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1

MDC-Analyzer: a novel degenerate primer design tool for the construction of intelligent mutagenesis libraries with contiguous sites.  

PubMed

Recent computational and bioinformatics advances have enabled the efficient creation of novel biocatalysts by reducing amino acid variability at hot spot regions. To further expand the utility of this strategy, we present here a tool called Multi-site Degenerate Codon Analyzer (MDC-Analyzer) for the automated design of intelligent mutagenesis libraries that can completely cover user-defined randomized sequences, especially when multiple contiguous and/or adjacent sites are targeted. By initially defining an objective function, the possible optimal degenerate PCR primer profiles could be automatically explored using the heuristic approach of Greedy Best-First-Search. Compared to the previously developed DC-Analyzer, MDC-Analyzer allows for the existence of a small amount of undesired sequences as a tradeoff between the number of degenerate primers and the encoded library size while still providing all the benefits of DC-Analyzer with the ability to randomize multiple contiguous sites. MDC-Analyzer was validated using a series of randomly generated mutation schemes and experimental case studies on the evolution of halohydrin dehalogenase, which proved that the MDC methodology is more efficient than other methods and is particularly well-suited to exploring the sequence space of proteins using data-driven protein engineering strategies. PMID:24924390

Tang, Lixia; Wang, Xiong; Ru, Beibei; Sun, Hengfei; Huang, Jian; Gao, Hui

2014-06-01

2

Macular Degeneration  

MedlinePLUS

... macular degeneration (AMD), is a leading cause of vision loss in Americans 60 and older. It is a disease that destroys your sharp, central vision. You need central vision to see objects clearly ...

3

Cerebellar Degeneration  

MedlinePLUS

... the spinal cord, medulla oblongata, cerebral cortex, and brain stem. Cerebellar degeneration may be the result of inherited ... in ongoing loss of neurons in the cerebellum, brain stem, and spinal cord transmissible spongiform encephalopathies (such as ...

4

Phosphoproteomic analysis reveals site-specific changes in GFAP and NDRG2 phosphorylation in frontotemporal lobar degeneration.  

PubMed

Frontotemporal lobar degeneration (FTLD) is a progressive neurodegenerative disease characterized by behavioral abnormalities, personality changes, language dysfunction, and can co-occur with the development of motor neuron disease. One major pathological form of FTLD is characterized by intracellular deposition of ubiquitinated and phosphorylated TAR DNA binding protein-43 (TDP-43), suggesting that dysregulation in phosphorylation events may contribute to disease progression. However, to date systematic analysis of the phosphoproteome in FTLD brains has not been reported. In this study, we employed immobilized metal affinity chromatography (IMAC) followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify phosphopeptides from FTLD and age-matched control post-mortem human brain tissue. Using this approach, we identified 786 phosphopeptides in frontal cortex (control and FTLD), in which the population of phosphopeptides represented approximately 50% of the total peptides analyzed. Label-free quantification using spectral counts revealed six proteins with significant changes in the FTLD phosphoproteome. N-myc-Downstream regulated gene 2 (NDRG2) and glial fibrillary acidic protein (GFAP) had an increased number of phosphospectra in FTLD, whereas microtubule associated protein 1A (MAP1A), reticulon 4 (RTN4; also referred to as neurite outgrowth inhibitor (Nogo)), protein kinase C gamma (PRKCG), and heat shock protein 90 kDa alpha, class A member 1(HSP90AA1) had significantly fewer phosphospectra compared to control brain. To validate these differences, we examined NDRG2 phosphorylation in FTLD brain by immunoblot analyses, and using a phosphoserine-13 (pSer13) GFAP monoclonal antibody we show an increase in pSer13 GFAP levels by immunoblot concomitant with increased overall GFAP levels in FTLD cases. These data highlight the utility of combining proteomic and phosphoproteomic strategies to characterize post-mortem human brain tissue. PMID:20886841

Herskowitz, Jeremy H; Seyfried, Nicholas T; Duong, Duc M; Xia, Qiangwei; Rees, Howard D; Gearing, Marla; Peng, Junmin; Lah, James J; Levey, Allan I

2010-12-01

5

Striatopallidonigral degeneration  

PubMed Central

A 15-year-old girl is described with a sporadic, progressive illness manifested by unilateral limb rigidity and dystonia. Obvious dysarthria and some intellectual decline also were noted. Neuropathological findings included gross discoloration and shrinkage of the pallida and, microscopically, profound neuronal loss and gliosis of the caudata and putamena, with less severe neuronal loss from the pallida and substantia nigra. The disease bears some similarities to striatonigral degeneration, but certain clinical and morphological differences justify its consideration as a separate syndrome. ImagesFIG. 1FIG. 2FIG. 3FIG. 4FIG. 5 PMID:5565467

Bell, W. E.; McCormick, W. F.

1971-01-01

6

Precision half-life measurement of the 4-fold forbidden {beta} decay of {sup 50}V  

SciTech Connect

A sensitive search of the 4-fold forbidden nonunique decay of {sup 50}V has been performed. A total mass measuring time product of 186 kg d has been accumulated. A reliable half-life value with the highest precision so far of (2.29{+-}0.25)x10{sup 17} years of the electron capture decay of {sup 50}V into the first excited state of {sup 50}Ti could be obtained. A photon emission line following the {beta} decay into the first excited state of {sup 50}Cr could not be observed, resulting in a lower limit on the half-life of the {beta}-decay branch of 1.7x10{sup 18} years. This is not in good agreement with a claimed observation of this decay branch published in 1989.

Dombrowski, H.; Neumaier, S. [Physikalisch-Technische Bundesanstalt (PTB), D-38116 Braunschweig (Germany); Zuber, K. [Institut fuer Kern- und Teilchenphysik, Technische Universitaet Dresden, D-01069 Dresden (Germany)

2011-05-15

7

Crystalline structures of polymeric hydrocarbon with 3,4-fold helical chains  

PubMed Central

Molecular hydrocarbons are well-known to polymerize under pressure to form covalently bonded frameworks. Here we predict by ab initio calculations two distinct three-dimensional hydrocarbon crystalline structures composed of 3-fold and 4-fold helical CH chains in rhombohedral () and tetragonal (I41/a) symmetry, respectively. Both structures with 1:1 stoichiometry are found to be energetically more favorable than solid acetylene and cubane, and even more stable than benzene II solid at high pressure. The calculations on vibrational, electronic, and optical properties reveal that the new chiral hydrocarbons are dynamically stable with large bulk moduli around 200?GPa, and exhibit a transparent insulating behavior with indirect band gaps of 5.9 ~ 6.7?eV and anisotropic adsorption spectra. Such forms of hydrocarbon, once synthesized, would have wide applications in mechanical, optoelectronic, and biological materials. PMID:25579707

Lian, Chao-Sheng; Li, Han-Dong; Wang, Jian-Tao

2015-01-01

8

Crystalline structures of polymeric hydrocarbon with 3,4-fold helical chains.  

PubMed

Molecular hydrocarbons are well-known to polymerize under pressure to form covalently bonded frameworks. Here we predict by ab initio calculations two distinct three-dimensional hydrocarbon crystalline structures composed of 3-fold and 4-fold helical CH chains in rhombohedral () and tetragonal (I41/a) symmetry, respectively. Both structures with 1:1 stoichiometry are found to be energetically more favorable than solid acetylene and cubane, and even more stable than benzene II solid at high pressure. The calculations on vibrational, electronic, and optical properties reveal that the new chiral hydrocarbons are dynamically stable with large bulk moduli around 200?GPa, and exhibit a transparent insulating behavior with indirect band gaps of 5.9 ~ 6.7?eV and anisotropic adsorption spectra. Such forms of hydrocarbon, once synthesized, would have wide applications in mechanical, optoelectronic, and biological materials. PMID:25579707

Lian, Chao-Sheng; Li, Han-Dong; Wang, Jian-Tao

2015-01-01

9

The Sigma-1 Receptor Binds to the Nav1.5 Voltage-gated Na+ Channel with 4-Fold Symmetry*  

PubMed Central

The sigma-1 receptor (Sig1R) is up-regulated in many human tumors and plays a role in the control of cancer cell proliferation and invasiveness. At the molecular level, the Sig1R modulates the activity of various ion channels, apparently through a direct interaction. We have previously shown using atomic force microscopy imaging that the Sig1R binds to the trimeric acid-sensing ion channel 1A with 3-fold symmetry. Here, we investigated the interaction between the Sig1R and the Nav1.5 voltage-gated Na+ channel, which has also been implicated in promoting the invasiveness of cancer cells. We show that the Sig1R and Nav1.5 can be co-isolated from co-transfected cells, consistent with an intimate association between the two proteins. Atomic force microscopy imaging of the co-isolated proteins revealed complexes in which Nav1.5 was decorated by Sig1Rs. Frequency distributions of angles between pairs of bound Sig1Rs had two peaks, at ?90° and ?180°, and the 90° peak was about twice the size of the 180° peak. These results demonstrate that the Sig1R binds to Nav1.5 with 4-fold symmetry. Hence, each set of six transmembrane regions in Nav1.5 likely constitutes a Sig1R binding site, suggesting that the Sig1R interacts with the transmembrane regions of its partners. Interestingly, two known Sig1R ligands, haloperidol and (+)-pentazocine, disrupted the Nav1.5/Sig1R interaction both in vitro and in living cells. Finally, we show that endogenously expressed Sig1R and Nav1.5 also functionally interact. PMID:22952230

Balasuriya, Dilshan; Stewart, Andrew P.; Crottès, David; Borgese, Franck; Soriani, Olivier; Edwardson, J. Michael

2012-01-01

10

A 4-fold-symmetry hexagonal ruthenium for magnetic heterostructures exhibiting enhanced perpendicular magnetic anisotropy and tunnel magnetoresistance.  

PubMed

A 4-fold-symmetry hexagonal Ru emerging in epitaxial MgO/Ru/Co2 FeAl/MgO heterostructures is reported, in which an approximately Ru(022¯3) growth attributes to the lattice matching between MgO, Ru, and Co2 FeAl. Perpendicular magnetic anisotropy of the Co2 FeAl/MgO interface is substantially enhanced. The magnetic tunnel junctions (MTJs) incorporating this structure give rise to the largest tunnel magnetoresistance for perpendicular MTJs using low damping Heusler alloys. PMID:25123705

Wen, Zhenchao; Sukegawa, Hiroaki; Furubayashi, Takao; Koo, Jungwoo; Inomata, Koichiro; Mitani, Seiji; Hadorn, Jason Paul; Ohkubo, Tadakatsu; Hono, Kazuhiro

2014-10-01

11

Quantitative T2* (T2 star) relaxation times predict site specific proteoglycan content and residual mechanics of the intervertebral disc throughout degeneration.  

PubMed

Degeneration alters the biochemical composition of the disc, affecting the mechanical integrity leading to spinal instability. Quantitative T2* MRI probes water mobility within the macromolecular network, a potentially more sensitive assessment of disc health. We determined the relationship between T2* relaxation time and proteoglycan content, collagen content, and compressive mechanics throughout the degenerative spectrum. Eighteen human cadaveric lumbar (L4-L5) discs were imaged using T2* MRI. The T2* relaxation time at five locations (nucleous pulposus or NP, anterior annulus fibrosis or AF, posterior AF, inner AF, and outer AF) was correlated with sulfated-glycosaminoglycan (s-GAG) content, hydroxyproline content, and residual stress and strain at each location. T2* relaxation times were significantly correlated with s-GAG contents in all test locations and were particularly strong in the NP (r?=?0.944; p?

Ellingson, Arin M; Nagel, Tina M; Polly, David W; Ellermann, Jutta; Nuckley, David J

2014-08-01

12

Quantitative T2* (T2 Star) Relaxation Times Predict Site Specific Proteoglycan Content and Residual Mechanics of the Intervertebral Disc Throughout Degeneration  

PubMed Central

Degeneration alters the biochemical composition of the disc, affecting the mechanical integrity leading to spinal instability. Quantitative T2* MRI probes water mobility within the macromolecular network, a potentially more sensitive assessment of disc health. We determined the relationship between T2* relaxation time and proteoglycan content, collagen content, and compressive mechanics throughout the degenerative spectrum. Eighteen human cadaveric lumbar (L4–L5) discs were imaged using T2* MRI. The T2* relaxation time at five locations (nucleous pulposus or NP, anterior annulus fibrosis or AF, posterior AF, inner AF, and outer AF) was correlated with sulfated-glycosaminoglycan (s-GAG) content, hydroxyproline content, and residual stress and strain at each location. T2* relaxation times were significantly correlated with s-GAG contents in all test locations and were particularly strong in the NP (r = 0.944; p < 0.001) and inner AF (r = 0.782; p < 0.001). T2* relaxation times were also significantly correlated with both residual stresses and excised strains in the NP (r = 0.857; p < 0.001: r = 0.816; p < 0.001), inner AF (r = 0.535; p = 0.022: r = 0.516; p = 0.028), and outer AF (r = 0.668; p = 0.002: r = 0.458; p = 0.041). These strong correlations highlight T2* MRI’s ability to predict the biochemical and mechanical health of the disc. T2* MRI assessment of disc health is a clinically viable tool showing promise as a biomarker for distinguishing degenerative changes. PMID:24788830

Ellingson, Arin M.; Nagel, Tina M.; Polly, David W.; Ellermann, Jutta; Nuckley, David J.

2014-01-01

13

Subacute combined degeneration  

MedlinePLUS

Subacute combined degeneration is caused by a vitamin B12 deficiency. It mainly affects the spinal cord. But ... not know exactly how a lack of vitamin B12 damages the nerves. It is possible the lack ...

14

Double Degenerate Binary Systems  

SciTech Connect

In this study, angular momentum loss via gravitational radiation in double degenerate binary (DDB)systems (NS + NS, NS + WD, WD + WD, and AM CVn) is studied. Energy loss by gravitational waves has been estimated for each type of systems.

Yakut, K. [University of Ege, Department of Astronomy and Space Sciences, 35100-Izmir (Turkey)

2011-09-21

15

X-82 to Treat Age-related Macular Degeneration  

ClinicalTrials.gov

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

2015-01-21

16

Structures of carbon catabolite protein A–(HPr-Ser46-P) bound to diverse catabolite response element sites reveal the basis for high-affinity binding to degenerate DNA operators  

PubMed Central

In Gram-positive bacteria, carbon catabolite protein A (CcpA) is the master regulator of carbon catabolite control, which ensures optimal energy usage under diverse conditions. Unlike other LacI-GalR proteins, CcpA is activated for DNA binding by first forming a complex with the phosphoprotein HPr-Ser46-P. Bacillus subtilis CcpA functions as both a transcription repressor and activator and binds to more than 50 operators called catabolite response elements (cres). These sites are highly degenerate with the consensus, WTGNNARCGNWWWCAW. How CcpA–(HPr-Ser46-P) binds such diverse sequences is unclear. To gain insight into this question, we solved the structures of the CcpA–(HPr-Ser46-P) complex bound to three different operators, the synthetic (syn) cre, ackA2 cre and gntR-down cre. Strikingly, the structures show that the CcpA-bound operators display different bend angles, ranging from 31° to 56°. These differences are accommodated by a flexible linkage between the CcpA helix-turn-helix-loop-helix motif and hinge helices, which allows independent docking of these DNA-binding modules. This flexibility coupled with an abundance of non-polar residues capable of non-specific nucleobase interactions permits CcpA–(HPr-Ser46-P) to bind diverse operators. Indeed, biochemical data show that CcpA–(HPr-Ser46-P) binds the three cre sites with similar affinities. Thus, the data reveal properties that license this protein to function as a global transcription regulator. PMID:21106498

Schumacher, Maria A.; Sprehe, Mareen; Bartholomae, Maike; Hillen, Wolfgang; Brennan, Richard G.

2011-01-01

17

Kraepelin and degeneration theory.  

PubMed

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. PMID:18516511

Hoff, Paul

2008-06-01

18

Degenerate perturbation theory  

SciTech Connect

The algebraic structure of degenerate Rayleigh-Schroedinger perturbation theory is reviewed. There are a number of different but equivalent algorithms which generate this perturbation series; we argue that the frequent need to carry out infinite-order partial summations selects one of these algorithms as the most efficient. Recent developments include coupled-cluster formulations for open shells, a new diagrammatic representation, and the concept of incomplete model subspaces. These subjects are reviewed, as well as some applications.

Brandow, B.

1982-01-01

19

Alternative splicing and retinal degeneration  

PubMed Central

Alternative splicing is highly regulated in tissue-specific and development-specific patterns, and it has been estimated that 15% of disease-causing point mutations affect pre-mRNA splicing. In this review, we consider the cis-acting splice site and trans-acting splicing factor mutations that affect pre-mRNA splicing and contribute to retinal degeneration. Numerous splice site mutations have been identified in retinitis pigmentosa and various cone-rod dystrophies. For example, mutations in alternatively spliced retina-specific exons of the widely expressed RPGR and COL2A1 genes lead primarily to X-linked retinitis pigmentosa and ocular variants of Stickler Syndrome, respectively. Furthermore, mutations in general pre-mRNA splicing factors, such as PRPF31, PRPF8, and PRPF3, predominantly cause autosomal dominant retinitis pigmentosa. These findings suggest an important role for pre-mRNA splicing in retinal homeostasis and the pathogenesis of retinal degenerative diseases. The development of novel therapeutic strategies to modulate aberrant splicing, including small molecule based therapies, has the potential to lead to the development of new treatments for retinal degenerative diseases. PMID:23647439

Liu, Melissa M.; Zack, Donald J.

