loss on the density and morphology of astrocytes that expressed GFAP and vimentin in the visual cortex. We found that Pde6b(-) mice displayed 1) evidence of blindness at PND 49, with visual deficits detected at PND 35, 2) reduced GFAP mRNA expression in the visual cortex between PND 28 and PND 49, and 3) an increased ratio of vimentin:GFAP-labeled astrocytes at PND 49 with reduced GFAP cell body area. Together, these findings demonstrate that retinal degeneration modifies cellular and molecular indices of glial plasticity in a visual system with drastically reduced visual input. The functional consequences of these structural changes remain uncertain.

  6. ROCK-Isoform-Specific Polarization of Macrophages Associated with Age-Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Souska Zandi

    2015-02-01

    Full Text Available Age is a major risk factor in age-related macular degeneration (AMD, but the underlying cause is unknown. We find increased Rho-associated kinase (ROCK signaling and M2 characteristics in eyes of aged mice, revealing immune changes in aging. ROCK isoforms determine macrophage polarization into M1 and M2 subtypes. M2-like macrophages accumulated in AMD, but not in normal eyes, suggesting that these macrophages may be linked to macular degeneration. M2 macrophages injected into the mouse eye exacerbated choroidal neovascular lesions, while M1 macrophages ameliorated them, supporting a causal role for macrophage subtypes in AMD. Selective ROCK2 inhibition with a small molecule decreased M2-like macrophages and choroidal neovascularization. ROCK2 inhibition upregulated M1 markers without affecting macrophage recruitment, underlining the plasticity of these macrophages. These results reveal age-induced innate immune imbalance as underlying AMD pathogenesis. Targeting macrophage plasticity opens up new possibilities for more effective AMD treatment.

  7. Gene replacement therapy rescues photoreceptor degeneration in a murine model of Leber congenital amaurosis lacking RPGRIP.

    Science.gov (United States)

    Pawlyk, Basil S; Smith, Alexander J; Buch, Prateek K; Adamian, Michael; Hong, Dong-Hyun; Sandberg, Michael A; Ali, Robin R; Li, Tiansen

    2005-09-01

    Retinitis pigmentosa GTPase regulator (RPGR) is a photoreceptor protein anchored in the connecting cilia by an RPGR-interacting protein (RPGRIP). Loss of RPGRIP causes Leber congenital amaurosis (LCA), a severe form of photoreceptor degeneration. The current study was an investigation of whether somatic gene replacement could rescue degenerating photoreceptors in a murine model of LCA due to a defect in RPGRIP. An RPGRIP expression cassette, driven by a mouse opsin promoter, was packaged into recombinant adeno-associated virus (AAV). The AAV vector was delivered into the right eyes of RPGRIP(-/-) mice by a single subretinal injection into the superior hemisphere. The left eyes received a saline injection as a control. Full-field electroretinograms (ERGs) were recorded from both eyes at 2, 3, 4, and 5 months after injection. After the final follow-up, retinas were analyzed by immunostaining or by light and electron microscopy. Delivery of the AAV vector led to RPGRIP expression and restoration of normal RPGR localization at the connecting cilia. Photoreceptor preservation was evident by a thicker cell layer and well-developed outer segments in the treated eyes. Rescue was more pronounced in the superior hemisphere coincident with the site of delivery. Functional preservation was demonstrated by ERG. AAV-mediated RPGRIP gene replacement preserves photoreceptor structure and function in a mouse model of LCA, despite ongoing cell loss at the time of intervention. These results indicate that gene replacement therapy may be effective in patients with LCA due to a defect in RPGRIP and suggest that further preclinical development of gene therapy for this disorder is warranted.

  8. THE MIXED PROBLEM FOR DEGENERATE ELLIPTIC EQUATIONS OF SECOND ORDER

    Institute of Scientific and Technical Information of China (English)

    Guochun Wen

    2005-01-01

    The present paper deals with the mixed boundary value problem for elliptic equations with degenerate rank 0. We first give the formulation of the problem and estimates of solutions of the problem, and then prove the existence of solutions of the above problem for elliptic equations by the above estimates and the method of parameter extension. We use the complex method, namely first discuss the corresponding problem for degenerate elliptic complex equations of first order, afterwards discuss the above problem for degenerate elliptic equations of second order.

  9. Pathophysiological basis of lumbar disc degeneration: imaging analysis.

    Science.gov (United States)

    Ostrum, B J; Romy, M; Swartz, J D

    1993-12-01

    This article provides a brief synopsis of the pathoanatomic basis of disc degeneration. An attempt is made to correlate CT, MR and CT discographic findings. The T2-weighted sagittal images are the most sensitive for evaluating disc degeneration. The contour changes on axial CT and MR scans are sensitive for abnormalities but not always specific. The CT discogram adds information unavailable by other imaging methods pertaining to the internal architecture of the disc. It additionally defines focal nuclear herniations and also is helpful in evaluating the stage of disc degeneration.

  10. Pyridoxine neuropathy in rats: specific degeneration of sensory axons.

    Science.gov (United States)

    Windebank, A J; Low, P A; Blexrud, M D; Schmelzer, J D; Schaumburg, H H

    1985-11-01

    When rats received pyridoxine in doses large enough to cause neuropathy in humans, the animals developed gait ataxia that subsided after the toxin was withdrawn. By using quantitative histologic techniques, we found axonal degeneration of sensory system fibers and that the fibers derived from the ventral root were spared. Although the degeneration approached the dorsal root ganglion, neurons in the ganglion did not degenerate. We found no early decrease in oxygen consumption of nerve, suggesting that impaired oxidative metabolism was not the primary event.

  11. Case report 872. "Ancient" schwannoma (degenerated neurilemoma).

    Science.gov (United States)

    Schultz, E; Sapan, M R; McHeffey-Atkinson, B; Naidich, J B; Arlen, M

    1994-10-01

    A case of an ancient schwannoma was presented. The rare occurrence of this tumor has resulted in only a few reported cases with descriptions of its features on imaging. Our patient's tumor, like one previously reported case, demonstrated calcification on the plain film - a finding not associated with other histologic types of schwannomas. Angiography revealed the tumor to be hypervascular. Evaluation by MRI demonstrated a lobulated, encapsulated soft tissue mass containing several cystic areas that corresponded histologically to areas of necrosis. Hypertrophied blood vessels were seen in the periphery of the tumoral mass. Too few ancient schwannomas have been reported to conclude whether or not radiographic evidence of soft tissue calcification is characteristic of this histologically distinctive subtype of schwannoma. However, since calcification is seen histologically as part of the degenerating process, its presence on plain films could be a feature of this tumor. Furthermore, the presence of cystic areas on MRI is not surprising given the pathological changes that occur in this tumor. We suggest that a diagnosis of ancient schwannoma be considered when a patient presents with a hypervascular soft tissue mass containing amorphous calcification on plain films and cystic areas on MRI. Despite the nonspecificity of these imaging findings, this point is relevant because each of these features suggests the presence of a malignant mass. Awareness of the possibility of a benign ancient schwannoma could obviate unnecessary radical surgery.

  12. Correlations in a partially degenerate electron plasma

    Energy Technology Data Exchange (ETDEWEB)

    Chihara, Junzo [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

    1998-03-01

    The density-functional theory proves that an ion-electron mixture can be treated as a one-component liquid interacting only via a pairwise interaction in the evaluation of the ion-ion radial distribution function (RDF), and provides a set of integral equations: one is an integral equation for the ion-ion RDF and another for an effective ion-ion interaction, which depends on the ion-ion RDF. This formulation gives a set of integral equation to calculate plasma structures with combined use of the electron-electron correlations in a partially degenerate electron plasma. Therefore, it is important for this purpose to determine the electron-electron correlations at a arbitrary temperature. Here, they are calculated by the quantal version of the hypernetted chain (HNC) equation. On the basis of the jellium-vacancy model, the ionic and electronic structures of rubidium are calculated for the range from liquid metal to plasma states by increasing the temperature at the fixed density using the electron-correlation results. (author)

  13. Single degenerate supernova type Ia progenitors

    CERN Document Server

    Bours, M C P; Nelemans, G

    2013-01-01

    There is general agreement that supernovae Ia correspond to the thermonuclear runaway of a white dwarf that is part of a compact binary, but the details of the progenitor systems are still unknown and much debated. One of the proposed progenitor theories is the single-degenerate channel in which a white dwarf accretes from a companion, grows in mass, reaches a critical mass limit, and is then consumed after thermonuclear runaway sets in. However, there are major disagreements about the theoretical delay time distribution and the corresponding time-integrated supernova Ia rate from this channel. We investigate whether the differences are due to the uncertainty in the common envelope phase and the fraction of transferred mass that is retained by the white dwarf. This so-called retention efficiency may have a strong influence on the final amount and timing of supernovae Ia. Using the population synthesis code SeBa, we simulated large numbers of binaries for various assumptions on common envelopes and retention e...

  14. [Pharmacological concepts to treat hereditary retinal degenerations].

    Science.gov (United States)

    Poloschek, C M; Jägle, H

    2012-02-01

    This article reviews the current pharmacological strategies to treat inherited retinal degeneration. To date there is no causal therapy despite growing knowledge of the particular pathomechanisms. However, treatment is available for complications, such as cystic macular changes and cystoid macular edema. To reduce retinal thickness systemic or topical carboanhydrase inhibitors can be applied and in rare cases combined with steroids when indicated, however reduction of retinal thickness is not always accompanied by improvement of visual acuity. Regular follow-up with optical coherence tomography is required. In some cases, potentially neuroprotective agents (valproic acid, ciliary neurotrophic factor and Ca(2+ ) channel inhibitors) or food supplementation (vitamin A, lutein, synthetic retinoids and decosahexaenoic acid) may have a positive impact on disease progression (e.g. reduction in progression of visual field loss or individual electrophysiological parameters). However, beneficial effects and side effects, e.g. of vitamin A substitution, depend not only on the disease phenotype (such as retinitis pigmentosa) but also on the actual genotype. Furthermore, no data are available regarding the application of pharmaceuticals in the pediatric population.

  15. Quantum kinetic theories in degenerate plasmas

    Science.gov (United States)

    Brodin, Gert; Ekman, Robin; Zamanian, Jens

    2017-01-01

    In this review we give an overview of the recent work on quantum kinetic theories of plasmas. We focus, in particular, on the case where the electrons are fully degenerate. For such systems, perturbation methods using the distribution function can be problematic. Instead we present a model that considers the dynamics of the Fermi surface. The advantage of this model is that, even though the value of the distribution function can be greatly perturbed outside the equilibrium Fermi surface, deformation of the Fermi surface is small up to very large amplitudes. Next, we investigate the short-scale dynamics for which the Wigner-Moyal equation replaces the Vlasov equation. In particular, we study wave-particle interaction, and deduce that new types of wave damping can occur due to the simultaneous absorption (or emission) of multiple wave quanta. Finally, we consider exchange effects within a quantum kinetic formalism to find a model that is more accurate than those using exchange potentials from density functional theory. We deduce the exchange corrections to the dispersion relations for Langmuir and ion-acoustic waves. In comparison to results based on exchange potentials deduced from density functional theory we find that the latter models are reasonably accurate for Langmuir waves, but rather inaccurate for ion acoustic waves.

  16. Chronic nerve root entrapment: compression and degeneration

    Science.gov (United States)

    Vanhoestenberghe, A.

    2013-02-01

    Electrode mounts are being developed to improve electrical stimulation and recording. Some are tight-fitting, or even re-shape the nervous structure they interact with, for a more selective, fascicular, access. If these are to be successfully used chronically with human nerve roots, we need to know more about the possible damage caused by the long-term entrapment and possible compression of the roots following electrode implantation. As there are, to date, no such data published, this paper presents a review of the relevant literature on alternative causes of nerve root compression, and a discussion of the degeneration mechanisms observed. A chronic compression below 40 mmHg would not compromise the functionality of the root as far as electrical stimulation and recording applications are concerned. Additionally, any temporary increase in pressure, due for example to post-operative swelling, should be limited to 20 mmHg below the patient’s mean arterial pressure, with a maximum of 100 mmHg. Connective tissue growth may cause a slower, but sustained, pressure increase. Therefore, mounts large enough to accommodate the root initially without compressing it, or compliant, elastic, mounts, that may stretch to free a larger cross-sectional area in the weeks after implantation, are recommended.

  17. Animal models of age related macular degeneration.

    Science.gov (United States)

    Pennesi, Mark E; Neuringer, Martha; Courtney, Robert J

    2012-08-01

    Age related macular degeneration (AMD) is the leading cause of vision loss of those over the age of 65 in the industrialized world. The prevalence and need to develop effective treatments for AMD has lead to the development of multiple animal models. AMD is a complex and heterogeneous disease that involves the interaction of both genetic and environmental factors with the unique anatomy of the human macula. Models in mice, rats, rabbits, pigs and non-human primates have recreated many of the histological features of AMD and provided much insight into the underlying pathological mechanisms of this disease. In spite of the large number of models developed, no one model yet recapitulates all of the features of human AMD. However, these models have helped reveal the roles of chronic oxidative damage, inflammation and immune dysregulation, and lipid metabolism in the development of AMD. Models for induced choroidal neovascularization have served as the backbone for testing new therapies. This article will review the diversity of animal models that exist for AMD as well as their strengths and limitations.

  18. CERKL knockdown causes retinal degeneration in zebrafish.

    Directory of Open Access Journals (Sweden)

    Marina Riera

    Full Text Available The human CERKL gene is responsible for common and severe forms of retinal dystrophies. Despite intense in vitro studies at the molecular and cellular level and in vivo analyses of the retina of murine knockout models, CERKL function remains unknown. In this study, we aimed to approach the developmental and functional features of cerkl in Danio rerio within an Evo-Devo framework. We show that gene expression increases from early developmental stages until the formation of the retina in the optic cup. Unlike the high mRNA-CERKL isoform multiplicity shown in mammals, the moderate transcriptional complexity in fish facilitates phenotypic studies derived from gene silencing. Moreover, of relevance to pathogenicity, teleost CERKL shares the two main human protein isoforms. Morpholino injection has been used to generate a cerkl knockdown zebrafish model. The morphant phenotype results in abnormal eye development with lamination defects, failure to develop photoreceptor outer segments, increased apoptosis of retinal cells and small eyes. Our data support that zebrafish Cerkl does not interfere with proliferation and neural differentiation during early developmental stages but is relevant for survival and protection of the retinal tissue. Overall, we propose that this zebrafish model is a powerful tool to unveil CERKL contribution to human retinal degeneration.

  19. Diversity of Mitochondrial Pathology in a Mouse Model of Axonal Degeneration in Synucleinopathies

    Directory of Open Access Journals (Sweden)

    Akio Sekigawa

    2013-01-01

    Full Text Available There is mounting evidence for a role of mitochondrial dysfunction in the pathogenesis of α-synucleinopathies such as Parkinson's disease (PD and dementia with Lewy bodies (DLB. In particular, recent studies have demonstrated that failure of mitochondrial quality control caused by loss of function of the PTEN-induced kinase 1 (PINK1, PARK6 Parkin (PARK2 pathway may be causative in some familial PD. In sporadic PD, α-synuclein aggregation may interfere with mitochondrial function, and this might be further exacerbated by leucine-rich repeat kinase 2 (LRRK2. The majority of these findings have been obtained in Drosophila and cell cultures, whereas the objective of this paper is to discuss our recent results on the axonal pathology of brains derived from transgenic mice expressing α-synuclein or DLB-linked P123H β-synuclein. In line with the current view of the pathogenesis of sporadic PD, mitochondria abnormally accumulated in α-synuclein/LRRK2-immunopositive axonal swellings in mice expressing α-synuclein. Curiously, neither mitochondria nor LRRK2 was present in the swellings of mice expressing P123H β-synuclein, suggesting that α- and β-synuclein might play differential roles in the mitochondrial pathology of α-synucleinopathies.

  20. Alcohol Induced Hepatic Degeneration in a Hepatitis C Virus Core Protein Transgenic Mouse Model

    Directory of Open Access Journals (Sweden)

    Dong-Hyung Noh

    2014-03-01

    Full Text Available Hepatitis C virus (HCV has become a major public health issue. It is prevalent in most countries. HCV infection frequently begins without clinical symptoms, before progressing to persistent viremia, chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC in the majority of patients (70% to 80%. Alcohol is an independent cofactor that accelerates the development of HCC in chronic hepatitis C patients. The purpose of the current study was to evaluate ethanol-induced hepatic changes in HCV core-Tg mice and mutant core Tg mice. Wild type (NTG, core wild-Tg mice (TG-K, mutant core 116-Tg mice (TG-116 and mutant core 99-Tg mice (TG-99 were used in this investigation. All groups were given drinking water with 10% ethanol and 5% sucrose for 13 weeks. To observe liver morphological changes, we performed histopathological and immunohistochemical examinations. Histopathologically, NTG, TG-K and TG-116 mice showed moderate centrilobular necrosis, while severe centrilobular necrosis and hepatocyte dissociation were observed in TG-99 mice with increasing lymphocyte infiltration and piecemeal necrosis. In all groups, a small amount of collagen fiber was found, principally in portal areas. None of the mice were found to have myofibroblasts based on immunohistochemical staining specific for α-SMA. CYP2E1-positive cells were clearly detected in the centrilobular area in all groups. In the TG-99 mice, we also observed cells positive for CK8/18, TGF-β1 and phosphorylated (p-Smad2/3 and p21 around the necrotic hepatocytes in the centrilobular area (p < 0.01. Based on our data, alcohol intake induced piecemeal necrosis and hepatocyte dissociation in the TG-99 mice. These phenomena involved activation of the TGF-β1/p-Smad2/3/p21 signaling pathway in hepatocytes. Data from this study will be useful for elucidating the association between alcohol intake and HCV infection.

  1. Pathoproteomics of testicular tissue deficient in the GARP component VPS54. The wobbler mouse model of globozoospermia

    DEFF Research Database (Denmark)

    Jockusch, Harald; Holland, Ashlin; Staunten, Lisa

    2014-01-01

    In human globozoospermia, round-headed spermatozoa lack an acrosome and therefore cannot properly interact with oocytes. In the wobbler (WR) mouse, an L967Q missense mutation in the vesicular protein-sorting factor VPS54 causes motor neuron degeneration and globozoospermia. Although electron micr...

  2. Cloning of human and mouse genes homologous to RAD52, a yeast gene involved in DNA repair and recombination.

    NARCIS (Netherlands)

    D.F.R. Muris; O.Y. Bezzubova (Olga); J-M. Buerstedde; K. Vreeken; A.S. Balajee; C.J. Osgood; C. Troelstra (Christine); J.H.J. Hoeijmakers (Jan); K. Ostermann; H. Schmidt (Henning); A.T. Natarajan; J.C.J. Eeken; P.H.M. Lohmann (Paul); A. Pastink (Albert)

    1994-01-01

    textabstractThe RAD52 gene of Saccharomyces cerevisiae is required for recombinational repair of double-strand breaks. Using degenerate oligonucleotides based on conserved amino acid sequences of RAD52 and rad22, its counterpart from Schizosaccharomyces pombe, RAD52 homologs from man and mouse were

  3. [Progress on the degeneration mechanism of cave fishes' eyes].

    Science.gov (United States)

    Gu, Xian; Ning, Tiao; Xiao, Heng

    2012-08-01

    Attempts to understand the degeneration of the eyes in cave fish has largely been explained by either various extents of gradual degeneration, ranging from partial to total loss, observed in various species or by acceleration of loss caused by dark environments. However, neither the theory of biological evolution developed by Charles Darwin nor the neutral theory of molecular evolution formulated by Kimura Motoo adequately explains these phenomena. Recent trends in utilizing multidisciplinary research, however, have yielded better results, helping reveal a more complex picture of the mechanisms of degeneration. Here, we summarize the current progress of the research via morphology and anatomy, development biology, animal behavior science and molecular genetics, and offer some perspectives on the ongoing research into the development and degeneration of eyes in cave fish.

  4. Multiple solutions for possibly degenerate equations in divergence form

    Directory of Open Access Journals (Sweden)

    Andrea Pinamonti

    2016-08-01

    Full Text Available Via variational methods, we establish the existence of at least two distinct weak solutions for the Dirichlet problem associated to a possibly degenerate equation in divergence form.

  5. [Research advances in animal models of intervertebral disc degeneration].

    Science.gov (United States)

    Zhang, Wenli; Liu, Hao; Li, Tanzhu

    2007-11-01

    To review the research advances in animal models of human disc degeneration. The relative articles in recent years were extensively reviewed. Studies both at home and abroad were analyzed and classified. The advantages and disadvantages of each method were compared. Studies were classified as either experimentally induced models or spontaneous models. The induced models were subdivided as mechanical (alteration of forces on the normal disc), structural (injury or chemical alteration) and genetically induced models. Spontaneous models included those animals that naturally developed degenerative disc disease. Animal model of intervertebral disc degeneration is an important path for revealing the pathogenesis of human disc degeneration, and play an important role in testing novel interventions. With recent advances in the relevance of animal models and humans, it has a great prospect in study of human disc degeneration.

  6. The degenerate-internal-states approximation for cold collisions

    NARCIS (Netherlands)

    Maan, A.C.; Tiesinga, E.; Stoof, H.T.C.; Verhaar, B.J.

    1990-01-01

    The Degenerate-Internal-States approximation as well as its first-order correction are shown to provide a convenient method for calculating elastic and inelastic collision amplitudes for low temperature atomic scattering.

  7. The homogenization of a class of degenerate quasilinear parabolic equations

    Institute of Scientific and Technical Information of China (English)

    ZHANG Xingyou; HUANG Yong

    2003-01-01

    The homogenization of a class of degenerate quasilinear parabolic equations is studied. The Ap weight theory and the classical compensated compactness method are incorporated to obtain the homogenized equation.

  8. Age-related macular degeneration: current treatment and future options.

    Science.gov (United States)

    Moutray, Tanya; Chakravarthy, Usha

    2011-09-01

    Age-related macular degeneration is the leading cause of visual impairment among older adults in the developed world. Epidemiological studies have revealed a number of genetic, ocular and environmental risk factors for this condition, which can be addressed by disease reduction strategies. We discuss the various treatment options for dry and exudative age-related macular degeneration available and explain how the recommended treatment depends on the exact type, location and extent of the degeneration. Currently, vascular endothelial growth factor (VEGF) inhibition therapy is the best available treatment for exudative age-related macular degeneration but is limited by the need for repeated intravitreal injections. The current treatment regime is being refined through research on optimal treatment frequency and duration and type of anti-VEGF drug. Different modes of drug delivery are being developed and in the future other methods of VEGF inhibition may be used.

  9. Gene expression profile analysis of human intervertebral disc degeneration

    OpenAIRE

    Kai Chen; Dajiang Wu; Xiaodong Zhu; Haijian Ni; Xianzhao Wei; Ningfang Mao; Yang Xie; Yunfei Niu; Ming Li

    2013-01-01

    In this study, we used microarray analysis to investigate the biogenesis and progression of intervertebral disc degeneration. The gene expression profiles of 37 disc tissue samples obtained from patients with herniated discs and degenerative disc disease collected by the National Cancer Institute Cooperative Tissue Network were analyzed. Differentially expressed genes between more and less degenerated discs were identified by significant analysis of microarray. A total of 555 genes were signi...

  10. Controllability of Degenerating Reaction-Diffusion System in Electrocardiology

    CERN Document Server

    Bendahmane, Mostafa

    2011-01-01

    This paper is devoted to analyze the null controllability of a nonlinear reaction-diffusion system approximating a parabolic-elliptic system modeling electrical activity in the heart. The uniform, with respect to the degenerating parameter, null controllability of the approximating system by a single control force acting on a subdomain is shown. The proof needs a precisely estimate with respect to the degenerating parameter and it is done combining Carleman estimates and energy inequalities.

  11. Longitudinal, degenerate, and transversal parametric oscillation in a photorefractive media

    DEFF Research Database (Denmark)

    Pedersen, H.C.; Johansen, P.M.

    1996-01-01

    We present a theoretical model of photorefractive parametric oscillation that covers, for the first time, to our knowledge, the occurrence of the whole spectrum of parametric processes from transversal over degenerate to longitudinal parametric oscillation. It is shown that inclusion of so......-called noneigenwaves is essential for completing the model. We report on the first experiment that shows the transition from transversal over degenerate to longitudinal parametric oscillation. The experimental observations agree well with the theoretical predictions....

  12. Singular Fibers in Barking Families of Degenerations of Elliptic Curves

    CERN Document Server

    Okuda, Takayuki

    2012-01-01

    Takamura established a theory on splitting families of degenerations of complex curves. He introduced a powerful method for constructing a splitting family, called a barking family, in which there appear not only a singular fiber over the origin but also singular fibers over other points, called subordinate fibers. In this paper, for the case of degenerations of elliptic curves, we determine the types of these subordinate fibers.

  13. Degenerate four wave mixing in solid core photonic bandgap fibers

    DEFF Research Database (Denmark)

    Rasmussen, Per Dalgaard; Lægsgaard, Jesper; Bang, Ole

    2008-01-01

    Degenerate four wave mixing in solid core photonic bandgap fibers is studied theoretically. We demonstrate the possibility of generating parametric gain across bandgaps, and propose a specific design suited for degenerate four wave mixing when pumping at 532nmm. the possibility of tuning the effi...... the efficency of the parametric gain by varying the temperature is also considered. The sults are verified by numerical simultations of pulse propagation....

  14. [Depression in Patients with Age-Related Macular Degeneration].

    Science.gov (United States)

    Narváez, Yamile Reveiz; Gómez-Restrepo, Carlos

    2012-09-01

    Age-related macular degeneration is a cause for disability in the elderly since it greatly affects their quality of life and increases depression likelihood. This article discusses the negative effect depression has on patients with age-related macular degeneration and summarizes the interventions available for decreasing their depression index. Copyright © 2012 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  15. Linear and nonlinear degenerate abstract differential equations with small parameter

    OpenAIRE

    Shakhmurov, Veli B.

    2016-01-01

    The boundary value problems for linear and nonlinear regular degenerate abstract differential equations are studied. The equations have the principal variable coefficients and a small parameter. The linear problem is considered on a parameter-dependent domain (i.e., on a moving domain). The maximal regularity properties of linear problems and the optimal regularity of the nonlinear problem are obtained. In application, the well-posedness of the Cauchy problem for degenerate parabolic equation...

  16. CKD Increases the Risk of Age-Related Macular Degeneration

    OpenAIRE

    Liew, Gerald; Mitchell, Paul; Wong, Tien Yin; Iyengar, Sudha K; Wang, Jie Jin

    2008-01-01

    Age-related macular degeneration is the leading cause of irreversible blindness in the United States and often coexists with chronic kidney disease. Both conditions share common genetic and environmental risk factors. A total of 1183 participants aged 54+ were examined in the population-based, prospective cohort Blue Mountains Eye Study (Australia) to determine if chronic kidney disease increases the risk of age-related macular degeneration. Moderate chronic kidney disease (estimated glomerul...

  17. New solutions in pure gravity with degenerate tetrads

    CERN Document Server

    Kaul, Romesh K

    2016-01-01

    In first order formulation of pure gravity, we find a new class of solutions to the equations of motion represented by degenerate four-geometries. These configurations are described by non- invertible tetrads with two zero eigenvalues and admit non-vanishing torsion. The homogeneous ones among these infinitely many degenerate solutions admit a geometric classification provided by the three fundamental geometries that a closed two-surface can accomodate, namely, E^2 , S^2 and H^2.

  18. Frontotemporal Lobar Degeneration and microRNAs

    Directory of Open Access Journals (Sweden)

    Paola ePiscopo

    2016-02-01

    Full Text Available Frontotemporal lobar degeneration (FTLD includes a spectrum of disorders characterized by changes of personality and social behaviour and, often, a gradual and progressive language dysfunction. In the last years, several efforts have been fulfilled in identifying both genetic mutations and pathological proteins associated with FTLD. The molecular bases undergoing the onset and progression of the disease remain still unknown. Recent literature prompts an involvement of RNA metabolism in FTLD, particularly miRNAs. Dysregulation of miRNAs in several disorders, including neurodegenerative diseases, and increasing importance of circulating miRNAs in different pathologies has suggested to implement the study of their possible application as biological markers and new therapeutic targets; moreover, miRNA-based therapy is becoming a powerful tool to deepen the function of a gene, the mechanism of a disease, and validate therapeutic targets. Regarding FTLD, different studies showed that miRNAs are playing an important role. For example, several reports have evaluated miRNA regulation of the progranulin gene suggesting that it is under their control, as described for miR-29b, miR-107 and miR-659. More recently, it has been demonstrated that TMEM106B gene, which protein is elevated in FTLD-TDP brains, is repressed by miR-132/212 cluster; this post-transcriptional mechanism increases intracellular levels of progranulin, affecting its pathways. These findings if confirmed could suggest that these microRNAs have a role as potential targets for some related-FTLD genes. In this review, we focus on the emerging roles of the miRNAs in the pathogenesis of FTLD.

  19. Treatment of macular degeneration, according to Bangerter.

    Science.gov (United States)

    Teichmann, K D

    1997-10-30

    Age-related macular degeneration (AMD) is a common cause of visual loss among elderly patients. Although some risk factors have been determined, the ultimate cause of the disease is not known. For a long time, therapeutic nihilism has been the rule among ophthalmologists confronted with such patients. Bangerter has not shared this attitude, especially since the time that he incidentally discovered, more than 40 years ago, the beneficial effects of radiotherapy, in discouraging the growth of new vessels at the posterior pole of the eye. A variety of approaches are combined and used by Bangerter in the treatment of the different types of AMD, including retrobulbar injections of either vasodilating medications (in the dry - or atrophic - type) or corticosteroids (in the wet - or exudative - type), general medical measures aimed at improving metabolic and vascular functions such as supplementation with trace elements, antioxidants, and vitamins; ozone therapy; advice to increase physical fitness, improve nutrition, and abstain from smoking; and protection from excessive light exposure. Being convinced of the usefulness of his type of combination treatment, he has always rejected undertaking controlled clinical trials, of only single aspects of the therapy, as unethical and invalid. For this reason, scientific journals have not proven cooperative in several attempts at publishing his results, as collected in retrospective surveys. Recently, however, some of the several approaches combined by Bangerter in treating AMD have been pronounced effective by other investigators. We present here an overview of his treatment approaches, as few people are aware of them, to clear up misconceptions and to set records straight.

  20. Rehabilitation Approaches in Macular Degeneration Patients.

    Science.gov (United States)

    Maniglia, Marcello; Cottereau, Benoit R; Soler, Vincent; Trotter, Yves

    2016-01-01

    Age related macular degeneration (AMD) is a visual disease that affects elderly population. It entails a progressive loss of central vision whose consequences are dramatic for the patient's quality of life. Current rehabilitation programs are restricted to technical aids based on visual devices. They only temporarily improve specific visual functions such as reading skills. Considering the rapid increase of the aging population worldwide, it is crucial to intensify clinical research on AMD in order to develop simple and efficient methods that improve the patient's visual performances in many different contexts. One very promising approach to face this challenge is based on perceptual learning (PL). Through intensive practice, PL can induce neural plasticity in sensory cortices and result in long-lasting enhancements for various perceptual tasks in both normal and visually impaired populations. A growing number of studies showed how appropriate PL protocols improve visual functions in visual disorders, namely amblyopia, presbyopia or myopia. In order to successfully apply these approaches to more severe conditions such as AMD, numerous challenges have to be overcome. Indeed, the overall elderly age of patients and the reduced cortical surface that is devoted to peripheral vision potentially limit neural plasticity in this population. In addition, ocular fixation becomes much less stable because patients have to rely on peripheral fixation spots outside the scotoma whose size keeps on evolving. The aim of this review article is to discuss the recent literature on this topic and to offer a unified approach for developing new rehabilitation programs of AMD using PL. We argue that with an appropriate experimental and training protocol that is adapted to each patient needs, PL can offer fascinating opportunities for the development of simple, non-expensive rehabilitation approaches a large spectrum of visual functions in AMD patients.

  1. Perceptual learning in patients with macular degeneration

    Directory of Open Access Journals (Sweden)

    Tina ePlank

    2014-10-01

    Full Text Available Patients with age-related macular degeneration (AMD or hereditary macular dystrophies (JMD rely on an efficient use of their peripheral visual field. We trained eight AMD and five JMD patients to perform a texture-discrimination task (TDT at their preferred retinal locus (PRL used for fixation. Six training sessions of approximately one hour duration were conducted over a period of approximately 3 weeks. Before, during and after training twelve patients and twelve age-matched controls (the data from two controls had to be discarded later took part in three functional magnetic resonance imaging (fMRI sessions to assess training-related changes in the BOLD response in early visual cortex. Patients benefited from the training measurements as indexed by significant decrease (p=.001 in the stimulus onset asynchrony (SOA between the presentation of the texture target on background and the visual mask, and in a significant location specific effect of the PRL with respect to hit rate (p=.014. The following trends were observed: (i Improvement in Vernier acuity for an eccentric line-bisection task; (ii positive correlation between the development of BOLD signals in early visual cortex and initial fixation stability (r=0.531; (iii positive correlation between the increase in task performance and initial fixation stability (r=0.730. The first two trends were non-significant, whereas the third trend was significant at p=.014, Bonferroni corrected. Consequently, our exploratory study suggests that training on the TDT can enhance eccentric vision in patients with central vision loss. This enhancement is accompanied by a modest alteration in the BOLD response in early visual cortex.

  2. Rehabilitation Approaches in Macular Degeneration Patients

    Science.gov (United States)

    Maniglia, Marcello; Cottereau, Benoit R.; Soler, Vincent; Trotter, Yves

    2016-01-01

    Age related macular degeneration (AMD) is a visual disease that affects elderly population. It entails a progressive loss of central vision whose consequences are dramatic for the patient’s quality of life. Current rehabilitation programs are restricted to technical aids based on visual devices. They only temporarily improve specific visual functions such as reading skills. Considering the rapid increase of the aging population worldwide, it is crucial to intensify clinical research on AMD in order to develop simple and efficient methods that improve the patient’s visual performances in many different contexts. One very promising approach to face this challenge is based on perceptual learning (PL). Through intensive practice, PL can induce neural plasticity in sensory cortices and result in long-lasting enhancements for various perceptual tasks in both normal and visually impaired populations. A growing number of studies showed how appropriate PL protocols improve visual functions in visual disorders, namely amblyopia, presbyopia or myopia. In order to successfully apply these approaches to more severe conditions such as AMD, numerous challenges have to be overcome. Indeed, the overall elderly age of patients and the reduced cortical surface that is devoted to peripheral vision potentially limit neural plasticity in this population. In addition, ocular fixation becomes much less stable because patients have to rely on peripheral fixation spots outside the scotoma whose size keeps on evolving. The aim of this review article is to discuss the recent literature on this topic and to offer a unified approach for developing new rehabilitation programs of AMD using PL. We argue that with an appropriate experimental and training protocol that is adapted to each patient needs, PL can offer fascinating opportunities for the development of simple, non-expensive rehabilitation approaches a large spectrum of visual functions in AMD patients. PMID:28082876

  3. Generalized degeneracy, dynamic monopolies and maximum degenerate subgraphs

    CERN Document Server

    Zaker, Manouchehr

    2012-01-01

    A graph $G$ is said to be a $k$-degenerate graph if any subgraph of $G$ contains a vertex of degree at most $k$. Let $\\kappa$ be any non-negative function on the vertex set of $G$. We first define a $\\kappa$-degenerate graph. Next we give an efficient algorithm to determine whether a graph is $\\kappa$-degenerate. We revisit the concept of dynamic monopolies in graphs. The latter notion is used in formulation and analysis of spread of influence such as disease or opinion in social networks. We consider dynamic monopolies with (not necessarily positive) but integral threshold assignments. We obtain a sufficient and necessary relationship between dynamic monopolies and generalized degeneracy. As applications of the previous results we consider the problem of determining the maximum size of $\\kappa$-degenerate (or $k$-degenerate) induced subgraphs in any graph. We obtain some upper and lower bounds for the maximum size of any $\\kappa$-degenerate induced subgraph in general and regular graphs. All of our bounds ar...

  4. Classification of the lumbar disc degeneration using MRI

    Energy Technology Data Exchange (ETDEWEB)

    Yoshida, Hirotoshi; Shinomiya, Kenichi; Okamoto, Akihiko; Muto, Naoko; Furuya, Kotaro (Tokyo Medical and Dental Univ. (Japan). School of Medicine)

    1992-11-01

    Magnetic resonance (MR) imaging has been performed in consecutive 114 patients with a chief complaint of lumbar pain. A retrospective review of MR images of a total of 570 lumbar vertebrae from these patients were done to examine lumbar disc degeneration. According to the MR intensity of nucleus pulposus on T2-wighted sagittal images, lumbar disc degeneration was graded on a scale of 0-4: 0=uniform hyperintensity; 1=slight hypointensity; 2=centrally band-like hypointensity with marginal hyperintensity; 3=irregular hypointensity in both the central and marginal sites; 4=uniform hypointensity. Lumbar disc degeneration was observed in 76%; and it was rapidly increased in frequency in the 30 or older age groups. Of 570 vertebrae, 51 (8.9%) had narrowing of intervertebral cavity. For these vertebrae, a mean score of lumbar disc degeneration was 3.1. Lumbar disc herniation was seen in 93 vertebrae, with a mean score of lumbar disc degeneration being 3.07. Changes in vertebral body marrow were seen in 14 vertebrae (2.5%), in which a mean score of intervertebral disc degeneration was 3.71. (N.K.).

  5. CKD increases the risk of age-related macular degeneration.

    Science.gov (United States)

    Liew, Gerald; Mitchell, Paul; Wong, Tien Yin; Iyengar, Sudha K; Wang, Jie Jin

    2008-04-01

    Age-related macular degeneration is the leading cause of irreversible blindness in the United States and often coexists with chronic kidney disease. Both conditions share common genetic and environmental risk factors. A total of 1183 participants aged 54+ were examined in the population-based, prospective cohort Blue Mountains Eye Study (Australia) to determine if chronic kidney disease increases the risk of age-related macular degeneration. Moderate chronic kidney disease (estimated glomerular filtration rate macular degeneration was 3.9% in participants with no/mild chronic kidney disease (35 of 897) and 17.5% in those with moderate chronic kidney disease (50 of 286). After adjusting for age, sex, cigarette smoking, hypertension, complement factor H polymorphism, and other risk factors, persons with moderate chronic kidney disease were 3 times more likely to develop early age-related macular degeneration than persons with no/mild chronic kidney disease (odds ratio = 3.2; 95% confidence interval, 1.8 to 5.7, P macular degeneration (odds ratio = 2.0; 95% confidence interval, 1.5 to 2.8, P chronic kidney disease have a higher risk of early age-related macular degeneration, suggesting the possibility of shared pathophysiologic mechanisms between the two conditions.

  6. GARP2 accelerates retinal degeneration in rod cGMP-gated cation channel β-subunit knockout mice

    Science.gov (United States)

    DeRamus, Marci L.; Stacks, Delores A.; Zhang, Youwen; Huisingh, Carrie E.; McGwin, Gerald; Pittler, Steven J.

    2017-01-01

    The Cngb1 locus-encoded β-subunit of rod cGMP-gated cation channel and associated glutamic acid rich proteins (GARPs) are required for phototransduction, disk morphogenesis, and rod structural integrity. To probe individual protein structure/function of the GARPs, we have characterized several transgenic mouse lines selectively restoring GARPs on a Cngb1 knockout (X1−/−) mouse background. Optical coherence tomography (OCT), light and transmission electron microscopy (TEM), and electroretinography (ERG) were used to analyze 6 genotypes including WT at three and ten weeks postnatal. Comparison of aligned histology/OCT images demonstrated that GARP2 accelerates the rate of degeneration. ERG results are consistent with the structural analyses showing the greatest attenuation of function when GARP2 is present. Even 100-fold or more overexpression of GARP1 could not accelerate degeneration as rapidly as GARP2, and when co-expressed GARP1 attenuated the structural and functional deficits elicited by GARP2. These results indicate that the GARPs are not fully interchangeable and thus, likely have separate and distinct functions in the photoreceptor. We also present a uniform murine OCT layer naming nomenclature system that is consistent with human retina layer designations to standardize murine OCT, which will facilitate data evaluation across different laboratories. PMID:28198469

  7. The Knockout Mouse Project

    OpenAIRE

    Austin, Christopher P.; Battey, James F.; Bradley, Allan; Bucan, Maja; Capecchi, Mario; Collins, Francis S; Dove, William F.; Duyk, Geoffrey; Dymecki, Susan; Eppig, Janan T.; Grieder, Franziska B.; Heintz, Nathaniel; Hicks, Geoff; Insel, Thomas R; Joyner, Alexandra

    2004-01-01

    Mouse knockout technology provides a powerful means of elucidating gene function in vivo, and a publicly available genome-wide collection of mouse knockouts would be significantly enabling for biomedical discovery. To date, published knockouts exist for only about 10% of mouse genes. Furthermore, many of these are limited in utility because they have not been made or phenotyped in standardized ways, and many are not freely available to researchers. It is time to harness new technologies and e...

  8. Replacing the computer mouse

    OpenAIRE

    Dernoncourt, Franck

    2014-01-01

    In a few months the computer mouse will be half-a-century-old. It is known to have many drawbacks, the main ones being: loss of productivity due to constant switching between keyboard and mouse, and health issues such as RSI. Like the keyboard, it is an unnatural human-computer interface. However the vast majority of computer users still use computer mice nowadays. In this article, we explore computer mouse alternatives. Our research shows that moving the mouse cursor can be done efficiently ...

  9. An encyclopedia of mouse DNA elements (Mouse ENCODE).

    Science.gov (United States)

    Stamatoyannopoulos, John A; Snyder, Michael; Hardison, Ross; Ren, Bing; Gingeras, Thomas; Gilbert, David M; Groudine, Mark; Bender, Michael; Kaul, Rajinder; Canfield, Theresa; Giste, Erica; Johnson, Audra; Zhang, Mia; Balasundaram, Gayathri; Byron, Rachel; Roach, Vaughan; Sabo, Peter J; Sandstrom, Richard; Stehling, A Sandra; Thurman, Robert E; Weissman, Sherman M; Cayting, Philip; Hariharan, Manoj; Lian, Jin; Cheng, Yong; Landt, Stephen G; Ma, Zhihai; Wold, Barbara J; Dekker, Job; Crawford, Gregory E; Keller, Cheryl A; Wu, Weisheng; Morrissey, Christopher; Kumar, Swathi A; Mishra, Tejaswini; Jain, Deepti; Byrska-Bishop, Marta; Blankenberg, Daniel; Lajoie, Bryan R; Jain, Gaurav; Sanyal, Amartya; Chen, Kaun-Bei; Denas, Olgert; Taylor, James; Blobel, Gerd A; Weiss, Mitchell J; Pimkin, Max; Deng, Wulan; Marinov, Georgi K; Williams, Brian A; Fisher-Aylor, Katherine I; Desalvo, Gilberto; Kiralusha, Anthony; Trout, Diane; Amrhein, Henry; Mortazavi, Ali; Edsall, Lee; McCleary, David; Kuan, Samantha; Shen, Yin; Yue, Feng; Ye, Zhen; Davis, Carrie A; Zaleski, Chris; Jha, Sonali; Xue, Chenghai; Dobin, Alex; Lin, Wei; Fastuca, Meagan; Wang, Huaien; Guigo, Roderic; Djebali, Sarah; Lagarde, Julien; Ryba, Tyrone; Sasaki, Takayo; Malladi, Venkat S; Cline, Melissa S; Kirkup, Vanessa M; Learned, Katrina; Rosenbloom, Kate R; Kent, W James; Feingold, Elise A; Good, Peter J; Pazin, Michael; Lowdon, Rebecca F; Adams, Leslie B

    2012-08-13

    To complement the human Encyclopedia of DNA Elements (ENCODE) project and to enable a broad range of mouse genomics efforts, the Mouse ENCODE Consortium is applying the same experimental pipelines developed for human ENCODE to annotate the mouse genome.

  10. Risk factors of age-related macular degeneration in Argentina

    Directory of Open Access Journals (Sweden)

    María Eugenia Nano

    2013-04-01

    Full Text Available PURPOSES: To assess the risk factors of age-related macular degeneration in Argentina using a case-control study. METHODS: Surveys were used for subjects' antioxidant intake, age/gender, race, body mass index, hypertension, diabetes (and type of treatment, smoking, sunlight exposure, red meat consumption, fish consumption, presence of age-related macular degeneration and family history of age-related macular degeneration. Main effects models for logistic regression and ordinal logistic regression were used to analyze the results. RESULTS: There were 175 cases and 175 controls with a mean age of 75.4 years and 75.5 years, respectively, of whom 236 (67.4% were female. Of the cases with age-related macular degeneration, 159 (45.4% had age-related macular degeneration in their left eyes, 154 (44.0% in their right eyes, and 138 (39.4% in both eyes. Of the cases with age-related macular degeneration in their left eyes, 47.8% had the dry type, 40.3% had the wet type, and the type was unknown for 11.9%. The comparable figures for right eyes were: 51.9%, 34.4%, and 13.7%, respectively. The main effects model was dominated by higher sunlight exposure (OR [odds ratio]: 3.3 and a family history of age-related macular degeneration (OR: 4.3. Other factors included hypertension (OR: 2.1, smoking (OR: 2.2, and being of the Mestizo race, which lowered the risk of age-related macular degeneration (OR: 0.40. Red meat/fish consumption, body mass index, and iris color did not have an effect. Higher age was associated with progression to more severe age-related macular degeneration. CONCLUSION: Sunlight exposure, family history of age-related macular degeneration, and an older age were the significant risk factors. There may be other variables, as the risk was not explained very well by the existing factors. A larger sample may produce different and better results.

  11. Age-related neuronal degeneration: complementary roles of nucleotide excision repair and transcription-coupled repair in preventing neuropathology.

    Directory of Open Access Journals (Sweden)

    Dick Jaarsma

    2011-12-01

    Full Text Available Neuronal degeneration is a hallmark of many DNA repair syndromes. Yet, how DNA damage causes neuronal degeneration and whether defects in different repair systems affect the brain differently is largely unknown. Here, we performed a systematic detailed analysis of neurodegenerative changes in mouse models deficient in nucleotide excision repair (NER and transcription-coupled repair (TCR, two partially overlapping DNA repair systems that remove helix-distorting and transcription-blocking lesions, respectively, and that are associated with the UV-sensitive syndromes xeroderma pigmentosum (XP and Cockayne syndrome (CS. TCR-deficient Csa(-/- and Csb(-/- CS mice showed activated microglia cells surrounding oligodendrocytes in regions with myelinated axons throughout the nervous system. This white matter microglia activation was not observed in NER-deficient Xpa(-/- and Xpc(-/- XP mice, but also occurred in Xpd(XPCS mice carrying a point mutation (G602D in the Xpd gene that is associated with a combined XPCS disorder and causes a partial NER and TCR defect. The white matter abnormalities in TCR-deficient mice are compatible with focal dysmyelination in CS patients. Both TCR-deficient and NER-deficient mice showed no evidence for neuronal degeneration apart from p53 activation in sporadic (Csa(-/-, Csb(-/- or highly sporadic (Xpa(-/-, Xpc(-/- neurons and astrocytes. To examine to what extent overlap occurs between both repair systems, we generated TCR-deficient mice with selective inactivation of NER in postnatal neurons. These mice develop dramatic age-related cumulative neuronal loss indicating DNA damage substrate overlap and synergism between TCR and NER pathways in neurons, and they uncover the occurrence of spontaneous DNA injury that may trigger neuronal degeneration. We propose that, while Csa(-/- and Csb(-/- TCR-deficient mice represent powerful animal models to study the mechanisms underlying myelin abnormalities in CS, neuron

  12. Nucleolar disruption and cajal body disassembly are nuclear hallmarks of DNA damage-induced neurodegeneration in purkinje cells.

    Science.gov (United States)

    Baltanás, Fernando C; Casafont, Iñigo; Weruaga, Eduardo; Alonso, José R; Berciano, María T; Lafarga, Miguel

    2011-07-01

    The Purkinje cell (PC) degeneration (pcd) phenotype results from mutation in nna1 gene and is associated with the degeneration and death of PCs during the postnatal life. Although the pcd mutation is a model of the ataxic mouse, it shares clinical and pathological characteristics of inherited human spinocerebellar ataxias. PC degeneration in pcd mice provides a useful neuronal system to study nuclear mechanisms involved in DNA damage-dependent neurodegeneration, particularly the contribution of nucleoli and Cajal bodies (CBs). Both nuclear structures are engaged in housekeeping functions for neuronal survival, the biogenesis of ribosomes and the maturation of snRNPs and snoRNPs required for pre-mRNA and pre-rRNA processing, respectively. In this study, we use ultrastructural analysis, in situ transcription assay and molecular markers for DNA damage, nucleoli and CB components to demonstrate that PC degeneration involves the progressive accumulation of nuclear DNA damage associated with disruption of nucleoli and CBs, disassembly of polyribosomes into monoribosomes, ribophagy and shut down of nucleolar and extranucleolar transcription. Microarray analysis reveals that four genes encoding repressors of nucleolar rRNA synthesis (p53, Rb, PTEN and SNF2) are upregulated in the cerebellum of pcd mice. Collectively, these data support that nucleolar and CB alterations are hallmarks of DNA damage-induced neurodegeneration.

  13. Oocyte Degeneration Associated with Follicle Cells in Female Mactra chinensis (Bivalvia: Mactridae)

    OpenAIRE

    Kim, Sung Han; Chung, Ee-Yung; Lee, Ki-Young

    2014-01-01

    Ultrastructural studies of oocyte degeneration in the oocyte, and the functions of follicle cells during oocyte degeneration are described to clarify the reproductive mechanism on oocyte degeneration of Mactra chinensis using cytological methods. Commonly, the follicle cells are attached to the oocyte. Follicle cells play an important role in oocyte degeneration. In particular, the functions of follicle cells during oocyte degeneration are associated with phagocytosis and the intracellular di...

  14. Design of a novel quantitative PCR (QPCR-based protocol for genotyping mice carrying the neuroprotective Wallerian degeneration slow (Wlds gene

    Directory of Open Access Journals (Sweden)

    Coleman Michael P

    2007-10-01

    Full Text Available Abstract Background Mice carrying the spontaneous genetic mutation known as Wallerian degeneration slow (Wlds have a unique neuroprotective phenotype, where axonal and synaptic compartments of neurons are protected from degeneration following a wide variety of physical, toxic and inherited disease-inducing stimuli. This remarkable phenotype has been shown to delay onset and progression in several mouse models of neurodegenerative disease, suggesting that Wlds-mediated neuroprotection may assist in the identification of novel therapeutic targets. As a result, cross-breeding of Wlds mice with mouse models of neurodegenerative diseases is used increasingly to understand the roles of axon and synapse degeneration in disease. However, the phenotype shows strong gene-dose dependence so it is important to distinguish offspring that are homozygous or heterozygous for the mutation. Since the Wlds mutation comprises a triplication of a region already present in the mouse genome, the most stringent way to quantify the number of mutant Wlds alleles is using copy number. Current approaches to genotype Wlds mice are based on either Southern blots or pulsed field gel electrophoresis, neither of which are as rapid or efficient as quantitative PCR (QPCR. Results We have developed a rapid, robust and efficient genotyping method for Wlds using QPCR. This approach differentiates, based on copy number, homozygous and heterozygous Wlds mice from wild-type mice and each other. We show that this approach can be used to genotype mice carrying the spontaneous Wlds mutation as well as animals expressing the Wlds transgene. Conclusion We have developed a QPCR genotyping method that permits rapid and effective genotyping of Wlds copy number. This technique will be of particular benefit in studies where Wlds mice are cross-bred with other mouse models of neurodegenerative disease in order to understand the neuroprotective processes conferred by the Wlds mutation.

  15. Genetic association studies in lumbar disc degeneration: a systematic review.

    Directory of Open Access Journals (Sweden)

    Pasi J Eskola

    Full Text Available OBJECTIVE: Low back pain is associated with lumbar disc degeneration, which is mainly due to genetic predisposition. The objective of this study was to perform a systematic review to evaluate genetic association studies in lumbar disc degeneration as defined on magnetic resonance imaging (MRI in humans. METHODS: A systematic literature search was conducted in MEDLINE, MEDLINE In-Process, SCOPUS, ISI Web of Science, The Genetic Association Database and The Human Genome Epidemiology Network for information published between 1990-2011 addressing genes and lumbar disc degeneration. Two investigators independently identified studies to determine inclusion, after which they performed data extraction and analysis. The level of cumulative genetic association evidence was analyzed according to The HuGENet Working Group guidelines. RESULTS: Fifty-two studies were included for review. Forty-eight studies reported at least one positive association between a genetic marker and lumbar disc degeneration. The phenotype definition of lumbar disc degeneration was highly variable between the studies and replications were inconsistent. Most of the associations presented with a weak level of evidence. The level of evidence was moderate for ASPN (D-repeat, COL11A1 (rs1676486, GDF5 (rs143383, SKT (rs16924573, THBS2 (rs9406328 and MMP9 (rs17576. CONCLUSIONS: Based on this first extensive systematic review on the topic, the credibility of reported genetic associations is mostly weak. Clear definition of lumbar disc degeneration phenotypes and large population-based cohorts are needed. An international consortium is needed to standardize genetic association studies in relation to disc degeneration.