2014-01-01

20

Epidermal cells are the primary phagocytes in the fragmentation and clearance of degenerating dendrites in Drosophila  

PubMed Central

SUMMARY During developmental remodeling, neurites destined for pruning often degenerate on-site. Physical injury also induces degeneration of neurites distal to the injury site. Prompt clearance of degenerating neurites is important for maintaining tissue homeostasis and preventing inflammatory responses. Here we show that in both dendrite pruning and dendrite injury of Drosophila sensory neurons, epidermal cells rather than hemocytes are the primary phagocytes in clearing degenerating dendrites. Epidermal cells act via Draper-mediated recognition to facilitate dendrite degeneration and to engulf and degrade degenerating dendrites. Using multiple dendritic membrane markers to trace phagocytosis, we show that two members of the CD36 family, croquemort (crq) and debris buster (dsb), act at distinct stages of phagosome maturation for dendrite clearance. Our finding reveals the physiological importance of coordination between neurons and their surrounding epidermis, for both dendrite fragmentation and clearance. PMID:24412417

Xiao, Hui; Wang, Denan; Franc, Nathalie C.; Jan, Lily Yeh; Jan, Yuh-Nung

2014-01-01

21

Mitochondrial fission augments capsaicin-induced axonal degeneration.  

PubMed

Capsaicin, an agonist of transient receptor potential vanilloid receptor 1, induces axonal degeneration of peripheral sensory nerves and is commonly used to treat painful sensory neuropathies. In this study, we investigated the role of mitochondrial dynamics in capsaicin-induced axonal degeneration. In capsaicin-treated rodent sensory axons, axonal swellings, decreased mitochondrial stationary site length and reduced mitochondrial transport preceded axonal degeneration. Increased axoplasmic Ca(2+) mediated the alterations in mitochondrial length and transport. While sustaining mitochondrial transport did not reduce axonal swellings in capsaicin-treated axons, preventing mitochondrial fission by overexpression of mutant dynamin-related protein 1 increased mitochondrial length, retained mitochondrial membrane potentials and reduced axonal loss upon capsaicin treatment. These results establish that mitochondrial stationary site size significantly affects axonal integrity and suggest that inhibition of Ca(2+)-dependent mitochondrial fission facilitates mitochondrial function and axonal survival following activation of axonal cationic channels. PMID:25322817

Chiang, Hao; Ohno, Nobuhiko; Hsieh, Yu-Lin; Mahad, Don J; Kikuchi, Shin; Komuro, Hitoshi; Hsieh, Sung-Tsang; Trapp, Bruce D

2015-01-01

22

Degenerate quantum gases of strontium  

E-print Network

Degenerate quantum gases of alkaline-earth-like elements open new opportunities in research areas ranging from molecular physics to the study of strongly correlated systems. These experiments exploit the rich electronic structure of these elements, which is markedly different from the one of other species for which quantum degeneracy has been attained. Specifically, alkaline-earth-like atoms, such as strontium, feature metastable triplet states, narrow intercombination lines, and a non-magnetic, closed-shell ground state. This review covers the creation of quantum degenerate gases of strontium and the first experiments performed with this new system. It focuses on laser-cooling and evaporation schemes, which enable the creation of Bose-Einstein condensates and degenerate Fermi gases of all strontium isotopes, and shows how they are used for the investigation of optical Feshbach resonances, the study of degenerate gases loaded into an optical lattice, as well as the coherent creation of Sr_2 molecules.

Stellmer, Simon; Killian, Thomas C

2013-01-01

23

Iatrogenic corneal perforation in Terrien Marginal Degeneration.  

PubMed

This case report is about a rare disease with unusual presentation. Failure to recognise atypical presentation may lead to error in managing the patient and cause disastrous complications. Here we highlight a case of Terrien Marginal Degeneration in both eyes with atypical presentation; namely pseudopterygium. A 22 year old man was referred to our centre for iatrogenic right eye corneal perforation after having an atypical pterygium removed at another hospital. On arrival, his vision was 1/60 in both eyes with bilateral cornea Terrien Marginal Degeneration. His right eye anterior chamber was deep with a conjunctival flap covering the perforation site which was located from the 2.30 - 3.30 clock position nasally with no aqueous leak. However after a day his right eye anterior chamber became flat and there was fast aqueous leak from the perforation site. An emergency C shaped peripheral corneal lamellar keratoplasty was performed to seal the perforation. Post operatively his right eye improved to 6/24. PMID:23629570

M R, Kursiah

2013-04-01

24

4-fold enhancement in the critical current density of YBa{sub 2}Cu{sub 3}O{sub 7} films by practical ion irradiation  

SciTech Connect

We report an up-to-4-fold enhancement in the in-magnetic-field critical current density at 77 K of epitaxial YBa{sub 2}Cu{sub 3}O{sub 7} films on CeO{sub 2}-buffered SrTiO{sub 3} substrates by 3-MeV Au{sup 2+} irradiation. This indicates that irradiation using an industrially practical ion beam, which generally has kinetic energy less than 5 MeV, can provide a substantial increase in the in-field current performance of high-temperature superconductor films. Transmission electron microscopy results show that point-like defects smaller than 6 nm in diameter were created in the films by the irradiation.

Matsui, H.; Ogiso, H.; Yamasaki, H.; Kumagai, T.; Sohma, M.; Yamaguchi, I.; Manabe, T. [National Institute of Advanced Industrial Science and Technology, Tsukuba 3058565 (Japan)

2012-12-03

25

Unraveling of the E-helices and Disruption of 4-Fold Pores Are Associated with Iron Mishandling in a Mutant Ferritin Causing Neurodegeneration  

SciTech Connect

Mutations in the coding sequence of the ferritin light chain (FTL) gene cause a neurodegenerative disease known as neuroferritinopathy or hereditary ferritinopathy, which is characterized by the presence of intracellular inclusion bodies containing the mutant FTL polypeptide and by abnormal accumulation of iron in the brain. Here, we describe the x-ray crystallographic structure and report functional studies of ferritin homopolymers formed from the mutant FTL polypeptide p.Phe167SerfsX26, which has a C terminus that is altered in amino acid sequence and length. The structure was determined and refined to 2.85 {angstrom} resolution and was very similar to the wild type between residues Ile-5 and Arg-154. However, instead of the E-helices normally present in wild type ferritin, the C-terminal sequences of all 24 mutant subunits showed substantial amounts of disorder, leading to multiple C-terminal polypeptide conformations and a large disruption of the normally tiny 4-fold axis pores. Functional studies underscored the importance of the mutant C-terminal sequence in iron-induced precipitation and revealed iron mishandling by soluble mutant FTL homopolymers in that only wild type incorporated iron when in direct competition in solution with mutant ferritin. Even without competition, the amount of iron incorporation over the first few minutes differed severalfold. Our data suggest that disruption at the 4-fold pores may lead to direct iron mishandling through attenuated iron incorporation by the soluble form of mutant ferritin and that the disordered C-terminal polypeptides may play a major role in iron-induced precipitation and formation of ferritin inclusion bodies in hereditary ferritinopathy.

Baraibar, Martin A.; Muhoberac, Barry B.; Garringer, Holly J.; Hurley, Thomas D.; Vidal, Ruben (Indiana-Med); (IUPUI)

2010-03-12

26

Remote degeneration: insights from the hemicerebellectomy model.  

PubMed

When CNS lesions develop, neuronal degeneration occurs locally but in regions that are remote, yet functionally connected, to the primary lesion site. This process, known as "remote damage," significantly affects long-term outcomes in many CNS pathologies, such as stroke, multiple sclerosis, and traumatic brain and spinal cord injuries. Remote damage can last several days or months after the primary lesion, providing a window during which therapeutic approaches can be implemented to effect neuroprotection. The recognition of the importance of remote damage in determining disease outcomes has prompted considerable interest in examining remote damage-associated mechanisms, most of which is derived from the potential of this research to develop innovative pharmacological approaches for preserving neurons and improving functional outcomes. To this end, the hemicerebellectomy (HCb) experimental paradigm has been instrumental in highlighting the complexity and variety of the systems that are involved, identifying mechanisms of life/death decisions, and providing a testing ground for novel neuroprotective approaches. Inflammation, oxidative stress, apoptosis, autophagy, and neuronal changes in receptor mosaics are several remote damage mechanisms that have been identified and examined using the HCb model. In this review, we discuss our current understanding of remote degeneration mechanisms and their potential for exploitation with regard to neuroprotective approaches, focusing on HCb studies. PMID:25253422

Viscomi, Maria Teresa; Latini, Laura; Bisicchia, Elisa; Sasso, Valeria; Molinari, Marco

2015-02-01

27

Degenerate elliptic boundary value problems  

Microsoft Academic Search

In this paper we find conditions that guarantee that regular boundary value problems for elliptic differential-operator equations of the second order in an interval are coercive and Fredholm, and we prove the compactness of a resolvent. We apply this result to find some algebraic conditions that guarantee that regular boundary value problems for degenerate elliptic differential equations of the second

H. I. Karakas; V. B. Shakhmupov; S. Yakubov

1996-01-01

28

Equivalence of degenerate Hopf bifurcations  

Microsoft Academic Search

The author proves the equivalence of degenerate Hopf bifurcations which have all their closed orbits at the bifurcation point. Although these Hopf bifurcations have infinity codimension, they can nevertheless occur generically in dynamical systems under constraint such as in the Hamiltonian systems or in the replicator equations; and so in these contexts a treatment of their equivalence is required. The

A. Edalat

1991-01-01

29

Neuronal Degeneration in Canine Narcolepsy  

Microsoft Academic Search

Narcolepsy is a lifelong illness characterized by persistent sleepiness, hypnagogic hallucinations, and episodes of motor paralysis called cataplexy. We have tested the hypothesis that a transient neurodegenerative process is linked to symptom onset. Using the amino-cupric silver stain on brain sections from canine narcoleptics, we found elevated levels of axonal degeneration in the amygdala, basal forebrain (including the nucleus of

J. M. Siegel; R. Nienhuis; S. Gulyani; S. Ouyang; M. F. Wu; E. Mignot; R. C. Switzer; G. McMurry; M. Cornford

1999-01-01

30

Prime Vectors in Degenerate Lattices  

NASA Astrophysics Data System (ADS)

In this paper the distribution of prime vectors (i.e., vectors with prime components) in degenerate lattices A{Z}^n+\\bar b is investigated, and asymptotic formulas are obtained for the fraction \\pi(N,\\,A{Z}^n,\\,\\bar b) which are valid under certain restrictions on the matrix A, where A\\in {Z}^{m\\times n}, \\bar b\\in {Z}^m, and \\pi(N,\\,A{Z}^n+\\bar b) is the number of prime vectors of the degenerate lattice A{Z}^n+\\bar b with components not exceeding N.The main idea is to reduce the problem to that of solving systems of linear algebraic equations in prime numbers belonging to given arithmetic progressions. An asymptotic formula for the number of solutions of such systems is calculated with the help of a multidimensional variant of the circle method.Bibliography: 12 titles.

Tulyaganova, M. I.

1986-02-01

31

Retrograde and Wallerian Axonal Degeneration Occur Synchronously after Retinal Ganglion Cell Axotomy  

PubMed Central

Axonal injury and degeneration are pivotal pathological events in diseases of the nervous system. In the past decade, it has been recognized that the process of axonal degeneration is distinct from somal degeneration and that axoprotective strategies may be distinct from those that protect the soma. Preserving the cell body via neuroprotection cannot improve function if the axon is damaged, because the soma is still disconnected from its target. Therefore, understanding the mechanisms of axonal degeneration is critical for developing new therapeutic interventions for axonal disease treatment. We combined in vivo imaging with a multilaser confocal scanning laser ophthalmoscope and in vivo axotomy with a diode-pumped solid-state laser to assess the time course of Wallerian and retrograde degeneration of unmyelinated retinal ganglion cell axons in living rats for 4 weeks after intraretinal axotomy. Laser injury resulted in reproducible axon loss both distal and proximal to the site of injury. Longitudinal polarization-sensitive imaging of axons demonstrated that Wallerian and retrograde degeneration occurred synchronously. Neurofilament immunostaining of retinal whole-mounts confirmed axonal loss and demonstrated sparing of adjacent axons to the axotomy site. In vivo fluorescent imaging of axonal transport and photobleaching of labeled axons demonstrated that the laser axotomy model did not affect adjacent axon function. These results are consistent with a shared mechanism for Wallerian and retrograde degeneration. PMID:22642911

Kanamori, Akiyasu; Catrinescu, Maria-Magdalena; Belisle, Jonathan M.; Costantino, Santiago; Levin, Leonard A.

2013-01-01

32

Molecular genetics of retinal degeneration  

PubMed Central

Inherited retinal degeneration in Drosophila has been explored for insights into similar processes in humans. Based on the mechanisms, I divide these mutations in Drosophila into three classes. The first consists of genes that control the specialization of photoreceptor cells including the morphogenesis of visual organelles (rhabdomeres) that house the visual signaling proteins. The second class contains genes that regulate the activity or level of the major rhodopsin, Rh1, which is the light sensor and also provides a structural role for the maintenance of rhabdomeres. Some mutations in Rh1 (NinaE) are dominant due to constitutive activity or folding defects, like autosomal dominant retinitis pigmentosa (ADRP) in humans. The third class consists of genes that control the Ca2+ influx directly or indirectly by promoting the turnover of the second messenger and regeneration of PIP2, or mediate the Ca2+-dependent regulation of the visual response. These gene products are critical for the increase in cytosolic Ca2+ following light stimulation to initiate negative regulatory events. Here I will focus on the signaling mechanisms underlying the degeneration in norpA, and in ADRP-type NinaE mutants that produce misfolded Rh1. Accumulation of misfolded Rh1 in the ER triggers the unfolded protein response (UPR), while endosomal accumulation of activated Rh1 may initiate autophagy in norpA. Both autophagy and the UPR are beneficial for relieving defective endosomal trafficking and the ER stress, respectively. However, when photoreceptors fail to cope with the persistence of these stresses, a cell death program is activated leading to retinal degeneration. PMID:21897116

2011-01-01

33

Degeneration of a Nonrecombining Chromosome  

NASA Astrophysics Data System (ADS)

Comparative studies suggest that sex chromosomes begin as ordinary autosomes that happen to carry a major sex determining locus. Over evolutionary time the Y chromosome is selected to stop recombining with the X chromosome, perhaps in response to accumulation of alleles beneficial to the heterogametic but harmful to the homogametic sex. Population genetic theory predicts that a nonrecombining Y chromosome should degenerate. Here this prediction is tested by application of specific selection pressures to Drosophila melanogaster populations. Results demonstrate the decay of a nonrecombining, nascent Y chromosome and the capacity for recombination to ameliorate such decay.

Rice, William R.

1994-01-01

34

Bilateral Hypertrophic Olivary Degeneration in Wilson Disease  

PubMed Central

Hypertrophic olivary degeneration resulting from lesions of the dento-rubro-olivary pathway, also called Guillain-Mollaret-triangle, has been described previously in a number of cases. Reports about bilateral hypertrophic olivary degeneration of the inferior olivary nuclei are very limited, and the magnetic resonance imaging findings of hypertrophic olivary degeneration in Wilson disease have not yet been described to the best of our knowledge. Herein, we present the first report of bilateral hypertrophic olivary degeneration diagnosed by magnetic resonance imaging in a patient suffering from Wilson disease. PMID:23482821

Guenther, Peter; Hoffmann, Karl-Titus

2013-01-01

35

Wallerian degeneration is required for both neuropathic pain and sympathetic sprouting into the DRG  

Microsoft Academic Search

Chronic loose constriction of the sciatic nerve produces mechanoallodynia and thermal hyperalgesia in rats and mice, and the behaviour develops during the time in which the nerve distal to the ligature site is undergoing Wallerian degeneration. There is a sympathetic component to the pain generated by this and other rodent models of neuropathic pain, yet the site at which this

Matt S Ramer; Gavin D French; Mark A Bisby

1997-01-01

36

A STRONGLY DEGENERATE PARABOLIC AGGREGATION EQUATION  

E-print Network

A STRONGLY DEGENERATE PARABOLIC AGGREGATION EQUATION F. BETANCOURTA, R. B¨URGERB, AND K. H. KARLSENC Abstract. This paper is concerned with a strongly degenerate convection- diffusion equation in one of the given position. This equation can be understood as a model of aggregation of the individuals

37

Wallerian Degeneration of the Pontocerebellar Fibers  

Microsoft Academic Search

Summary: Two cases of pontine infarct with Wallerian degeneration (WD) of the pontocerebellar fibers are de- scribed. WD of pontocerebellar fibers, seen bilaterally along the transverse pontine fibers, is more visible in the middle cerebellar peduncles and extends into the white matter of the cerebellar hemispheres. Understanding the anatomy of the white matter and the temporal evolution of this degeneration

Tiziana De Simone; Caroline Regna-Gladin; Maria Rita Carriero; Laura Farina; Mario Savoiardo

38

Degenerate adiabatic perturbation theory: Foundations and applications  

NASA Astrophysics Data System (ADS)

We present details and expand on the framework leading to the recently introduced degenerate adiabatic perturbation theory [Phys. Rev. Lett. 104, 170406 (2010), 10.1103/PhysRevLett.104.170406], and on the formulation of the degenerate adiabatic theorem, along with its necessary and sufficient conditions [given in Phys. Rev. A 85, 062111 (2012), 10.1103/PhysRevA.85.062111]. We start with the adiabatic approximation for degenerate Hamiltonians that paves the way to a clear and rigorous statement of the associated degenerate adiabatic theorem, where the non-Abelian geometric phase (Wilczek-Zee phase) plays a central role to its quantitative formulation. We then describe the degenerate adiabatic perturbation theory, whose zeroth-order term is the degenerate adiabatic approximation, in its full generality. The parameter in the perturbative power-series expansion of the time-dependent wave function is directly associated to the inverse of the time it takes to drive the system from its initial to its final state. With the aid of the degenerate adiabatic perturbation theory we obtain rigorous necessary and sufficient conditions for the validity of the adiabatic theorem of quantum mechanics. Finally, to illustrate the power and wide scope of the methodology, we apply the framework to a degenerate Hamiltonian, whose closed-form time-dependent wave function is derived exactly, and also to other nonexactly solvable Hamiltonians whose solutions are numerically computed.