  16. Tyro3 Modulates Mertk-Associated Retinal Degeneration.

    Science.gov (United States)

    Vollrath, Douglas; Yasumura, Douglas; Benchorin, Gillie; Matthes, Michael T; Feng, Wei; Nguyen, Natalie M; Sedano, Cecilia D; Calton, Melissa A; LaVail, Matthew M

    2015-12-01

    Inherited photoreceptor degenerations (IPDs) are the most genetically heterogeneous of Mendelian diseases. Many IPDs exhibit substantial phenotypic variability, but the basis is usually unknown. Mutations in MERTK cause recessive IPD phenotypes associated with the RP38 locus. We have identified a murine genetic modifier of Mertk-associated photoreceptor degeneration, the C57BL/6 (B6) allele of which acts as a suppressor. Photoreceptors degenerate rapidly in Mertk-deficient animals homozygous for the 129P2/Ola (129) modifier allele, whereas animals heterozygous for B6 and 129 modifier alleles exhibit an unusual intermixing of degenerating and preserved retinal regions, with females more severely affected than males. Mertk-deficient mice homozygous for the B6 modifier allele display degeneration only in the far periphery, even at 8 months of age, and have improved retinal function compared to animals homozygous for the 129 allele. We genetically mapped the modifier to an approximately 2-megabase critical interval that includes Tyro3, a paralog of Mertk. Tyro3 expression in the outer retina varies with modifier genotype in a manner characteristic of a cis-acting expression quantitative trait locus (eQTL), with the B6 allele conferring an approximately three-fold higher expression level. Loss of Tyro3 function accelerates the pace of photoreceptor degeneration in Mertk knockout mice, and TYRO3 protein is more abundant in the retinal pigment epithelium (RPE) adjacent to preserved central retinal regions of Mertk knockout mice homozygous for the B6 modifier allele. Endogenous human TYRO3 protein co-localizes with nascent photoreceptor outer segment (POS) phagosomes in a primary RPE cell culture assay, and expression of murine Tyro3 in cultured cells stimulates phagocytic ingestion of POS. Our findings demonstrate that Tyro3 gene dosage modulates Mertk-associated retinal degeneration, provide strong evidence for a direct role for TYRO3 in RPE phagocytosis, and suggest

  17. Tyro3 Modulates Mertk-Associated Retinal Degeneration.

    Directory of Open Access Journals (Sweden)

    Douglas Vollrath

    2015-12-01

    Full Text Available Inherited photoreceptor degenerations (IPDs are the most genetically heterogeneous of Mendelian diseases. Many IPDs exhibit substantial phenotypic variability, but the basis is usually unknown. Mutations in MERTK cause recessive IPD phenotypes associated with the RP38 locus. We have identified a murine genetic modifier of Mertk-associated photoreceptor degeneration, the C57BL/6 (B6 allele of which acts as a suppressor. Photoreceptors degenerate rapidly in Mertk-deficient animals homozygous for the 129P2/Ola (129 modifier allele, whereas animals heterozygous for B6 and 129 modifier alleles exhibit an unusual intermixing of degenerating and preserved retinal regions, with females more severely affected than males. Mertk-deficient mice homozygous for the B6 modifier allele display degeneration only in the far periphery, even at 8 months of age, and have improved retinal function compared to animals homozygous for the 129 allele. We genetically mapped the modifier to an approximately 2-megabase critical interval that includes Tyro3, a paralog of Mertk. Tyro3 expression in the outer retina varies with modifier genotype in a manner characteristic of a cis-acting expression quantitative trait locus (eQTL, with the B6 allele conferring an approximately three-fold higher expression level. Loss of Tyro3 function accelerates the pace of photoreceptor degeneration in Mertk knockout mice, and TYRO3 protein is more abundant in the retinal pigment epithelium (RPE adjacent to preserved central retinal regions of Mertk knockout mice homozygous for the B6 modifier allele. Endogenous human TYRO3 protein co-localizes with nascent photoreceptor outer segment (POS phagosomes in a primary RPE cell culture assay, and expression of murine Tyro3 in cultured cells stimulates phagocytic ingestion of POS. Our findings demonstrate that Tyro3 gene dosage modulates Mertk-associated retinal degeneration, provide strong evidence for a direct role for TYRO3 in RPE phagocytosis

  18. The MOUSE Squad

    Science.gov (United States)

    Borja, Rhea R.

    2004-01-01

    This article presents a New York city after-school program started by MOUSE (Making Opportunities for Upgrading Schools and Education), a national nonprofit group that teaches students how to fix computers, and equips them with the communication and problem-solving skills to help them in the working world. The MOUSE program is part of a trend…

  19. [Optogenetics and prosthetic treatment of retinal degeneration].

    Science.gov (United States)

    Kirpichnikov, M P; Ostrovskiy, M A

    2015-01-01

    This is a review of the current state of optogenetics-based research in the field of ophthalmology and physiology of vision. Optogenetics employs an interdisciplinary approach that amalgamates gene engineering, optics, and physiology. It involves exogenous expression of a light-activated protein in a very particular retinal cell enabling regulation (stimulation vs. inhibition) of its physiological activity. The experience with gene therapy came in very useful for optogenetics. However, unlike gene therapy, which is aimed at repairing damaged genes or replacing them with healthy ones, optogenetics is focused on protein genes delivery for further molecular control of the cell. In retina, the loss of photoreceptors is not necessarily followed by neuronal loss (at least ganglion cells remain intact), which determines the practicability of prosthetic treatment. Clinical trials can now be considered, owing to the first successful conversion of ganglion cells of mouse degenerative retinas into artificial photoreceptive cells with ON and OFF receptive fields, which is crucial for spatial vision. The following issues are reviewed here in detail: 1. Choice of cell targets within the degenerative retina. 2. Strategy of utilizing the existing light-sensitive agents and development of new optogenetic tools. 3. Gene delivery and expression in retinal cells. 4. Methods of evaluating the treatment success. 5. Selection criteria for optogenetic prosthetics. The conclusion discusses currently unsolved problems and prospects for optogenetic approaches to retinal prosthetics.

  20. Mouse genome database 2016.

    Science.gov (United States)

    Bult, Carol J; Eppig, Janan T; Blake, Judith A; Kadin, James A; Richardson, Joel E

    2016-01-01

    The Mouse Genome Database (MGD; http://www.informatics.jax.org) is the primary community model organism database for the laboratory mouse and serves as the source for key biological reference data related to mouse genes, gene functions, phenotypes and disease models with a strong emphasis on the relationship of these data to human biology and disease. As the cost of genome-scale sequencing continues to decrease and new technologies for genome editing become widely adopted, the laboratory mouse is more important than ever as a model system for understanding the biological significance of human genetic variation and for advancing the basic research needed to support the emergence of genome-guided precision medicine. Recent enhancements to MGD include new graphical summaries of biological annotations for mouse genes, support for mobile access to the database, tools to support the annotation and analysis of sets of genes, and expanded support for comparative biology through the expansion of homology data.

  1. Notochord Cells in Intervertebral Disc Development and Degeneration

    Directory of Open Access Journals (Sweden)

    Matthew R. McCann

    2016-01-01

    Full Text Available The intervertebral disc is a complex structure responsible for flexibility, multi-axial motion, and load transmission throughout the spine. Importantly, degeneration of the intervertebral disc is thought to be an initiating factor for back pain. Due to a lack of understanding of the pathways that govern disc degeneration, there are currently no disease-modifying treatments to delay or prevent degenerative disc disease. This review presents an overview of our current understanding of the developmental processes that regulate intervertebral disc formation, with particular emphasis on the role of the notochord and notochord-derived cells in disc homeostasis and how their loss can result in degeneration. We then describe the role of small animal models in understanding the development of the disc and their use to interrogate disc degeneration and associated pathologies. Finally, we highlight essential development pathways that are associated with disc degeneration and/or implicated in the reparative response of the tissue that might serve as targets for future therapeutic approaches.

  2. Genetic Mouse Models of Huntington's Disease: Focus on Electrophysiological Mechanisms

    Directory of Open Access Journals (Sweden)

    Carlos Cepeda

    2010-03-01

    Full Text Available The discovery of the HD (Huntington's disease gene in 1993 led to the creation of genetic mouse models of the disease and opened the doors for mechanistic studies. In particular, the early changes and progression of the disease could be followed and examined systematically. The present review focuses on the contribution of these genetic mouse models to the understanding of functional changes in neurons as the HD phenotype progresses, and concentrates on two brain areas: the striatum, the site of most conspicuous pathology in HD, and the cortex, a site that is becoming increasingly important in understanding the widespread behavioural abnormalities. Mounting evidence points to synaptic abnormalities in communication between the cortex and striatum and cell-cell interactions as major determinants of HD symptoms, even in the absence of severe neuronal degeneration and death.

  3. Mapping of the Mouse Actin Capping Protein Beta Subunit Gene

    Directory of Open Access Journals (Sweden)

    Cooper John A

    2000-07-01

    Full Text Available Abstract Background Capping protein (CP, a heterodimer of α and β subunits, is found in all eukaryotes. CP binds to the barbed ends of actin filaments in vitro and controls actin assembly and cell motility in vivo. Vertebrates have three isoforms of CPβ produced by alternatively splicing from one gene; lower organisms have one gene and one isoform. Results We isolated genomic clones corresponding to the β subunit of mouse CP and identified its chromosomal location by interspecies backcross mapping. Conclusions The CPβ gene (Cappb1 mapped to Chromosome 4 between Cdc42 and D4Mit312. Three mouse mutations, snubnose, curly tail, and cribriform degeneration, map in the vicinity of the β gene.

  4. Frontotemporal lobar degeneration: recent progress in antemortem diagnosis.

    Science.gov (United States)

    Bian, Hong; Grossman, Murray

    2007-07-01

    Frontotemporal lobar degeneration (FTLD) is a neurodegenerative disorder characterized by changes in behaviour and language dysfunction. Two broad pathological subdivisions of FTLD are recognized in a recent classification scheme based on biochemical features: tau-positive pathology due to the accumulation of various forms of the microtubule-associated protein tau, such as FTLD with Pick bodies and corticobasal degeneration; and tau-negative pathology such as frontotemporal lobar degeneration with ubiquitin/TDP-43-immunoreactive inclusions. Etiologically based treatments aim to target the mechanisms underlying the accumulation of these abnormal proteins in these conditions. It is essential for us to develop biomarkers that support the accurate diagnosis of the specific diseases causing FTLD. These biomarkers also can be useful in assessing efficacy during treatment trials. This review summarizes the epidemiologic, clinical, neuropsychological, imaging and cerebrospinal fluid (CSF) biomarker features that can help identify these pathologically defined conditions during life.

  5. Radiative generation of neutrino mixing: degenerate masses and threshold corrections

    CERN Document Server

    Hollik, Wolfgang Gregor

    2014-01-01

    Degenerate neutrino masses are excluded by experiment. The experimentally measured mass squared differences together with the yet undetermined absolute neutrino mass scale allow for a quasi-degenerate mass spectrum. For the lightest neutrino mass larger than roughly 0.1 eV, we analyse the influence of threshold corrections at the electroweak scale. We show that typical one-loop corrections can generate the observed neutrino mixing as well as the mass differences starting from exactly degenerate masses at the tree-level. Those threshold corrections have to be explicitly flavour violating. Flavour diagonal, non-universal corrections are not sufficient to simultaneously generate the correct mixing and the mass differences. We apply the new insights to an extension of the Minimal Supersymmetric Standard Model with non-minimal flavour violation in the soft breaking terms and discuss the low-energy threshold corrections to the light neutrino mass matrix in that model.

  6. Degeneration of host prothoracic glands caused by Campoletis chlorideae polydnavirus

    Institute of Scientific and Technical Information of China (English)

    ZHANG Cong; YAN Yunhua; WANG Chenzhu

    2003-01-01

    The development of last instar Helicoverpa armigera prothoracic glands was investigated first; then the effects on the prothoracic glands of Helicoverpa armigera was studied by injection with calyx fluid and polydnavirus (PDV) from the endoparasitoid Campoletis chlorideae. Results showed that 3 female equivalents of calyx fluid or 4 female equivalents of PDV induced degeneration of host prothoracic glands. 24 h after calyx fluid or PDV injection the ultrastructure of the gland cells showed a significant decrease in intercellular channel system, while an increase in the number of round mitochondria, lysosomes and whorled figures, the organelle of some cells has degenerated and only organelle debris remained in the cells. These results suggest that calyx fluid or PDV cause the inactivation and degeneration of host prothoracic glands.

  7. A geometrical approach to degenerate scalar-tensor theories

    CERN Document Server

    Chagoya, Javier

    2016-01-01

    Degenerate scalar-tensor theories are recently proposed covariant theories of gravity coupled with a scalar field. Despite being characterised by higher order equations of motion, they do not propagate more than three degrees of freedom, thanks to the existence of constraints. We discuss a geometrical approach to degenerate scalar-tensor systems, and analyse its consequences. We show that some of these theories emerge as a certain limit of DBI Galileons. In absence of dynamical gravity, these systems correspond to scalar theories enjoying a symmetry which is different from Galileon invariance. The scalar theories have however problems concerning the propagation of fluctuations around a time dependent background. These issues can be tamed by breaking the symmetry by hand, or by minimally coupling the scalar with dynamical gravity in a way that leads to degenerate scalar-tensor systems. We show that distinct theories can be connected by a relation which generalizes Galileon duality, in certain cases also when g...

  8. Genome-wide analysis of core promoter elements from conserved human and mouse orthologous pairs

    OpenAIRE

    Jin, Victor X.; Singer, Gregory AC; Agosto-Pérez, Francisco J; Liyanarachchi, Sandya; Davuluri, Ramana V.

    2006-01-01

    Background The canonical core promoter elements consist of the TATA box, initiator (Inr), downstream core promoter element (DPE), TFIIB recognition element (BRE) and the newly-discovered motif 10 element (MTE). The motifs for these core promoter elements are highly degenerate, which tends to lead to a high false discovery rate when attempting to detect them in promoter sequences. Results In this study, we have performed the first analysis of these core promoter elements in orthologous mouse a...

  9. Rapid glutamate receptor 2 trafficking during retinal degeneration

    Directory of Open Access Journals (Sweden)

    Lin Yanhua

    2012-02-01

    Full Text Available Abstract Background Retinal degenerations, such as age-related macular degeneration (AMD and retinitis pigmentosa (RP, are characterized by photoreceptor loss and anomalous remodeling of the surviving retina that corrupts visual processing and poses a barrier to late-stage therapeutic interventions in particular. However, the molecular events associated with retinal remodeling remain largely unknown. Given our prior evidence of ionotropic glutamate receptor (iGluR reprogramming in retinal degenerations, we hypothesized that the edited glutamate receptor 2 (GluR2 subunit and its trafficking may be modulated in retinal degenerations. Results Adult albino Balb/C mice were exposed to intense light for 24 h to induce light-induced retinal degeneration (LIRD. We found that prior to the onset of photoreceptor loss, protein levels of GluR2 and related trafficking proteins, including glutamate receptor-interacting protein 1 (GRIP1 and postsynaptic density protein 95 (PSD-95, were rapidly increased. LIRD triggered neuritogenesis in photoreceptor survival regions, where GluR2 and its trafficking proteins were expressed in the anomalous dendrites. Immunoprecipitation analysis showed interaction between KIF3A and GRIP1 as well as PSD-95, suggesting that KIF3A may mediate transport of GluR2 and its trafficking proteins to the novel dendrites. However, in areas of photoreceptor loss, GluR2 along with its trafficking proteins nearly vanished in retracted retinal neurites. Conclusions All together, LIRD rapidly triggers GluR2 plasticity, which is a potential mechanism behind functionally phenotypic revisions of retinal neurons and neuritogenesis during retinal degenerations.

  10. PHOTORECEPTOR DEGENERATION IN A MOUNTAIN LION CUB (PUMA CONCOLOR).

    Science.gov (United States)

    DiSalvo, Andrew R; Reilly, Christopher M; Wiggans, K Tomo; Woods, Leslie W; Wack, Ray F; Clifford, Deana L

    2016-12-01

    An orphaned 4-mo-old female mountain lion cub ( Puma concolor ) was captured along the coastline in Montaña de Oro State Park in Los Osos, California, USA. Following suspicion that the cub was visually impaired, ophthalmic examination revealed diffuse bilateral retinal atrophy. Due to a poor prognosis, humane euthanasia was elected. Necropsy and histopathological findings were consistent with photoreceptor degeneration. Based on the cub's signalment, history, and histopathology, a genetic or nutritional etiology was suspected, with the former etiology more strongly supported. To the authors' knowledge, this is the first report of photoreceptor degeneration in a wild felid and should be considered in cases of blindness.

  11. Studies of the doubly degenerate product Jahn-Teller system

    Institute of Scientific and Technical Information of China (English)

    QIU Qing-chun

    2007-01-01

    The static product Jahn-Teller (JT) system with two doubly-degenerate electronic open shells coupling to a single e-mode is further studied in the electronic space using the isostationary function method and the energy minimization procedure. These effects are vividly described by the coupling of two electronic vectors that belong to two different E-spaces. The energy levels in the trough positions are also investigated and it is found that the two doubly degenerate electronic levels are generally lifted by the product JT coupling.

  12. Polarization degenerate micropillars fabricated by designing elliptical oxide apertures

    CERN Document Server

    Bakker, Morten P; Zhan, Alan; Coldren, Larry A; van Exter, Martin P; Bouwmeester, Dirk

    2014-01-01

    A method for fabrication of polarization degenerate oxide apertured micropillar cavities is demon- strated. Micropillars are etched such that the size and shape of the oxide front is controlled. The polarization splitting in the circular micropillar cavities due to the native and strain induced bire- fringence can be compensated by elongating the oxide front in the [110] direction, thereby reducing stress in this direction. By using this technique we fabricate a polarization degenerate cavity with a quality factor of 1.7*?10^4 and a mode volume of 2.7 u?m3, enabling a calculated maximum Purcell factor of 11.

  13. N=2 gauge theories and degenerate fields of Toda theory

    CERN Document Server

    Kanno, Shoichi; Shiba, Shotaro; Tachikawa, Yuji

    2009-01-01

    We discuss the correspondence between degenerate fields of the W_N algebra and punctures of Gaiotto's description of the Seiberg-Witten curve of N=2 superconformal gauge theories. Namely, we find that the type of degenerate fields of the W_N algebra, with null states at level one, is classified by Young diagrams with N boxes, and that the singular behavior of the Seiberg-Witten curve near the puncture agrees with that of W_N generators. We also find how to translate mass parameters of the gauge theory to the momenta of the Toda theory.

  14. Rare case of giant broad ligament fibroid with myxoid degeneration

    Directory of Open Access Journals (Sweden)

    R R Godbole

    2012-01-01

    Full Text Available Giant fibroids are known to arise from the uterus, although very rarely from extra-uterine sites. Among extra-uterine fibroids, broad ligament fibroids generally achieve enormous size and generally present with pressure symptom like bladder and bowel dysfunction. Myxoid degeneration is a rare complication of benign fibroid, where presence of cystic changes mimics the metastatic malignant ovarian tumor. We report a case of true broad ligament fibroid measured about 13 kg. This case is reported for its rarity and the diagnostic difficulties in differentiating malignant ovarian tumor and benign fibroid with myxoid degeneration.

  15. Design of the Advanced Virgo non-degenerate recycling cavities

    Energy Technology Data Exchange (ETDEWEB)

    Granata, M; Barsuglia, M [Laboratoire Astroparticule et Cosmologie (APC) 10 rue Alice Domon et Leonie Duquet, 75013 Paris (France); Flaminio, R [Laboratoire des Materiaux Avances (LMA), IN2P3/CNRS F-69622 Villeurbanne, Lyon (France); Freise, A [School of Physics and Astronomy, University of Birmingham Birmingham, B15 2TT (United Kingdom); Hild, S [Institute for Gravitational Research, Department of Physics and Astronomy University of Glasgow, Glasgow, G12 8QQ (United Kingdom); Marque, J, E-mail: granata@apc.univ-paris7.f [European Gravitational Observatory (EGO) I-56021 Cascina (Italy)

    2010-05-01

    Advanced Virgo is the project to upgrade the interferometric gravitational wave detector Virgo, and it foresees the implementation of power and signal non-degenerate recycling cavities. Such cavities suppress the build-up of high order modes of the resonating sidebands, with some advantage for the commissioning of the detector and the build-up of the gravitational signal. Here we present the baseline design of the Advanced Virgo non-degenerate recycling cavities, giving some preliminary results of simulations about the tolerances of this design to astigmatism, mirror figure errors and thermal lensing.

  16. 抗Yo抗体阳性的副肿瘤性小脑变性分析%Anti-Yo antibody-associated paraneoplastic cerebellar degeneration: a report of 6 patients

    Institute of Scientific and Technical Information of China (English)

    关鸿志; 任海涛; 彭斌; 倪俊; 李力波; 卢强; 钱敏; 崔丽英

    2015-01-01

    Objective Paraneoplastic cerebellar degeneration (PCD) is a neurological syndrome characterized by subacute cerebellar ataxia,specific tumour types and associated antineuronal antibodies.We attempted to identify patient-,tumour-and treatment-related characteristics associated with PCD with anti-Yo antibodies.Methods We examined the antineuronal antibodies associated and studied the neurological symptoms and signs,associated tumours,disability of PCD with anti-Yo antibodies.Results Six patients had anti-Yo antibody-associated PCD.All patients are female with mean age of 55 years.All cases presented with subacute cerebellar ataxia progressive over 1 to 9 weeks (mean 6.23 weeks).The majority of patients had both truncal and appendicular ataxia with unstable gait and dizziness.Spontaneous nystagmus presented in all cases including rotary nystagmus in three cases,horizontal nystagmus in two cases,opsoclonus-like nystagmus in one case.Dysarthria,dysphasia,double vision and behavior changes presented in some cases.Modified Rankin Scale scores were 4-5,indicating severe disability.On cerebrospinal fluid examination,mild increases of white blood cell counts were found in four cases and mild elevation of protein concentration in two cases.Cerebrospinal fluid cytology showed lymphocytic inflammation in 3 cases.The most commonly associated tumours were ovary cancer in four cases while cancer of bladder was found in one patient.Only one patient improved neurologically after receiving anti-tumour treatment and immunotherapy with intravenous immunoglobulin in 3 cases.Conclusions Anti-Yo antibodies are wellcharacterised on coneuronal antibodies associated with PCD related to gynaecological cancer.Diagnosis and treatment of underlying neoplasm is critical for the patient with subacute cerebellar ataxia and positive antiYo antibody.Anti-Yo antibody-associated PCD usually results in severe disability with poor prognosis even after anti-tumor and immunotherapy.%目的 通过抗Yo抗

  17. Bax-induced apoptosis in Leber's congenital amaurosis: a dual role in rod and cone degeneration.

    Directory of Open Access Journals (Sweden)

    Séverine Hamann

    Full Text Available Pathogenesis in the Rpe65(-/- mouse model of Leber's congenital amaurosis (LCA is characterized by a slow and progressive degeneration of the rod photoreceptors. On the opposite, cones degenerate rapidly at early ages. Retinal degeneration in Rpe65(-/- mice, showing a null mutation in the gene encoding the retinal pigment epithelium 65-kDa protein (Rpe65, was previously reported to depend on continuous activation of a residual transduction cascade by unliganded opsin. However, the mechanisms of apoptotic signals triggered by abnormal phototransduction remain elusive. We previously reported that activation of a Bcl-2-dependent pathway was associated with apoptosis of rod photoreceptors in Rpe65(-/- mice during the course of the disease. In this study we first assessed whether activation of Bcl-2-mediated apoptotic pathway was dependent on constitutive activation of the visual cascade through opsin apoprotein. We then challenged the direct role of pro-apoptotic Bax protein in triggering apoptosis of rod and cone photoreceptors.Quantitative PCR analysis showed that increased expression of pro-apoptotic Bax and decreased level of anti-apoptotic Bcl-2 were restored in Rpe65(-/-/Gnat1(-/- mice lacking the Gnat1 gene encoding rod transducin. Moreover, photoreceptor apoptosis was prevented as assessed by TUNEL assay. These data indicate that abnormal activity of opsin apoprotein induces retinal cell apoptosis through the Bcl-2-mediated pathway. Following immunohistological and real-time PCR analyses, we further observed that decreased expression of rod genes in Rpe65-deficient mice was rescued in Rpe65(-/-/Bax(-/- mice. Histological and TUNEL studies confirmed that rod cell demise and apoptosis in diseased Rpe65(-/- mice were dependent on Bax-induced pathway. Surprisingly, early loss of cones was not prevented in Rpe65(-/-/Bax(-/- mice, indicating that pro-apoptotic Bax was not involved in the pathogenesis of cone cell death in Rpe65-deficient mice

  18. Mouse Genome Informatics (MGI)

    Data.gov (United States)

    U.S. Department of Health & Human Services — MGI is the international database resource for the laboratory mouse, providing integrated genetic, genomic, and biological data to facilitate the study of human...

  19. Mouse Phenome Database (MPD)

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Mouse Phenome Database (MPD) has characterizations of hundreds of strains of laboratory mice to facilitate translational discoveries and to assist in selection...

  20. The relationship between apoptosis of endplate chondrocytes and aging and degeneration of the intervertebral disc.

    Science.gov (United States)

    Ariga, K; Miyamoto, S; Nakase, T; Okuda, S; Meng, W; Yonenobu, K; Yoshikawa, H

    2001-11-15

    Apoptosis in cervical intervertebral disc cells and cartilaginous endplate cells was examined by the nick end labeling (TUNEL) technique during the process of natural aging and in a mouse experimental spondylosis model. To determine the role of apoptosis in aging and degeneration of intervertebral discs by monitoring chronologic changes in the quantity and localization of apoptotic cells. Apoptosis occurs within human intervertebral discs, but little is known about the pathologic significance of this process. On the other hand, the cartilaginous endplate is known to decrease in thickness and to disappear with aging and degeneration. The cause of this age-related change remains unclear. A mouse spondylosis model was prepared via surgical resection of the posterior spinal element in 12 mice to examine the experimentally induced spondylosis process. Eighteen naturally aged mice were also used to examine the influence of aging. Paraffin-embedded midsagittal sections of the cervical spine were obtained 2, 3, 6, and 12 months after surgery in the spondylosis model and in the age-matched naturally aged mice, as well as in 4-week-old and 18-month-old naturally aged mice. Sections were stained with hematoxylin and eosin, safranin-O, and the TUNEL procedure. The number of apoptotic cells and vital cells were counted in the cartilaginous endplate of the intervertebral disc excluding the growth cartilage, and the degree of disappearance of the cartilaginous endplate was evaluated. Apoptosis, particularly noticeable in the cartilaginous endplate, increased with age and resulted in a marked decrease in cell density. Subsequently, the structure of the cartilaginous endplate began to disappear. Apoptosis was more evident and the structure of the cartilaginous endplate began to disappear more rapidly in the surgically treated group than in the naturally aged group. TUNEL-positive cells in the cartilaginous endplate increased with age, with destruction of the cartilaginous endplate

  1. Oocyte Degeneration Associated with Follicle Cells in Female Mactra chinensis (Bivalvia: Mactridae).

    Science.gov (United States)

    Kim, Sung Han; Chung, Ee-Yung; Lee, Ki-Young

    2014-12-01

    Ultrastructural studies of oocyte degeneration in the oocyte, and the functions of follicle cells during oocyte degeneration are described to clarify the reproductive mechanism on oocyte degeneration of Mactra chinensis using cytological methods. Commonly, the follicle cells are attached to the oocyte. Follicle cells play an important role in oocyte degeneration. In particular, the functions of follicle cells during oocyte degeneration are associated with phagocytosis and the intracellular digestion of products. In this study, morphologically similar degenerated phagosomes (various lysosomes), which were observed in the degenerated oocytes, appeared in the follicle cells. After the spawning of the oocytes, the follicle cells were involved in oocyte degeneration through phagocytosis by phagolysosomes. Therefore, it can be assumed that follicle cells reabsorb phagosomes from degenerated oocytes. In this study, the presence of lipid granules, which occurred from degenerating yolk granules, gradually increased in degenerating oocytes. The function of follicle cells can accumulate reserves of lipid granules and glycogen in the cytoplasm, which can be employed by the vitellogenic oocyte. Based on observations of follicle cells attached to degenerating oocytes after spawning, the follicle cells of this species are involved in the lysosomal induction of oocyte degeneration for the reabsorption of phagosomes (phagolysosomes) in the cytoplasm for nutrient storage, as seen in other bivalves.

  2. Awareness, Knowledge, and Concern about Age-Related Macular Degeneration

    Science.gov (United States)

    Cimarolli, Verena R.; Laban-Baker, Allie; Hamilton, Wanda S.; Stuen, Cynthia

    2012-01-01

    Age-related macular degeneration (AMD)--a common eye disease causing vision loss--can be detected early through regular eye-health examinations, and measures can be taken to prevent visual decline. Getting eye examinations requires certain levels of awareness, knowledge, and concern related to AMD. However, little is known about AMD-related…

  3. Degeneration, Rigidity and Irreducible Components of Hopf Algebras

    Institute of Scientific and Technical Information of China (English)

    Abdenacer Makhlouf

    2005-01-01

    The aim of this work is to discuss the concepts of degeneration, deformation and rigidity of Hopf algebras and to apply them to the geometric study of the varieties of Hopf algebras. The main result is the description of the n-dimensional rigid Hopf algebras and the irreducible components for n < 14 and n = p2 with p a prime number.

  4. Non-Degenerate Four- Wave Mixing in Microstructure Fibres

    Institute of Scientific and Technical Information of China (English)

    ZHANG Xia; REN Xiao-Min; WANG Zi-Nan; XU Yong-Zhao; ZHANG Rui-Rui; HUANG Yong-Qing; CHEN Xue

    2007-01-01

    Non-degenerate four wave mixing based on third-order susceptibility χ3 in high nonlinearity microstructure fibres is experimentally demonstrated. The Stokes and anti-Stokes peaks are observed simultaneously by launching 10-fs pulses from an 800nm Ti:sapphire laser into the fibre.

  5. Natural history of seminiferous tubule degeneration in Klinefelter syndrome

    DEFF Research Database (Denmark)

    Aksglaede, Lise; Wikström, Anne M; Rajpert-De Meyts, Ewa

    2006-01-01

    Klinefelter syndrome (47,XXY) is characterized by small, firm testis, gynaecomastia, azoospermia and hypergonadotropic hypogonadism. Degeneration of the seminiferous tubules in 47,XXY males is a well-described phenomenon. It begins in the fetus, progresses through infancy and accelerates dramatic...

  6. Global existence for a degenerate haptotaxis model of cancer invasion

    Science.gov (United States)

    Zhigun, Anna; Surulescu, Christina; Uatay, Aydar

    2016-12-01

    We propose and study a strongly coupled PDE-ODE system with tissue-dependent degenerate diffusion and haptotaxis that can serve as a model prototype for cancer cell invasion through the extracellular matrix. We prove the global existence of weak solutions and illustrate the model behavior by numerical simulations for a two-dimensional setting.

  7. Critical configurations for a system of semi degenerate fermions

    Energy Technology Data Exchange (ETDEWEB)

    Arguelles, Carlos R.; Ruffini, Remo [ICRANet, Piazzale della Repubblica, Pescara (Italy); Sapienza University of Rome, Rome (Italy); Fraga, Bernardo M. [Sapienza University of Rome, Rome (Italy); Universite de Nice Sophia Antipolis, CEDEX (France)

    2014-09-15

    We study an isothermal system of semi degenerate self-gravitating fermions in general relativity. Such systems present mass density solutions with a central degenerate core, a plateau and a tail, this last following a power law behavior r{sup -2}. The different solutions are governed by the free parameters of the model: the degeneracy and the temperature parameters at the center and the particle mass m. We then analyze in detail the free parameter space for a fixed m in the keV region, by studying the one-parameter sequences of equilibrium configurations up to the critical point, which is represented by the maximum in a central density (ρ{sub 0}) vs. core mass (M{sub c}) diagram. We show that for fully degenerate cores, the known expression for the critical core mass M{sup cr}{sub c} {sup a}pprox{sup m3}{sub pl}/m{sup 2} is obtained, while for low degenerate cores, the critical core mass increases, showing temperature effects in a nonlinear way. The main result of this work is that when applying this theory to model the distribution of dark matter in galaxies from the very center to the outer halos, we do not find any critical corehalo configuration of self-gravitating fermions that would be able to explain the super-massive dark object in their centers and the outer halo simultaneously.

  8. RIEMANN-HILBERT PROBLEMS OF DEGENERATE HYPERBOLIC SYSTEM

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    This paper is concerned with the Riemann-Hilbert problems of degenerate hyperbolic system in two general domains, where the boundary curves are given by the parameter equations of the arc length s. We prove the existence and uniqueness of solutions to the Riemann-Hilbert problems by conformal deformations. The corre-sponding representations of solutions to the problems are also presented.

  9. Advancing Research and Treatment for Frontotemporal Lobar Degeneration (ARTFL)

    Science.gov (United States)

    2017-08-23

    FTLD; Progressive Supranuclear Palsy (PSP); Frontotemporal Dementia (FTD); Corticobasal Degeneration (CBD); PPA Syndrome; Behavioral Variant Frontotemporal Dementia (bvFTD); Semantic Variant Primary Progressive Aphasia (svPPA); Nonfluent Variant Primary Progressive Aphasia (nfvPPA); FTD With Amyotrophic Lateral Sclerosis (FTD/ALS); Amyotrophic Lateral Sclerosis (ALS); Oligosymptomatic PSP (oPSP); Corticobasal Syndrome (CBS)

  10. Lie algebras and degenerate Affine Hecke Algebras of type A

    CERN Document Server

    Arakawa, T

    1997-01-01

    We construct a family of exact functors from the BGG category of representations of the Lie algebra sl to the category of finite-dimensional representations of the degenerate (or graded) affine Hecke algebra H of GL. These functors transform Verma modules to standard modules or zero, and simple modules to simple modules or zero. Any simple H-module can be thus obtained.

  11. Sequential changes in MR imaging of human wallerian degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Orita, Tetsuji; Tsurutani, Tohru; Izumihara, Akifumi; Kajiwara, Koji (Shuto General Hospital, Yamaguchi (Japan)); Matsunaga, Tokio

    1994-05-01

    MRI of wallerian degeneration of the pyramidal tract in the brainstem was repeatedly performed on the same coronal slice in 10 patients, who had infarction or hemorrhage of the basal ganglia and had the exact onset of hemiparesis. The processes of wallerian degeneration were divided into four stages by proton-density weighted images. In stage 1, the axon began to degenerate and was destroyed. It occurred during the first 0.7 month and resulted in no signal intensity abnormality. In stage 2, axon debris disappeared from degenerating tracts. Myelin structure was preserved and myelin lipid remained intact. The lipid water ratio in the tissue became large and the tissue was more hydrophobic. From 0.7 to 2.0 months, low signal intensity was observed. In stage 3, subsequent myelin lipid breakdown began and the lipid/water ratio in the tissue tended to be small. There was no abnormal signal intensity. In stage 4, lipid began to be removed from the tissue. The lipid/water ratio became smaller and the tissue became hydrophilic. Gliosis was more prominent. High signal intensity was observed. (author).

  12. Adjacent segment degeneration: observations in a goat spinal fusion study

    NARCIS (Netherlands)

    R.J.W. Hoogendoorn; M.N. Helder; P.I.J.M. Wuisman; R.A. Bank; V. Everts; T.H. Smit

    2008-01-01

    Study Design. The adjacent discs of 13 goats, originally used in a lumbar spinal fusion model study, were analyzed for symptoms of intervertebral disc degeneration by means of magnetic resonance imaging (MRI), macroscopy, and histology. These goats were followed for 6 months and the results were com

  13. Perturbative methods for inverse problems on degenerate differential equations

    Directory of Open Access Journals (Sweden)

    Angelo Favini

    2012-12-01

    Full Text Available Pertubation results for linear relations satisfying a resolvent condition of weak parabolic type are established. Such results are applied to solve some inverse problems for degenerate differential equations, supplying a new method which avoids any fixed-point argument and essentially consists in reducing the original inverse problem to an auxiliary direct one.

  14. A study of retrograde degeneration of median nerve forearm ...

    African Journals Online (AJOL)

    Mona Mokhtar El Bardawil

    2013-10-22

    Oct 22, 2013 ... forearm segment in patients with CTS and its relation to variable severity of CTS in Egyptian patients. Patients ... Retrograde degeneration is not related to grade of severity of CTS. .... dominant hand using NEUROPACK 2 Electroneuromyog- ... was evaluated using Fisher Exact and Monte Carlo test.18,19.

  15. On dRGT massive gravity with degenerate reference metrics

    CERN Document Server

    Cao, Li-Ming; Zhang, Yun-Long

    2015-01-01

    In dRGT massive gravity, to get the equations of motion, the square root tensor is assumed to be invertible in the variation of the action. However, this condition can not be fulfilled when the reference metric is degenerate. This implies that the resulting equations of motion might be different from the case where the reference metric has full rank. In this paper, by generalizing the Moore-Penrose inverse to the symmetric tensor on Lorentz manifolds, we get the equations of motion of the theory with degenerate reference metric. It is found that the equations of motion are a little bit different from those in the non-degenerate cases. Based on the result of the equations of motion, for the $(2+n)$-dimensional solutions with the symmetry of $n$-dimensional maximally symmetric space, we prove a generalized Birkhoff theorem in the case where the degenerate reference metric has rank $n$, i.e., we show that the solutions must be Schwarzschild-type or Nariai-Bertotti-Robinson-type under the assumptions.

  16. Gestural Imitation and Limb Apraxia in Corticobasal Degeneration

    Science.gov (United States)

    Salter, Jennifer E.; Roy, Eric A.; Black, Sandra E.; Joshi, Anish; Almeida, Quincy

    2004-01-01

    Limb apraxia is a common symptom of corticobasal degeneration (CBD). While previous research has shown that individuals with CBD have difficulty imitating transitive (tool-use actions) and intransitive non-representational gestures (nonsense actions), intransitive representational gestures (actions without a tool) have not been examined. In the…

  17. Cesare Lombroso: an anthropologist between evolution and degeneration.

    Science.gov (United States)

    Mazzarello, Paolo

    2011-01-01

    Cesare Lombroso (1835-1909) was a prominent Italian medical doctor and intellectual in the second half of the nineteenth century. He became world famous for his theory that criminality, madness and genius were all sides of the same psychobiological condition: an expression of degeneration, a sort of regression along the phylogenetic scale, and an arrest at an early stage of evolution. Degeneration affected criminals especially, in particular the "born delinquent" whose development had stopped at an early stage, making them the most "atavistic" types of human being. Lombroso also advocated the theory that genius was closely linked with madness. A man of genius was a degenerate, an example of retrograde evolution in whom madness was a form of "biological compensation" for excessive intellectual development. To confirm this theory, in August 1897, Lombroso, while attending the Twelfth International Medical Congress in Moscow, decided to meet the great Russian writer Lev Tolstoy in order to directly verify, in him, his theory of degeneration in the genius. Lombroso's anthropological ideas fuelled a heated debate on the biological determinism of human behaviour.

  18. Degenerated human intervertebral discs contain autoantibodies against extracellular matrix proteins

    Directory of Open Access Journals (Sweden)

    S Capossela

    2014-04-01

    Full Text Available Degeneration of intervertebral discs (IVDs is associated with back pain and elevated levels of inflammatory cells. It has been hypothesised that discogenic pain is a direct result of vascular and neural ingrowth along annulus fissures, which may expose the avascular nucleus pulposus (NP to the systemic circulation and induce an autoimmune reaction. In this study, we confirmed our previous observation of antibodies in human degenerated and post-traumatic IVDs cultured in vitro. We hypothesised that the presence of antibodies was due to an autoimmune reaction against specific proteins of the disc. Furthermore we identified antigens which possibly trigger an autoimmune response in degenerative disc diseases. We demonstrated that degenerated and post-traumatic IVDs contain IgG antibodies against typical extracellular proteins of the disc, particularly proteins of the NP. We identified IgGs against collagen type II and aggrecan, confirming an autoimmune reaction against the normally immune privileged NP. We also found specific IgGs against collagens types I and V, but not against collagen type III. In conclusion, this study confirmed the association between disc degeneration and autoimmunity, and may open the avenue for future studies on developing prognostic, diagnostic and therapy-monitoring markers for degenerative disc diseases.

  19. Oscillatory integrals for phase functions having certain degenerate critical points

    Institute of Scientific and Technical Information of China (English)

    Jinmyong KIM; ZHENG Quan

    2008-01-01

    The paper is concerned with oscillatory integrals for phase functions having certain de-generate critical points. Under a finite type condition of phase functions we show the estimate of oscillatory integrals of the first kind. The decay of the oscillatory integral depends on indices of the finite type, the spatial dimension and the symbol.

  20. The Experience of Age-Related Macular Degeneration

    Science.gov (United States)

    Wong, Elaine Y. H.; Guymer, Robyn H.; Hassell, Jennifer B.; Keeffe, Jill E.

    2004-01-01

    This qualitative article describes the impact of age-related macular degeneration (ARMD) among 15 participants: how a person makes sense of ARMD, the effect of ARMD on the person's quality of life, the psychological disturbances associated with the limitations of ARMD, and the influence of ARMD on social interactions. Such in-depth appreciation of…

  1. Exact null controllability of degenerate evolution equations with scalar control

    Energy Technology Data Exchange (ETDEWEB)

    Fedorov, Vladimir E; Shklyar, Benzion

    2012-12-31

    Necessary and sufficient conditions for the exact null controllability of a degenerate linear evolution equation with scalar control are obtained. These general results are used to examine the exact null controllability of the Dzektser equation in the theory of seepage. Bibliography: 13 titles.

  2. Hedgehog signalling controls eye degeneration in blind cavefish.

    Science.gov (United States)

    Yamamoto, Yoshiyuki; Stock, David W; Jeffery, William R

    2004-10-14

    Hedgehog (Hh) proteins are responsible for critical signalling events during development but their evolutionary roles remain to be determined. Here we show that hh gene expression at the embryonic midline controls eye degeneration in blind cavefish. We use the teleost Astyanax mexicanus, a single species with an eyed surface-dwelling form (surface fish) and many blind cave forms (cavefish), to study the evolution of eye degeneration. Small eye primordia are formed during cavefish embryogenesis, which later arrest in development, degenerate and sink into the orbits. Eye degeneration is caused by apoptosis of the embryonic lens, and transplanting a surface fish embryonic lens into a cavefish optic cup can restore a complete eye. Here we show that sonic hedgehog (shh) and tiggy-winkle hedgehog (twhh) gene expression is expanded along the anterior embryonic midline in several different cavefish populations. The expansion of hh signalling results in hyperactivation of downstream genes, lens apoptosis and arrested eye growth and development. These features can be mimicked in surface fish by twhh and/or shh overexpression, supporting the role of hh signalling in the evolution of cavefish eye regression.

  3. Conservation of retinal circadian rhythms during cavefish eye degeneration.

    Science.gov (United States)

    Espinasa, Luis; Jeffery, William R

    2006-01-01

    Regressive evolution of morphological features is a common evolutionary event. However, the relationship between structural degeneration and loss of physiological function is often unclear because the ancestral and derived states of a character are usually not available for comparison. Here, we report studies on retinomotor rhythms during development of the blind cavefish Astyanax mexicanus, a single teleost species consisting of a sighted surface-dwelling form (surface fish) and several blind cave-dwelling (cavefish) forms. The eyed and blind forms of Astyanax diverged from a common sighted ancestor within the past million years. Despite the absence of functional eyes in cavefish adults, optic primordia are formed in embryos, but then gradually arrest in development, degenerate, and sink into the orbits. Although a layered retina is formed in cavefish embryos, it is deficient in photoreceptor cells, and in some cases the retinal pigment epithelium has lost its pigmentation. We show that the capacity to exhibit light-entrained retinomotor rhythms has been conserved in the degenerating embryonic eyes of two different Astyanax cavefish populations. The results indicate that loss of circadian retinal function does not precede and is therefore not required for eye degeneration in the blind cavefish.

  4. Adaptive evolution of eye degeneration in the Mexican blind cavefish.

    Science.gov (United States)

    Jeffery, W R

    2005-01-01

    The evolutionary mechanisms responsible for eye degeneration in cave-adapted animals have not been resolved. Opposing hypotheses invoking neural mutation or natural selection, each with certain genetic and developmental expectations, have been advanced to explain eye regression, although little or no experimental evidence has been presented to support or reject either theory. Here we review recent developmental and molecular studies in the teleost Astyanax mexicanus, a single species consisting of a sighted surface-dwelling form (surface fish) and many blind cave-dwelling forms (cavefish), which shed new light on this problem. The manner of eye development and degeneration, the ability to experimentally restore eyes, gene expression patterns, and comparisons between different cavefish populations all provide important clues for understanding the evolutionary forces responsible for eye degeneration. A key discovery is that Hedgehog midline signaling is expanded and inhibits eye formation by inducing lens apoptosis in cavefish embryos. Accordingly, eyes could have been lost by default as a consequence of natural selection for constructive traits, such as feeding structures, which are positively regulated by Hh signaling. We conclude from these studies that eye degeneration in cavefish may be caused by adaptive evolution and pleiotropy.

  5. Two degenerate boundary equilibrium bifurcations in planar Filippov systems

    NARCIS (Netherlands)

    Dercole, F.; Della Rossa, F.; Colombo, A.; Kuznetsov, Yuri

    2011-01-01

    We contribute to the analysis of codimension-two bifurcations in discontinuous systems by studying all equilibrium bifurcations of 2D Filippov systems that involve a sliding limit cycle. There are only two such local bifurcations: (1) a degenerate boundary focus, which we call the homoclinic boundar

  6. Can vertebral density changes be explained by intervertebral disc degeneration?

    NARCIS (Netherlands)

    Homminga, Jasper Johan; Aquarius, R.; Bulsink, Vera Elisabeth; Jansen, C.T.J.; Verdonschot, Nicolaas Jacobus Joseph

    2012-01-01

    One of the major problems facing the elderly spine is the occurrence of vertebral fractures due to low bone mass. Although typically attributed to osteoporosis, disc degeneration has also been suggested to play a role in vertebral fractures. Existing bone adaptation theories and simulations may

  7. Existence of solutions for a nonlinear degenerate elliptic system

    Directory of Open Access Journals (Sweden)

    Nguyen Minh

    2004-07-01

    Full Text Available In this paper, we study the existence of solutions for degenerate elliptic systems. We use the sub-super solution method, and the existence of classical and weak solutions. Some sub-supersolutions are constructed explicitly, when the nonlinearities have critical or supercritical growth.

  8. QUENCHING PROBLEMS OF DEGENERATE FUNCTIONAL REACTION-DIFFUSION EQUATION

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    This paper is concerned with the quenching problem of a degenerate functional reaction-diffusion equation. The quenching problem and global existence of solution for the reaction-diffusion equation are derived and, some results of the positive steady state solutions for functional elliptic boundary value are also presented.

  9. Degenerated human intervertebral discs contain autoantibodies against extracellular matrix proteins.

    Science.gov (United States)

    Capossela, S; Schläfli, P; Bertolo, A; Janner, T; Stadler, B M; Pötzel, T; Baur, M; Stoyanov, J V

    2014-04-04

    Degeneration of intervertebral discs (IVDs) is associated with back pain and elevated levels of inflammatory cells. It has been hypothesised that discogenic pain is a direct result of vascular and neural ingrowth along annulus fissures, which may expose the avascular nucleus pulposus (NP) to the systemic circulation and induce an autoimmune reaction. In this study, we confirmed our previous observation of antibodies in human degenerated and post-traumatic IVDs cultured in vitro. We hypothesised that the presence of antibodies was due to an autoimmune reaction against specific proteins of the disc. Furthermore we identified antigens which possibly trigger an autoimmune response in degenerative disc diseases. We demonstrated that degenerated and post-traumatic IVDs contain IgG antibodies against typical extracellular proteins of the disc, particularly proteins of the NP. We identified IgGs against collagen type II and aggrecan, confirming an autoimmune reaction against the normally immune privileged NP. We also found specific IgGs against collagens types I and V, but not against collagen type III. In conclusion, this study confirmed the association between disc degeneration and autoimmunity, and may open the avenue for future studies on developing prognostic, diagnostic and therapy-monitoring markers for degenerative disc diseases.

  10. On the validity of the degenerate Ginzburg-Landau equation

    NARCIS (Netherlands)

    Shepeleva, A.

    2001-01-01

    The Ginzburg{Landau equation which describes nonlinear modulation of the amplitude of the basic pattern does not give a good approximation when the Landau constant (which describes the in uence of the nonlinearity) is small. In this paper a derivation of the so{called degenerate (or generalized) Gin

  11. Calpains mediate axonal cytoskeleton disintegration during Wallerian degeneration.

    Science.gov (United States)

    Ma, Marek; Ferguson, Toby A; Schoch, Kathleen M; Li, Jian; Qian, Yaping; Shofer, Frances S; Saatman, Kathryn E; Neumar, Robert W

    2013-08-01

    In both the central nervous system (CNS) and peripheral nervous system (PNS), transected axons undergo Wallerian degeneration. Even though Augustus Waller first described this process after transection of axons in 1850, the molecular mechanisms may be shared, at least in part, by many human diseases. Early pathology includes failure of synaptic transmission, target denervation, and granular disintegration of the axonal cytoskeleton (GDC). The Ca(2+)-dependent protease calpains have been implicated in GDC but causality has not been established. To test the hypothesis that calpains play a causal role in axonal and synaptic degeneration in vivo, we studied transgenic mice that express human calpastatin (hCAST), the endogenous calpain inhibitor, in optic and sciatic nerve axons. Five days after optic nerve transection and 48 h after sciatic nerve transection, robust neurofilament proteolysis observed in wild-type controls was reduced in hCAST transgenic mice. Protection of the axonal cytoskeleton in sciatic nerves of hCAST mice was nearly complete 48 h post-transection. In addition, hCAST expression preserved the morphological integrity of neuromuscular junctions. However, compound muscle action potential amplitudes after nerve transection were similar in wild-type and hCAST mice. These results, in total, provide direct evidence that calpains are responsible for the morphological degeneration of the axon and synapse during Wallerian degeneration.

  12. Complement factor d in age-related macular degeneration

    NARCIS (Netherlands)

    Stanton, C.M.; Yates, J.R.W.; Hollander, A.I. den; Seddon, J.M.; Swaroop, A.; Stambolian, D.; Fauser, S.; Hoyng, C.B.; Yu, Y.; Atsuhiro, K.; Branham, K.; Othman, M.; Chen, W.; Kortvely, E.; Chalmers, K.; Hayward, C.; Moore, A.T.; Dhillon, B.; Ueffing, M.; Wright, A.F.

    2011-01-01

    Purpose. To examine the role of complement factor D (CFD) in age-related macular degeneration (AMD) by analysis of genetic association, copy number variation, and plasma CFD concentrations. Methods. Single nucleotide polymorphisms (SNPs) in the CFD gene were genotyped and the results analyzed by

  13. Degenerate Orbit Flip Homoclinic Bifurcations with Higher Dimensions

    Institute of Scientific and Technical Information of China (English)

    Ran Chao WU; Jian Hua SUN

    2006-01-01

    Bifurcations of a degenerate homoclinic orbit with orbit flip in high dimensional system are existence and uniqueness of 1-homoclinic orbit and 1-periodic orbit are given. Also considered is the existence of 2-homoclinic orbit and 2-periodic orbit. In additon, the corresponding bifurcation surfaces are given.

  14. Remarks on Cyclotomic and Degenerate Cyclotomic BMW Algebras

    CERN Document Server

    Goodman, Frederick M

    2010-01-01

    We relate the structure of cyclotomic and degenerate cyclotomic BMW algebras, for arbitrary parameter values, to that for admissible parameter values. In particular, we show that these algebras are cellular. We characterize those parameter sets for affine BMW algebras over an algebraically closed field that permit the algebras to have non--trivial cyclotomic quotients.

  15. Unmyelinated nerve fiber degeneration in chronic inflammatory demyelinating polyneuropathy

    NARCIS (Netherlands)

    Bosboom, WMJ; Van den Berg, LH; Dieks, HJG; Plante, E; Veldman, H; Franssen, H; Wokke, JHJ

    2000-01-01

    To determine whether unmyelinated nerve fibers escape degeneration as one might expect in an immune response exclusively directed at myelin, we performed a morphometric examination of unmyelinated axons and myelinated nerve fibers in sural nerve biopsy specimens of 14 patients with a chronic inflamm

  16. Anisotropic uniqueness classes for a degenerate parabolic equation

    Energy Technology Data Exchange (ETDEWEB)

    Vil' danova, V F [Bashkir State Pedagogical University, Ufa (Russian Federation); Mukminov, F Kh [Bashkir State University, Ufa (Russian Federation)

    2013-11-30

    Anisotropic uniqueness classes of Tacklind type are identified for a degenerate linear parabolic equation of the second order in an unbounded domain. The Cauchy problem and mixed problems with boundary conditions of the first and third type are considered. Bibliography: 18 titles.

  17. Longitudinal dielectric permeability in quantum non-degenerate and maxwellian collisional plasma with constant collision frequency

    OpenAIRE

    Latyshev, A. V.; Yushkanov, A. A.

    2013-01-01

    The formula for dielectric function of non-degenerate and maxwellian collisional plasmas is transformed to the form, convenient for research. Graphic comparison of longitudinal dielectric functions of quantum and classical non-degenerate collisional plasmas is made.

  18. The analyticity of solutions to a class of degenerate elliptic equations

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    In the present paper,the analyticity of solutions to a class of degenerate elliptic equations is obtained.A kind of weighted norms are introduced and under such norms some degenerate elliptic operators are of weak coerciveness.

  19. Gender difference in genetic association between IL1A variant and early lumbar disc degeneration

    DEFF Research Database (Denmark)

    Eskola, Pasi J; Kjær, Per; Sorensen, Joan S;

    2012-01-01

    The purpose of the present study was to analyze the associations between specific genetic markers and early disc degeneration (DD) or early disc degeneration progression (DDP) defined by magnetic resonance imaging (MRI)....

  20. Viruses associated with ovarian degeneration in Apis mellifera L. queens.

    Directory of Open Access Journals (Sweden)

    Laurent Gauthier

    Full Text Available Queen fecundity is a critical issue for the health of honeybee (Apis mellifera L. colonies, as she is the only reproductive female in the colony and responsible for the constant renewal of the worker bee population. Any factor affecting the queen's fecundity will stagnate colony development, increasing its susceptibility to opportunistic pathogens. We discovered a pathology affecting the ovaries, characterized by a yellow discoloration concentrated in the apex of the ovaries resulting from degenerative lesions in the follicles. In extreme cases, marked by intense discoloration, the majority of the ovarioles were affected and these cases were universally associated with egg-laying deficiencies in the queens. Microscopic examination of the degenerated follicles showed extensive paracrystal lattices of 30 nm icosahedral viral particles. A cDNA library from degenerated ovaries contained a high frequency of deformed wing virus (DWV and Varroa destructor virus 1 (VDV-1 sequences, two common and closely related honeybee Iflaviruses. These could also be identified by in situ hybridization in various parts of the ovary. A large-scale survey for 10 distinct honeybee viruses showed that DWV and VDV-1 were by far the most prevalent honeybee viruses in queen populations, with distinctly higher prevalence in mated queens (100% and 67%, respectively for DWV and VDV-1 than in virgin queens (37% and 0%, respectively. Since very high viral titres could be recorded in the ovaries and abdomens of both functional and deficient queens, no significant correlation could be made between viral titre and ovarian degeneration or egg-laying deficiency among the wider population of queens. Although our data suggest that DWV and VDV-1 have a role in extreme cases of ovarian degeneration, infection of the ovaries by these viruses does not necessarily result in ovarian degeneration, even at high titres, and additional factors are likely to be involved in this pathology.