Rigolin, Gustavo; Ortiz, Gerardo

2014-08-01

39

Laser therapy and macular degeneration  

NASA Astrophysics Data System (ADS)

Among macular diseases, choroidal neovascularization (CNV) is one of the most common causes of visual loss, especially in the form associated with age-related macular degeneration and pathologic myopia. Research on these diseases has recently evaluated new treatment modalities that use laser light differently; among these, photodynamic therapy (PDT) has been introduced in the clinical practice, allowing us to expand the possibility of reducing visual loss in patients affected by CNV. With PDT, a photosensitizer (verteporfin, VisudyneTM) is injected intravenously, and it selectively binds to new vessels; low-power laser light exposure then activates the drug, leading to oxidative damage of the endothelium and new vessels thrombosis. Yet, other therapies, such as transpupillary termotherapy, or the use of photocoagulation to cause feeder-vessel occlusion, could proof effective, but they need further investigation.

Menchini, Ugo; Virgili, Gianni; Giansanti, Fabrizio; Giacomelli, Giovanni; Cappelli, Stefania

2001-10-01

40

Cognitive impairment in spinocerebellar degeneration.  

PubMed

It has been reported that patients with spinocerebellar degenerations (SCDs) have cognitive dysfunction as well as limb and truncal ataxia, dysarthria and dysphagia. We review cognitive dysfunction in common types of SCD, including spinocerebellar ataxia types 1, 2, 3, 6, and 17, dentatorubral-pallidoluysian atrophy, Friedreich's ataxia, and multiple system atrophy. There are few studies that address cognitive function in SCD. Although there are few comparison studies among the various SCDs, cognitive dysfunction may be more common and severe in spinocerebellar ataxia type 17 and dentatorubral-pallidoluysian atrophy. While cognitive dysfunction in SCD appears to represent frontal dysfunction, the mechanisms of cognitive dysfunction have not been directly clarified. Nevertheless, various lesions, including those in the cerebrocerebellar circuitry, cortico-striatal-thalamocortical circuitry, and the frontal lobe, may influence cognitive function to various degrees for each disease. PMID:19295212

Kawai, Y; Suenaga, M; Watanabe, H; Sobue, G

2009-01-01

41

Genetics of Frontotemporal Lobar Degeneration  

PubMed Central

Frontotemporal lobar degeneration (FTLD), the most frequent neurodegenerative disorder with a presenile onset, presents with a spectrum of clinical manifestations, ranging from behavioral and executive impairment to language disorders and motor dysfunction. Familial aggregation is frequently reported, and about 10% of cases have an autosomal dominant transmission. Microtubule associated protein tau (MAPT) gene mutations have been the first ones identified and are associated with early onset behavioral variant frontotemporal dementia phenotype. More recently, progranulin gene (GRN) mutations were recognized in association with familial form of FTLD. In addition, other genes are linked to rare cases of familial FTLD. Lastly, a number of genetic risk factors for sporadic forms have also been identified. In this review, current knowledge about mutations at the basis of familial FTLD will be described, together with genetic risk factors influencing the susceptibility to FTLD. PMID:22536193

Galimberti, Daniela; Scarpini, Elio

2012-01-01

42

Total absorption by degenerate critical coupling  

NASA Astrophysics Data System (ADS)

We consider a mirror-symmetric resonator with two ports. We show that, when excited from a single port, complete absorption can be achieved through critical coupling to degenerate resonances with opposite symmetry. Moreover, any time two resonances with opposite symmetry are degenerate in frequency and absorption is always significantly enhanced. In contrast, when two resonances with the same symmetry are nearly degenerate, there is no absorption enhancement. We numerically demonstrate these effects using a graphene monolayer on top of a photonic crystal slab, illuminated from a single side in the near-infrared.

Piper, Jessica R.; Liu, Victor; Fan, Shanhui

2014-06-01

43

Total absorption by degenerate critical coupling  

SciTech Connect

We consider a mirror-symmetric resonator with two ports. We show that, when excited from a single port, complete absorption can be achieved through critical coupling to degenerate resonances with opposite symmetry. Moreover, any time two resonances with opposite symmetry are degenerate in frequency and absorption is always significantly enhanced. In contrast, when two resonances with the same symmetry are nearly degenerate, there is no absorption enhancement. We numerically demonstrate these effects using a graphene monolayer on top of a photonic crystal slab, illuminated from a single side in the near-infrared.

Piper, Jessica R., E-mail: jrylan@stanford.edu; Liu, Victor; Fan, Shanhui, E-mail: shanhui@stanford.edu [Ginzton Laboratory, Department of Electrical Engineering, Stanford University, Stanford, California 94305 (United States)

2014-06-23

44

Advances in the management of macular degeneration  

PubMed Central

Current management of age-related macular degeneration (AMD) can be divided into two categories: first, anti-vasoendothelial growth factor (anti-VEGF) injection for wet macular degeneration; second, anti-oxidant vitamins for dry macular degeneration. New therapies are being developed for both of these diseases using novel technologies and different modes of administration. The hope is that some of these therapies will achieve significant improvement to current management and prevent future loss of vision in this devastating eye condition. PMID:24860651

2014-01-01

45

Peripheral Glia Have a Pivotal Role in the Initial Response to Axon Degeneration of Peripheral Sensory Neurons in Zebrafish  

PubMed Central

Axon degeneration is a feature of many peripheral neuropathies. Understanding the organismal response to this degeneration may aid in identifying new therapeutic targets for treatment. Using a transgenic zebrafish line expressing a bacterial nitroreductase (Ntr)/mCherry fusion protein in the peripheral sensory neurons of the V, VII, IX, and X cranial nerves, we were able to induce and visualize the pathology of axon degeneration in vivo. Exposure of 4 days post fertilization Ntr larvae to the prodrug metronidazole (Met), which Ntr metabolizes into cytotoxic metabolites, resulted in dose-dependent cell death and axon degeneration. This was limited to the Ntr-expressing sensory neurons, as neighboring glia and motor axons were unaffected. Cell death was rapid, becoming apparent 3–4 hours after Met treatment, and was followed by phagocytosis of soma and axon debris by cells within the nerves and ganglia beginning at 4–5 hours of exposure. Although neutrophils appear to be activated in response to the degenerating neurons, they did not accumulate at the sites of degeneration. In contrast, macrophages were found to be attracted to the sites of the degenerating axons, where they phagocytosed debris. We demonstrated that peripheral glia are critical for both the phagocytosis and inflammatory response to degenerating neurons: mutants that lack all peripheral glia (foxD3?/?; Ntr) exhibit a much reduced reaction to axonal degeneration, resulting in a dramatic decrease in the clearance of debris, and impaired macrophage recruitment. Overall, these results show that this zebrafish model of peripheral sensory axon degeneration exhibits many aspects common to peripheral neuropathies and that peripheral glia play an important role in the initial response to this process. PMID:25058656

Pope, Holly M.; Voigt, Mark M.

2014-01-01

46

Nmnat2 delays axon degeneration in superior cervical ganglia dependent on its NAD synthesis activity.  

PubMed

Axon degeneration is an active program of self-destruction observed in many physiological and pathological settings. There are three Nicotinamide mononucleotide adenylyl transferase (Nmnat, EC2.7.7.1) in mammals. Overexpression of Nmnat1 or Nmnat3 can delay axon degeneration, while the role of Nmnat2 in axon degeneration remains largely unknown. Here we found that Nmnat2 was specifically and highly expressed in brain compared with Nmnat1 and Nmnat3. Furthermore, we found brain Nmnat2 was correlated with Alzheimer's disease in APPswe/PS1dE9 transgenic mice. Nmnat2 delayed Wallerian degeneration in cultured superior cervical ganglia (SCGs) from morphological changes, microtubule destruction and neurofilament degradation, mutation of the conserved enzyme activity site in Nmnat2 disrupted its enzyme activity as well as the axon-protective function. Our results demonstrate that the brain-specific Nmnat2 delays injury-induced axon degeneration dependent on its NAD synthesis activity. These findings provide new clues to further study the molecular mechanisms of axon degeneration and the related neurodegenerative diseases. PMID:19778564

Yan, Tingting; Feng, Yan; Zheng, Jin; Ge, Xinjian; Zhang, Yi; Wu, Dongmei; Zhao, Jian; Zhai, Qiwei

2010-01-01

47

EXCEPTIONAL BUNDLES ASSOCIATED TO DEGENERATIONS OF SURFACES  

E-print Network

EXCEPTIONAL BUNDLES ASSOCIATED TO DEGENERATIONS OF SURFACES PAUL HACKING 1. Introduction In 1981 J HACKING F deforms in a unique way to a family of exceptional bundles on the fibers of Y/(0 S). Theorem 1

Hacking, Paul

48

A new degenerate Fermi gas apparatus  

E-print Network

In the summer of 2004, the BEC 2 lab of Wolfgang Ketterle's group at MIT started a new research direction of studying degenerate fermionic Lithium atoms in optical lattices. The major contributions to the new experimental ...

Setiawan, Widagdo

2007-01-01

49

Macular Degeneration Prevention and Risk Factors  

MedlinePLUS

... Individuals with diets high in fat, cholesterol and sugar, and low in antioxidants are more likely to be affected by age-related macular degeneration. Obesity - Overweight individuals are more likely to be affected ...

50

Admissibility Conditions for Degenerate Cyclotomic BMW Algebras  

E-print Network

We study admissibility conditions for the parameters of degenerate cyclotomic BMW algebras. We show that the u-admissibility condition of Ariki, Mathas and Rui is equivalent to a simple module theoretic condition.

Goodman, Frederick M

2009-01-01

51

Retinal Degenerations: Planning for the Future  

Microsoft Academic Search

Retinal degenerations are a leading cause of blindness in many parts of the world (Bunker et al., 1984; Grondahl, 1987; Berson,\\u000a 1993; Klein et al., 1995; Attebo et al., 1996; Klaver et al., 1998; Novak-Laus et al., 2002). In the United States an estimated\\u000a 6 million people have age-related macular degeneration with a decrease in central vision after age 60.

Eliot L. Berson

52

[Presacral schwannoma with degenerated areas ("ancient schwannoma")].  

PubMed

A presacral, degenerative schwannoma ("ancient schwannoma") is a rare entity. The clinical signs are nonspecific, and a reliable preoperative diagnosis is difficult. Tumor heterogeneity with calcifications may be seen in degenerated schwannomas on MRI or CT but not necessarily. First-line treatment is complete surgical excision. We present the case of a 44-year-old male who required surgery for a presacral mass. Histopathological examination revealed the diagnosis of a schwannoma with degenerated areas. PMID:20694717

Netsch, C; Oberhagemann, K; Bach, T; Feyerabend, B; Gross, A J

2010-10-01

53

Shear viscosity of degenerate electron matter  

E-print Network

We calculate the partial electron shear viscosity $\\eta_{ee}$ limited by electron-electron collisions in a strongly degenerate electron gas taking into account the Landau damping of transverse plasmons. The Landau damping strongly suppresses $\\eta_{ee}$ in the domain of ultrarelativistic degenerate electrons and modifies its %asymptotic temperature behavior. The efficiency of the electron shear viscosity in the cores of white dwarfs and envelopes of neutron stars is analyzed.

P. S. Shternin

2008-03-27

54

The Gravitational Demise of Cold Degenerate Stars  

E-print Network

We consider the long term fate and evolution of cold degenerate stars under the action of gravity alone. Although such stars cannot emit radiation through the Hawking mechanism, the wave function of the star will contain a small admixture of black hole states. These black hole states will emit radiation and hence the star can lose its mass energy in the long term. We discuss the allowed range of possible degenerate stellar evolution within this framework.

Fred C. Adams; Greg Laughlin; Manasse Mbonye; Malcolm J. Perry

1998-08-23

55

Age-related macular degeneration.  

PubMed

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, and the prevalence of the disease increases exponentially with every decade after age 50 years. It is a multifactorial disease involving a complex interplay of genetic, environmental, metabolic, and functional factors. Besides smoking, hypertension, obesity, and certain dietary habits, a growing body of evidence indicates that inflammation and the immune system may play a key role in the development of the disease. AMD may progress from the early form to the intermediate form and then to the advanced form, where two subtypes exist: the nonneovascular (dry) type and the neovascular (wet) type. The results from the Age-Related Eye Disease Study have shown that for the nonneovascular type of AMD, supplementation with high-dose antioxidants (vitamin C, vitamin E, and ?-carotene) and zinc is recommended for those with the intermediate form of AMD in one or both eyes or with advanced AMD or vision loss due to AMD in one eye. As for the neovascular type of the advanced AMD, the current standard of therapy is intravitreal injections of vascular endothelial growth factor inhibitors. In addition, lifestyle and dietary modifications including improved physical activity, reduced daily sodium intake, and reduced intake of solid fats, added sugars, cholesterol, and refined grain foods are recommended. To date, no study has demonstrated that AMD can be cured or effectively prevented. Clearly, more research is needed to fully understand the pathophysiology as well as to develop prevention and treatment strategies for this devastating disease. PMID:23580402

Cheung, Lily K; Eaton, Angie

2013-08-01

56

Protection of Retina by ?B Crystallin in Sodium Iodate Induced Retinal Degeneration  

PubMed Central

Age-related macular degeneration (AMD) is a leading cause of blindness in the developed world. The retinal pigment epithelium (RPE) is a critical site of pathology in AMD and ?B crystallin expression is increased in RPE and associated drusen in AMD. The purpose of this study was to investigate the role of ?B crystallin in sodium iodate (NaIO3)-induced retinal degeneration, a model of AMD in which the primary site of pathology is the RPE. Dose dependent effects of intravenous NaIO3 (20-70 mg/kg) on development of retinal degeneration (fundus photography) and RPE and retinal neuronal loss (histology) were determined in wild type and ?B crystallin knockout mice. Absence of ?B crystallin augmented retinal degeneration in low dose (20 mg/kg) NaIO3-treated mice and increased retinal cell apoptosis which was mainly localized to the RPE layer. Generation of reactive oxygen species (ROS) was observed with NaIO3 in mouse and human RPE which increased further after ?B crystallin knockout or siRNA knockdown, respectively. NaIO3 upregulated AKT phosphorylation and peroxisome proliferator–activator receptor–? (PPAR?) which was suppressed after ?B crystallin siRNA knockdown. Further, PPAR? ligand inhibited NaIO3-induced ROS generation. Our data suggest that ?B crystallin plays a critical role in protection of NaIO3-induced oxidative stress and retinal degeneration in part through upregulation of AKT phosphorylation and PPAR? expression. PMID:24874187

Zhou, Peng; Kannan, Ram; Spee, Christine; Sreekumar, Parameswaran G.; Dou, Guorui; Hinton, David R.

2014-01-01

57

The periodic table of n-categories for low dimensions I: degenerate categories and degenerate bicategories  

E-print Network

The periodic table of n-categories for low dimensions I: degenerate categories and degenerate bicategories Eugenia Cheng and Nick Gurski Abstract. We examine the periodic table of weak n the first few entries in the "Periodic Table" of n- categories. This table was first described by Baez

Cheng, Eugenia

58

Optic pathway degeneration in Japanese black cattle.  

PubMed

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. PMID:25421501

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

2014-11-25

59

Antioxidative nanofullerol prevents intervertebral disk degeneration  

PubMed Central

Compelling evidence suggests that reactive oxygen species (ROS) play a pivotal role in disk degeneration. Fullerol nanoparticles prepared in aqueous solution have been demonstrated to have outstanding ability to scavenge ROS. In this report, in vitro and in vivo models were used to study the efficacy of fullerol in preventing disk degeneration. For in vitro experiments, a pro-oxidant H2O2 or an inflammatory cytokine interleukin (IL)-1? was employed to induce degenerated phenotypes in human nucleus pulposus cells encapsulated in alginate beads, and fullerol was added in the culture medium. For the animal study, an annulus-puncture model with rabbit was created, and fullerol was injected into disks. It was shown that cytotoxicity and cellular ROS level induced by H2O2 were significantly diminished by fullerol. IL-1?-induced nitric oxide generation in culture medium was suppressed by fullerol as well. Gene-profile and biochemical assays showed that fullerol effectively reversed the matrix degradation caused by either H2O2 or IL-1?. The animal study delineated that intradiskal injection of fullerol prevented disk degeneration, increasing water and proteoglycan content and inhibiting ectopic bone formation. These results suggest that antioxidative fullerol may have a potential therapeutic application for disk degeneration. PMID:24876775

Yang, Xinlin; Jin, Li; Yao, Lu; Shen, Francis H; Shimer, Adam L; Li, Xudong

2014-01-01

60

A Review of Secondary Photoreceptor Degenerations in Systemic Disease.  

PubMed

Photoreceptor neuronal degenerations are common and incurable causes of human blindness with one in 2000 affected. Approximately, half of all patients are associated with known mutations in more than 200 disease genes. Most retinal degenerations are restricted to the retina (primary retinal degeneration) but photoreceptor degeneration can also be found in a wide variety of systemic and syndromic diseases. These are called secondary retinal degenerations. We review several well-known systemic diseases with retinal degenerations (RD). We discuss RD with hearing loss, RD with brain disease, and RD with musculoskeletal disease. We then postulate which retinal degenerations may also have previously undetected systemic features. Emerging new and exciting evidence is showing that ubiquitously expressed genes associated with multitissue syndromic disorders may also harbor mutations that cause isolated primary retinal degeneration. Examples are RPGR, CEP290, CLN3, MFSD5, and HK1 mutations that cause a wide variety of primary retinal degenerations with intact systems. PMID:25475108

Mysore, Naveen; Koenekoop, Jamie; Li, Shen; Ren, Huanan; Keser, Vafa; Lopez-Solache, Irma; Koenekoop, Robert K

2014-12-01

61

Autophagy in axonal and dendritic degeneration  

PubMed Central

Axonal and dendritic degeneration is a common, early pathological feature of many neurodegenerative disorders and thought to be regulated by mechanisms distinct from that of the soma death. The unique structures of axons and dendrites (collectively neurites) may cause them to be particularly vulnerable to the accumulation of protein aggregates and damaged organelles. Autophagy is a known catabolic mechanism whereby cells clear protein aggregates and damaged organelles. Basal autophagy occurs continuously as a housekeeping function, and can be acutely expanded in response to various stress or injuries. Emerging evidence shows that insufficient or excessive autophagy contributes to neuritic degeneration. Here, we review the recent progress that has begun to reveal the role of autophagy in neuritic functions and degeneration. PMID:23639383

Yang, Yi; Coleman, Michael; Zhang, Lihui; Zheng, Xiaoxiang; Yue, Zhenyu

2013-01-01

62

Ill-posedness of degenerate dispersive equations  

NASA Astrophysics Data System (ADS)

In this paper we provide numerical and analytical evidence that some degenerate dispersive partial differential equations are ill-posed. Specifically we study the K (2, 2) equation ut = (u2)xxx + (u2)x and the ‘degenerate Airy’ equation ut = 2uuxxx. For K (2, 2) our results are computational in nature: we conduct a series of numerical simulations which demonstrate that data which is very small in H2 can be of unit size at a fixed time which is independent of the data's size. For the degenerate Airy equation, our results are fully rigorous: we prove the existence of a compactly supported self-similar solution which, when combined with certain scaling invariances, implies ill-posedness (also in H2).

Ambrose, David M.; Simpson, Gideon; Wright, J. Douglas; Yang, Dennis G.

2012-09-01

63

Degenerate Quantum Codes for Pauli Channels  

E-print Network

A striking feature of quantum error correcting codes is that they can sometimes be used to correct more errors than they can uniquely identify. Such degenerate codes have long been known, but have remained poorly understood. We provide a heuristic for designing degenerate quantum codes for high noise rates, which is applied to generate codes that can be used to communicate over almost any Pauli channel at rates that are impossible for a nondegenerate code. The gap between nondegenerate and degenerate code performance is quite large, in contrast to the tiny magnitude of the only previous demonstration of this effect. We also identify a channel for which none of our codes outperform the best nondegenerate code and show that it is nevertheless quite unlike any channel for which nondegenerate codes are known to be optimal.

Graeme Smith; John A. Smolin

2006-04-14

64

Pathogenesis of tendinopathies: inflammation or degeneration?  

PubMed Central

The intrinsic pathogenetic mechanisms of tendinopathies are largely unknown and whether inflammation or degeneration has the prominent role is still a matter of debate. Assuming that there is a continuum from physiology to pathology, overuse may be considered as the initial disease factor; in this context, microruptures of tendon fibers occur and several molecules are expressed, some of which promote the healing process, while others, including inflammatory cytokines, act as disease mediators. Neural in-growth that accompanies the neovessels explains the occurrence of pain and triggers neurogenic-mediated inflammation. It is conceivable that inflammation and degeneration are not mutually exclusive, but work together in the pathogenesis of tendinopathies. PMID:19591655

Abate, Michele; Gravare-Silbernagel, Karin; Siljeholm, Carl; Di Iorio, Angelo; De Amicis, Daniele; Salini, Vincenzo; Werner, Suzanne; Paganelli, Roberto

2009-01-01

65

Kinematic control of robot with degenerate wrist  

NASA Technical Reports Server (NTRS)

Kinematic resolved rate equations allow an operator with visual feedback to dynamically control a robot hand. When the robot wrist is degenerate, the computed joint angle rates exceed operational limits, and unwanted hand movements can result. The generalized matrix inverse solution can also produce unwanted responses. A method is introduced to control the robot hand in the region of the degenerate robot wrist. The method uses a coordinated movement of the first and third joints of the robot wrist to locate the second wrist joint axis for movement of the robot hand in the commanded direction. The method does not entail infinite joint angle rates.

Barker, L. K.; Moore, M. C.

1984-01-01

66

Snowflake degeneration of an intraocular lens.  

PubMed

Snowflake degeneration of intraocular lenses is a recently recognized late postoperative complication of cataract surgery. All known cases reported to date in the literature have involved polymethyl methacrylate (PMMA) lens optic material. Reported herein is an atypical variant of snowflake degeneration of a PMMA posterior chamber intraocular lens in an 81-year-old woman, 7 years post implantation. The aetiology of the atypical late opacification of the intraocular lens is this case is unclear, and no clinical risk factors appear to have been identified. PMID:15498068

Garrott, Helen; O'Day, Justin

2004-10-01

67

Two stream instabilities in degenerate quantum plasmas  

E-print Network

The quantum mechanical effect on the plasma two-stream instability is studied based on the dielectric function approach. The analysis suggests that the degenerate plasma relevant to the inertial confinement fusion behaves differently from classical plasmas when the electron drift velocity is comparable to the Fermi velocity. For high wave vector comparable to the Fermi wave vector, the degenerate quantum plasma has larger regime of the two-stream instabilities than the classical plasma. A regime, where the plasma waves with the frequency larger than 1.5 times of the Langmuir wave frequency become unstable to the two-stream instabilities, is identified.

S. Son

2013-10-18

68

Impaired Vascular Contractility and Aortic Wall Degeneration in Fibulin-4 Deficient Mice: Effect of Angiotensin II Type 1 (AT1) Receptor Blockade  

PubMed Central

Medial degeneration is a key feature of aneurysm disease and aortic dissection. In a murine aneurysm model we investigated the structural and functional characteristics of aortic wall degeneration in adult fibulin-4 deficient mice and the potential therapeutic role of the angiotensin (Ang) II type 1 (AT1) receptor antagonist losartan in preventing aortic media degeneration. Adult mice with 2-fold (heterozygous Fibulin-4+/R) and 4-fold (homozygous Fibulin-4R/R) reduced expression of fibulin-4 displayed the histological features of cystic media degeneration as found in patients with aneurysm or dissection, including elastin fiber fragmentation, loss of smooth muscle cells, and deposition of ground substance in the extracellular matrix of the aortic media. The aortic contractile capacity, determined by isometric force measurements, was diminished, and was associated with dysregulation of contractile genes as shown by aortic transcriptome analysis. These structural and functional alterations were accompanied by upregulation of TGF-? signaling in aortas from fibulin-4 deficient mice, as identified by genome-scaled network analysis as well as by immunohistochemical staining for phosphorylated Smad2, an intracellular mediator of TGF-?. Tissue levels of Ang II, a regulator of TGF-? signaling, were increased. Prenatal treatment with the AT1 receptor antagonist losartan, which blunts TGF-? signaling, prevented elastic fiber fragmentation in the aortic media of newborn Fibulin-4R/R mice. Postnatal losartan treatment reduced haemodynamic stress and improved lifespan of homozygous knockdown fibulin-4 animals, but did not affect aortic vessel wall structure. In conclusion, the AT1 receptor blocker losartan can prevent aortic media degeneration in a non-Marfan syndrome aneurysm mouse model. In established aortic aneurysms, losartan does not affect aortic architecture, but does improve survival. These findings may extend the potential therapeutic application of inhibitors of the renin-angiotensin system to the preventive treatment of aneurysm disease. PMID:21858106

Moltzer, Els; te Riet, Luuk; Swagemakers, Sigrid M. A.; van Heijningen, Paula M.; Vermeij, Marcel; van Veghel, Richard; Bouhuizen, Angelique M.; van Esch, Joep H. M.; Lankhorst, Stephanie; Ramnath, Natasja W. M.; de Waard, Monique C.; Duncker, Dirk J.; van der Spek, Peter J.; Rouwet, Ellen V.; Danser, A. H. Jan; Essers, Jeroen

2011-01-01

69

Impaired vascular contractility and aortic wall degeneration in fibulin-4 deficient mice: effect of angiotensin II type 1 (AT1) receptor blockade.  

PubMed

Medial degeneration is a key feature of aneurysm disease and aortic dissection. In a murine aneurysm model we investigated the structural and functional characteristics of aortic wall degeneration in adult fibulin-4 deficient mice and the potential therapeutic role of the angiotensin (Ang) II type 1 (AT(1)) receptor antagonist losartan in preventing aortic media degeneration. Adult mice with 2-fold (heterozygous Fibulin-4(+/R)) and 4-fold (homozygous Fibulin-4(R/R)) reduced expression of fibulin-4 displayed the histological features of cystic media degeneration as found in patients with aneurysm or dissection, including elastin fiber fragmentation, loss of smooth muscle cells, and deposition of ground substance in the extracellular matrix of the aortic media. The aortic contractile capacity, determined by isometric force measurements, was diminished, and was associated with dysregulation of contractile genes as shown by aortic transcriptome analysis. These structural and functional alterations were accompanied by upregulation of TGF-? signaling in aortas from fibulin-4 deficient mice, as identified by genome-scaled network analysis as well as by immunohistochemical staining for phosphorylated Smad2, an intracellular mediator of TGF-?. Tissue levels of Ang II, a regulator of TGF-? signaling, were increased. Prenatal treatment with the AT(1) receptor antagonist losartan, which blunts TGF-? signaling, prevented elastic fiber fragmentation in the aortic media of newborn Fibulin-4(R/R) mice. Postnatal losartan treatment reduced haemodynamic stress and improved lifespan of homozygous knockdown fibulin-4 animals, but did not affect aortic vessel wall structure. In conclusion, the AT(1) receptor blocker losartan can prevent aortic media degeneration in a non-Marfan syndrome aneurysm mouse model. In established aortic aneurysms, losartan does not affect aortic architecture, but does improve survival. These findings may extend the potential therapeutic application of inhibitors of the renin-angiotensin system to the preventive treatment of aneurysm disease. PMID:21858106

Moltzer, Els; te Riet, Luuk; Swagemakers, Sigrid M A; van Heijningen, Paula M; Vermeij, Marcel; van Veghel, Richard; Bouhuizen, Angelique M; van Esch, Joep H M; Lankhorst, Stephanie; Ramnath, Natasja W M; de Waard, Monique C; Duncker, Dirk J; van der Spek, Peter J; Rouwet, Ellen V; Danser, A H Jan; Essers, Jeroen

2011-01-01

70

Constitutive activation of phototransduction by K296E opsin is not a cause of photoreceptor degeneration.  

PubMed Central

The missense mutation Lys-296-->Glu (K296E) in the rhodopsin gene produces an opsin with no chromophore binding site and therefore is not activated by light. Nevertheless, the mutant opsin constitutively activates transducin in vitro and causes photoreceptor degeneration in vivo, possibly by continuously activating the phototransduction cascade, analogous to constant exposure to environmental light. We studied the K296E mutation in eight lines of transgenic mice. Each line developed photoreceptor degeneration with the rate of degeneration increasing monotonically as the ratio of mutant:wild-type opsin mRNA increased. At no time in the course of degeneration was there endogenous light adaptation in the retina as measured by the electroretinogram. The mutant opsin was found to be invariably phosphorylated and stably bound to arrestin. Light-independent activation of transducin was demonstrated only after the removal of arrestin and dephosphorylation of K296E opsin. Thus, K296E opsin in vivo does not activate the phototransduction cascade because it is shut off by photoreceptor inactivation mechanisms. Our data show that the K296E mutation does not cause photoreceptor degeneration by continuous activation of phototransduction. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:7724596

Li, T; Franson, W K; Gordon, J W; Berson, E L; Dryja, T P

1995-01-01

71

Driving and Age-Related Macular Degeneration  

PubMed Central

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, and considers directions for future research. PMID:20046818

Owsley, Cynthia; McGwin, Gerald

2009-01-01

72

Ecological transition predictably associated with gene degeneration.  

PubMed

Gene degeneration or loss can significantly contribute to phenotypic diversification, but may generate genetic constraints on future evolutionary trajectories, potentially restricting phenotypic reversal. Such constraints may manifest as directional evolutionary trends when parallel phenotypic shifts consistently involve gene degeneration or loss. Here, we demonstrate that widespread parallel evolution in Penstemon from blue to red flowers predictably involves the functional inactivation and degeneration of the enzyme flavonoid 3',5'-hydroxylase (F3'5'H), an anthocyanin pathway enzyme required for the production of blue floral pigments. Other types of genetic mutations do not consistently accompany this phenotypic shift. This pattern may be driven by the relatively large mutational target size of degenerative mutations to this locus and the apparent lack of associated pleiotropic effects. The consistent degeneration of F3'5'H may provide a mechanistic explanation for the observed asymmetry in the direction of flower color evolution in Penstemon: Blue to red transitions are common, but reverse transitions have not been observed. Although phenotypic shifts in this system are likely driven by natural selection, internal constraints may generate predictable genetic outcomes and may restrict future evolutionary trajectories. PMID:25371436

Wessinger, Carolyn A; Rausher, Mark D

2015-02-01

73

The Wnt signaling pathway in retinal degenerations.  

PubMed

The retina is a complex tissue composed of multiple interconnected cell layers, highly specialized for transforming light and color into electrical signals perceived by the brain. Damage or death of the primary light-sensing cells, the photoreceptors, results in devastating effects on vision. Despite the identification of numerous mutations that cause inherited retinal degenerations, the cellular and molecular mechanisms leading from the primary mutations to photoreceptor apoptosis are not understood. Wnt signaling has essential regulatory functions in a wide variety of critical developmental processes. Our research and others' have suggested that the Wnt pathway may be involved in retinal degeneration. Wnt ligands regulate developmental death of Drosophila photoreceptors, dysregulated Wnt signaling is involved in neuronal degeneration elsewhere in the central nervous system and Wnts control the expression of pro-survival growth factors in mammalian tissues. Additionally, altered expression of Wnt pathway genes, including the anti-apoptotic Wnt signaling regulator Dickkopf 3 (Dkk3), were observed during photoreceptor loss. This review examines the evidence and develops a model proposing a pro-survival role for Wnt signaling during photoreceptor injury. Because manipulating Wnt signaling has been demonstrated to have therapeutic potential for the treatment of Alzheimers disease, understanding the involvement of Wnts in photoreceptor death will determine whether targeting the Wnt pathway should also be considered as a possible therapeutic strategy for retinal degenerations. PMID:16012046

Hackam, Abigail S

2005-06-01

74

Genetic susceptibility to age related macular degeneration  

Microsoft Academic Search

Age related macular degeneration (AMD) is the leading cause of visual impairment in the elderly and a major cause of blindness in the developed world. The disease can take two forms, geographic atrophy and choroidal neovascularisation. The pathogenesis of AMD is poorly understood. There are undoubtedly environmental and other risk factors involved and the adverse effect of smoking is well

John R W Yates; Anthony T Moore

2000-01-01

75

Admissibility Conditions for Degenerate Cyclotomic BMW Algebras  

Microsoft Academic Search

We study admissibility conditions for the parameters of degenerate cyclotomic\\u000aBMW algebras. We show that the u-admissibility condition of Ariki, Mathas and\\u000aRui is equivalent to a simple module theoretic condition.

Frederick M. Goodman

2009-01-01

76

Affine and degenerate affine BMW algebras: Actions on tensor space  

E-print Network

Affine and degenerate affine BMW algebras: Actions on tensor space Zajj Daugherty Department Actions of classical type tantalizers 8 2.1 The degenerate affine BMW algebra action . . . . . . . . . . . . . . . . . . . . . 13 2.2 The affine BMW algebra action . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 3

Ram, Arun

77

Family-Specific Degenerate Primer Design: A Tool to Design Consensus Degenerated Oligonucleotides  

PubMed Central

Designing degenerate PCR primers for templates of unknown nucleotide sequence may be a very difficult task. In this paper, we present a new method to design degenerate primers, implemented in family-specific degenerate primer design (FAS-DPD) computer software, for which the starting point is a multiple alignment of related amino acids or nucleotide sequences. To assess their efficiency, four different genome collections were used, covering a wide range of genomic lengths: Arenavirus (10 × 104 nucleotides), Baculovirus (0.9 × 105 to 1.8 × 105?bp), Lactobacillus sp. (1 × 106 to 2 × 106?bp), and Pseudomonas sp. (4 × 106 to 7 × 106?bp). In each case, FAS-DPD designed primers were tested computationally to measure specificity. Designed primers for Arenavirus and Baculovirus were tested experimentally. The method presented here is useful for designing degenerate primers on collections of related protein sequences, allowing detection of new family members. PMID:23533783

Goñi, Sandra Elizabeth; Lozano, Mario Enrique

2013-01-01

78

Interferon-? induces progressive nigrostriatal degeneration and basal ganglia calcification.  

PubMed

We found that CNS-directed expression of interferon-? (IFN-?) resulted in basal ganglia calcification, reminiscent of human idiopathic basal ganglia calcification (IBGC), and nigrostriatal degeneration. Our results indicate that IFN-? mediates age-progressive nigrostriatal degeneration in the absence of exogenous stressors. Further study of this model may provide insight into selective nigrostriatal degeneration in human IBGC and other Parkinson syndromes. PMID:21572432

Chakrabarty, Paramita; Ceballos-Diaz, Carolina; Lin, Wen-Lang; Beccard, Amanda; Jansen-West, Karen; McFarland, Nikolaus R; Janus, Christopher; Dickson, Dennis; Das, Pritam; Golde, Todd E

2011-06-01

79

Interferon-? induces progressive nigrostriatal degeneration and basal ganglia calcification  

PubMed Central

We report that CNS directed expression of Interferon (IFN) -? results in basal ganglia calcification, reminiscent of human idiopathic basal ganglia calcification (IBGC), and nigrostriatal degeneration. Our results show that IFN-? mediates age-progressive nigrostriatal degeneration in the absence of exogenous stressors. Further study of this model may provide unique insight into selective nigrostriatal degeneration in human IBGC and other Parkinson syndromes. PMID:21572432

Chakrabarty, Paramita; Ceballos-Diaz, Carolina; Lin, Wen-Lang; Beccard, Amanda; Jansen-West, Karen; McFarland, Nikolaus R; Janus, Christopher; Dickson, Dennis; Das, Pritam; Golde, Todd E

2013-01-01

80

Influences of osteoporosis and disc degeneration on lumbar spinal stability  

Microsoft Academic Search

Disc degeneration and osteoporosis are two main factors affecting the elderly and impacting the quality of life. The aims of this study were to provide the information on mechanical changes resulting from disc degeneration and osteoporosis and further to understand their roles in segmental instability. The influences of disc degeneration and osteoporosis were investigated using a 3?dimensional finite element model

2003-01-01

81

Iron homeostasis and toxicity in retinal degeneration  

PubMed Central

Iron is essential for many metabolic processes but can also cause damage. As a potent generator of hydroxyl radical, the most reactive of the free radicals, iron can cause considerable oxidative stress. Since iron is absorbed through diet but not excreted except through menstruation, total body iron levels build up with age. Macular iron levels increase with age, in both men and women. This iron has the potential to contribute to retinal degeneration. Here we present an overview of the evidence suggesting that iron may contribute to retinal degenerations. Intraocular iron foreign bodies cause retinal degeneration. Retinal iron buildup resulting from hereditary iron homeostasis disorders aceruloplasminemia, Friedreich’s Ataxia, and panthothenate kinase associated neurodegeneration cause retinal degeneration. Mice with targeted mutation of the iron exporter ceruloplasmin have age-dependent retinal iron overload and a resulting retinal degeneration with features of age-related macular degeneration (AMD). Post mortem retinas from patients with AMD have more iron and the iron carrier transferrin than age- matched controls. Over the past ten years much has been learned about the intricate network of proteins involved in iron handling. Many of these, including transferrin, transferrin receptor, divalent metal transporter 1, ferritin, ferroportin, ceruloplasmin, hephaestin, iron regulatory protein, and histocompatibility leukocyte antigen class I-like protein involved in iron homeostasis (HFE) have been found in the retina. Some of these proteins have been found in the cornea and lens as well. Levels of the iron carrier transferrin are high in the aqueous and vitreous humors. The functions of these proteins in other tissues, combined with studies on cultured ocular tissues, genetically engineered mice, and eye exams on patients with hereditary iron diseases provide clues regarding their ocular functions. Iron may play a role in a broad range of ocular diseases, including glaucoma, cataract, AMD, and conditions causing intraocular hemorrhage. While iron deficiency must be prevented, the therapeutic potential of limiting iron induced ocular oxidative damage is high. Systemic, local, or topical iron chelation with an expanding repertoire of drugs has clinical potential. PMID:17921041

He, Xining; Hahn, Paul; Iacovelli, Jared; Wong, Robert; King, Chih; Bhisitkul, Robert; Massaro-Giordano, Mina; Dunaief, Joshua L.