  1. THE REGULAR SOLUTIONS OF THE ISENTROPIC EULER EQUATIONS WITH DEGENERATE LINEAR DAMPING

    Institute of Scientific and Technical Information of China (English)

    ZHU XUSHENG; WANG WEIKE

    2005-01-01

    The regular solutions of the isentropic Euler equations with degenerate linear damping for a perfect gas are studied in this paper. And a critical degenerate linear damping coefficient is found, such that if the degenerate linear damping coefficient is larger than it and the gas lies in a compact domain initially, then the regular solution will blow up in finite time; if the degenerate linear damping coefficient is less than it, then undersome hypotheses on the initial data, the regular solution exists globally.

  2. Gender difference in genetic association between IL1A variant and early lumbar disc degeneration

    DEFF Research Database (Denmark)

    Eskola, Pasi J; Kjær, Per; Sorensen, Joan S

    2012-01-01

    The purpose of the present study was to analyze the associations between specific genetic markers and early disc degeneration (DD) or early disc degeneration progression (DDP) defined by magnetic resonance imaging (MRI).......The purpose of the present study was to analyze the associations between specific genetic markers and early disc degeneration (DD) or early disc degeneration progression (DDP) defined by magnetic resonance imaging (MRI)....

  3. Lipids, lipid genes, and incident age-related macular degeneration: The three continent age-related macular degeneration consortium

    NARCIS (Netherlands)

    R. Klein (Ronald); C.E. Myers (Chelsea); G.H.S. Buitendijk (Gabrielle); E. Rochtchina (Elena); X. Gao (Xiaoyi); P.T.V.M. de Jong (Paulus); T.A. Sivakumaran (Theru); G. Burlutsky (George); R. McKean-Cowdin (Roberta); A. Hofman (Albert); S.K. Iyengar (Sudha); K.E. Lee (Kristine); B.H.Ch. Stricker (Bruno); J.R. Vingerling (Hans); P. Mitchell (Paul); B.E.K. Klein (Barbara); C.C.W. Klaver (Caroline); J.J. Wang (Jie Jin)

    2014-01-01

    textabstractPurpose To describe associations of serum lipid levels and lipid pathway genes to the incidence of age-related macular degeneration (AMD). Design Meta-analysis. Methods setting: Three population-based cohorts. population: A total of 6950 participants from the Beaver Dam Eye Study (BDES),

  4. Lipids, lipid genes, and incident age-related macular degeneration : the three continent age-related macular degeneration consortium

    NARCIS (Netherlands)

    Klein, Ronald; Myers, Chelsea E; Buitendijk, Gabriëlle H S; Rochtchina, Elena; Gao, Xiaoyi; de Jong, Paulus T V M; Sivakumaran, Theru A; Burlutsky, George; McKean-Cowdin, Roberta; Hofman, Albert; Iyengar, Sudha K; Lee, Kristine E; Stricker, Bruno H; Vingerling, Johannes R; Mitchell, Paul; Klein, Barbara E K; Klaver, Caroline C W; Wang, Jie Jin

    PURPOSE: To describe associations of serum lipid levels and lipid pathway genes to the incidence of age-related macular degeneration (AMD). DESIGN: Meta-analysis. METHODS: setting: Three population-based cohorts. population: A total of 6950 participants from the Beaver Dam Eye Study (BDES), Blue

  5. Neuron loss and degeneration in the progression of TDP-43 in frontotemporal lobar degeneration.

    Science.gov (United States)

    Yousef, Ahmed; Robinson, John L; Irwin, David J; Byrne, Matthew D; Kwong, Linda K; Lee, Edward B; Xu, Yan; Xie, Sharon X; Rennert, Lior; Suh, EunRan; Van Deerlin, Vivianna M; Grossman, Murray; Lee, Virginia M-Y; Trojanowski, John Q

    2017-09-06

    Frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) is associated with the accumulation of pathological neuronal and glial intracytoplasmic inclusions as well as accompanying neuron loss. We explored if cortical neurons detected by NeuN decreased with increasing TDP-43 inclusion pathology in the postmortem brains of 63 patients with sporadic and familial FTLD-TDP. Semi-automated quantitative algorithms to quantify histology in tissue sections stained with antibodies specific for pathological or phosphorylated TDP-43 (pTDP-43) and NeuN were developed and validated in affected (cerebral cortex) and minimally affected (cerebellar cortex) brain regions of FTLD-TDP cases. Immunohistochemistry (IHC) for NeuN and other neuronal markers found numerous neurons lacking reactivity, suggesting NeuN may reflect neuron health rather than neuron loss in FTLD. We found three patterns of NeuN and pTDP-43 reactivity in our sample of cortical tissue representing three intracortical region-specific stages of FTLD-TDP progression: Group 1 showed low levels of pathological pTDP-43 and high levels NeuN, while Group 2 showed increased levels of pTDP-43, and Group 3 tissues were characterized by reduced staining for both pTDP-43 and NeuN. Comparison of non-C9orf72/GRN FTLD-TDP with cases linked to both GRN mutations and C9orf72 expansions showed a significantly increased frequency of Group 3 histopathology in the latter cases, suggesting more advanced cortical disease. Hence, we propose that IHC profiles of pTDP-43 and NeuN reflect the burden of pTDP-43 and its deleterious effects on neuron health.

  6. Identifying microRNAs involved in degeneration of the organ of corti during age-related hearing loss.

    Directory of Open Access Journals (Sweden)

    Qian Zhang

    Full Text Available MicroRNAs (miRNAs, a class of short non-coding RNAs that regulate the expression of mRNA targets, are important regulators of cellular senescence and aging. We questioned which miRNAs are involved in age-related degeneration of the organ of Corti (OC, the auditory sensory epithelium that transduces mechanical stimuli to electrical activity in the inner ear. Degeneration of the OC is generally accepted as the main cause of age-related hearing loss (ARHL, a progressive loss of hearing in individuals as they grow older. To determine which miRNAs are involved in the onset and progression of ARHL, miRNA gene expression in the OC of two mouse strains, C57BL/6J and CBA/J, was compared at three different ages using GeneChip miRNA microarray and was validated by real-time PCR. We showed that 111 and 71 miRNAs exhibited differential expression in the C57 and CBA mice, respectively, and that downregulated miRNAs substantially outnumbered upregulated miRNAs during aging. miRNAs that had approximately 2-fold upregulation included members of miR-29 family and miR-34 family, which are known regulators of pro-apoptotic pathways. In contrast, miRNAs that were downregulated by about 2-fold were members of the miR-181 family and miR-183 family, which are known to be important for proliferation and differentiation, respectively. The shift of miRNA expression favoring apoptosis occurred earlier than detectable hearing threshold elevation and hair cell loss. Our study suggests that changes in miRNA expression precede morphological and functional changes, and that upregulation of pro-apoptotic miRNAs and downregulation of miRNAs promoting proliferation and differentiation are both involved in age-related degeneration of the OC.

  7. Decreased fixation stability of the preferred retinal location in juvenile macular degeneration

    NARCIS (Netherlands)

    Bethlehem, Richard A I; Dumoulin, Serge O.; Dalmaijer, Edwin S.; Smit, Miranda; Berendschot, Tos T J M; Nijboer, Tanja C W; Van Der Stigchel, Stefan

    2014-01-01

    Macular degeneration is the main cause for diminished visual acuity in the elderly. The juvenile form of macular degeneration has equally detrimental consequences on foveal vision. To compensate for loss of foveal vision most patients with macular degeneration adopt an eccentric preferred retinal lo

  8. THE ALL-DELAY STABILITY OF DEGENERATE DIFFERENTIAL SYSTEMS WITH DELAY

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    In this paper,the all-delay stability of degenerate differential systems with delay is discussed.We come up with some new criteria for evaluating the all-delay stability of degenerate differential systems with delay and degenerate neutral differential systems with delay.Also,we give an example to illustrate the main results.

  9. Peripheral motor axons of SOD1(G127X) mutant mice are susceptible to activity-dependent degeneration

    DEFF Research Database (Denmark)

    Alvarez Herrero, Susana; Calin, A; Graffmo, K S

    2013-01-01

    Motor neuron disorders may be associated with mitochondrial dysfunction, and repetitive electrical impulse conduction during energy restriction has been found to cause neuronal degeneration. The aim of this study was to investigate the vulnerability of motor axons of a presymptomatic late......-onset, fast-progression SOD1(G127X) mouse model of amyotrophic lateral sclerosis to long-lasting, high-frequency repetitive activity. Tibial nerves were stimulated at ankle in 7 to 8-month-old SOD1(G127X) mice when they were clinically indistinguishable from wild-type (WT) mice. The evoked compound muscle...... action potentials and ascending compound nerve action potentials were recorded from plantar muscles and from the sciatic nerve, respectively. Repetitive stimulation (RS) was carried out in interrupted trains of 200-Hz for 3h. During the stimulation-sequence there was progressive conduction failure in WT...

  10. Selective inhibition of caspases in skeletal muscle reverses the apoptotic synaptic degeneration in slow-channel myasthenic syndrome.

    Science.gov (United States)

    Zhu, Haipeng; Pytel, Peter; Gomez, Christopher M

    2014-01-01

    Slow-channel syndrome (SCS) is a congenital myasthenic disorder caused by point mutations in subunits of skeletal muscle acetylcholine receptor leading to Ca(2+) overload and degeneration of the postsynaptic membrane, nuclei and mitochondria of the neuromuscular junction (NMJ). In both SCS muscle biopsies and transgenic mouse models for SCS (mSCS), the endplate regions are shrunken, and there is evidence of DNA damage in the subsynaptic region. Activated caspase-9, -3 and -7 are intensely co-localized at the NMJ, and the Ca(2+)-activated protease, calpain, and the atypical cyclin-dependent kinase (Cdk5) are overactivated in mSCS. Thus, the true mediator(s) of the disease process is not clear. Here, we demonstrate that selective inhibition of effector caspases, caspase-3 and -7, or initiator caspase, caspase-9, in limb muscle in vivo by localized expression of recombinant inhibitor proteins dramatically decreases subsynaptic DNA damage, increases endplate area and improves ultrastructural abnormalities in SCS transgenic mice. Calpain and Cdk5 are not affected by this treatment. On the other hand, inhibition of Cdk5 by expression of a dominant-negative form of Cdk5 has no effect on the degeneration. Together with previous studies, these results indicate that focal activation of caspase activity at the NMJ is the principal pathological process responsible for the synaptic apoptosis in SCS. Thus, treatments that reduce muscle caspase activity are likely to be of benefit for SCS patients.

  11. Gene therapy with a promoter targeting both rods and cones rescues retinal degeneration caused by AIPL1 mutations.

    Science.gov (United States)

    Sun, X; Pawlyk, B; Xu, X; Liu, X; Bulgakov, O V; Adamian, M; Sandberg, M A; Khani, S C; Tan, M-H; Smith, A J; Ali, R R; Li, T

    2010-01-01

    Aryl hydrocarbon receptor-interacting protein-like 1 (AIPL1) is required for the biosynthesis of photoreceptor phosphodiesterase (PDE). Gene defects in AIPL1 cause a heterogeneous set of conditions ranging from Leber's congenital amaurosis (LCA), the severest form of early-onset retinal degeneration, to milder forms such as retinitis pigmentosa (RP) and cone-rod dystrophy. In mice, null and hypomorphic alleles cause retinal degeneration similar to human LCA and RP, respectively. Thus these mouse models represent two ends of the disease spectrum associated with AIPL1 gene defects in humans. We evaluated whether adeno-associated virus (AAV)-mediated gene replacement therapy in these models could restore PDE biosynthesis in rods and cones and thereby improve photoreceptor survival. We validated the efficacy of human AIPL1 (isoform 1) replacement gene controlled by a promoter derived from the human rhodopsin kinase (RK) gene, which is active in both rods and cones. We found substantial and long-term rescue of the disease phenotype as a result of transgene expression. This is the first gene therapy study in which both rods and cones were targeted successfully with a single photoreceptor-specific promoter. We propose that the vector and construct design used in this study could serve as a prototype for a human clinical trial.

  12. Androgen receptor YAC transgenic mice recapitulate SBMA motor neuronopathy and implicate VEGF164 in the motor neuron degeneration.

    Science.gov (United States)

    Sopher, Bryce L; Thomas, Patrick S; LaFevre-Bernt, Michelle A; Holm, Ida E; Wilke, Scott A; Ware, Carol B; Jin, Lee-Way; Libby, Randell T; Ellerby, Lisa M; La Spada, Albert R

    2004-03-04

    X-linked spinal and bulbar muscular atrophy (SBMA) is an inherited neuromuscular disorder characterized by lower motor neuron degeneration. SBMA is caused by polyglutamine repeat expansions in the androgen receptor (AR). To determine the basis of AR polyglutamine neurotoxicity, we introduced human AR yeast artificial chromosomes carrying either 20 or 100 CAGs into mouse embryonic stem cells. The AR100 transgenic mice developed a late-onset, gradually progressive neuromuscular phenotype accompanied by motor neuron degeneration, indicating striking recapitulation of the human disease. We then tested the hypothesis that polyglutamine-expanded AR interferes with CREB binding protein (CBP)-mediated transcription of vascular endothelial growth factor (VEGF) and observed altered CBP-AR binding and VEGF reduction in AR100 mice. We found that mutant AR-induced death of motor neuron-like cells could be rescued by VEGF. Our results suggest that SBMA motor neuronopathy involves altered expression of VEGF, consistent with a role for VEGF as a neurotrophic/survival factor in motor neuron disease.

  13. Hypertrophic Olivary Degeneration and Palatal or Oculopalatal Tremor

    Directory of Open Access Journals (Sweden)

    Caroline Tilikete

    2017-06-01

    Full Text Available Hypertrophic degeneration of the inferior olive is mainly observed in patients developing palatal tremor (PT or oculopalatal tremor (OPT. This syndrome manifests as a synchronous tremor of the palate (PT and/or eyes (OPT that may also involve other muscles from the branchial arches. It is associated with hypertrophic inferior olivary degeneration that is characterized by enlarged and vacuolated neurons, increased number and size of astrocytes, severe fibrillary gliosis, and demyelination. It appears on MRI as an increased T2/FLAIR signal intensity and enlargement of the inferior olive. There are two main conditions in which hypertrophic degeneration of the inferior olive occurs. The most frequent, studied, and reported condition is the development of PT/OPT and hypertrophic degeneration of the inferior olive in the weeks or months following a structural brainstem or cerebellar lesion. This “symptomatic” condition requires a destructive lesion in the Guillain–Mollaret pathway, which spans from the contralateral dentate nucleus via the brachium conjunctivum and the ipsilateral central tegmental tract innervating the inferior olive. The most frequent etiologies of destructive lesion are stroke (hemorrhagic more often than ischemic, brain trauma, brainstem tumors, and surgical or gamma knife treatment of brainstem cavernoma. The most accepted explanation for this symptomatic PT/OPT is that denervated olivary neurons released from inhibitory inputs enlarge and develop sustained synchronized oscillations. The cerebellum then modulates/accentuates this signal resulting in abnormal motor output in the branchial arches. In a second condition, PT/OPT and progressive cerebellar ataxia occurs in patients without structural brainstem or cerebellar lesion, other than cerebellar atrophy. This syndrome of progressive ataxia and palatal tremor may be sporadic or familial. In the familial form, where hypertrophic degeneration of the inferior olive may not

  14. Mouse bladder wall injection.

    Science.gov (United States)

    Fu, Chi-Ling; Apelo, Charity A; Torres, Baldemar; Thai, Kim H; Hsieh, Michael H

    2011-07-12

    Mouse bladder wall injection is a useful technique to orthotopically study bladder phenomena, including stem cell, smooth muscle, and cancer biology. Before starting injections, the surgical area must be cleaned with soap and water and antiseptic solution. Surgical equipment must be sterilized before use and between each animal. Each mouse is placed under inhaled isoflurane anesthesia (2-5% for induction, 1-3% for maintenance) and its bladder exposed by making a midline abdominal incision with scissors. If the bladder is full, it is partially decompressed by gentle squeezing between two fingers. The cell suspension of interest is intramurally injected into the wall of the bladder dome using a 29 or 30 gauge needle and 1 cc or smaller syringe. The wound is then closed using wound clips and the mouse allowed to recover on a warming pad. Bladder wall injection is a delicate microsurgical technique that can be mastered with practice.

  15. Hematopoietic lineage skewing and intestinal epithelia degeneration in aged mice with telomerase RNA component deletion.

    Science.gov (United States)

    Chen, Jichun; Bryant, Mark A; Dent, James J; Sun, Yu; Desierto, Marie J; Young, Neal S

    2015-12-01

    A deletion of a telomerase RNA component (Terc(-/-)) in C57BL/6 (B6) mice resulted in hematopoietic lineage skewing with increased neutrophils and CD11b(+) myeloid cells and decreased red blood cells and CD45R(+) B lymphocytes when animals reach ages older than 12 months. There was no decline in bone marrow (BM) c-Kit(+)Sca-1(+)Lin(-) (KSL) cells in old Terc(-/-) mice, and the lineage skewing phenomenon was not transferred when BM cells from old Terc(-/-) donors were transplanted into young B6 recipients. Necropsy and histological examinations found minimal to no change in the lung, spleen and liver but detected severe epithelia degeneration, ulceration and infection in small and large intestines, leading to enteritis, typhlitis and colitis in old Terc(-/-) mice. In a mouse model of dextran-sulfate-sodium-induced typhlitis and colitis, development of intestinal pathology was associated with increases in neutrophils and CD11b(+) myeloid cells and a decrease in CD45R(+) B cells, similar to those observed in old Terc(-/-) mice. Treatment of 11-13 month old Terc(-/-) mice with antibiotic trimethoprim-sulfa water reduced neutrophils and myeloid cells and increased B lymphocytes in the blood, indicating that mitigation of intestinal infection and inflammation could alleviate hematological abnormalities in old Terc(-/-) animals.

  16. Imaging axonal degeneration and repair in pre-clinical animal models of multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Soumya S Yandamuri

    2016-05-01

    Full Text Available Multiple sclerosis (MS is a central nervous system (CNS disease characterized by chronic neuroinflammation, demyelination, and axonal damage. Infiltration of activated lymphocytes and myeloid cells are thought to be primarily responsible for white matter damage and axonopathy. Over time, this neurologic damage manifests clinically as debilitating motor and cognitive symptoms. Existing MS therapies focus on symptom relief and delay of disease progression through reduction of neuroinflammation. However, long-term strategies to remyelinate, protect, or regenerate axons have remained elusive, posing a challenge to treating progressive forms of MS. Preclinical mouse models and techniques such as immunohistochemistry, flow cytometry, and genomic and proteomic analysis have provided advances in our understanding of discrete time-points of pathology following disease induction. More recently, in vivo and in situ two-photon microscopy (2P has made it possible to visualize continuous real-time cellular behavior and structural changes occurring within the CNS during neuropathology. Research utilizing 2P imaging to study axonopathy in neuroinflammatory demyelinating disease has focused on five areas: (1 axonal morphologic changes (2 organelle transport and health, (3 relationship to inflammation, (4 neuronal excitotoxicity, and (5 regenerative therapies. 2P imaging may also be used to identify novel therapeutic targets via identification and clarification of dynamic cellular and molecular mechanisms of axonal regeneration and remyelination. Here, we review tools that have made 2P accessible for imaging neuropathologies and advances in our understanding of axonal degeneration and repair in preclinical models of demyelinating diseases.

  17. CCR3 is a target for age-related macular degeneration diagnosis and therapy.

    Science.gov (United States)

    Takeda, Atsunobu; Baffi, Judit Z; Kleinman, Mark E; Cho, Won Gil; Nozaki, Miho; Yamada, Kiyoshi; Kaneko, Hiroki; Albuquerque, Romulo J C; Dridi, Sami; Saito, Kuniharu; Raisler, Brian J; Budd, Steven J; Geisen, Pete; Munitz, Ariel; Ambati, Balamurali K; Green, Martha G; Ishibashi, Tatsuro; Wright, John D; Humbles, Alison A; Gerard, Craig J; Ogura, Yuichiro; Pan, Yuzhen; Smith, Justine R; Grisanti, Salvatore; Hartnett, M Elizabeth; Rothenberg, Marc E; Ambati, Jayakrishna

    2009-07-09

    Age-related macular degeneration (AMD), a leading cause of blindness worldwide, is as prevalent as cancer in industrialized nations. Most blindness in AMD results from invasion of the retina by choroidal neovascularisation (CNV). Here we show that the eosinophil/mast cell chemokine receptor CCR3 is specifically expressed in choroidal neovascular endothelial cells in humans with AMD, and that despite the expression of its ligands eotaxin-1, -2 and -3, neither eosinophils nor mast cells are present in human CNV. Genetic or pharmacological targeting of CCR3 or eotaxins inhibited injury-induced CNV in mice. CNV suppression by CCR3 blockade was due to direct inhibition of endothelial cell proliferation, and was uncoupled from inflammation because it occurred in mice lacking eosinophils or mast cells, and was independent of macrophage and neutrophil recruitment. CCR3 blockade was more effective at reducing CNV than vascular endothelial growth factor A (VEGF-A) neutralization, which is in clinical use at present, and, unlike VEGF-A blockade, is not toxic to the mouse retina. In vivo imaging with CCR3-targeting quantum dots located spontaneous CNV invisible to standard fluorescein angiography in mice before retinal invasion. CCR3 targeting might reduce vision loss due to AMD through early detection and therapeutic angioinhibition.

  18. Structure of nearly degenerate dipole bands in {sup 108}Ag

    Energy Technology Data Exchange (ETDEWEB)

    Sethi, J. [Tata Institute of Fundamental Research, Colaba, Mumbai 400 005 (India); Palit, R., E-mail: palit@tifr.res.in [Tata Institute of Fundamental Research, Colaba, Mumbai 400 005 (India); Saha, S.; Trivedi, T. [Tata Institute of Fundamental Research, Colaba, Mumbai 400 005 (India); Bhat, G.H.; Sheikh, J.A. [Department of Physics, University of Kashmir, Srinagar 190 006 (India); Datta, P. [Ananda Mohan College, Kolkata 700009 (India); Carroll, J.J. [US Army Research Laboratory, Adelphi, MD 20783 (United States); Chattopadhyay, S. [Saha Institute of Nuclear Physics, Kolkata 700064 (India); Donthi, R. [Tata Institute of Fundamental Research, Colaba, Mumbai 400 005 (India); Garg, U. [University of Notre Dame, Notre Dame, IN 46556 (United States); Jadhav, S.; Jain, H.C. [Tata Institute of Fundamental Research, Colaba, Mumbai 400 005 (India); Karamian, S. [Joint Institute for Nuclear Research, Dubna 141980 (Russian Federation); Kumar, S. [University of Delhi, Delhi 110007 (India); Litz, M.S. [US Army Research Laboratory, Adelphi, MD 20783 (United States); Mehta, D. [Panjab University, Chandigarh 160014 (India); Naidu, B.S. [Tata Institute of Fundamental Research, Colaba, Mumbai 400 005 (India); Naik, Z. [Sambalpur University, Sambalpur 143005 (India); Sihotra, S. [Panjab University, Chandigarh 160014 (India); and others

    2013-08-09

    The high spin negative parity states of {sup 108}Ag have been investigated with the {sup 11}B + {sup 100}Mo reaction at 39 MeV beam energy using the INGA facility at TIFR, Mumbai. From the γ–γ coincidence analysis, an excited negative parity band has been established and found to be nearly degenerate with the ground state band. The spin and parity of the levels are assigned using angular correlation and polarization measurements. This pair of degenerate bands in {sup 108}Ag is studied using the recently developed microscopic triaxial projected shell model approach. The observed energy levels and the ratio of the electromagnetic transition probabilities of these bands in this isotope are well reproduced by the present model. Further, it is shown that the partner band has a different quasiparticle structure as compared to the yrast band.

  19. Olivary degeneration after cerebellar or brain stem haemorrhage: MRI

    Energy Technology Data Exchange (ETDEWEB)

    Uchino, A. (Dept. of Radiology, Kyushu Univ. Hospital, Fukuoka (Japan) Dept. of Radiology, Kyushu Rosai Hospital, Kitakyushu (Japan)); Hasuo, K. (Dept. of Radiology, Kyushu Univ. Hospital, Fukuoka (Japan)); Uchida, K. (Dept. of Radiology, Kyushu Rosai Hospital, Kitakyushu (Japan)); Matsumoto, S. (Dept. of Radiology, Kyushu Univ. Hospital, Fukuoka (Japan)); Tsukamoto, Y. (Dept. of Radiology, Kyushu Rosai Hospital, Kitakyushu (Japan)); Ohno, M. (Dept. of Radiology, Kyushu Rosai Hospital, Kitakyushu (Japan)); Masuda, K. (Dept. of Radiology, Kyushu Univ. Hospital, Fukuoka (Japan))

    1993-05-01

    Magnetic resonance (MR) images of seven patients with olivary degeneration caused by cerebellar or brain stem haemorrhages were reviewed. In four patients with cerebellar haemorrhage, old haematomas were identified as being located in the dentate nucleus; the contralateral inferior olivary nuclei were hyperintense on proton-density- and T2-weighted images. In two patients with pontine haemorrhages, the old haematomas were in the tegmentum and the ipsilateral inferior olivary nuclei, which were hyperintense. In one case of midbrain haemorrhage, the inferior olivary nuclei were hyperintense bilaterally. The briefest interval from the ictus to MRI was 2 months. Hypertrophic olivary nuclei were observed only at least 4 months after the ictus. Olivary degeneration after cerebellar or brain stem haemorrhage should not be confused with ischaemic, neoplastic, or other primary pathological conditions of the medulla. (orig.)

  20. Identifying Initial Condition in Degenerate Parabolic Equation with Singular Potential

    Directory of Open Access Journals (Sweden)

    K. Atifi

    2017-01-01

    Full Text Available A hybrid algorithm and regularization method are proposed, for the first time, to solve the one-dimensional degenerate inverse heat conduction problem to estimate the initial temperature distribution from point measurements. The evolution of the heat is given by a degenerate parabolic equation with singular potential. This problem can be formulated in a least-squares framework, an iterative procedure which minimizes the difference between the given measurements and the value at sensor locations of a reconstructed field. The mathematical model leads to a nonconvex minimization problem. To solve it, we prove the existence of at least one solution of problem and we propose two approaches: the first is based on a Tikhonov regularization, while the second approach is based on a hybrid genetic algorithm (married genetic with descent method type gradient. Some numerical experiments are given.