2007-01-01

82

Why do some intervertebral discs degenerate, when others (in the same spine) do not?  

PubMed

This review suggests why some discs degenerate rather than age normally. Intervertebral discs are avascular pads of fibrocartilage that allow movement between vertebral bodies. Human discs have a low cell density and a limited ability to adapt to mechanical demands. With increasing age, the matrix becomes yellowed, fibrous, and brittle, but if disc structure remains intact, there is little impairment in function, and minimal ingrowth of blood vessels or nerves. Approximately half of old lumbar discs degenerate in the sense of becoming physically disrupted. The posterior annulus and lower lumbar discs are most affected, presumably because they are most heavily loaded. Age and genetic inheritance can weaken discs to such an extent that they are physically disrupted during everyday activities. Damage to the endplate or annulus typically decompresses the nucleus, concentrates stress within the annulus, and allows ingrowth of nerves and blood vessels. Matrix disruption progresses by mechanical and biological means. The site of initial damage leads to two disc degeneration "phenotypes": endplate-driven degeneration is common in the upper lumbar and thoracic spine, and annulus-driven degeneration is common at L4-S1. Discogenic back pain can be initiated by tissue disruption, and amplified by inflammation and infection. Healing is possible in the outer annulus only, where cell density is highest. We conclude that some discs degenerate because they are disrupted by excessive mechanical loading. This can occur without trauma if tissues are weakened by age and genetic inheritance. Moderate mechanical loading, in contrast, strengthens all spinal tissues, including discs. Clin. Anat. 28:195-204, 2015. © 2014 Wiley Periodicals, Inc. PMID:24753325

Adams, Michael A; Lama, Polly; Zehra, Uruj; Dolan, Patricia

2015-03-01

83

Role of Rhodopsin and Arrestin Phosphorylation in Retinal Degeneration of Drosophila  

PubMed Central

Arrestins belong to a family of multifunctional adaptor proteins that regulate internalization of diverse receptors including G-protein coupled receptors (GPCRs). Defects associated with endocytosis of GPCRs have been linked to human diseases. We employed eGFP-tagged arrestin 2 (Arr2) to monitor the turnover of the major rhodopsin (Rh1) in live Drosophila. We demonstrate that during degeneration of norpAP24 photoreceptors the loss of Rh1 is parallel to the disappearance of rhabdomeres, the specialized visual organelle that houses Rh1. The cause of degeneration in norpAP24 is due to a failure to activate CaMKII and RDGC because of a loss of light-dependent Ca2+ entry. A lack of activation in CaMKII, which phosphorylates Arr2, leads to hypophosphorylated Arr2, while a lack of activation of RDGC, which dephosphorylates Rh1, results in hyperphosphorylated Rh1. We investigated how reversible phosphorylation of Rh1 and Arr2 contributes to photoreceptor degeneration. To uncover the consequence underlying a lack of CaMKII activation, we characterized ala1 flies in which CaMKII was suppressed by an inhibitory peptide, and showed that morphology of rhabdomeres was not affected. In contrast, we found that expression of phosphorylation deficient Rh1s, which either lack the C-terminus or contain Ala substitution in the phosphorylation sites, was able to prevent degeneration of norpAP24 photoreceptors. This suppression is not due to a loss of Arr2 interaction. Importantly, co-expression of these modified Rh1s offered protective effects, which greatly delayed photoreceptor degeneration. Taken together, we conclude that phosphorylation of Rh1 is the major determinant that orchestrates its internalization leading to retinal degeneration. PMID:22855823

Kristaponyte, Inga; Hong, Yuan; Lu, Haiqin; Shieh, Bih-Hwa

2012-01-01

84

Small automorphic representations and degenerate Whittaker vectors  

E-print Network

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.

Gustafsson, Henrik P A; Persson, Daniel

2014-01-01

85

Degenerate Odd Poisson Bracket on Grassmann Variables  

NASA Astrophysics Data System (ADS)

A linear degenerate odd Poisson bracket (antibracket) realized solely on Grassmann variables is presented. It is revealed that this bracket has at once three nilpotent $\\Delta$-like differential operators of the first, the second and the third orders with respect to the Grassmann derivatives. It is shown that these $\\Delta$-like operators together with the Grassmann-odd nilpotent Casimir function of this bracket form a finite-dimensional Lie superalgebra.

Soroka, V. A.

2000-05-01

86

Neovascular Age-Related Macular Degeneration  

Microsoft Academic Search

Purpose: Neovascular age-related macular degeneration (AMD) is a leading cause of blindness, with an increasing incidence as the elderly population expands. Large, multi-center, randomized, clinical trials have been conducted exploring the safety and efficacy of anti-VEGF treatments. This paper aims to discuss the safety and efficacy of pegaptanib, ranibizumab, aflibercept and bevacizumab. New therapeutic agents and treatment strategies are also

Daniele Veritti; Valentina Sarao; Paolo Lanzetta

2012-01-01

87

Propagation of Disturbances in Degenerate Quantum Systems  

E-print Network

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 affect the propagation of disturbances. We find that even in the case of approximate degeneracy, a disturbance can be propagated throughout a finite system.

Nicholas Chancellor; Stephan Haas

2011-07-06

88

Self-assembly with degenerate prototropy.  

PubMed

This work describes a rational approach for addressing the prototropy-related problems in heterocycle-based self-assembling systems by the use of degenerate prototropy. As a proof of principle, the utility of degenerate prototropy is demonstrated herein by developing heterocycle-based AADD-type self-assembling modules that exist as "single set of protameric pair (duplex)" in both solution and solid states. These self-assembling modules are quickly accessible in good yield by reacting 2-amino-5,5-disubstituted-1H-pyrimidine-4,6-diones, available in one step by the condensation of alpha,alpha-dialkyl malonates and free guanidine, with isocyanates. Evidence from NMR spectroscopy, ESI mass spectrometry, and single-crystal X-ray diffraction studies confirmed the formation of molecular duplexes. The effect of electronic repulsion in duplex formation is also investigated. Their ready synthetic accessibility, remarkably high propensity to crystal formation, and the novel property of degenerate prototropy would make these novel self-assembling molecules promising candidates for many proposed applications. PMID:16050710

Baruah, Pranjal K; Gonnade, Rajesh; Phalgune, Usha D; Sanjayan, Gangadhar J

2005-08-01

89

Facet joint orientation, facet and costovertebral joint osteoarthrosis, disc degeneration, vertebral body osteophytosis, and Schmorl's nodes in the thoracolumbar junctional region of cadaveric spines.  

PubMed

The disc degeneration in the thoracolumbar junctional region (T10-L1) of 37 male cadaveric spines was recorded with the use of discography. From 24 of these spines the facet joint orientation and degenerative findings of the facet and costovertebral joints, vertebral bodies (osteophytosis) and discs, and Schmorl's nodes were recorded directly from bones. At T11-12, the most common site for the transitional zone between thoracic and lumbar facet type, there was a marked variation in the orientation of facets. The occurrence of degenerative findings and Schmorl's nodes at the three levels in the region differed. At T10-11, disc degeneration, vertebral body osteophytosis, and Schmorl's nodes were most common (anterior degeneration). At T12-L1, facet and costovertebral joint degeneration were dominant (posterior degeneration). At T11-12, disc degeneration, vertebral body osteophytosis, Schmorl's nodes, and facet and costovertebral joint degeneration all occurred (anterior and posterior degeneration). The results point to a pathoanatomic association between degenerative changes and facet orientation. PMID:3629397

Malmivaara, A; Videman, T; Kuosma, E; Troup, J D

1987-06-01

90

Wallerian degeneration: the innate-immune response to traumatic nerve injury  

PubMed Central

Traumatic injury to peripheral nerves results in the loss of neural functions. Recovery by regeneration depends on the cellular and molecular events of Wallerian degeneration that injury induces distal to the lesion site, the domain through which severed axons regenerate back to their target tissues. Innate-immunity is central to Wallerian degeneration since innate-immune cells, functions and molecules that are produced by immune and non-immune cells are involved. The innate-immune response helps to turn the peripheral nerve tissue into an environment that supports regeneration by removing inhibitory myelin and by upregulating neurotrophic properties. The characteristics of an efficient innate-immune response are rapid onset and conclusion, and the orchestrated interplay between Schwann cells, fibroblasts, macrophages, endothelial cells, and molecules they produce. Wallerian degeneration serves as a prelude for successful repair when these requirements are met. In contrast, functional recovery is poor when injury fails to produce the efficient innate-immune response of Wallerian degeneration. PMID:21878125

2011-01-01

91

TGF-?1 is critical for Wallerian degeneration after rat sciatic nerve injury.  

PubMed

Wallerian degeneration (WD) is a process of axonal degeneration distal to the injury site followed by a robust regenerative response. It involves degeneration and regeneration which can be directly induced by nerve injury and activated by transcription factors. Although WD has been studied extensively, the precise mechanisms of transcription factors regulating WD are still elusive. In this study, we reported the effect of transforming growth factor-?1 (TGF-?1) on WD after rat sciatic nerve injury. The data showed that TGF-?1 may express in injured rat sciatic nerve and cultured Schwann cells (SCs). Knock down of TGF-?1 expressions resulted in the reduction of SC proliferation and apoptosis, up regulation of cytokines and Smad2, 4. Enhanced expression of TGF-?1 could promote SC proliferation and apoptosis, down regulation of cytokines and Smad2, 4. Altered expressions of TGF-?1 may affect Smad and AKT but not c-Jun and extracellular regulated protein kinase (ERK) pathways. Our results revealed the role of TGF-?1 on WD and provided the basis for the molecular mechanisms of TGF-?1-regulated nerve degeneration and/or regeneration. PMID:25451291

Li, M; Zhang, P; Li, H; Zhu, Y; Cui, S; Yao, D

2015-01-22

92

[Progressive centripetal degeneration in polyneuropathies (author's transl)].  

PubMed

This is a clinicopathologic report on three patients with sensory polyneuropathies of different origin. Sensory loss involved all four limbs reaching the upper third of the thighs and the elbow level or higher, in all three patients. In addition to the limbs the central region of the anterior aspect of the trunk, from lower abdomen up to level T2, and on the top of the scalp were involved. There was minimal weakness. This pattern of sensory deficit can best be explained by a length dependent degeneration of fibers. Familial amyloidosis, Portugese type, was responsible for the neuropathy in the first patient, diabetes mellitus in the second and alcoholism in the third one. On teased nerve fiber study, single regenerating fibers were isolated on sural nerve biopsy specimens from patients 1 and 2. Segmental demyelination and/or remyelination occurred in 11 per cent of the fibres in patient 1, in 36 per cent in patient 2 and in 4 of the 19 fibres isolated in patient 3. On cross sections of nerve specimens embedded in Epon there was a striking loss of myelinated fibres which was less important and predominated on smaller fibres in patients 1 and 2. On electron microscopic examination loss of unmyelinated fibres was conspicuous in all three patients. On single fiber studies as well as on sections of embedded specimens, myelinated fibres occasionally showed demyelination in contact to amyloid deposits. The present study demonstrates that in this pattern of neuropathy degeneration of myelinated fibers begins in the distal part of longest axons and may be associated with axonal sprouting in more proximal parts of degenerating axons. As the neuropathy progresses axons of shorter and shorter length become involved. PMID:6275481

Saïd, G

1981-01-01

93

Retinoid receptors trigger neuritogenesis in retinal degenerations  

PubMed Central

Anomalous neuritogenesis is a hallmark of neurodegenerative disorders, including retinal degenerations, epilepsy, and Alzheimer's disease. The neuritogenesis processes result in a partial reinnervation, new circuitry, and functional changes within the deafferented retina and brain regions. Using the light-induced retinal degeneration (LIRD) mouse model, which provides a unique platform for exploring the mechanisms underlying neuritogenesis, we found that retinoid X receptors (RXRs) control neuritogenesis. LIRD rapidly triggered retinal neuron neuritogenesis and up-regulated several key elements of retinoic acid (RA) signaling, including retinoid X receptors (RXRs). Exogenous RA initiated neuritogenesis in normal adult retinas and primary retinal cultures and exacerbated it in LIRD retinas. However, LIRD-induced neuritogenesis was partly attenuated in retinol dehydrogenase knockout (Rdh12?/?) mice and by aldehyde dehydrogenase inhibitors. We further found that LIRD rapidly increased the expression of glutamate receptor 2 and ? Ca2+/calmodulin-dependent protein kinase II (?CaMKII). Pulldown assays demonstrated interaction between ?CaMKII and RXRs, suggesting that CaMKII pathway regulates the activities of RXRs. RXR antagonists completely prevented and RXR agonists were more effective than RA in inducing neuritogenesis. Thus, RXRs are in the final common path and may be therapeutic targets to attenuate retinal remodeling and facilitate global intervention methods in blinding diseases and other neurodegenerative disorders.—Lin, Y., Jones, B. W., Liu, A., Tucker, J. F., Rapp, K., Luo, L., Baehr, W., Bernstein, P. S., Watt, C. B., Yang, J.-H., Shaw, M. V., Marc, R. E. Retinoid receptors trigger neuritogenesis in retinal degenerations. PMID:21940995

Lin, Yanhua; Jones, Bryan W.; Liu, Aihua; Tucker, James F.; Rapp, Kevin; Luo, Ling; Baehr, Wolfgang; Bernstein, Paul S.; Watt, Carl B.; Yang, Jia-Hui; Shaw, Marguerite V.; Marc, Robert E.

2012-01-01

94

Affine and degenerate affine BMW algebras: Actions on tensor space  

E-print Network

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.

Daugherty, Zajj; Virk, Rahbar

2012-01-01

95

Affine and degenerate affine BMW algebras: The center  

E-print Network

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...

Daugherty, Zajj; Virk, Rahbar

2011-01-01

96

Degenerate stars. XII - Recognition of hot nondegenerates  

NASA Astrophysics Data System (ADS)

Fifty-one newly observed degenerate stars and 14 nondegenerates include 13 faint red stars, most of which do not show any lines except DF, Gr 554. Hot subdwarfs and an X-ray source are discussed along with the problem of low-resolution spectroscopic classification of dense hot stars. The multichannel spectrum of the carbon-rich magnetic star LP 790-29 is examined by fitting the undisturbed parts of the spectrum to a black body of 7625 K by the least squares method; the Swan bands absorb 600 A of the spectrum assuming that the blocked radiation is redistributed in the observed region.

Greenstein, J. L.

1980-12-01

97

Degenerate thermal pulses in AGB stars  

E-print Network

We report on the discovery of a new kind of thermal pulse in intermediate mass AGB stars. Deep dredge-up during normal thermal pulses on the AGB leads to the formation of a long, unburnt tail to the helium profile. Eventually the tail ignites under partially degenerate conditions producing a strong shell flash with very deep subsequent dredge-up. The carbon content of the intershell convective region (X_C ~ 0.6) is substantially higher than in a normal thermal pulse (X_C ~ 0.25) and about 4 times more carbon is dredged-up than in a normal pulse.

Cheryl Frost; John Lattanzio; Peter Wood

1998-03-05

98

Cone Degeneration Following Rod Ablation in a Reversible Model of Retinal Degeneration  

PubMed Central

Purpose. Amphibian retinas regenerate after injury, making them ideal for studying the mechanisms of retinal regeneration, but this leaves their value as models of retinal degeneration in question. The authors asked whether the initial cellular changes after rod loss in the regenerative model Xenopus laevis mimic those observed in nonregenerative models. They also asked whether rod loss was reversible. Methods. The authors generated transgenic X. laevis expressing the Escherichia coli enzyme nitroreductase (NTR) under the control of the rod-specific rhodopsin (XOP) promoter. NTR converts the antibiotic metronidazole (Mtz) into an interstrand DNA cross-linker. A visually mediated behavioral assay and immunohistochemistry were used to determine the effects of Mtz on the vision and retinas of XOPNTR F1 tadpoles. Results. NTR expression was detected only in the rods of XOPNTR tadpoles. Mtz treatment resulted in rapid vision loss and near complete ablation of rod photoreceptors by day 12. Müller glial cell hypertrophy and progressive cone degeneration followed rod cell ablation. When animals were allowed to recover, new rods were born and formed outer segments. Conclusions. The initial secondary cellular changes detected in the rodless tadpole retina mimic those observed in other models of retinal degeneration. The rapid and synchronous rod loss in XOPNTR animals suggested this model may prove useful in the study of retinal degeneration. Moreover, the regenerative capacity of the Xenopus retina makes these animals a valuable tool for identifying the cellular and molecular mechanisms at work in lower vertebrates with the remarkable capacity of retinal regeneration. PMID:20720220

Choi, Rene Y.; Engbretson, Gustav A.; Solessio, Eduardo C.; Jones, Georgette A.; Coughlin, Adam; Aleksic, Ilija

2011-01-01

99

Axon degeneration: Molecular mechanisms of a self-destruction pathway  

PubMed Central

Axon degeneration is a characteristic event in many neurodegenerative conditions including stroke, glaucoma, and motor neuropathies. However, the molecular pathways that regulate this process remain unclear. Axon loss in chronic neurodegenerative diseases share many morphological features with those in acute injuries, and expression of the Wallerian degeneration slow (WldS) transgene delays nerve degeneration in both events, indicating a common mechanism of axonal self-destruction in traumatic injuries and degenerative diseases. A proposed model of axon degeneration is that nerve insults lead to impaired delivery or expression of a local axonal survival factor, which results in increased intra-axonal calcium levels and calcium-dependent cytoskeletal breakdown. PMID:22232700

Medress, Zachary A.; Barres, Ben A.