  1. Rosette Central Configurations, Degenerate central configurations and bifurcations

    CERN Document Server

    Lei, Jinzhi

    2009-01-01

    In this paper we find a class of new degenerate central configurations and bifurcations in the Newtonian $n$-body problem. In particular we analyze the Rosette central configurations, namely a coplanar configuration where $n$ particles of mass $m_1$ lie at the vertices of a regular $n$-gon, $n$ particles of mass $m_2$ lie at the vertices of another $n$-gon concentric with the first, but rotated of an angle $\\pi/n$, and an additional particle of mass $m_0$ lies at the center of mass of the system. This system admits two mass parameters $\\mu=m_0/m_1$ and $\\ep=m_2/m_1$. We show that, as $\\mu$ varies, if $n> 3$, there is a degenerate central configuration and a bifurcation for every $\\ep>0$, while if $n=3$ there is a bifurcations only for some values of $\\epsilon$.

  2. Low Starting Electron Beam Current in Degenerate Band Edge Oscillators

    CERN Document Server

    Othman, Mohamed A K; Figotin, Alexander; Capolino, Filippo

    2016-01-01

    We propose a new principle of operation in vacuum electron-beam-based oscillators that leads to a low beam current for starting oscillations. The principle is based on super synchronous operation of an electron beam interacting with four degenerate electromagnetic modes in a slow-wave structure (SWS). The four mode super synchronous regime is associated with a very special degeneracy condition in the dispersion diagram of a cold periodic SWS called degenerate band edge (DBE). This regime features a giant group delay in the finitelength SWS and low starting-oscillation beam current. The starting beam current is at least an order of magnitude smaller compared to a conventional backward wave oscillator (BWO) of the same length. As a representative example we consider a SWS conceived by a periodically-loaded metallic waveguide supporting a DBE, and investigate starting-oscillation conditions using Pierce theory generalized to coupled transmission lines (CTL). The proposed super synchronism regime can be straightf...

  3. Nonlinear electromagnetic waves in a degenerate electron-positron plasma

    Energy Technology Data Exchange (ETDEWEB)

    El-Labany, S.K., E-mail: skellabany@hotmail.com [Department of Physics, Faculty of Science, Damietta University, New Damietta (Egypt); El-Taibany, W.F., E-mail: eltaibany@hotmail.com [Department of Physics, College of Science for Girls in Abha, King Khalid University, Abha (Saudi Arabia); El-Samahy, A.E.; Hafez, A.M.; Atteya, A., E-mail: ahmedsamahy@yahoo.com, E-mail: am.hafez@sci.alex.edu.eg, E-mail: ahmed_ateya2002@yahoo.com [Department of Physics, Faculty of Science, Alexandria University, Alexandria (Egypt)

    2015-08-15

    Using the reductive perturbation technique (RPT), the nonlinear propagation of magnetosonic solitary waves in an ultracold, degenerate (extremely dense) electron-positron (EP) plasma (containing ultracold, degenerate electron, and positron fluids) is investigated. The set of basic equations is reduced to a Korteweg-de Vries (KdV) equation for the lowest-order perturbed magnetic field and to a KdV type equation for the higher-order perturbed magnetic field. The solutions of these evolution equations are obtained. For better accuracy and searching on new features, the new solutions are analyzed numerically based on compact objects (white dwarf) parameters. It is found that including the higher-order corrections results as a reduction (increment) of the fast (slow) electromagnetic wave amplitude but the wave width is increased in both cases. The ranges where the RPT can describe adequately the total magnetic field including different conditions are discussed. (author)

  4. Degeneration in dysplastic hips. A computer tomography study

    DEFF Research Database (Denmark)

    Jacobsen, Steffen; Rømer, Lone; Søballe, Kjeld

    2005-01-01

    BACKGROUND: Hip dysplasia is considered pre-osteoarthritic, causing degeneration in young individuals. OBJECTIVE: To determine the pattern of degenerative change in moderate to severely dysplastic hips in young patients. DESIGN AND PATIENTS: One hundred and ninety-three consecutively......-referred younger patients with hip pain believed to be caused by hip dysplasia constituted the study cohort. The average age was 35.5 years (range, 15-61 years). They were examined by close-cut transverse pelvic and knee computed tomography and antero-posterior radiographs (CT). We identified 197 hips...... with moderate to severe dysplasia, and 78 hips with normal morphology in the study cohort, whilst 111 hip joints were borderline dysplastic according to preset definitions. Comparative analyses of anatomy and distribution of degeneration between dysplastic and normal hips in the study cohort were performed...

  5. Vegetation Evolution with Degenerating Soil Ecology Under Unequal Competition

    Institute of Scientific and Technical Information of China (English)

    LIN Zhen-Shan; QI Xiang-Zhen

    2004-01-01

    A vegetation evolution model influenced by a degeneration of soil ecological functions was set up. Three ideal communities of a) trees, b) shrubs, and c) herbage populations were first simulated. Then numerical simulations of the evolutionary and developmental processes of a natural forest community, which is composed of over 100 species,were conducted. Results of the study showed that a) in all communities, soil degeneration not only drove some weaker species to extinction, but also a few dominant ones; b) there were different response scales with species in an ideal tree metapopulation that could persist as long as a thousand years, with shrubs in an ideal shrub metapopulation that could persevere for several hundred years, and with species in an ideal herbage metapopulation that could become extinct within 10 years; and c) each metapopulation experienced three evolutionary stages during adaptation to the environment: a) the stage of compelled adaptation or resistance, b) the adjusted stage, and c) the stabilized stage.

  6. Type I seesaw mechanism for quasi degenerate neutrinos

    CERN Document Server

    Joshipura, Anjan S; Vempati, Sudhir K

    2009-01-01

    We discuss symmetries and scenarios leading to quasi-degenerate neutrinos in type-I seesaw models. The existence of degeneracy in the present approach is not linked to any specific structure for the Dirac neutrino Yukawa coupling matrix $y_D$ and holds in general. Basic input is the application of the minimal flavour violation principle to the leptonic sector. Generalizing this principle, we assume that the structure of the right handed neutrino mass matrix is determined by $y_D$ and the charged lepton Yukawa coupling matrix $y_l$ in an effective theory invariant under specific groups ${\\cal G}_F$ contained in the full symmetry group of the kinetic energy terms. ${\\cal G}_F$ invariance also leads to specific structure for the departure from degeneracy. The neutrino mass matrix (with degenerate mass $m_0$) resulting after seesaw mechanism has a simple form ${\\cal M}_\

  7. Nonlinear Electromagnetic Waves in a Degenerate Electron-Positron Plasma

    Science.gov (United States)

    El-Labany, S. K.; El-Taibany, W. F.; El-Samahy, A. E.; Hafez, A. M.; Atteya, A.

    2015-08-01

    Using the reductive perturbation technique (RPT), the nonlinear propagation of magnetosonic solitary waves in an ultracold, degenerate (extremely dense) electron-positron (EP) plasma (containing ultracold, degenerate electron, and positron fluids) is investigated. The set of basic equations is reduced to a Korteweg-de Vries (KdV) equation for the lowest-order perturbed magnetic field and to a KdV type equation for the higher-order perturbed magnetic field. The solutions of these evolution equations are obtained. For better accuracy and searching on new features, the new solutions are analyzed numerically based on compact objects (white dwarf) parameters. It is found that including the higher-order corrections results as a reduction (increment) of the fast (slow) electromagnetic wave amplitude but the wave width is increased in both cases. The ranges where the RPT can describe adequately the total magnetic field including different conditions are discussed.

  8. A Case of Corticobasal Degeneration Studied with Positron Emission Tomography

    Directory of Open Access Journals (Sweden)

    H. Nagasawa

    1993-01-01

    Full Text Available We measured cerebral blood flow, oxygen metabolism, glucose utilization, and dopamine metabolism in the brain of a patient with corticobasal degeneration using positron emission tomography (PET. The clinical picture is distinctive, comprising features referable to both cortical and basal ganglionic dysfunction. Brain imagings of glucose and dopamine metabolism can demonstrate greater abnormalities in the cerebral cortex and in the striatum contralateral to the more affected side than those of blood flow and oxygen metabolism. This unique combination study measuring both cerebral glucose utilization and dopamine metabolism in the nigrostriatal system can provide efficient information about the dysfunctions which are correlated with individual clinical symptoms, and this study is essential to diagnosis of corticobasal degeneration.

  9. Cardiac valve degeneration in a patient with Sneddon syndrome.

    Science.gov (United States)

    Diosteanu, Raluca; Schuler, Gerhard; Müller, Ulrike

    2015-06-01

    Sneddon syndrome--a rare cause of aortic and mitral valve stenosis. Sneddon syndrome is a rare disorder that leads to repeated occurrence of cerebrovascular disease and skin manifestation, defined as livedo racemosa generalisata. The authors report the occurrence of multiple valve degenerations in a 49-year-old patient with Sneddon syndrome, which seemed to have been asymptomatic through a long period of time and was diagnosed as it needed a complex surgical intervention.

  10. Smoking and Age-Related Macular Degeneration: Review and Update

    Science.gov (United States)

    Velilla, Sara; García-Medina, José Javier; García-Layana, Alfredo; Pons-Vázquez, Sheila; Pinazo-Durán, M. Dolores; Gómez-Ulla, Francisco; Arévalo, J. Fernando; Díaz-Llopis, Manuel; Gallego-Pinazo, Roberto

    2013-01-01

    Age-related macular degeneration (AMD) is one of the main socioeconomical health issues worldwide. AMD has a multifactorial etiology with a variety of risk factors. Smoking is the most important modifiable risk factor for AMD development and progression. The present review summarizes the epidemiological studies evaluating the association between smoking and AMD, the mechanisms through which smoking induces damage to the chorioretinal tissues, and the relevance of advising patients to quit smoking for their visual health. PMID:24368940

  11. Long term behaviour of singularly perturbed parabolic degenerated equation

    Directory of Open Access Journals (Sweden)

    Ibrahima Faye

    2016-12-01

    Full Text Available In this paper we consider models built in [4] for short-term, mean-term and long-term morphodynamics of dunes and megariples. We give an existence and uniqueness result for long term dynamics of dunes. This result is based on a periodic-in-time-and-space solution existence result for degenerated parabolic equation that we set out. Finally the mean-term and long-term models are homogenized.

  12. The role of epigenetics in age-related macular degeneration

    OpenAIRE

    Gemenetzi, M; Lotery, A.J.

    2014-01-01

    It is becoming increasingly evident that epigenetic mechanisms influence gene expression and can explain how interactions between genetics and the environment result in particular phenotypes during development. The extent to which this epigenetic effect contributes to phenotype heritability in age-related macular degeneration (AMD) is currently ill defined. However, emerging evidence suggests that epigenetic changes are relevant to AMD and as such provide an exciting new avenue of research fo...

  13. Prosopagnosia: A rare presenting manifestation of frontotemporal lobar degeneration

    Directory of Open Access Journals (Sweden)

    George Arun

    2009-01-01

    Full Text Available Frontotemporal dementia is an important neurodegenerative disorder accounting for a significant proportion of dementia cases with onset before 60 years of age. Apart from the well recognized behavioral changes the disease has many other distinctive features like predominant language involvement alone or associated features of motor neuron disease or parkinsonism etc. which at times may be the presenting manifestation itself. In the following article we describe a rare presenting manifestation; prosopagnosia, in the setting of frontotemporal degeneration

  14. Degenerate neutrinos in left-right symmetric theory

    Energy Technology Data Exchange (ETDEWEB)

    Joshipura, A.S. (Theory Group, Physical Research Laboratory, Navrangpura, Ahmedabad 380009 (India))

    1995-02-01

    Various hints on the neutrino masses, namely, (i) the solar neutrino deficit, (ii) the atmospheric neutrino deficit, (iii) the need for the dark matter, and/or (iv) the nonzero neutrinoless double [beta] decay collectively imply that all the three neutrinos must be nearly degenerate. This feature can be understood in the left-right symmetric theory. We present a model based on the group SU(2)[sub [ital L

  15. Degenerate Plebanski Sector and its Spin Foam Quantization

    CERN Document Server

    Alexandrov, Sergei

    2012-01-01

    We show that the degenerate sector of Spin(4) Plebanski formulation of four-dimensional gravity is exactly solvable and describes covariantly embedded SU(2) BF theory. This fact provides its spin foam quantization and allows to test various approaches of imposing the simplicity constraints. Our analysis suggests a unique method of imposing the constraints which leads to a consistent and well defined spin foam model.

  16. Binocular Refraction in Patients with Age-Related Macular Degeneration

    OpenAIRE

    Skrbek, Matěj

    2013-01-01

    We’ve been finding possible association of central vision damage with binocular vision disorders in our clients suffering from age-related macular degeneration (ARMD), but whose visual acuity still allowed us to examine their binocular vision. Our findings show that there is a significant number of patients with heterophoria in horizontal, as well as vertical direction. The clients rate the vision with prismatic correction as more comfortable, clearer and long-term tolerable. Getting used ...

  17. Vitreomacular traction and age-related macular degeneration.

    Science.gov (United States)

    Green-Simms, Amy E; Bakri, Sophie J

    2011-05-01

    The interaction between the vitreous and the internal limiting membrane of the retina is important in the pathoetiology of numerous ocular disease processes. Recent studies have focused on the vitreo-retinal interface in the context of age-related macular degeneration (AMD), linking vitreo-retinal adhesion to exudative AMD in particular. This review summarizes our knowledge of vitreous anatomy and recent investigations regarding vitreomacular adhesion and AMD.

  18. Nerve Degeneration and Regeneration Associated with NF1 Tumors

    Science.gov (United States)

    2014-09-01

    Associated with NF1 Tumors PRINCIPAL INVESTIGATOR: David F. Muir CONTRACTING ORGANIZATION: University of Florida...NUMBER Nerve Degeneration and Regeneration Associated with NF1 Tumors 5b. GRANT NUMBER W81XWH-11-1-0145 5c...for  the   eradication  of  PNSTs.    Our  preliminary  studies  indicate  that  PDT  effectively  kills  human   NF1

  19. Axon degeneration: make the Schwann cell great again

    Directory of Open Access Journals (Sweden)

    Keit Men Wong

    2017-01-01

    Full Text Available Axonal degeneration is a pivotal feature of many neurodegenerative conditions and substantially accounts for neurological morbidity. A widely used experimental model to study the mechanisms of axonal degeneration is Wallerian degeneration (WD, which occurs after acute axonal injury. In the peripheral nervous system (PNS, WD is characterized by swift dismantling and clearance of injured axons with their myelin sheaths. This is a prerequisite for successful axonal regeneration. In the central nervous system (CNS, WD is much slower, which significantly contributes to failed axonal regeneration. Although it is well-documented that Schwann cells (SCs have a critical role in the regenerative potential of the PNS, to date we have only scarce knowledge as to how SCs 'sense' axonal injury and immediately respond to it. In this regard, it remains unknown as to whether SCs play the role of a passive bystander or an active director during the execution of the highly orchestrated disintegration program of axons. Older reports, together with more recent studies, suggest that SCs mount dynamic injury responses minutes after axonal injury, long before axonal breakdown occurs. The swift SC response to axonal injury could play either a pro-degenerative role, or alternatively a supportive role, to the integrity of distressed axons that have not yet committed to degenerate. Indeed, supporting the latter concept, recent findings in a chronic PNS neurodegeneration model indicate that deactivation of a key molecule promoting SC injury responses exacerbates axonal loss. If this holds true in a broader spectrum of conditions, it may provide the grounds for the development of new glia-centric therapeutic approaches to counteract axonal loss.

  20. Ignition Regime for Fusion in a Degenerate Plasma

    Energy Technology Data Exchange (ETDEWEB)

    Son, S.; Fisch, N.J.

    2005-12-01

    We identify relevant parameter regimes in which aneutronic fuels can undergo fusion ignition in hot-ion degenerate plasma. Because of relativistic effects and partial degeneracy, the self-sustained burning regime is considerably larger than previously calculated. Inverse bremsstrahlung plays a major role in containing the reactor energy. We solve the radiation transfer equation and obtain the contribution to the heat conductivity from inverse bremsstrahlung.

  1. Ultra-low frequency shock dynamics in degenerate relativistic plasmas

    Science.gov (United States)

    Islam, S.; Sultana, S.; Mamun, A. A.

    2017-09-01

    A degenerate relativistic three-component plasma model is proposed for ultra-low frequency shock dynamics. A reductive perturbation technique is adopted, leading to Burgers' nonlinear partial differential equation. The properties of the shock waves are analyzed via the stationary shock wave solution for different plasma configuration parameters. The role of different intrinsic plasma parameters, especially the relativistic effects on the linear wave properties and also on the shock dynamics, is briefly discussed.

  2. Ultrafast Degenerate Transient Lens Spectroscopy in Semiconductor Nanosctructures

    Directory of Open Access Journals (Sweden)

    Leontyev A.V.

    2015-01-01

    Full Text Available We report the non-resonant excitation and probing of the nonlinear refractive index change in bulk semiconductors and semiconductor quantum dots through degenerate transient lens spectroscopy. The signal oscillates at the center laser field frequency, and the envelope of the former in quantum dots is distinctly different from the one in bulk sample. We discuss the applicability of this technique for polarization state probing in semiconductor media with femtosecond temporal resolution.

  3. Pinpointing the Earliest Defects in Age-Related Macular Degeneration

    OpenAIRE

    Magnusson, Kristinn P; Shan Duan; Haraldur Sigurdsson; Hjorvar Petursson; Zhenglin Yang; Yu Zhao; Bernstein, Paul S.; Jian Ge; Fridbert Jonasson; Einar Stefansson; Gudleif Helgadottir; Norman A Zabriskie; Thorlakur Jonsson; Asgeir Björnsson; Theodora Thorlacius

    2005-01-01

    BACKGROUND: Age-related macular degeneration (AMD) is the most common cause of irreversible visual impairment in the developed world. The two forms of advanced AMD, geographic atrophy and neovascular AMD, represent different pathological processes in the macula that lead to loss of central vision. Soft drusen, characterized by deposits in the macula without visual loss, are considered to be a precursor of advanced AMD. Recently, it has been proposed that a common missense variant, Y402H, in t...

  4. Stereotactic radiotherapy in neovascular age-related macular degeneration

    OpenAIRE

    Ranjbar, Mahdy; Kurz, Maximilian; Holzhey, Annekatrin; Melchert, Corinna; Rades, Dirk; Grisanti, Salvatore

    2016-01-01

    Abstract Stereotactic radiotherapy (SRT) is a new approach to treat neovascular age-related macular degeneration (nAMD). The INTREPID trial suggested that SRT could reduce the frequency of regular intravitreal injections (IVIs) with antivascular endothelial growth factor drugs, which are necessary to control disease activity. However, the efficacy of SRT in nAMD and resulting morphological changes have not been validated under real-life circumstances, an issue, which we would like to address ...

  5. The Burden of Age-Related Macular Degeneration

    OpenAIRE

    Jordana K. Schmier; Mechelle L. Jones; Halpern, Michael T.

    2006-01-01

    As age-related macular degeneration (AMD) becomes more prevalent as a result of longer life expectancy and the number of elderly people worldwide, it will become increasingly important to understand its potential health and economic impact for appropriate healthcare planning. This review identified published literature on costs and resource use associated with AMD. Despite the increasing prevalence of AMD, the worldwide burden of illness is unknown. Several studies of direct medical costs, bo...

  6. An Immunologic Study on Age-related Macular Degeneration

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    Forty-one patients with age-related macular degeneration(AMD) were detected for serum autoantibodies against normal humanretinal protein by means of Western immunoblot analysis.Twenty-sevenout of the 41 patients showed positive response,with a rate of 66 percent.The positive rate of antiretinal antibody in the AMD patients wassignificantly higher than that in normal controls (18%) and in patients withother retinal diseases (24%) (p<0.0005).These antiretinal antibodies fromthe AMD patients partly reacted...

  7. Taurine Provides Neuroprotection against Retinal Ganglion Cell Degeneration

    OpenAIRE

    Nicolas Froger; Lucia Cadetti; Henri Lorach; Joao Martins; Alexis-Pierre Bemelmans; Elisabeth Dubus; Julie Degardin; Dorothée Pain; Valérie Forster; Laurent Chicaud; Ivana Ivkovic; Manuel Simonutti; Stéphane Fouquet; Firas Jammoul; Thierry Léveillard

    2012-01-01

    Retinal ganglion cell (RGC) degeneration occurs in numerous retinal diseases leading to blindness, either as a primary process like in glaucoma, or secondary to photoreceptor loss. However, no commercial drug is yet directly targeting RGCs for their neuroprotection. In the 70s, taurine, a small sulfonic acid provided by nutrition, was found to be essential for the survival of photoreceptors, but this dependence was not related to any retinal disease. More recently, taurine deprivation was inc...

  8. Genetic susceptibility of intervertebral disc degeneration among young Finnish adults

    OpenAIRE

    2011-01-01

    Abstract Background Disc degeneration (DD) is a common condition that progresses with aging. Although the events leading to DD are not well understood, a significant genetic influence has been found. This study was undertaken to assess the association between relevant candidate gene polymorphisms and moderate DD in a well-defined and characterized cohort of young adults. Focusing on young age can be valuable in determining genetic predisposition to DD. Methods We investigated the associations...

  9. Long term behaviour of singularly perturbed parabolic degenerated equation

    CERN Document Server

    Faye, Ibrahima; Seck, Diaraf

    2011-01-01

    In this paper we consider models for short-term, mean-term and long-term morphodynamics of dunes and megariples. We give an existence and uniqueness result for long term dynamics of dunes. This result is based on a time-space periodic solution existence result for degenerated parabolic equation that we set out. Finally the mean-term and long-term models are homogenized.

  10. Some new examples of non-degenerate quiver potentials

    CERN Document Server

    de Völcsey, Louis de Thanhoffer

    2010-01-01

    We prove a technical result which allows us to establish the non-degeneracy of potentials on quivers in some previously unknown cases. Our result applies to McKay quivers and also to potentials derived from geometric helices on Del Pezzo surfaces. On the other hand we also give an example of a skew group ring with a degenerate potential. This shows that for 3-CY orders Iyama-Reiten mutations cannot always be iterated indefinitely.

  11. Geriatric vision loss due to cataracts, macular degeneration, and glaucoma.

    Science.gov (United States)

    Eichenbaum, Joseph W

    2012-01-01

    The major causes of impaired vision in the elderly population of the United States are cataracts, macular degeneration, and open-angle glaucoma. Cataracts and macular degeneration usually reduce central vision, especially reading and near activities, whereas chronic glaucoma characteristically attacks peripheral vision in a silent way, impacting balance, walking, and driving. Untreated, these visual problems lead to issues with regard to taking medications, keeping track of finances and personal information, walking, watching television, and attending the theater, and often create social isolation. Thus, visually impaired individuals enter nursing homes 3 years earlier, have twice the risk of falling, and have 4× the risk of hip fracture. Consequently, many elderly with low vision exercise greater demands on community services. With the prospect of little improvement and sustained visual loss, in the face of poor tolerance of low-vision services and not accepting magnification as the only way to read, clinical depression is common. In many instances, however, early and accurate diagnosis can result in timely treatment and can preserve quality of life. This review will look at current diagnostic and therapeutic considerations. Currently, about 20.5 million people in the United States have cataracts. The number will reach 30 million by 2020. About 1.75 million Americans currently have some form of macular degeneration, and the number is estimated to increase to 2.95 million in 2020. Approximately 2.2 million Americans have glaucoma, and by 2020 that number is estimated to be close to 3.4 million people. It is projected that by 2030 there will be 72.1 million seniors. With some overlap of the above 3 groups conservatively estimated (if you add the 2030 cataract group to the macular degeneration and glaucoma groups), then about 1 in 2 senior individuals by 2030 may have some significant ocular disease, which could account for about 50% of the healthcare budget for the

  12. Present and Possible Therapies for Age-Related Macular Degeneration

    OpenAIRE

    Muhammad Khan; Ketan Agarwal; Mohamed Loutfi; Ahmed Kamal

    2014-01-01

    Age-related macular degeneration (AMD) is the most common cause of blindness in the elderly population worldwide and is defined as a chronic, progressive disorder characterized by changes occurring within the macula reflective of the ageing process. At present, the prevalence of AMD is currently rising and is estimated to increase by a third by 2020. Although our understanding of the several components underpinning the pathogenesis of this condition has increased significantly, the treatment ...

  13. Smoking and Age-Related Macular Degeneration: Review and Update

    Directory of Open Access Journals (Sweden)

    Sara Velilla

    2013-01-01

    Full Text Available Age-related macular degeneration (AMD is one of the main socioeconomical health issues worldwide. AMD has a multifactorial etiology with a variety of risk factors. Smoking is the most important modifiable risk factor for AMD development and progression. The present review summarizes the epidemiological studies evaluating the association between smoking and AMD, the mechanisms through which smoking induces damage to the chorioretinal tissues, and the relevance of advising patients to quit smoking for their visual health.

  14. Early detection of age related macular degeneration: current status

    OpenAIRE

    Schwartz, Roy; Loewenstein, Anat

    2015-01-01

    Early diagnosis and treatment of choroidal neovascularization (CNV), a main cause of severe vision loss in age related macular degeneration (AMD), is crucial in order to preserve vision and the quality of life of patients. This review summarizes current literature on the subject of early detection of CNV, both in the clinic setting and mainly in the patient’s home. New technologies are evolving to allow for earlier detection and thus vision preservation in AMD patients.

  15. Early detection of age related macular degeneration: current status.

    Science.gov (United States)

    Schwartz, Roy; Loewenstein, Anat

    2015-01-01

    Early diagnosis and treatment of choroidal neovascularization (CNV), a main cause of severe vision loss in age related macular degeneration (AMD), is crucial in order to preserve vision and the quality of life of patients. This review summarizes current literature on the subject of early detection of CNV, both in the clinic setting and mainly in the patient's home. New technologies are evolving to allow for earlier detection and thus vision preservation in AMD patients.

  16. Results of submacular surgery in age-related macula degeneration

    OpenAIRE

    Laue, Jessica

    2010-01-01

    Due to a disruption of barrier function of the membrane Bruch and a change of the phagocities retinal pigment epithelial (rpe), exists possibility for progress of pathologist invasion of new vessels from the choroidea under the retina. On the position of the macula it will cause quick loss of central visual acuity. The most frequent cause for a choroidal neovascular membrane (CNV) is age-related macula degeneration (AMD); further causes are based on idiopathic or postinflammable reasons. ...

  17. Nuclear trafficking in amyotrophic lateral sclerosis and frontotemporal lobar degeneration.

    Science.gov (United States)

    Prpar Mihevc, Sonja; Darovic, Simona; Kovanda, Anja; Bajc Česnik, Ana; Župunski, Vera; Rogelj, Boris

    2017-01-01

    Amyotrophic lateral sclerosis and frontotemporal lobar degeneration are two ends of a phenotypic spectrum of disabling, relentlessly progressive and ultimately fatal diseases. A key characteristic of both conditions is the presence of TDP-43 (encoded by TARDBP) or FUS immunoreactive cytoplasmic inclusions in neuronal and glial cells. This cytoplasmic mislocalization of otherwise predominantly nuclear RNA binding proteins implies a perturbation of the nucleocytoplasmic shuttling as a possible event in the pathogenesis. Compromised nucleocytoplasmic shuttling has recently also been associated with a hexanucleotide repeat expansion mutation in C9orf72, which is the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal lobar degeneration, and leads to accumulation of cytoplasmic TDP-43 inclusions. Mutation in C9orf72 may disrupt nucleocytoplasmic shuttling on the level of C9ORF72 protein, the transcribed hexanucleotide repeat RNA, and/or dipeptide repeat proteins translated form the hexanucleotide repeat RNA. These defects of nucleocytoplasmic shuttling may therefore, constitute the common ground of the underlying disease mechanisms in different molecular subtypes of amyotrophic lateral sclerosis and frontotemporal lobar degeneration. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  18. Surface Graphite Degeneration in Ductile Iron Castings for Resin Molds

    Institute of Scientific and Technical Information of China (English)

    Iulian Riposan; Mihai Chisamera; Stelian Stan; Torbjorn Skaland

    2008-01-01

    The objective of this paper is to review the factors influencing the formation of degenerated graph-ite layers on the surfaces of ductile iron castings for chemical rosins-acid molding and coro-making systems and how to reduce this defect. In the rosin mold technique the sulphur in the P-toluol sulphonic acid (PTSA),usually used as the hardener, has been identified as one factor causing graphite degeneration at the metal-mold interface. Less than 0.15% S in the mold (or even less than 0.07% S) can reduce the surface layer depth. Oxygen may also have an effect, especially for sulphur containing systems with turbulent flows in the mold, water-bearing no-bake binder systems, Mg-Silica reactions, or dross formation conditions. Despite the lower level of nitrogen in the iron melt after magnesium treatment (less than 90 ppm), nitrogen bearing res-ins have a profound effect on the frequency and severity of surface pinholes, but a limited influence on sur-face graphite degeneration.

  19. Inpatient Rehabilitation Performance of Patients with Paraneoplastic Cerebellar Degeneration

    Science.gov (United States)

    Fu, Jack B.; Raj, Vishwa S.; Asher, Arash; Lee, Jay; Guo, Ying; Konzen, Benedict S.; Bruera, Eduardo

    2014-01-01

    Objective To evaluate the functional improvement of rehabilitation inpatients with paraneoplastic cerebellar degeneration. Design Retrospective Review Setting Three tertiary referral based hospitals. Interventions Medical records were retrospectively analyzed for demographic, laboratory, medical and functional data. Main Outcome Measure Functional Independence Measure (FIM) Participants Cancer rehabilitation inpatients admitted to three different cancer centers with a diagnosis of paraneoplastic cerebellar degeneration (n=7). Results All 7 patients were white females. Median age was 62. Primary cancers included ovarian carcinoma (2), small cell lung cancer (2), uterine carcinoma (2), and invasive ductal breast carcinoma. Mean admission total FIM score was 61.0 (SD=23.97). Mean discharge total FIM score was 73.6 (SD=29.35). The mean change in total FIM score was 12.6 (p=.0018). The mean length of rehabilitation stay was 17.1 days. The mean total FIM efficiency was 0.73. 5/7 (71%) patients were discharged home. 1/7 (14%) was discharged to a nursing home. 1/7 (14%) transferred to the primary acute care service. Conclusions This is the first study to demonstrate the functional performance of a group of rehabilitation inpatients with paraneoplastic cerebellar degeneration. Despite the poor neurologic prognosis associated with this syndrome, these patients made significant functional improvements on inpatient rehabilitation. When appropriate, inpatient rehabilitation should be considered. Further studies with larger sample sizes are needed. PMID:25051460

  20. TURBULENCE TRANSPORT OF SURFACTANT SOLUTION FLOW DURING DRAG REDUCTION DEGENERATION

    Institute of Scientific and Technical Information of China (English)

    GU Wei-guo; WANG De-zhong

    2012-01-01

    Turbulence transport of surfactant solution flow during drag reduction degeneration is investigated experimentally in a two-dimensional channel.Particle Image Velocimetry (P1V) system is used to take two-dimensional velocity frames in the streamwise and wall-normal plane.The additive of surfactant is cetyltrimethyl ammonium chloride (CTAC) with the mass concentration of 25 ppm.Drag reduction degeneration happens in the CTAC solution flow,exhibiting the maximal drag reduction at Re =25000and losing drag reduction completely at Re =40 000.The velocity frames are statistically analyzed in four quadrants which are divided by the u -axis and v-axis.It is found that the phenomenon of“Zero Reynolds shear stress” is caused by the decrease of wallnormal fluctuations and its symmetrical distribution in quadrants.The increase of Reynolds number leads to the enhancement of turbulence burst phenomenon.During thc drag reduction degeneration,the CTAC solution flow contains both high turbulence intensity and drag reduction states.

  1. Comparison of spectral linewidths for quantum degenerate bosons and fermions

    CERN Document Server

    Notermans, R P M J W; Vassen, W

    2016-01-01

    We observe a dramatic difference in optical line shapes of a $^4$He Bose-Einstein condensate and a $^3$He degenerate Fermi gas by measuring the 1557-nm $2~^3S-2~^1S$ magnetic dipole transition (8 Hz natural linewidth) in an optical dipole trap. The 15 kHz FWHM condensate line shape is only broadened by mean field interactions, whereas the degenerate Fermi gas line shape is broadened to 75 kHz FWHM due to the Pauli exclusion principle. The asymmetric optical line shapes are observed in excellent agreement with line shape models for the quantum degenerate gases. For $^4$He a triplet-singlet s-wave scattering length $a=+50(10)_{\\text{stat}}(43)_{\\text{syst}}~a_0$ is extracted. The high spectral resolution reveals a doublet in the absorption spectrum of the BEC, and this effect is understood by the presence of a weak optical lattice in which a degeneracy of the lattice recoil and the spectroscopy photon recoil leads to Bragg-like scattering.

  2. A Mouse Model for Laser-induced Choroidal Neovascularization.

    Science.gov (United States)

    Shah, Ronil S; Soetikno, Brian T; Lajko, Michelle; Fawzi, Amani A

    2015-12-27

    The mouse laser-induced choroidal neovascularization (CNV) model has been a crucial mainstay model for neovascular age-related macular degeneration (AMD) research. By administering targeted laser injury to the RPE and Bruch's membrane, the procedure induces angiogenesis, modeling the hallmark pathology observed in neovascular AMD. First developed in non-human primates, the laser-induced CNV model has come to be implemented into many other species, the most recent of which being the mouse. Mouse experiments are advantageously more cost-effective, experiments can be executed on a much faster timeline, and they allow the use of various transgenic models. The miniature size of the mouse eye, however, poses a particular challenge when performing the procedure. Manipulation of the eye to visualize the retina requires practice of fine dexterity skills as well as simultaneous hand-eye-foot coordination to operate the laser. However, once mastered, the model can be applied to study many aspects of neovascular AMD such as molecular mechanisms, the effect of genetic manipulations, and drug treatment effects. The laser-induced CNV model, though useful, is not a perfect model of the disease. The wild-type mouse eye is otherwise healthy, and the chorio-retinal environment does not mimic the pathologic changes in human AMD. Furthermore, injury-induced angiogenesis does not reflect the same pathways as angiogenesis occurring in an age-related and chronic disease state as in AMD. Despite its shortcomings, the laser-induced CNV model is one of the best methods currently available to study the debilitating pathology of neovascular AMD. Its implementation has led to a deeper understanding of the pathogenesis of AMD, as well as contributing to the development of many of the AMD therapies currently available.

  3. Colonization, mouse-style

    Directory of Open Access Journals (Sweden)

    Searle Jeremy B

    2010-10-01

    Full Text Available Abstract Several recent papers, including one in BMC Evolutionary Biology, examine the colonization history of house mice. As well as background for the analysis of mouse adaptation, such studies offer a perspective on the history of movements of the humans that accidentally transported the mice. See research article: http://www.biomedcentral.com/1471-2148/10/325

  4. Mouse Leydig Tumor Cells

    Directory of Open Access Journals (Sweden)

    Bo-Syong Pan

    2011-01-01

    Full Text Available Cordycepin is a natural pure compound extracted from Cordyceps sinensis (CS. We have demonstrated that CS stimulates steroidogenesis in primary mouse Leydig cell and activates apoptosis in MA-10 mouse Leydig tumor cells. It is highly possible that cordycepin is the main component in CS modulating Leydig cell functions. Thus, our aim was to investigate the steroidogenic and apoptotic effects with potential mechanism of cordycepin on MA-10 mouse Leydig tumor cells. Results showed that cordycepin significantly stimulated progesterone production in dose- and time-dependent manners. Adenosine receptor (AR subtype agonists were further used to treat MA-10 cells, showing that A1, A 2A , A 2B , and A3, AR agonists could stimulate progesterone production. However, StAR promoter activity and protein expression remained of no difference among all cordycepin treatments, suggesting that cordycepin might activate AR, but not stimulated StAR protein to regulate MA-10 cell steroidogenesis. Meanwhile, cordycepin could also induce apoptotic cell death in MA-10 cells. Moreover, four AR subtype agonists induced cell death in a dose-dependent manner, and four AR subtype antagonists could all rescue cell death under cordycepin treatment in MA-10 cells. In conclusion, cordycepin could activate adenosine subtype receptors and simultaneously induce steroidogenesis and apoptosis in MA-10 mouse Leydig tumor cells.

  5. The Mouse SAGE Site: database of public mouse SAGE libraries.

    Science.gov (United States)

    Divina, Petr; Forejt, Jirí

    2004-01-01

    The Mouse SAGE Site is a web-based database of all available public libraries generated by the Serial Analysis of Gene Expression (SAGE) from various mouse tissues and cell lines. The database contains mouse SAGE libraries organized in a uniform way and provides web-based tools for browsing, comparing and searching SAGE data with reliable tag-to-gene identification. A modified approach based on the SAGEmap database is used for reliable tag identification. The Mouse SAGE Site is maintained on an ongoing basis at the Institute of Molecular Genetics, Academy of Sciences of the Czech Republic and is accessible at the internet address http://mouse.biomed.cas.cz/sage/.

  6. Relationship of Tear Size and Location to Fatty Degeneration of the Rotator Cuff

    Science.gov (United States)

    Kim, H. Mike; Dahiya, Nirvikar; Teefey, Sharlene A.; Keener, Jay D.; Galatz, Leesa M.; Yamaguchi, Ken

    2010-01-01

    Background: Fatty degeneration of the rotator cuff muscles may have detrimental effects on both anatomical and functional outcomes following shoulder surgery. The purpose of this study was to investigate the relationship between tear geometry and muscle fatty degeneration in shoulders with a deficient rotator cuff. Methods: Ultrasonograms of both shoulders of 262 patients were reviewed to assess the type of rotator cuff tear and fatty degeneration in the supraspinatus and infraspinatus muscles. The 251 shoulders with a full-thickness tear underwent further evaluation for tear size and location. The relationship of tear size and location to fatty degeneration of the supraspinatus and infraspinatus muscles was investigated with use of statistical comparisons and regression models. Results: Fatty degeneration was found almost exclusively in shoulders with a full-thickness rotator cuff tear. Of the 251 shoulders with a full-thickness tear, eighty-seven (34.7%) had fatty degeneration in either the supraspinatus or infraspinatus, or both. Eighty-two (32.7%) of the 251 full-thickness tears had a distance of 0 mm between the biceps tendon and anterior margin of the tear. Ninety percent of the full-thickness tears with fatty degeneration in both muscles had a distance of 0 mm posterior from the biceps, whereas only 9% of those without fatty degeneration had a distance of 0 mm. Tears with fatty degeneration had significantly greater width and length than those without fatty degeneration (p infraspinatus fatty degeneration. Conclusions: Fatty degeneration of the rotator cuff muscles is closely associated with tear size and location. The finding of this study suggests that the integrity of the anterior supraspinatus tendon is important to the development of fatty degeneration. Patients with full-thickness tears that extend through this area may benefit from earlier surgical intervention if fatty degeneration has not already occurred. Additionally, the findings suggest the

  7. Degeneration modulates retinal response to transient exogenous oxidative injury.

    Directory of Open Access Journals (Sweden)

    Michal Lederman

    Full Text Available PURPOSE: Oxidative injury is involved in retinal and macular degeneration. We aim to assess if retinal degeneration associated with genetic defect modulates the retinal threshold for encountering additional oxidative challenges. METHODS: Retinal oxidative injury was induced in degenerating retinas (rd10 and in control mice (WT by intravitreal injections of paraquat (PQ. Retinal function and structure was evaluated by electroretinogram (ERG and histology, respectively. Oxidative injury was assessed by immunohistochemistry for 4-Hydroxy-2-nonenal (HNE, and by Thiobarbituric Acid Reactive Substances (TBARS and protein carbonyl content (PCC assays. Anti-oxidant mechanism was assessed by quantitative real time PCR (QPCR for mRNA of antioxidant genes and genes related to iron metabolism, and by catalase activity assay. RESULTS: Three days following PQ injections (1 µl of 0.25, 0.75, and 2 mM the average ERG amplitudes decreased more in the WT mice compared with the rd10 mice. For example, following 2 mM PQ injection, ERG amplitudes reduced 1.84-fold more in WT compared with rd10 mice (p = 0.02. Injection of 4 mM PQ resulted in retinal destruction. Altered retina morphology associated with PQ was substantially more severe in WT eyes compared with rd10 eyes. Oxidative injury according to HNE staining and TBARS assay increased 1.3-fold and 2.1-fold more, respectively, in WT compared with rd10 mice. At baseline, prior to PQ injection, mRNA levels of antioxidant genes (Superoxide Dismutase1, Glutathione Peroxidase1, Catalase and of Transferrin measured by quantitative PCR were 2.1-7.8-fold higher in rd10 compared with WT mice (p<0.01 each, and catalase activity was 1.7-fold higher in rd10 (p = 0.0006. CONCLUSIONS: This data suggests that degenerating rd10 retinas encounter a relatively lower degree of damage in response to oxidative injury compared with normal retinas. Constitutive up-regulation of the oxidative defense mechanism in degenerating retinas

  8. Mouse Model Resources for Vision Research

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    Jungyeon Won

    2011-01-01

    Full Text Available The need for mouse models, with their well-developed genetics and similarity to human physiology and anatomy, is clear and their central role in furthering our understanding of human disease is readily apparent in the literature. Mice carrying mutations that alter developmental pathways or cellular function provide model systems for analyzing defects in comparable human disorders and for testing therapeutic strategies. Mutant mice also provide reproducible, experimental systems for elucidating pathways of normal development and function. Two programs, the Eye Mutant Resource and the Translational Vision Research Models, focused on providing such models to the vision research community are described herein. Over 100 mutant lines from the Eye Mutant Resource and 60 mutant lines from the Translational Vision Research Models have been developed. The ocular diseases of the mutant lines include a wide range of phenotypes, including cataracts, retinal dysplasia and degeneration, and abnormal blood vessel formation. The mutations in disease genes have been mapped and in some cases identified by direct sequencing. Here, we report 3 novel alleles of Crxtvrm65, Rp1tvrm64, and Rpe65tvrm148 as successful examples of the TVRM program, that closely resemble previously reported knockout models.

  9. Animals deficient in C2Orf71, an autosomal recessive retinitis pigmentosa-associated locus, develop severe early-onset retinal degeneration.

    Science.gov (United States)

    Kevany, Brian M; Zhang, Ning; Jastrzebska, Beata; Palczewski, Krzysztof

    2015-05-01

    Genetic mapping was recently used to identify the underlying cause for a previously uncharacterized cohort of autosomal recessive retinitis pigmentosa cases. Genetic mapping of affected individuals resulted in the identification of an uncharacterized gene, C2Orf71, as the causative locus. However, initial homology searches failed to reveal similarities to any previously characterized protein or domain. To address this issue, we characterized the mouse homolog, BC027072. Immunohistochemistry with a custom polyclonal antibody showed staining localized to the inner segments (IS) of photoreceptor cells, as well as the outer segments (OS) of cone cells. A knockout mouse line (BC(-/-)) was generated and demonstrated that loss of this gene results in a severe, early-onset retinal degeneration. Histology and electron microscopy (EM) revealed disorganized OS as early as 3 weeks with complete loss by 24 weeks of age. EM micrographs displayed packets of cellular material containing OS discs or IS organelles in the OS region and abnormal retinal pigmented epithelium cells. Analyses of retinoids and rhodopsin levels showed retinal degenerations. Although its function remains unknown, this protein appears essential for normal OS development/maintenance and vision in humans and mice. RNAseq data are available in the GEO database under accession: GSE63810.

  10. Accumulation of Misfolded SOD1 in Dorsal Root Ganglion Degenerating Proprioceptive Sensory Neurons of Transgenic Mice with Amyotrophic Lateral Sclerosis

    Directory of Open Access Journals (Sweden)

    Javier Sábado

    2014-01-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is an adult-onset progressive neurodegenerative disease affecting upper and lower motoneurons (MNs. Although the motor phenotype is a hallmark for ALS, there is increasing evidence that systems other than the efferent MN system can be involved. Mutations of superoxide dismutase 1 (SOD1 gene cause a proportion of familial forms of this disease. Misfolding and aggregation of mutant SOD1 exert neurotoxicity in a noncell autonomous manner, as evidenced in studies using transgenic mouse models. Here, we used the SOD1G93A mouse model for ALS to detect, by means of conformational-specific anti-SOD1 antibodies, whether misfolded SOD1-mediated neurotoxicity extended to neuronal types other than MNs. We report that large dorsal root ganglion (DRG proprioceptive neurons accumulate misfolded SOD1 and suffer a degenerative process involving the inflammatory recruitment of macrophagic cells. Degenerating sensory axons were also detected in association with activated microglial cells in the spinal cord dorsal horn of diseased animals. As large proprioceptive DRG neurons project monosynaptically to ventral horn MNs, we hypothesise that a prion-like mechanism may be responsible for the transsynaptic propagation of SOD1 misfolding from ventral horn MNs to DRG sensory neurons.

  11. SNAREs Interact with Retinal Degeneration Slow and Rod Outer Segment Membrane Protein-1 during Conventional and Unconventional Outer Segment Targeting.

    Science.gov (United States)

    Zulliger, Rahel; Conley, Shannon M; Mwoyosvi, Maggie L; Stuck, Michael W; Azadi, Seifollah; Naash, Muna I

    2015-01-01

    Mutations in the photoreceptor protein peripherin-2 (also known as RDS) cause severe retinal degeneration. RDS and its homolog ROM-1 (rod outer segment protein 1) are synthesized in the inner segment and then trafficked into the outer segment where they function in tetramers and covalently linked larger complexes. Our goal is to identify binding partners of RDS and ROM-1 that may be involved in their biosynthetic pathway or in their function in the photoreceptor outer segment (OS). Here we utilize several methods including mass spectrometry after affinity purification, in vitro co-expression followed by pull-down, in vivo pull-down from mouse retinas, and proximity ligation assay to identify and confirm the SNARE proteins Syntaxin 3B and SNAP-25 as novel binding partners of RDS and ROM-1. We show that both covalently linked and non-covalently linked RDS complexes interact with Syntaxin 3B. RDS in the mouse is trafficked from the inner segment to the outer segment by both conventional (i.e., Golgi dependent) and unconventional secretory pathways, and RDS from both pathways interacts with Syntaxin3B. Syntaxin 3B and SNAP-25 are enriched in the inner segment (compared to the outer segment) suggesting that the interaction with RDS/ROM-1 occurs in the inner segment. Syntaxin 3B and SNAP-25 are involved in mediating fusion of vesicles carrying other outer segment proteins during outer segment targeting, so could be involved in the trafficking of RDS/ROM-1.

  12. Cloning and characterization of mouse growth hormone-releasing hormone (GRH) complementary DNA: increased GRH messenger RNA levels in the growth hormone-deficient lit/lit mouse.

    Science.gov (United States)

    Frohman, M A; Downs, T R; Chomczynski, P; Frohman, L A

    1989-10-01

    We have isolated and cloned the full length cDNA for mouse GH-releasing hormone (mGRH) from mouse hypothalamus using a recently described strategy involving the polymerase chain reaction technique (PCR). Degenerate oligonucleotide primers were selected based on short (six amino acids) conserved regions in the human and rat GRH peptides that would recognize DNA sequences encoding similar amino acids regardless of codon usage. Primer-extended cDNA was amplified by PCR on cDNA templates prepared by reverse transcribing total mouse hypothalamic RNA. After cloning and sequencing the initial product, the 3' and 5' ends of mGRH were generated using a separate PCR strategy (RACE protocol). The mGRH cDNA encodes a 103-amino acid reading frame, structurally similar to the human and rat GRH genes, containing a signal sequence, a 42-residue GRH peptide, and a 31-residue C-terminal region. Although the structures of mouse and rat GRH are highly conserved in the signal peptide and C-terminal region, there is considerable diversity in the GRH region, which exhibits nearly comparable homology with the rat (68%) and human (62%) structures. Differences between mouse and rat GRH were also found in the amino acid cleavage sites at the 5' and 3' ends of the mature peptide and at the polyadenylation signal.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. Programmed necrosis, not apoptosis, is a key mediator of cell loss and DAMP-mediated inflammation in dsRNA-induced retinal degeneration.

    Science.gov (United States)

    Murakami, Y; Matsumoto, H; Roh, M; Giani, A; Kataoka, K; Morizane, Y; Kayama, M; Thanos, A; Nakatake, S; Notomi, S; Hisatomi, T; Ikeda, Y; Ishibashi, T; Connor, K M; Miller, J W; Vavvas, D G

    2014-02-01

    There is no known treatment for the dry form of an age-related macular degeneration (AMD). Cell death and inflammation are important biological processes thought to have central role in AMD. Here we show that receptor-interacting protein (RIP) kinase mediates necrosis and enhances inflammation in a mouse model of retinal degeneration induced by dsRNA, a component of drusen in AMD. In contrast to photoreceptor-induced apoptosis, subretinal injection of the dsRNA analog poly(I : C) caused necrosis of the retinal pigment epithelium (RPE), as well as macrophage infiltration into the outer retinas. In Rip3(-/-) mice, both necrosis and inflammation were prevented, providing substantial protection against poly(I : C)-induced retinal degeneration. Moreover, after poly(I : C) injection, Rip3(-/-) mice displayed decreased levels of pro-inflammatory cytokines (such as TNF-α and IL-6) in the retina, and attenuated intravitreal release of high-mobility group box-1 (HMGB1), a major damage-associated molecular pattern (DAMP). In vitro, poly(I : C)-induced necrosis were inhibited in Rip3-deficient RPE cells, which in turn suppressed HMGB1 release and dampened TNF-α and IL-6 induction evoked by necrotic supernatants. On the other hand, Rip3 deficiency did not modulate directly TNF-α and IL-6 production after poly(I : C) stimulation in RPE cells or macrophages. Therefore, programmed necrosis is crucial in dsRNA-induced retinal degeneration and may promote inflammation by regulating the release of intracellular DAMPs, suggesting novel therapeutic targets for diseases such as AMD.

  14. Isolation of Mouse Neutrophils.

    Science.gov (United States)

    Swamydas, Muthulekha; Luo, Yi; Dorf, Martin E; Lionakis, Michail S

    2015-08-03

    Neutrophils represent the first line of defense against bacterial and fungal pathogens. Indeed, patients with inherited and acquired qualitative and quantitative neutrophil defects are at high risk for developing bacterial and fungal infections and suffering adverse outcomes from these infections. Therefore, research aiming at defining the molecular factors that modulate neutrophil effector function under homeostatic conditions and during infection is essential for devising strategies to augment neutrophil function and improve the outcome of infected individuals. This unit describes a reproducible density gradient centrifugation-based protocol that can be applied in any laboratory to harvest large numbers of highly enriched and highly viable neutrophils from the bone marrow of mice both at the steady state and following infection with Candida albicans as described in UNIT. In another protocol, we also present a method that combines gentle enzymatic tissue digestion with a positive immunomagnetic selection technique or Fluorescence-activated cell sorting (FACS) to harvest highly pure and highly viable preparations of neutrophils directly from mouse tissues such as the kidney, the liver or the spleen. Finally, methods for isolating neutrophils from mouse peritoneal fluid and peripheral blood are included. Mouse neutrophils isolated by these protocols can be used for examining several aspects of cellular function ex vivo including pathogen binding, phagocytosis and killing, neutrophil chemotaxis, oxidative burst, degranulation and cytokine production, and for performing neutrophil adoptive transfer experiments.

  15. RIKEN mouse genome encyclopedia.

    Science.gov (United States)

    Hayashizaki, Yoshihide

    2003-01-01

    We have been working to establish the comprehensive mouse full-length cDNA collection and sequence database to cover as many genes as we can, named Riken mouse genome encyclopedia. Recently we are constructing higher-level annotation (Functional ANnoTation Of Mouse cDNA; FANTOM) not only with homology search based annotation but also with expression data profile, mapping information and protein-protein database. More than 1,000,000 clones prepared from 163 tissues were end-sequenced to classify into 159,789 clusters and 60,770 representative clones were fully sequenced. As a conclusion, the 60,770 sequences contained 33,409 unique. The next generation of life science is clearly based on all of the genome information and resources. Based on our cDNA clones we developed the additional system to explore gene function. We developed cDNA microarray system to print all of these cDNA clones, protein-protein interaction screening system, protein-DNA interaction screening system and so on. The integrated database of all the information is very useful not only for analysis of gene transcriptional network and for the connection of gene to phenotype to facilitate positional candidate approach. In this talk, the prospect of the application of these genome resourced should be discussed. More information is available at the web page: http://genome.gsc.riken.go.jp/.

  16. Mouse models in oncoimmunology.

    Science.gov (United States)

    Zitvogel, Laurence; Pitt, Jonathan M; Daillère, Romain; Smyth, Mark J; Kroemer, Guido

    2016-12-01

    Fundamental cancer research and the development of efficacious antineoplastic treatments both rely on experimental systems in which the relationship between malignant cells and immune cells can be studied. Mouse models of transplantable, carcinogen-induced or genetically engineered malignancies - each with their specific advantages and difficulties - have laid the foundations of oncoimmunology. These models have guided the immunosurveillance theory that postulates that evasion from immune control is an essential feature of cancer, the concept that the long-term effects of conventional cancer treatments mostly rely on the reinstatement of anticancer immune responses and the preclinical development of immunotherapies, including currently approved immune checkpoint blockers. Specific aspects of pharmacological development, as well as attempts to personalize cancer treatments using patient-derived xenografts, require the development of mouse models in which murine genes and cells are replaced with their human equivalents. Such 'humanized' mouse models are being progressively refined to characterize the leukocyte subpopulations that belong to the innate and acquired arms of the immune system as they infiltrate human cancers that are subjected to experimental therapies. We surmise that the ever-advancing refinement of murine preclinical models will accelerate the pace of therapeutic optimization in patients.