2012-01-01

100

Variational functions in degenerate open quantum systems  

SciTech Connect

We have derived a Lyapunov functional for a degenerate open atomic system. This functional develops monotonically towards its stationary state. The open system is described by a Lindblad-type master equation. For the construction of the variational functional it is necessary that the Lindblad operator can be diagonalized. Since the generator of motion is non-Hermitian, diagonalization is, in general, only possible if the eigenvalues are nondegenerate. In this paper, we propose that in a physical system the biorthogonal eigenbasis of the Lindblad operator remains complete even when degeneracy is present. Thus diagonalization of the Lindblad operator, and consequently the construction of the variational functional, is still possible. We discuss the reasons and illustrate the theory of the variational functional for a driven {lambda}-type three-level atom with degenerate ground state. The degeneracy has interesting effects on the variational functional in the steady state with respect to its interpretation as an entropic quantity. In case of the driven three-level atom, the dark state turns out to be an isentropic state.

Jakob, Matthias; Stenholm, Stig [Laser Physics and Quantum Optics, Royal Institute of Technology (KTH), Alba Nova, Roslagstullsbacken 21, SE-10691 Stockholm (Sweden)

2004-04-01

101

The formation of primordial degenerate protostars  

NASA Astrophysics Data System (ADS)

Low rates of accretion (less than 10 exp -10 solar masses/yr) of metal-free gas onto a small (less than 0.15 solar masses) protostellar core allow efficient cooling of the settling gas and yield very degenerate interior conditions. The steady-state, spherically symmetric flow near such a protostar is modeled. The calculations include a shock which stands above the stellar surface, a cooling region in which bremsstrahlung is the dominant radiative mechanism, an absorption layer just above the protostellar surface in which ionizing radiation is reprocessed, and a settling region in which the newly accreted material cools and joins the hydrostatic atmosphere of the protostar. In addition, there exists an external H II-like region in the preshock region. The transition between degenerate and nondegenerate conditions is a strong function of both mass and accretion rate. Opacity in the outer layers is primarily due to collision-induced absorption. An extensive set of solutions is provided in which a given interior flux is carried by convection at large depths. Some astrophysical implications of accretion at the rates considered are briefly discussed.

Lenzuni, Paolo; Chernoff, David F.; Salpeter, Edwin E.

1992-07-01

102

Genetic susceptibility to age related macular degeneration  

PubMed Central

Age related macular degeneration (AMD) is the leading cause of visual impairment in the elderly and a major cause of blindness in the developed world. The disease can take two forms, geographic atrophy and choroidal neovascularisation. The pathogenesis of AMD is poorly understood. There are undoubtedly environmental and other risk factors involved and the adverse effect of smoking is well established. Several studies have shown that genetic factors are important but leave uncertainty about the magnitude and nature of the genetic component and whether it varies with the type of AMD. Several hereditary retinal dystrophies show similarities to AMD and these genes are potential candidate susceptibility genes. Particular interest has focused on the ABCR gene which is responsible for autosomal recessive Stargardt macular dystrophy. It has been claimed that heterozygotes for ABCR mutations are predisposed to AMD but the data are conflicting. Studies of the genes responsible for autosomal dominant Sorsby fundus dystrophy, Doyne honeycomb retinal dystrophy, and Best disease have given negative results. In one large AMD family, linkage has been reported to markers in 1q25-q31. Recent data suggest that the ApoE ?4 allele may be associated with reduced risk of AMD. A better understanding of the genetic factors in AMD would contribute to understanding the pathogenesis. If those at risk could be identified it may be possible to modify lifestyle or develop novel therapies in the presymptomatic stage to prevent disease or decrease its severity.???Keywords: age related macular degeneration; genetic susceptibility PMID:10662806

Yates, J.; Moore, A.

2000-01-01

103

Metabolic anatomy of paraneoplastic cerebellar degeneration  

SciTech Connect

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.

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

1988-06-01

104

Progressive retinal degeneration in ranch mink.  

PubMed

Retinal degeneration was prevalent in a large group of sapphire and pastel mink (Mustela vison) kept for studies on slow viral diseases. Nearly 78% of those two to eight years old were affected. The retinopathy was equally common in both sexes but more frequent in sapphires (85%) than in pastels (63%), and it was severe more often in sapphires than in pastels. By light microscopy, the primary change appeared to be progressive degeneration of fully developed photoreceptors, beginning in their outer segments. In many mink, including some younger ones, the rods and cones and outer nuclear layer had disappeared from all but the far periphery of the fundus. The inner retinal layers were spared until late in the disease, and the pigment epithelium remained essentially unchanged. The cause of the retinopathy was not established. It may represent an abiotrophy in which the structural integrity of the photoreceptors began to wane in many mink after they reached two years of age. Apart from reducing visual acuity, the retinopathy has implications for the photoperiodic control of fur growth and reproduction in this highly light-sensitive carnivore. PMID:6710807

Hadlow, W J

1984-01-01

105

Quantum Degenerate Gases of Atomic Strontium  

NASA Astrophysics Data System (ADS)

This talk will describe the production and properties of a Bose-Einstein condensate of ^84Sr and a quantum degenerate mixture of ^87Sr (fermion) and ^88Sr (boson). ^88Sr has a small negative scattering length leading to a maximum condensate size for our trapping conditions of about 10^4 atoms. ^87Sr is used to sympathetically cool ^88Sr, but it is also of interest for study of quantum degenerate Fermi gases because it has a large nuclear spin (I=9/2). Alkaline-earth metal atoms and atoms with similar electronic structure are of interest for quantum computing proposals, cold collision studies, and investigation of quantum fluids. There are a wealth of isotopes that allow mass-tuning of interactions and creation of various quantum mixtures. The two-valence electrons lead to a singlet ground state and narrow intercombination transitions to metastable triplet states, offering the promise of low-loss optical Feshbach resonances for manipulating scattering lengths. Fermions often have large nuclear spin, which is decoupled from electronic degrees of freedom and leads to a large degree of symmetry and degeneracy in the interaction Hamiltonian. Work done in collaboration with Y.N. Martinez de Escobar, P.G. Mickelson, M. Yan, B.J. DeSalvo, and S.B. Nagel, Rice University.

Killian, T. C.

2010-03-01

106

Differential Modulation of Retinal Degeneration by Ccl2 and Cx3cr1 Chemokine Signalling  

PubMed Central

Microglia and macrophages are recruited to sites of retinal degeneration where local cytokines and chemokines determine protective or neurotoxic microglia responses. Defining the role of Ccl2-Ccr2 and Cx3cl1-Cx3cr1 signalling for retinal pathology is of particular interest because of its potential role in age-related macular degeneration (AMD). Ccl2, Ccr2, and Cx3cr1 signalling defects impair macrophage trafficking, but have, in several conflicting studies, been reported to show different degrees of age-related retinal degeneration. Ccl2/Cx3cr1 double knockout (CCDKO) mice show an early onset retinal degeneration and have been suggested as a model for AMD. In order to understand phenotypic discrepancies in different chemokine knockout lines and to study how defects in Ccl2 and/or Cx3cr1 signalling contribute to the described early onset retinal degeneration, we defined primary and secondary pathological events in CCDKO mice. To control for genetic background variability, we compared the original phenotype with that of single Ccl2, Cx3cr1 and Ccl2/Cx3cr1 double knockout mice obtained from backcrosses of CCDKO with C57Bl/6 mice. We found that the primary pathological event in CCDKO mice develops in the inferior outer nuclear layer independently of light around postnatal day P14. RPE and vascular lesions develop secondarily with increasing penetrance with age and are clinically similar to retinal telangiectasia not to choroidal neovascularisation. Furthermore, we provide evidence that a third autosomal recessive gene causes the degeneration in CCDKO mice and in all affected re-derived lines and subsequently demonstrated co-segregation of the naturally occurring RD8 mutation in the Crb1 gene. By comparing CCDKO mice with re-derived CCl2?/?/Crb1Rd8/RD8, Cx3cr1?/?/Crb1Rd8/RD8 and CCl2?/?/Cx3cr1?/?/Crb1Rd8/RD8 mice, we observed a differential modulation of the retinal phenotype by genetic background and both chemokine signalling pathways. These findings indicate that CCDKO mice are not a model of AMD, but a model for an inherited retinal degeneration that is differentially modulated by Ccl2-Ccr2 and Cx3cl1-Cx3cr1 chemokine signalling. PMID:22545116

Luhmann, Ulrich F. O.; Lange, Clemens A.; Robbie, Scott; Munro, Peter M. G.; Cowing, Jill A.; Armer, Hannah E. J.; Luong, Vy; Carvalho, Livia S.; MacLaren, Robert E.; Fitzke, Frederick W.; Bainbridge, James W. B.; Ali, Robin R.

2012-01-01

107

Optimal Control for Degenerate Parabolic Equations with Logistic Growth*  

E-print Network

(x;t) of the population to be trapped is the control in our problem. We can treat zero Dirichlet (z = 0) or Neumann(no uxOptimal Control for Degenerate Parabolic Equations with Logistic Growth* by Suzanne M. Lenhart1 and Jiongmin Yong2 Abstract. This paper considers the optimal control of a degenerate parabolic partial dif

108

Optimal Control for Degenerate Parabolic Equations with Logistic Growth*  

E-print Network

) of the population to be trapped is the control in our problem. We can treat zero Dirichlet (z = 0) or Neumann (noOptimal Control for Degenerate Parabolic Equations with Logistic Growth* by Suzanne M. Lenhart 1 and Jiongmin Yong 2 Abstract. This paper considers the optimal control of a degenerate parabolic partial dif

109

Myocyte degeneration and cell death in hibernating human myocardium  

Microsoft Academic Search

Objectives. The aim of this study was to analyze the morphologic characteristics of myocyte degeneration leading to replacement fibrosis in hibernating myocardium by use of electron microscopy and immunohistochemical techniques.Background. Data on the ultrastructure and the cytoskeleton of cardiomyocytes in myocardial hibernation are scare. Incomplete or delayed functional recovery might be due to a variable degree of cardiomyocyte degeneration in

Ernst R. Schwartz; Jutta Schaper; Juergen vom Dahl; Carsten Altehoefer; Beate Grohmann; Friedrich Schoendube; Florence H. Sheehan; Rainer Uebis; Udalrich Buell; Bruno J. Messmer; Wolfgang Schaper; Peter Hanrath

1996-01-01

110

ANNULAR TEARS AND DISC DEGENERATION IN THE LUMBAR SPINE  

Microsoft Academic Search

Histology suggested that peripheral tears were due to trauma rather than biochemical degradation, and that they developed independently of nuclear degeneration. The association of peripheral annular lesions with low back pain is uncertain but our study suggests that they may have a role in the pathogenesis of discogemc pain. The degenerating human intervertebral disc shows dehydration and fraying of the

L. OSTI; B. VERNON-ROBERTS; R. MOORE; R. D. FRASER

111

VISCOSITY SOLUTIONS TO DEGENERATE COMPLEX MONGE-AMP`ERE EQUATIONS  

E-print Network

VISCOSITY SOLUTIONS TO DEGENERATE COMPLEX MONGE-AMP`ERE EQUATIONS PHILIPPE EYSSIDIEUX, VINCENT an alternative approach based on the concept of viscosity solutions and compare systematically viscosity concepts PDE approach to second-order degenerate elliptic equations is the method of viscosity solutions

Boyer, Edmond

112

Intervertebral disc (IVD): Structure, degeneration, repair and regeneration  

Microsoft Academic Search

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

Benjamin R. Whatley; Xuejun Wen

113

Conjunctival intraepithelial neoplasia with corneal furrow degeneration  

PubMed Central

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. PMID:25116776

Rishi, Pukhraj; Shields, Carol L; Eagle, Ralph C

2014-01-01

114

Odor identification in frontotemporal lobar degeneration subtypes.  

PubMed

Odor identification impairment is a feature of several neurodegenerative disorders. Although neurodegenerative changes in the frontotemporal lobar degeneration (FTLD) subtypes involve areas important for olfactory processing, data on olfactory function in these patients are limited. An 18-item, multiple-choice odor identification test developed at our memory clinic, the Motol Hospital smell test, was administered to 9 patients with behavioral variant frontotemporal dementia, 13 patients with the language variants, primary nonfluent aphasia (n = 7) and semantic dementia (n = 6), and 8 patients with progressive supranuclear palsy. Compared to the control group (n = 15), all FTLD subgroups showed significant impairment of odor identification (P < .05). The differences between the FTLD subgroups were not significant. No correlation between odor identification and neuropsychological tests results was found. Our data suggest that odor identification impairment is a symptom common to FTLD syndromes, and it seems to be based on olfactory structure damage rather than cognitive decline. PMID:24939002

Magerova, Hana; Vyhnalek, Martin; Laczo, Jan; Andel, Ross; Rektorova, Irena; Kadlecova, Alexandra; Bojar, Martin; Hort, Jakub

2014-12-01

115

Output radiation from a degenerate parametric oscillator  

E-print Network

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.

Sintayehu Tesfa

2007-02-12

116

Degenerate R-S perturbation theory  

NASA Technical Reports Server (NTRS)

A concise, systematic procedure is given for determining the Rayleigh-Schrodinger energies and wave functions of degenerate states to arbitrarily high orders even when the degeneracies of the various states are resolved in arbitrary orders. The procedure is expressed in terms of an iterative cycle in which the energy through the (2n+1)st order is expressed in terms of the partially determined wave function through the n-th order. Both a direct and an operator derivation are given. The two approaches are equivalent and can be transcribed into each other. The direct approach deals with the wave functions (without the use of formal operators) and has the advantage that it resembles the usual treatment of nondegenerate perturbations and maintains close contact with the basic physics. In the operator approach, the wave functions are expressed in terms of infinite order operators which are determined by the successive resolution of the space of the zeroth order functions.

Hirschfelder, J. O.; Certain, P. R.

1973-01-01

117

Degenerating Kähler structures and geometric quantization  

NASA Astrophysics Data System (ADS)

We review some recent results on the problem of the choice of polarization in geometric quantization. Specifically, we describe the general philosophy, developed by the author together with his collaborators, of treating real polarizations as limits of degenerating families of holomorphic polarizations. We first review briefly the general framework of geometric quantization, with a particular focus on the problem of the dependence of quantization on the choice of polarization. The problem of quantization in real polarizations is emphasized. We then describe the relation between quantization in real and Kähler polarizations in some families of symplectic manifolds, that can be explicitly quantized and that constitute an important class of examples: cotangent bundles of Lie groups, abelian varieties and toric varieties. Applications to theta functions and moduli spaces of vector bundles on curves are also reviewed.

Nunes, João P.

2014-10-01

118

Anterior insula degeneration in frontotemporal dementia  

PubMed Central

The human anterior insula is anatomically and functionally heterogeneous, containing key nodes within distributed speech–language and viscero-autonomic/social–emotional networks. The frontotemporal dementias selectively target these large-scale systems, leading to at least three distinct clinical syndromes. Examining these disorders, researchers have begun to dissect functions which rely on specific insular nodes and networks. In the behavioral variant of frontotemporal dementia, early-stage frontoinsular degeneration begets progressive “Salience Network” breakdown that leaves patients unable to model the emotional impact of their own actions or inactions. Ongoing studies seek to clarify local microcircuit- and cellular-level factors that confer selective frontoinsular vulnerability. The search for frontotemporal dementia treatments will depend on a rich understanding of insular biology and could help clarify specialized human language, social, and emotional functions. PMID:20512369

2010-01-01

119

Computer assisted characterization of cervical intervertebral disc degeneration in MRI  

NASA Astrophysics Data System (ADS)

A texture-based pattern recognition system is proposed for the automatic characterization of cervical intervertebral disc degeneration from saggital magnetic resonance images of the spine. A case sample of 50 manually segmented ROIs, corresponding to 25 normal and 25 degenerated discs, was analyzed and textural features were generated from each disc-ROI. Student's t-test verified the existence of statistically significant differences between textural feature values generated from normal and degenerated discs. This finding is indicative of disc image texture differentiation due to the degeneration of the disc. The generated features were employed in the design of a pattern recognition system based on the Least Squares Minimum Distance classifier. The system achieved a classification accuracy of 94{%} and it may be of value to physicians for the assessment of cervical intervertebral disc degeneration in MRI.

Michopoulou, S.; Boniatis, I.; Costaridou, L.; Cavouras, D.; Panagiotopoulos, E.; Panayiotakis, G.

2009-05-01

120

Anomalous skin effects in a weakly magnetized degenerate electron plasma  

NASA Astrophysics Data System (ADS)

Fully relativistic analysis of anomalous skin effects for parallel propagating waves in a weakly magnetized degenerate electron plasma is presented and a graphical comparison is made with the results obtained using relativistic Maxwellian distribution function [G. Abbas, M. F. Bashir, and G. Murtaza, Phys. Plasmas 18, 102115 (2011)]. It is found that the penetration depth for R- and L-waves for degenerate case is qualitatively small in comparison with the Maxwellian plasma case. The quantitative reduction due to weak magnetic field in the skin depth in R-wave for degenerate plasma is large as compared to the non-degenerate one. By ignoring the ambient magnetic field, previous results for degenerate field free case are salvaged [A. F. Alexandrov, A. S. Bogdankevich, and A. A. Rukhadze, Principles of Plasma Electrodynamics (Springer-Verlag, Berlin/Heidelberg, 1984), p. 90].

Abbas, G.; Sarfraz, M.; Shah, H. A.

2014-09-01

121

Anomalous skin effects in a weakly magnetized degenerate electron plasma  

SciTech Connect

Fully relativistic analysis of anomalous skin effects for parallel propagating waves in a weakly magnetized degenerate electron plasma is presented and a graphical comparison is made with the results obtained using relativistic Maxwellian distribution function [G. Abbas, M. F. Bashir, and G. Murtaza, Phys. Plasmas 18, 102115 (2011)]. It is found that the penetration depth for R- and L-waves for degenerate case is qualitatively small in comparison with the Maxwellian plasma case. The quantitative reduction due to weak magnetic field in the skin depth in R-wave for degenerate plasma is large as compared to the non-degenerate one. By ignoring the ambient magnetic field, previous results for degenerate field free case are salvaged [A. F. Alexandrov, A. S. Bogdankevich, and A. A. Rukhadze, Principles of Plasma Electrodynamics (Springer-Verlag, Berlin/Heidelberg, 1984), p. 90].

Abbas, G., E-mail: gohar.abbas@gcu.edu.pk; Sarfraz, M. [Department of Physics, GC University Lahore, Katchery Road, Lahore 54000 (Pakistan); Shah, H. A. [Forman Christian College University, Farozpur Road, Lahore 54600 (Pakistan)

2014-09-15

122

Choriocapillaris breakdown precedes retinal degeneration in age-related macular degeneration.  

PubMed

This work presents a combined light and electron microscopical approach to investigate the initial breakdown of the retinal pigment epithelium (RPE) and choriocapillaris (CC) in age-related macular degeneration (AMD). Perimacular sections of 12 dry and wet AMD eyes (82 ± 15 years) and 7 age-matched controls (75 ± 10 years) without retinal pathology were investigated. Disease progression was classified into 5 stages of retinal degeneration to investigate the concurrent CC breakdown. Special emphasis was laid on transitions where intact CC-RPE-retina complexes went over into highly atrophied areas. AMD sections showed elevated loss of photoreceptors, RPE and CC (p < 0.01), and thickened Bruch's membrane with increased basal laminar and linear deposits compared with controls. Up to 27% of the CC was lost in controls although RPE and retina were still intact. This primary loss of CC further increased with AMD (up to 100%). The data implicate that CC breakdown already occurs during normal aging and precedes degeneration of the RPE and retina with AMD, defining AMD as a vascular disease. Particular attention should be given to the investigation of early AMD stages and transitional stages to the late stage that reveal a possible sequence of degenerative steps with aging and AMD. PMID:24925811

Biesemeier, Antje; Taubitz, Tatjana; Julien, Sylvie; Yoeruek, Efdal; Schraermeyer, Ulrich

2014-11-01

123

Differential Light-induced Responses in Sectorial Inherited Retinal Degeneration.  

PubMed

Retinitis pigmentosa (RP) is a group of genetically and clinically heterogeneous inherited degenerative retinopathies caused by abnormalities of photoreceptors or retinal pigment epithelium in the retina leading to progressive sight loss. Rhodopsin is the prototypical G-protein-coupled receptor located in the vertebrate retina and is responsible for dim light vision. Here, novel M39R and N55K variants were identified as causing an intriguing sector phenotype of RP in affected patients, with selective degeneration in the inferior retina. To gain insights into the molecular aspects associated with this sector RP phenotype, whose molecular mechanism remains elusive, the mutations were constructed by site-directed mutagenesis, expressed in heterologous systems, and studied by biochemical, spectroscopic, and functional assays. M39R and N55K opsins had variable degrees of chromophore regeneration when compared with WT opsin but showed no gross structural misfolding or altered trafficking. M39R showed a faster rate for transducin activation than WT rhodopsin with a faster metarhodopsinII decay, whereas N55K presented a reduced activation rate and an altered photobleaching pattern. N55K also showed an altered retinal release from the opsin binding pocket upon light exposure, affecting its optimal functional response. Our data suggest that these sector RP mutations cause different protein phenotypes that may be related to their different clinical progression. Overall, these findings illuminate the molecular mechanisms of sector RP associated with rhodopsin mutations. PMID:25359768

Ramon, Eva; Cordomí, Arnau; Aguilà, Mònica; Srinivasan, Sundaramoorthy; Dong, Xiaoyun; Moore, Anthony T; Webster, Andrew R; Cheetham, Michael E; Garriga, Pere

2014-12-26

124

Sprouting of axonal collaterals after spinal cord injury is prevented by delayed axonal degeneration.  

PubMed

After an incomplete spinal cord injury (SCI), partial recovery of locomotion is accomplished with time. Previous studies have established a functional link between extension of axon collaterals from spared spinal tracts and locomotor recovery after SCI, but the tissular signals triggering collateral sprouting have not been identified. Here, we investigated whether axonal degeneration after SCI contributes to the sprouting of collaterals from axons spared after injury. To this end, we evaluated collateral sprouting from BDA-labeled uninjured corticospinal axons after spinal cord hemisection (SCI(H)) in wild type (WT) mouse and Wld(S) mouse strains, which shows a significant delay in Wallerian degeneration after injury. After SCI(H), spared fibers of WT mice extend collateral sprouts to both intact and denervated sides of the spinal cord distant from the injury site. On the contrary, in the Wld(S) mice collateral sprouting from spared fibers was greatly reduced after SCI(H). Consistent with a role for collateral sprouting in functional recovery after SCI, locomotor recovery after SCI(H) was impaired in Wld(S) mice compared to WT animals. In conclusion, our results identify axonal degeneration as one of the triggers for collateral sprouting from the contralesional uninjured fibers after an SCI(H). These results open the path for identifying molecular signals associated with tissular changes after SCI that promotes collateral sprouting and functional recovery. PMID:25079366

Collyer, E; Catenaccio, A; Lemaitre, D; Diaz, P; Valenzuela, V; Bronfman, F; Court, F A

2014-11-01

125

WldS prevents axon degeneration through increased mitochondrial flux and enhanced mitochondrial Ca2+ buffering  

PubMed Central

Summary WldS (slow Wallerian degeneration) is a remarkable protein that can suppress Wallerian degeneration of axons and synapses [1] but how it exerts this effect remains unclear [2]. Here, using Drosophila and mouse models, we identify mitochondria as a key site of action for WldS neuroprotective function. Targeting the NAD+ biosynthetic enzyme Nmnat to mitochondria was sufficient to fully phenocopy WldS, and WldS was specifically localized to mitochondria in synaptic preparations from mouse brain. Axotomy of live wild type axons induced a dramatic spike in axoplasmic Ca2+ and termination of mitochondrial movement—WldS potently suppressed both of these events. Surprisingly, WldS also promoted increased basal mitochondrial motility in axons before injury, and genetically suppressing mitochondrial motility in vivo dramatically reduced the protective effect of WldS. Intriguingly, purified mitochondria from WldS mice exhibited enhanced Ca2+ buffering capacity. We propose that the enhanced Ca2+ buffering capacity of WldS+ mitochondria leads to increased mitochondrial motility, suppression of axotomy-induced Ca2+ elevation in axons, and thereby suppression of Wallerian degeneration. PMID:22425157

Avery, Michelle A.; Rooney, Timothy M.; Pandya, Jignesh D.; Wishart, Thomas M.; Gillingwater, Thomas H.; Geddes, James W.; Sullivan, Patrick; Freeman, Marc R.

2014-01-01

126

Potential regenerative treatment strategies for intervertebral disc degeneration in dogs  

PubMed Central

Pain due to spontaneous intervertebral disc (IVD) disease is common in dogs. In chondrodystrophic (CD) dogs, IVD disease typically develops in the cervical or thoracolumbar spine at about 3–7 years of age, whereas in non-chondrodystrophic (NCD) dogs, it usually develops in the caudal cervical or lumbosacral spine at about 6–8 years of age. IVD degeneration is characterized by changes in the biochemical composition and mechanical integrity of the IVD. In the degenerated IVD, the content of glycosaminoglycan (GAG, a proteoglycan side chain) decreases and that of denatured collagen increases. Dehydration leads to tearing of the annulus fibrosus (AF) and/or disc herniation, which is clinically characterized by pain and/or neurological signs. Current treatments (physiotherapy, anti-inflammatory/analgesic medication, surgery) for IVD disease may resolve neurological deficits and reduce pain (although in many cases insufficient), but do not lead to repair of the degenerated disc. For this reason, there is interest in new regenerative therapies that can repair the degenerated disc matrix, resulting in restoration of the biomechanical function of the IVD. CD dogs are considered a suitable animal model for human IVD degeneration because of their spontaneous IVD degeneration, and therefore studies investigating cell-, growth factor-, and/or gene therapy-based regenerative therapies with this model provide information relevant to both human and canine patients. The aim of this article is to review potential regenerative treatment strategies for canine IVD degeneration, with specific emphasis on cell-based strategies. PMID:24387033

2014-01-01

127

Age related macular degeneration and visual disability.  

PubMed

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 substantial benefit in people with age-related macular degeneration. Prescription filters are one of the most beneficial visual aids that people with macular degeneration. In principle, one aims both at reducing short-wavelength light to reduce glare and at identifying light with specific wavelengths (colours) preferred by the patient for viewing. In both instances, such interventions result in apparent improved contrast sensitivity and better visual acuity. Although specific tests are performed to determine the best colour, tint, lens material, and type of frame for the patient's need, no scientific protocol has been developed so far to assist in prescribing tinted or selective transmission lenses . Magnifying optical lenses are available in a wide range of dioptric powers and are made from materials that correct for weight (plastic), thickness (high index), spherical aberrations (aspherical), and variable light intensities (photochromatic). These lenses can be used as loose lenses, mounted on optical frames, or used with a wide variety of attachments. As the dioptric power of plus lenses increases, the viewing distance of the target decreases, hence their usefulness mainly for tasks requiring near resolution acuity, like reading. Magnification can also be achieved with the use of telescopic devices that are built of two or more plus and (or) minus (minifying) optical lenses. Normal resolution acuity levels can be achieved with these devices for all viewing distances. Therefore, all telescopic devices are useful only for stationary patient tasks that do not require mobility and orientation. Electronic magnification has the great advantage over plus lenses of producing an acuity reserve enabling reading skills for almost all levels of visual acuity. The additional benefit provided is preservation of binocularity, even at high levels of visual disparity between the two eyes. Vision rehabilitation can help patients to maximize their remaining vision and adapt to activities of daily living. The support of the patient's social network is critical to patient's well-bei

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

2011-02-01

128

Lifting degenerate neutrino masses, threshold corrections and maximal mixing  

E-print Network

In the scenario with degenerate neutrino masses at tree-level, we show how threshold corrections with either non-trivial or trivial mixing at tree-level have the power to generate the observed deviations from a degenerate spectrum. Moreover, it is possible to also generate the mixing fully radiatively when there is trivial mixing at tree-level. We give a brief overview over the topic and discuss the outcome of threshold corrections for degenerate neutrino masses in a supersymmetric model. A detailed description can be found in [arXiv:1412.4585].

Hollik, Wolfgang Gregor

2014-01-01

129

Degeneration of the costovertebral articulation: a cause of pulmonary pseudolesion.  

PubMed

The objective was to report examples of degeneration of the costovertebral articulation producing a pulmonary pseudolesion. Three cases in which a nodular opacity seen on plain radiograph was determined to be secondary to degeneration of the costovertebral articulation were compiled, one of which was confirmed by CT. Pseudolesions produced by degenerative osteophytes of the vertebral spine and anomalous articulations between transverse processes are more commonly identified, but less well described is the pseudolesion produced by degeneration of the costovertebral articulation. Recognition of this etiology may prevent misconstruing the lesion as a significant finding. PMID:15290470

Leibowitz, Rebecca T; Keats, Theodore E

2004-04-01

130

Bilateral aniridia lenticular coloboma and snowflake retinal degeneration.  

PubMed

A 6-year-old boy presented with bilateral aniridia associated with lens coloboma and snowflake retinal degeneration. Ophthalmologic examination revealed bilateral corneal peripheral epithelial thickening and aniridia. Additionally, the patient had lenticular coloboma and snowflake retinal degeneration in both eyes. Intraocular pressure was 22 mm Hg bilaterally. The patient also had pendular nystagmus. Uncorrected visual acuity was counting fingers at 2 meters for both eyes, but improved to 0.2 and 0.05, respectively, with correction. Congenital aniridia has been reported with various ophthalmic pathologies, but this is the first case to display bilateral lenticular coloboma and snowflake retinal degeneration associated with aniridia. PMID:19205498

Doganay, Selim; Emre, Sinan; Firat, Penpegül

2009-01-01

131

Age-related macular degeneration: choroidal ischaemia?  

PubMed Central

Aim Our aim is to use ultrasound to non-invasively detect differences in choroidal microarchitecture possibly related to ischaemia among normal eyes and those with wet and dry age-related macular degeneration (AMD). Design Prospective case series of subjects with dry AMD, wet AMD and age-matched controls. Methods Digitised 20?MHz B-scan radiofrequency ultrasound data of the region of the macula were segmented to extract the signal from the retina and choroid. This signal was processed by a wavelet transform, and statistical modelling was applied to the wavelet coefficients to examine differences among dry, wet and non-AMD eyes. Receiver operating characteristic (ROC) analysis was used to evaluate a multivariate classifier. Results In the 69 eyes of 52 patients, 18 did not have AMD, 23 had dry AMD and 28 had wet AMD. Multivariate models showed statistically significant differences between groups. Multiclass ROC analysis of the best model showed an excellent volume-under-curve of 0.892±0.17. The classifier is consistent with ischaemia in dry AMD. Conclusions Wavelet augmented ultrasound is sensitive to the organisational elements of choroidal microarchitecture relating to scatter and fluid tissue boundaries such as seen in ischaemia and inflammation, allowing statistically significant differentiation of dry, wet and non-AMD eyes. This study further supports the association of ischaemia with dry AMD and provides a rationale for treating dry AMD with pharmacological agents to increase choroidal perfusion. ClinicalTrials.gov registration NCT00277784. PMID:23740965

Coleman, D Jackson; Silverman, Ronald H; Rondeau, Mark J; Lloyd, Harriet O; Khanifar, Aziz A; Chan, R V Paul

2013-01-01

132

Quantitative Peptidomics of Purkinje Cell Degeneration Mice  

PubMed Central

Cytosolic carboxypeptidase 1 (CCP1) is a metallopeptidase that removes C-terminal and side-chain glutamates from tubulin. The Purkinje cell degeneration (pcd) mouse lacks CCP1 due to a mutation. Previously, elevated levels of peptides derived from cytosolic and mitochondrial proteins were found in adult pcd mouse brain, raising the possibility that CCP1 functions in the degradation of intracellular peptides. To test this hypothesis, we used a quantitative peptidomics technique to compare peptide levels in wild-type and pcd mice, examining adult heart, spleen, and brain, and presymptomatic 3 week-old amygdala and cerebellum. Contrary to adult mouse brain, young pcd brain and adult heart and spleen did not show a large increase in levels of intracellular peptides. Unexpectedly, levels of peptides derived from secretory pathway proteins were altered in adult pcd mouse brain. The pattern of changes for the intracellular and secretory pathway peptides in pcd mice was generally similar to the pattern observed in mice lacking primary cilia. Collectively, these results suggest that intracellular peptide accumulation in adult pcd mouse brain is a secondary effect and is not due to a role of CCP1 in peptide turnover. PMID:23593366

Berezniuk, Iryna; Sironi, Juan J.; Wardman, Jonathan; Pasek, Raymond C.; Berbari, Nicolas F.; Yoder, Bradley K.; Fricker, Lloyd D.

2013-01-01

133

Quantum weak chaos in a degenerate system  

E-print Network

Quantum weak chaos is studied in a perturbed degenerate system --- a charged particle interacting with a monochromatic wave in a transverse magnetic field. The evolution operator for an arbitrary number of periods of the external field is built and its structure is explored in terms of the QE (quasienergy eigenstates) under resonance condition (wave frequency $=$ cyclotron frequency) in the regime of weak classical chaos. The new phenomenon of diffusion via the quantum separatrices and the influence of chaos on diffusion are investigated and, in the quasi classical limit, compared with its classical dynamics. We determine the crossover from purely quantum diffusion to a diffusion which is the quantum manifestation of classical diffusion along the stochastic web. This crossover results from the non-monotonic dependence of the characteristic localization length of the QE states on the wave amplitude. The width of the quantum separatrices was computed and compared with the width of the classical stochastic web. We give the physical parameters which can be realized experimentally to show the manifestation of quantum chaos in nonlinear acoustic resonance.

V. Ya. Demikhovskii; D. I. Kamenev; G. A. Luna-Acosta

1998-09-27

134

Statistical physics of age related macular degeneration  

NASA Astrophysics Data System (ADS)

Age-related macular degeneration (AMD) is the leading cause of blindness beyond the age of 50 years. The most common pathogenic mechanism that leads to AMD is choroidal neovascularization (CNV). CNV is produced by accumulation of residual material caused by aging of retinal pigment epithelium cells (RPE). The RPE is a phagocytic system that is essential for renewal of photoreceptors (rods and cones). With time, incompletely degraded membrane material builds up in the form of lipofuscin. Lipofuscin is made of free-radical-damaged protein and fat, which forms not only in AMD, but also Alzheimer disease and Parkinson disease. The study of lipofuscin formation and growth is important, because of their association with cellular aging. We introduce a model of non-equilibrium cluster growth and aggregation that we have developed for studying the formation and growth of lipofuscin in the aging RPE. Our results agree with a linear growth of the number of lipofuscin granules with age. We apply the dynamic scaling approach to our model and find excellent data collapse for the cluster size distribution. An unusual feature of our model is that while small particles are removed from the RPE the larger ones become fixed and grow by aggregation.