  17. Ex vivo quantitative multiparametric MRI mapping of human meniscus degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Nebelung, Sven; Kuhl, Christiane; Truhn, Daniel [Aachen University Hospital, Department of Diagnostic and Interventional Radiology, Aachen (Germany); Tingart, Markus; Jahr, Holger [Aachen University Hospital, Department of Orthopaedics, Aachen (Germany); Pufe, Thomas [RWTH Aachen University, Institute of Anatomy and Cell Biology, Aachen (Germany)

    2016-12-15

    To evaluate the diagnostic performance of T1, T1ρ, T2, T2*, and UTE-T2* (ultrashort-echo time-enhanced T2*) mapping in the refined graduation of human meniscus degeneration with histology serving as standard-of-reference. This IRB-approved intra-individual comparative ex vivo study was performed on 24 lateral meniscus body samples obtained from 24 patients undergoing total knee replacement. Samples were assessed on a 3.0-T MRI scanner using inversion-recovery (T1), spin-lock multi-gradient-echo (T1ρ), multi-spin-echo (T2) and multi-gradient-echo (T2* and UTE-T2*) sequences to determine relaxation times of quantitative MRI (qMRI) parameters. Relaxation times were calculated on the respective maps, averaged to the entire meniscus and to its zones. Histologically, samples were analyzed on a four-point score according to Williams (0-III). QMRI results and Williams (sub)scores were correlated using Spearman's ρ, while Williams grade-dependent differences were assessed using Kruskal-Wallis and Dunn's tests. Sensitivities and specificities in the detection of intact (Williams grade [WG]-0) and severely degenerate meniscus (WG-II-III) were calculated. Except for T2*, significant increases in qMRI parameters with increasing Williams grades were observed. T1, T1ρ, T2, and UTE-T2* exhibited high sensitivity and variable specificity rates. Significant marked-to-strong correlations were observed for these parameters with each other, with histological WGs and the subscores tissue integrity and cellularity. QMRI mapping holds promise in the objective evaluation of human meniscus. Although sufficient discriminatory power of T1, T1ρ, T2, and UTE-T2* was only demonstrated for the histological extremes, these data may aid in the future MRI-based parameterization and quantification of human meniscus degeneration. (orig.)

  18. Taurine Provides Neuroprotection against Retinal Ganglion Cell Degeneration

    Science.gov (United States)

    Froger, Nicolas; Cadetti, Lucia; Lorach, Henri; Martins, Joao; Bemelmans, Alexis-Pierre; Dubus, Elisabeth; Degardin, Julie; Pain, Dorothée; Forster, Valérie; Chicaud, Laurent; Ivkovic, Ivana; Simonutti, Manuel; Fouquet, Stéphane; Jammoul, Firas; Léveillard, Thierry; Benosman, Ryad; Sahel, José-Alain; Picaud, Serge

    2012-01-01

    Retinal ganglion cell (RGC) degeneration occurs in numerous retinal diseases leading to blindness, either as a primary process like in glaucoma, or secondary to photoreceptor loss. However, no commercial drug is yet directly targeting RGCs for their neuroprotection. In the 70s, taurine, a small sulfonic acid provided by nutrition, was found to be essential for the survival of photoreceptors, but this dependence was not related to any retinal disease. More recently, taurine deprivation was incriminated in the retinal toxicity of an antiepileptic drug. We demonstrate here that taurine can improve RGC survival in culture or in different animal models of RGC degeneration. Taurine effect on RGC survival was assessed in vitro on primary pure RCG cultures under serum-deprivation conditions, and on NMDA-treated retinal explants from adult rats. In vivo, taurine was administered through the drinking water in two glaucomatous animal models (DBA/2J mice and rats with vein occlusion) and in a model of Retinitis pigmentosa with secondary RGC degeneration (P23H rats). After a 6-day incubation, 1 mM taurine significantly enhanced RGCs survival (+68%), whereas control RGCs were cultured in a taurine-free medium, containing all natural amino-acids. This effect was found to rely on taurine-uptake by RGCs. Furthermore taurine (1 mM) partly prevented NMDA-induced RGC excitotoxicity. Finally, taurine supplementation increased RGC densities both in DBA/2J mice, in rats with vein occlusion and in P23H rats by contrast to controls drinking taurine-free water. This study indicates that enriched taurine nutrition can directly promote RGC survival through RGC intracellular pathways. It provides evidence that taurine can positively interfere with retinal degenerative diseases. PMID:23115615

  19. The role of epigenetics in age-related macular degeneration.

    Science.gov (United States)

    Gemenetzi, M; Lotery, A J

    2014-12-01

    It is becoming increasingly evident that epigenetic mechanisms influence gene expression and can explain how interactions between genetics and the environment result in particular phenotypes during development. The extent to which this epigenetic effect contributes to phenotype heritability in age-related macular degeneration (AMD) is currently ill defined. However, emerging evidence suggests that epigenetic changes are relevant to AMD and as such provide an exciting new avenue of research for AMD. This review addresses information on the impact of posttranslational modification of the genome on the pathogenesis of AMD, such as DNA methylation changes affecting antioxidant gene expression, hypoxia-regulated alterations in chromatin structure, and histone acetylation status in relation to angiogenesis and inflammation. It also contains information on the role of non-coding RNA-mediated gene regulation in AMD at a posttranscriptional (before translation) level. Our aim was to review the epigenetic mechanisms that cause heritable changes in gene activity without changing the DNA sequence. We also describe some long-term alterations in the transcriptional potential of a cell, which are not necessarily heritable but remains to be defined in the future. Increasing understanding of the significance of common and rare genetic variants and their relationship to epigenetics and environmental influences may help in establishing methods to assess the risk of AMD. This in turn may allow new therapeutic interventions for the leading cause of central vision impairment in patients over the age of 50 years in developed countries. Search strategy We searched the MEDLINE/PubMed database following MeSH suggestions for articles including the terms: 'ocular epigenetic mechanisms', 'human disease epigenetics', and 'age-related macular degeneration genetics'. The headline used to locate related articles in PubMed was 'epigenetics in ocular disease', and to restrict search, we used the

  20. Striatal degeneration impairs language learning: evidence from Huntington's disease.

    Science.gov (United States)

    De Diego-Balaguer, R; Couette, M; Dolbeau, G; Dürr, A; Youssov, K; Bachoud-Lévi, A-C

    2008-11-01

    Although the role of the striatum in language processing is still largely unclear, a number of recent proposals have outlined its specific contribution. Different studies report evidence converging to a picture where the striatum may be involved in those aspects of rule-application requiring non-automatized behaviour. This is the main characteristic of the earliest phases of language acquisition that require the online detection of distant dependencies and the creation of syntactic categories by means of rule learning. Learning of sequences and categorization processes in non-language domains has been known to require striatal recruitment. Thus, we hypothesized that the striatum should play a prominent role in the extraction of rules in learning a language. We studied 13 pre-symptomatic gene-carriers and 22 early stage patients of Huntington's disease (pre-HD), both characterized by a progressive degeneration of the striatum and 21 late stage patients Huntington's disease (18 stage II, two stage III and one stage IV) where cortical degeneration accompanies striatal degeneration. When presented with a simplified artificial language where words and rules could be extracted, early stage Huntington's disease patients (stage I) were impaired in the learning test, demonstrating a greater impairment in rule than word learning compared to the 20 age- and education-matched controls. Huntington's disease patients at later stages were impaired both on word and rule learning. While spared in their overall performance, gene-carriers having learned a set of abstract artificial language rules were then impaired in the transfer of those rules to similar artificial language structures. The correlation analyses among several neuropsychological tests assessing executive function showed that rule learning correlated with tests requiring working memory and attentional control, while word learning correlated with a test involving episodic memory. These learning impairments significantly

  1. Taurine provides neuroprotection against retinal ganglion cell degeneration.

    Directory of Open Access Journals (Sweden)

    Nicolas Froger

    Full Text Available Retinal ganglion cell (RGC degeneration occurs in numerous retinal diseases leading to blindness, either as a primary process like in glaucoma, or secondary to photoreceptor loss. However, no commercial drug is yet directly targeting RGCs for their neuroprotection. In the 70s, taurine, a small sulfonic acid provided by nutrition, was found to be essential for the survival of photoreceptors, but this dependence was not related to any retinal disease. More recently, taurine deprivation was incriminated in the retinal toxicity of an antiepileptic drug. We demonstrate here that taurine can improve RGC survival in culture or in different animal models of RGC degeneration. Taurine effect on RGC survival was assessed in vitro on primary pure RCG cultures under serum-deprivation conditions, and on NMDA-treated retinal explants from adult rats. In vivo, taurine was administered through the drinking water in two glaucomatous animal models (DBA/2J mice and rats with vein occlusion and in a model of Retinitis pigmentosa with secondary RGC degeneration (P23H rats. After a 6-day incubation, 1 mM taurine significantly enhanced RGCs survival (+68%, whereas control RGCs were cultured in a taurine-free medium, containing all natural amino-acids. This effect was found to rely on taurine-uptake by RGCs. Furthermore taurine (1 mM partly prevented NMDA-induced RGC excitotoxicity. Finally, taurine supplementation increased RGC densities both in DBA/2J mice, in rats with vein occlusion and in P23H rats by contrast to controls drinking taurine-free water. This study indicates that enriched taurine nutrition can directly promote RGC survival through RGC intracellular pathways. It provides evidence that taurine can positively interfere with retinal degenerative diseases.

  2. Taurine provides neuroprotection against retinal ganglion cell degeneration.

    Science.gov (United States)

    Froger, Nicolas; Cadetti, Lucia; Lorach, Henri; Martins, Joao; Bemelmans, Alexis-Pierre; Dubus, Elisabeth; Degardin, Julie; Pain, Dorothée; Forster, Valérie; Chicaud, Laurent; Ivkovic, Ivana; Simonutti, Manuel; Fouquet, Stéphane; Jammoul, Firas; Léveillard, Thierry; Benosman, Ryad; Sahel, José-Alain; Picaud, Serge

    2012-01-01

    Retinal ganglion cell (RGC) degeneration occurs in numerous retinal diseases leading to blindness, either as a primary process like in glaucoma, or secondary to photoreceptor loss. However, no commercial drug is yet directly targeting RGCs for their neuroprotection. In the 70s, taurine, a small sulfonic acid provided by nutrition, was found to be essential for the survival of photoreceptors, but this dependence was not related to any retinal disease. More recently, taurine deprivation was incriminated in the retinal toxicity of an antiepileptic drug. We demonstrate here that taurine can improve RGC survival in culture or in different animal models of RGC degeneration. Taurine effect on RGC survival was assessed in vitro on primary pure RCG cultures under serum-deprivation conditions, and on NMDA-treated retinal explants from adult rats. In vivo, taurine was administered through the drinking water in two glaucomatous animal models (DBA/2J mice and rats with vein occlusion) and in a model of Retinitis pigmentosa with secondary RGC degeneration (P23H rats). After a 6-day incubation, 1 mM taurine significantly enhanced RGCs survival (+68%), whereas control RGCs were cultured in a taurine-free medium, containing all natural amino-acids. This effect was found to rely on taurine-uptake by RGCs. Furthermore taurine (1 mM) partly prevented NMDA-induced RGC excitotoxicity. Finally, taurine supplementation increased RGC densities both in DBA/2J mice, in rats with vein occlusion and in P23H rats by contrast to controls drinking taurine-free water. This study indicates that enriched taurine nutrition can directly promote RGC survival through RGC intracellular pathways. It provides evidence that taurine can positively interfere with retinal degenerative diseases.

  3. Analysis of meniscal degeneration and meniscal gene expression

    Directory of Open Access Journals (Sweden)

    Norton James H

    2010-01-01

    Full Text Available Abstract Background Menisci play a vital role in load transmission, shock absorption and joint stability. There is increasing evidence suggesting that OA menisci may not merely be bystanders in the disease process of OA. This study sought: 1 to determine the prevalence of meniscal degeneration in OA patients, and 2 to examine gene expression in OA meniscal cells compared to normal meniscal cells. Methods Studies were approved by our human subjects Institutional Review Board. Menisci and articular cartilage were collected during joint replacement surgery for OA patients and lower limb amputation surgery for osteosarcoma patients (normal control specimens, and graded. Meniscal cells were prepared from these meniscal tissues and expanded in monolayer culture. Differential gene expression in OA meniscal cells and normal meniscal cells was examined using Affymetrix microarray and real time RT-PCR. Results The grades of meniscal degeneration correlated with the grades of articular cartilage degeneration (r = 0.672; P HLA-DPA1, integrin, beta 2 (ITGB2, ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1, ankylosis, progressive homolog (ANKH and fibroblast growth factor 7 (FGF7, were expressed at significantly higher levels in OA meniscal cells compared to normal meniscal cells. Importantly, many of the genes that have been shown to be differentially expressed in other OA cell types/tissues, including ADAM metallopeptidase with thrombospondin type 1 motif 5 (ADAMTS5 and prostaglandin E synthase (PTGES, were found to be expressed at significantly higher levels in OA meniscal cells. This consistency suggests that many of the genes detected in our study are disease-specific. Conclusion Our findings suggest that OA is a whole joint disease. Meniscal cells may play an active role in the development of OA. Investigation of the gene expression profiles of OA meniscal cells may reveal new therapeutic targets for OA therapy and also may uncover novel

  4. Natural history of seminiferous tubule degeneration in Klinefelter syndrome.

    Science.gov (United States)

    Aksglaede, Lise; Wikström, Anne M; Rajpert-De Meyts, Ewa; Dunkel, Leo; Skakkebaek, Niels E; Juul, Anders

    2006-01-01

    Klinefelter syndrome (47,XXY) is characterized by small, firm testis, gynaecomastia, azoospermia and hypergonadotropic hypogonadism. Degeneration of the seminiferous tubules in 47,XXY males is a well-described phenomenon. It begins in the fetus, progresses through infancy and accelerates dramatically at the time of puberty with complete hyalinization of the seminiferous tubules, although a few tubules with spermatogenesis may be present in adult life. Activation of the pituitary-gonadal axis at 3 months of age is seen in Klinefelter boys similar to healthy boys. However, the level of testosterone in Klinefelter boys is significantly lower than in controls. After this 'minipuberty', the hormone levels decline to normal prepubertal levels until puberty. In puberty, an initial rise in testosterone, inhibin B, LH and FSH occurs in Klinefelter boys. However, the rise in testosterone levels off and ends at a low-normal level in young adults. Likewise, serum concentration of inhibin B exhibits a dramatic decline to a low, often undetectable level, concomitantly with a rise in FSH, reflecting the degeneration of the seminiferous tubules. Many hypotheses about the underlying mechanism of the depletion of the germ cells in Klinefelter males have been reported and include insufficient supranumerary X-chromosome inactivation, Leydig cell insufficiency and disturbed regulation of apoptosis of Sertoli and Leydig cells. However, at present, the exact mechanism remains unclear. In this article, we summarize current knowledge on the development of the classical endocrinological and histological features of 47,XXY males from fetus to adulthood and review the literature concerning the degeneration of the seminiferous tubules in this syndrome.

  5. New developments in age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Lyndon da Cruz

    2008-09-01

    Full Text Available The World Health Organization (WHO estimates that over 3 million people (9% of global blindness are blinded by age-related macular degeneration (AMD. AMD affects people over the age of 55. There are two main types of AMD, dry and wet. In dry AMD, patients slowly lose vision through progressive atrophy of the macular tissue. Wet, or exudative, AMD, is associated with new blood vessels called subretinal neovascular membranes (or SRNVM and affected patients lose vision more rapidly due to fluid leakage and haemorrhage at the macula.

  6. Future Therapies of Wet Age-Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Makoto Ishikawa

    2015-01-01

    Full Text Available Age-related macular degeneration (AMD is the leading cause of blindness in the elderly population, and the prevalence of the disease increases exponentially with every decade after the age of 50 years. While VEGF inhibitors are promising drugs for treating patients with ocular neovascularization, there are limitations to their potential for improving vision in AMD patients. Thus, future therapies are required to have the potential to improve visual outcomes. This paper will summarize the future strategies and therapeutic targets that are aimed at enhancing the efficacy and duration of effect of antiangiogenic strategies.

  7. Preventing depression in age-related macular degeneration.

    Science.gov (United States)

    Rovner, Barry W; Casten, Robin J; Hegel, Mark T; Leiby, Benjamin E; Tasman, William S

    2007-08-01

    Age-related macular degeneration is a prevalent disease of aging that may cause irreversible vision loss, disability, and depression. The latter is rarely recognized or treated in ophthalmologic settings. To determine whether problem-solving treatment can prevent depressive disorders in patients with recent vision loss. Randomized, controlled trial. Outpatient ophthalmology offices in Philadelphia, Pennsylvania. Two hundred six patients aged 65 years or older with recent diagnoses of neovascular age-related macular degeneration in one eye and pre-existing age-related macular degeneration in the fellow eye. Patients were randomly assigned to problem-solving treatment (n = 105) or usual care (n = 101). Problem-solving treatment therapists delivered 6 sessions during 8 weeks in subjects' homes. Outcomes were assessed at 2 months for short-term effects and 6 months for maintenance effects. These included DSM-IV-defined diagnoses of depressive disorders, National Eye Institute Vision Function Questionnaire-17 scores, and rates of relinquishing valued activities. The 2-month incidence rate of depressive disorders in problem-solving-treated subjects was significantly lower than controls (11.6% vs 23.2%, respectively; odds ratio, 0.39; 95% confidence interval, 0.17-0.92; P = .03). Problem-solving treatment also reduced the odds of relinquishing a valued activity (odds ratio, 0.48; 95% confidence interval, 0.25-0.96; P = .04). This effect mediated the relationship between treatment group and depression. By 6 months, most earlier observed benefits had diminished, though problem-solving treatment subjects were less likely to suffer persistent depression (chi2(1,3) = 8.46; P = .04). Problem-solving treatment prevented depressive disorders and loss of valued activities in patients with age-related macular degeneration as a short-term treatment, but these benefits were not maintained over time. Booster or rescue treatments may be necessary to sustain problem-solving treatment

  8. A Degenerate Bogdanov-Takens Normal Form for FLRW Cosmologies

    CERN Document Server

    Kohli, Ikjyot Singh

    2016-01-01

    In this paper, we first show that the Einstein field equations for all perfect-fluid FLRW cosmologies can be written as a planar dynamical system with the equation of state parameter $w$ and cosmological constant $\\Lambda$ as parameters. An important equilibrium point of this dynamical system is the origin which represents Minkowski spacetime. It is shown that the Einstein field equations in a neigbourhood of this point are equivalent to a degenerate Bogdanov-Takens normal form. This normal form admits a set of equilibrium points that describes a set of solutions to the Einstein field equations that have a constant rate of expansion, negative spatial curvature, zero cosmological constant and dust.

  9. Age-related macular degeneration: Complement in action.

    Science.gov (United States)

    van Lookeren Campagne, Menno; Strauss, Erich C; Yaspan, Brian L

    2016-06-01

    The complement system plays a key role in host-defense against common pathogens but must be tightly controlled to avoid inflammation and tissue damage. Polymorphisms in genes encoding two important negative regulators of the alternative complement pathway, complement factor H (CFH) and complement factor I (CFI), are associated with the risk for Age-Related Macular Degeneration (AMD), a leading cause of vision impairment in the ageing population. In this review, we will discuss the genetic basis of AMD and the potential impact of complement de-regulation on disease pathogenesis. Finally, we will highlight recent therapeutic approaches aimed at controlling complement activation in patients with AMD.

  10. Einstein Universe under Deconstruction: the case with degenerate fermions

    CERN Document Server

    Kan, Nahomi; Shiraishi, Kiyoshi

    2011-01-01

    We study self-consistent static solutions for an Einstein universe in a graph-based induced gravity. In the generalization of the deconstruction model based on the graph, the eigenvalues of the graph Laplacian and the adjacent matrix gives the mass spectrum the particles. Thus we can easily control UV divergences at one-loop level in such a model. We use the calculation method with the spectrum distribution function of the graph and search for the static solution supported by the degenerate pressure of the fermion (at zero temperature). The report is based on arXiv:1110.5697.

  11. Degenerate-band-edge engineering inspired by nonlocal transformation optics

    Directory of Open Access Journals (Sweden)

    Moccia Massimo

    2016-01-01

    Full Text Available We address the engineering of degenerate-band-edge effects in nonlocal metamaterials. Our approach, inspired by nonlocal-transformation-optics concepts, is based on the approximation of analytically-derived nonlocal constitutive “blueprints”. We illustrate the synthesis procedure, and present and validate a possible implementation based on multilayered metamaterials featuring anisotropic constituents. We also elucidate the physical mechanisms underlying our approach and proposed configuration, and highlight the substantial differences with respect to other examples available in the topical literature.

  12. Intervertebral disc (IVD): Structure, degeneration, repair and regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Whatley, Benjamin R.; Wen Xuejun, E-mail: xjwen@clemson.edu

    2012-02-01

    Low back pain affects a large portion of the population, resulting in high care costs for therapy and treatment. One primary cause of low back pain is the degeneration of the intervertebral disc (IVD) resulting in the compression of the spinal nerves and adjacent vertebrae. Exact causes of degeneration are unknown, but it is thought that natural aging, and both biological and genetic factors may play a significant role in the degenerative process. Conventional methods to alleviate low back pain include spinal fusion and artificial disc replacement. Traditional treatments through spinal fusion may eliminate pain yet do not restore disc function and lead to further degeneration of adjacent levels by altering disc biomechanics and natural kinematics. Recently, artificial IVD replacements have started to gain interest, with two IVD implants currently approved in the United States. Although these implants facilitate the preservation of motions and disc space height, they are unable to sustain compressive forces due to their lack of elasticity. In addition, the implants may produce wear debris that can cause osteolysis and other deleterious effects. As an alternative to these conventional approaches, tissue engineered IVD constructs offer the advantage of biointegration while preserving the essential attributes of natural motion and disc space restoration. There is a great need for the development of tissue engineered scaffolds that simulate the natural 3D morphology and microenvironment of the targeted tissue. Scaffolds should facilitate biological transport to satisfy nutrition and waste removal requirements within the IVD. The discrete tissue architectures of the nucleus pulposus (NP) and annulus fibrosus (AF) have posed great challenges to IVD tissue engineering. Current attempts have not been able to satisfy the biological functions and/or mechanical properties of native tissue. Therefore, these current scaffolds are far from satisfactory. This review highlights the

  13. Military Degeneration and Decline of the Roman Empire

    Institute of Scientific and Technical Information of China (English)

    江静

    2013-01-01

    The cause of the decline of Roman Empire is a mystery to many historians of western civilization. Political and social weakness, or economic retroversion are conceived to be contributable factors. This issue, however, is approached here from the perspective of military degeneration, which closely relates to political anarchy, economic depression and barbarian invasions, and therefore, makes it for the most part convenient for the third-century Persian Sassanids and Germanic peoples to invade into the Empire, and wipes Romans out on the historical stage.

  14. On dRGT massive gravity with degenerate reference metrics

    OpenAIRE

    CAO, LI-MING; Peng, Yuxuan; Zhang, Yun-Long(State Key Laboratory of Theoretical Physics, Institute of Theoretical Physics, Chinese Academy of Sciences, Beijing, 100190, China)

    2015-01-01

    In dRGT massive gravity, to get the equations of motion, the square root tensor is assumed to be invertible in the variation of the action. However, this condition can not be fulfilled when the reference metric is degenerate. This implies that the resulting equations of motion might be different from the case where the reference metric has full rank. In this paper, by generalizing the Moore-Penrose inverse to the symmetric tensor on Lorentz manifolds, we get the equations of motion of the the...

  15. Neuroleptic Malignant Syndrome in a Patient with Corticobasal Degeneration

    Directory of Open Access Journals (Sweden)

    Myung Jun Lee

    2011-10-01

    Full Text Available Parkinson’s disease is a principal underlying disease of neuroleptic malignant syndrome (NMS occurring in parkinsonian disorders, but NMS may occur in patients with progressive supranuclear palsy and multiple system atrophy. We report first patient with corticobasal degeneration (CBD who developed NMS after abrupt reduction of antiparkinsonian medication and concurrent infection. It should be kept in mind that the prevention of infectious illness, which is common complication in parkinson-plus syndrome, is important, and dose reduction or withdrawal of anti-parkinsonian medications should be carefully performed even in the patients with CBD who are expected to be unresponsive to levodopa treatment.

  16. Symmetrical infantile thalamic degeneration with focal cytoplasmic calcification.

    Science.gov (United States)

    Ambler, M; O'Neil, W

    1975-10-27

    Infantile thalamic degeneration is a rare clinico-pathological entity. Restricted location of the lesion and peculiar cytopathological changes serve to distinguish this disorder from other common encephalopathies. Optical and ultrastructural studies demonstrate cytoplasmic calcopherules in previously viable cells. According to current concepts of acute cellular reactions to injury and mechanism of intracellular calcification, the cytological changes cannot be attributed to either hypoxic ischemic cell change or dystrophic calcification. By analogy to other human and pathological material, the most likely basis for nondystrophic calcopherule formation is toxic or infectious injury with local synthesis, or autophagic or phagolysosomal degradation of cellular debris of specific chemical composition favoring calcium deposition.

  17. Vision rehabilitation of persons with age related macular degeneration.

    Science.gov (United States)

    Siemsen, Dennis W; Brown, William L

    2011-05-01

    As the population of the United States ages, there is an increase in the number of persons with age related macular degeneration (ARMD). Even as new prevention and treatment techniques are developed, the vision loss associated with ARMD may lead to loss of independence and quality of life. Low vision is a rehabilitative process designed to improve visual function and restore independence. This paper is a review of the current research related to low vision in the areas of magnification, contrast and illumination, reading, training, driving and outcomes assessment.

  18. Binocular refraction in patients with age-related macular degeneration.

    Science.gov (United States)

    Skrbek, Matej

    2013-04-01

    We've been finding possible association of central vision damage with binocular vision disorders in our clients suffering from age-related macular degeneration (ARMD), but whose visual acuity still allowed us to examine their binocular vision. Our findings show that there is a significant number of patients with heterophoria in horizontal, as well as vertical direction. The clients rate the vision with prismatic correction as more comfortable, clearer and long-term tolerable. Getting used to prismatic correction was spontaneous and non-problematic. Based on these results we expect to find possibly the most effective rehabilitation of vision in patients suffering from ARMD.

  19. Degenerate-band-edge engineering inspired by nonlocal transformation optics

    Directory of Open Access Journals (Sweden)

    Moccia Massimo

    2016-01-01

    Full Text Available We address the engineering of degenerate-band-edge effects in nonlocal metamaterials. Our approach, inspired by nonlocal-transformation-optics concepts, is based on the approximation of analytically-derived nonlocal constitutive “blueprints”. We illustrate the synthesis procedure, and present and validate a possible implementation based on multilayered metamaterials featuring anisotropic constituents. We also elucidate the physical mechanisms underlying our approach and proposed configuration, and highlight the substantial differences with respect to other examples available in the topical literature.

  20. Coherence switching of a degenerate VECSEL for multimodality imaging

    CERN Document Server

    Knitter, Sebastian; Redding, Brandon; Khokha, Mustafa K; Choma, Michael A; Cao, Hui

    2015-01-01

    We demonstrate a VECSEL (vertical external cavity surface emitting laser) based degenerate source with an adjustable degree of spatial coherence that is electrically pumped, mechanically compact and supports continuous-wave emission. The laser operation can be switched between a large number of mutually incoherent spatial modes and few-mode operation at little power loss. This technology allows multimodality imaging, where low spatial coherence illumination is used for traditional high-speed video-microscopy and high spatial coherence illumination is used to extract dynamic information of flow processes. The initial demonstration is performed on imaging embryo heart function in Xenopus, which is an important animal model for human heart disease.