Family, Fereydoon; Mazzitello, K. I.; Arizmendi, C. M.; Grossniklaus, H. E.

135

CERKL knockdown causes retinal degeneration in zebrafish.  

PubMed

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. PMID:23671706

Riera, Marina; Burguera, Demian; Garcia-Fernàndez, Jordi; Gonzàlez-Duarte, Roser

2013-01-01

136

Rhodopsin homeostasis and retinal degeneration: lessons from the fly  

PubMed Central

Rhodopsins (Rh) are G-protein-coupled receptors that function as light sensors in photoreceptors. In humans, mutations in Rhodopsins cause retinitis pigmentosa, a degenerative disease that ultimately results in blindness. Studies in Drosophila have provided many insights into basic Rhodopsin biology and identified pathways that lead to retinal degeneration. It has been shown that because Rhodopsin is very abundant in photoreceptors, its accumulation in numerous organelles induces severe stress and results in degeneration of these cells. Moreover, genetic lesions that affect proper activation of membrane-bound Rh lead to disruption in Ca2+ homeostasis which also causes photoreceptor degeneration. Here, we review the molecular signals involved in Rhodopsin homeostasis and the mechanisms underlying retinal degeneration in flies, and discuss possible links to human diseases. PMID:24012059

Xiong, Bo; Bellen, Hugo J.

2013-01-01

137

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

PubMed

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. PMID:22855449

Gu, Xian; Ning, Tiao; Xiao, Heng

2012-08-01

138

Suppression of Density Fluctuations in a Quantum Degenerate Fermi Gas  

E-print Network

We study density profiles of an ideal Fermi gas and observe Pauli suppression of density fluctuations (atom shot noise) for cold clouds deep in the quantum degenerate regime. Strong suppression is observed for probe volumes ...

Sanner, Christian Burkhard

139

Degenerate Primer Design via Clustering School of Computer Science,  

E-print Network

Degenerate Primer Design via Clustering Xintao Wei School of Computer Science, Florida. of Biological Sciences, Florida International University, University Park, Miami, FL 33199, USA. kuhnd Narasimhan School of Computer Science, Florida International University, University Park, Miami, FL 33199,USA

Narasimhan, Giri

140

Hypertrophic olivary degeneration and cerebrovascular disease: movement in a triangle.  

PubMed

Hypertrophic olivary degeneration is a rare kind of trans-synaptic degeneration that occurs after lesions of the dentatorubro-olivary pathway. The lesions, commonly unilateral, may result from hemorrhage due to vascular malformation, trauma, surgical intervention or hypertension, tumor, or ischemia. Bilateral cases are extremely rare. This condition is classically associated with development of palatal tremor, but clinical manifestations can include other involuntary movements. We describe 2 cases: unilateral hypertrophic olivary degeneration in a 60-year-old man with contralateral athetosis and neurologic worsening developing several years after a pontine hemorrhage and bilateral hypertrophic olivary degeneration in a 77-year-old woman with development of palatal tremor, probably secondary to pontine ischemic lesions (small vessel disease). PMID:25455430

Santos, Ana Filipa; Rocha, Sofia; Varanda, Sara; Pinho, João; Rodrigues, Margarida; Ramalho Fontes, João; Soares-Fernandes, João; Ferreira, Carla

2015-02-01

141

Designing multiple degenerate primers via consecutive pairwise alignments  

PubMed Central

Background Different algorithms have been proposed to solve various versions of degenerate primer design problem. For one of the most general cases, multiple degenerate primer design problem, very few algorithms exist, none of them satisfying the criterion of designing low number of primers that cover high number of sequences. Besides, the present algorithms require high computation capacity and running time. Results PAMPS, the method presented in this work, usually results in a 30% reduction in the number of degenerate primers required to cover all sequences, compared to the previous algorithms. In addition, PAMPS runs up to 3500 times faster. Conclusion Due to small running time, using PAMPS allows designing degenerate primers for huge numbers of sequences. In addition, it results in fewer primers which reduces the synthesis costs and improves the amplification sensitivity. PMID:18221562

Najafabadi, Hamed Shateri; Torabi, Noorossadat; Chamankhah, Mahmood

2008-01-01

142

Axonal degeneration in multiple sclerosis: The mitochondrial hypothesis  

Microsoft Academic Search

Multiple sclerosis (MS) is a chronic disease of the central nervous system, affecting more than 2 million people worldwide.\\u000a Traditionally considered an inflammatory demyelinating disease, recent evidence now points to axonal degeneration as crucial\\u000a to the development of irreversible disability. Studies show that axonal degeneration occurs throughout the entire course of\\u000a MS. Although the specific mechanisms causing axonal damage may

Kimmy G. Su; Gary Banker; Dennis Bourdette; Michael Forte

2009-01-01

143

Phonon emission in a degenerate semiconductor at low lattice temperatures  

NASA Astrophysics Data System (ADS)

The characteristics of phonon growth in a degenerate semiconductor at low lattice temperatures have been studied for inelastic interaction of non-equilibrium electrons with the intravalley acoustic phonons. The energy of the phonon and the full form of the phonon distribution are taken into account. The results reveal significant changes in the growth characteristics compared to the same for a non-degenerate material.

Midday, S.; Nag, S.; Bhattacharya, D. P.

2015-02-01

144

Stem cell regeneration of degenerated intervertebral discs: Current status  

Microsoft Academic Search

Low back pain (LBP) is one of the most common musculoskeletal conditions, and intervertebral disc (IVD) degeneration is associated\\u000a with most cases. Although many treatment options are available, they focus on the removal of symptoms rather than repair of\\u000a the degenerate tissue. However, there is a growing interest in the potential of cell-based tissue engineering strategies for\\u000a regeneration of the

Stephen M. Richardson; Judith A. Hoyland

2008-01-01

145

Axonal Degeneration Is Mediated by the Mitochondrial Permeability Transition Pore  

PubMed Central

Axonal degeneration is an active process that has been associated with neurodegenerative conditions triggered by mechanical, metabolic, infectious, toxic, hereditary and inflammatory stimuli. This degenerative process can cause permanent loss of function, so it represents a focus for neuroprotective strategies. Several signaling pathways are implicated in axonal degeneration, but identification of an integrative mechanism for this self-destructive process has remained elusive. Here, we show that rapid axonal degeneration triggered by distinct mechanical and toxic insults is dependent on the activation of the mitochondrial permeability transition pore (mPTP). Both pharmacological and genetic targeting of cyclophilin D, a functional component of the mPTP, protects severed axons and vincristine-treated neurons from axonal degeneration in ex vivo and in vitro mouse and rat model systems. These effects were observed in axons from both the peripheral and central nervous system. Our results suggest that the mPTP is a key effector of axonal degeneration, upon which several independent signaling pathways converge. Since axonal and synapse degeneration are increasingly considered early pathological events in neurodegeneration, our work identifies a potential target for therapeutic intervention in a wide variety of conditions that lead to loss of axons and subsequent functional impairment. PMID:21248121

Barrientos, Sebastian A.; Martinez, Nicolas W.; Yoo, Soonmoon; Jara, Juan S.; Zamorano, Sebastian; Hetz, Claudio; Twiss, Jeffery L.; Alvarez, Jaime; Court, Felipe A.

2011-01-01

146

N -methyl- N -nitrosourea-induced retinal degeneration in mice.  

PubMed

Mouse retinal degeneration models have been investigated for many years in the hope of understanding the mechanism of photoreceptor cell death. N -methyl- N -nitrosourea (MNU) has been previously shown to induce outer retinal degeneration in mice. After MNU was intraperitoneally injected in C57/BL mice, we observed a gradual decrease in the outer nuclear layer (ONL) thickness associated with photoreceptor outer segment loss, bipolar cell dendritic retraction and reactive gliosis. Reactive gliosis was confirmed by increased GFAP protein levels. More serious damage to the central retina as opposed to the peripheral retina was found in the MNU-induced retinal degeneration model. Retinal ganglion cells (RGC) appear to be spared for at least two months after MNU treatment. Following retinal vessel labelling, we observed vascular complexes in the distal vessels, indicating retinal vessel damage. In the remnant retinal photoreceptor of the MNU-treated mouse, concentrated colouring nuclei were detected by electron microscopy, together with the loss of mitochondria and displaced remnant synaptic ribbons in the photoreceptor. We also observed decreased mitochondrial protein levels and increased amounts of nitrosylation/nitration in the photoreceptors. The mechanism of MNU-induced apoptosis may result from oxidative stress or the loss of retinal blood supply. MNU-induced mouse retinal degeneration in the outer retina is a useful animal model for photoreceptor degeneration diseases, such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP). PMID:24509257

Chen, Yuan-Yuan; Liu, Shi-Liang; Hu, Dan-Ping; Xing, Yi-Qiao; Shen, Yin

2014-04-01

147

Prolonged prevention of retinal degeneration with retinylamine loaded nanoparticles.  

PubMed

Retinal degeneration impairs the vision of millions in all age groups worldwide. Increasing evidence suggests that the etiology of many retinal degenerative diseases is associated with impairment in biochemical reactions involved in the visual cycle, a metabolic pathway responsible for regeneration of the visual chromophore (11-cis-retinal). Inefficient clearance of toxic retinoid metabolites, especially all-trans-retinal, is considered responsible for photoreceptor cytotoxicity. Primary amines, including retinylamine, are effective in lowing the concentration of all-trans-retinal within the retina and thus prevent retina degeneration in mouse models of human retinopathies. Here we achieved prolonged prevention of retinal degeneration by controlled delivery of retinylamine to the eye from polylactic acid nanoparticles in Abca4(-/-)Rdh8(-/-) (DKO) mice, an animal model of Stargardt disease/age-related macular degeneration. Subcutaneous administration of the nanoparticles containing retinylamine provided a constant supply of the drug to the eye for about a week and resulted in effective prolonged prevention of light-induced retinal degeneration in DKO mice. Retinylamine nanoparticles hold promise for prolonged prophylactic treatment of human retinal degenerative diseases, including Stargardt disease and age-related macular degeneration. PMID:25617130

Puntel, Anthony; Maeda, Akiko; Golczak, Marcin; Gao, Song-Qi; Yu, Guanping; Palczewski, Krzysztof; Lu, Zheng-Rong

2015-03-01

148

?-Catenin expression during vascular development and degeneration of avian mesonephros  

PubMed Central

?-Catenin is a structural component of adherens junctions, a regulator of the Wnt signalling pathway and a transcriptional co-activator with a key role in vascular patterning. The avian mesonephros is a transitory embryonic kidney that is used in the study of vascular development and degeneration. Here we examine ?-catenin expression in this model during vascular development and degeneration. Quail embryos with developing or degenerating mesonephros were studied, on day 6 (30HH) or day 11 of incubation (40HH), respectively. QH1 whole mounts of developing mesonephros revealed numerous angioblast-like cells situated in the paramesonephric duct that seem to invade the mesonephros. Although these cells did not express ?-catenin, the surrounding periductal mesenchymal cells translocated high levels of ?-catenin into the nucleus. In contrast, degenerating mesonephros were devoid of angioblast-like cells and ?-catenin was lower than in the developing mesonephros. ?-Catenin was significantly reduced in the glomerular capillary tuffs, indicating that it was particularly down-regulated in the vascular system. No sex-related differences in ?-catenin expression were observed in degenerating mesonephros. Furthermore, two special populations of glomerular and peritubular endothelial cells were observed in degenerating mesonephros: one translocating ?-catenin into the nucleus and the other in apoptosis that did not translocate it. In conclusion, our results indicate that the paramesonephric duct is a potential new vasculogenetic pathway, and suggest that ?-catenin plays a role in the fate of mesonephric endothelial cells. PMID:15730481

Nacher, Victor; Carretero, Ana; Navarro, Marc; Armengol, Clara; Llombart, Cristina; Blasi, Juan; Ruberte, Jesús

2005-01-01

149

Distinct optical properties of relativistically degenerate matter  

NASA Astrophysics Data System (ADS)

In this paper, we use the collisional quantum magnetohydrodynamic (CQMHD) model to derive the transverse dielectric function of a relativistically degenerate electron fluid and investigate various optical parameters, such as the complex refractive index, the reflection and absorption coefficients, the skin-depth and optical conductivity. In this model we take into accounts effects of many parameters such as the atomic-number of the constituent ions, the electron exchange, electron diffraction effect and the electron-ion collisions. Study of the optical parameters in the solid-density, the warm-dense-matter, the big-planetary core, and the compact star number-density regimes reveals that there are distinct differences between optical characteristics of the latter and the former cases due to the fundamental effects of the relativistic degeneracy and other quantum mechanisms. It is found that in the relativistic degeneracy plasma regime, such as found in white-dwarfs and neutron star crusts, matter possess a much sharper and well-defined step-like reflection edge beyond the x-ray electromagnetic spectrum, including some part of gamma-ray frequencies. It is also remarked that the magnetic field intensity only significantly affects the plasma reflectivity in the lower number-density regime, rather than the high density limit. Current investigation confirms the profound effect of relativistic degeneracy on optical characteristics of matter and can provide an important plasma diagnostic tool for studying the physical processes within the wide scope of quantum plasma regimes be it the solid-density, inertial-confined, or astrophysical compact stars.

Akbari-Moghanjoughi, M.

2014-06-01

150

Perceptual learning in patients with macular degeneration  

PubMed Central

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 = 0.001) 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 = 0.014). 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 = 0.014, 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. PMID:25368597

Plank, Tina; Rosengarth, Katharina; Schmalhofer, Carolin; Goldhacker, Markus; Brandl-Rühle, Sabine; Greenlee, Mark W.

2014-01-01

151

Distinct optical properties of relativistically degenerate matter  

SciTech Connect

In this paper, we use the collisional quantum magnetohydrodynamic (CQMHD) model to derive the transverse dielectric function of a relativistically degenerate electron fluid and investigate various optical parameters, such as the complex refractive index, the reflection and absorption coefficients, the skin-depth and optical conductivity. In this model we take into accounts effects of many parameters such as the atomic-number of the constituent ions, the electron exchange, electron diffraction effect and the electron-ion collisions. Study of the optical parameters in the solid-density, the warm-dense-matter, the big-planetary core, and the compact star number-density regimes reveals that there are distinct differences between optical characteristics of the latter and the former cases due to the fundamental effects of the relativistic degeneracy and other quantum mechanisms. It is found that in the relativistic degeneracy plasma regime, such as found in white-dwarfs and neutron star crusts, matter possess a much sharper and well-defined step-like reflection edge beyond the x-ray electromagnetic spectrum, including some part of gamma-ray frequencies. It is also remarked that the magnetic field intensity only significantly affects the plasma reflectivity in the lower number-density regime, rather than the high density limit. Current investigation confirms the profound effect of relativistic degeneracy on optical characteristics of matter and can provide an important plasma diagnostic tool for studying the physical processes within the wide scope of quantum plasma regimes be it the solid-density, inertial-confined, or astrophysical compact stars.

Akbari-Moghanjoughi, M. [Department of Physics, Faculty of Sciences, Azarbaijan Shahid Madani University, Tabriz 51745-406 (Iran, Islamic Republic of); International Centre for Advanced Studies in Physical Sciences and Institute for Theoretical Physics, Ruhr University Bochum, Bochum D-44780 (Germany)

2014-06-15

152

Astrocytic inclusions in progressive supranuclear palsy and corticobasal degeneration.  

PubMed

Tufted astrocytes (TAs) in progressive supranuclear palsy (PSP) and astrocytic plaques (APs) in corticobasal degeneration (CBD) have been regarded as the pathological hallmarks of major sporadic 4-repeat tauopathies. To better define the astrocytic inclusions in PSP and CBD and to outline the pathological features of each disease, we reviewed 95 PSP cases and 30 CBD cases that were confirmed at autopsy. TAs exhibit a radial arrangement of thin, long, branching accumulated tau protein from the cytoplasm to the proximal processes of astrocytes. APs show a corona-like arrangement of tau aggregates in the distal portions of astrocytic processes and are composed of fuzzy, short processes. Immunoelectron microscopic examination using quantum dot nanocrystals revealed filamentous tau accumulation of APs located in the immediate vicinity of the synaptic structures, which suggested synaptic dysfunction by APs. The pathological subtypes of PSP and CBD have been proposed to ensure that the clinical phenotypes are in accordance with the pathological distribution and degenerative changes. The pathological features of PSP are divided into 3 representative subtypes: typical PSP type, pallido-nigro-luysian type (PNL type), and CBD-like type. CBD is divided into three pathological subtypes: typical CBD type, basal ganglia- predominant type, and PSP-like type. TAs are found exclusively in PSP, while APs are exclusive to CBD, regardless of the pathological subtypes, although some morphological variations exist, especially with regard to TAs. The overlap of the pathological distribution of PSP and CBD makes their clinical diagnosis complicated, although the presence of TAs and APs differentiate these two diseases. The characteristics of tau accumulation in both neurons and glia suggest a different underlying mechanism with regard to the sites of tau aggregation and fibril formation between PSP and CBD: proximal-dominant aggregation of TAs and formation of filamentous NFTs in PSP in contrast to the distal-dominant aggregation of APs and formation of less filamentous pretangles in CBD. PMID:25124031

Yoshida, Mari

2014-12-01

153

Genetic Association Studies in Lumbar Disc Degeneration: A Systematic Review  

PubMed Central

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. PMID:23185509

Eskola, Pasi J.; Lemmelä, Susanna; Kjaer, Per; Solovieva, Svetlana; Männikkö, Minna; Tommerup, Niels; Lind-Thomsen, Allan; Husgafvel-Pursiainen, Kirsti; Cheung, Kenneth M. C.; Chan, Danny

2012-01-01

154

Trilayer graphene nanoribbon carrier statistics in degenerate and non degenerate limits  

NASA Astrophysics Data System (ADS)

We present trilayer graphene nanoribbon carrier statistics in the degenerate and the nondegenerate limits. Within zero to 3kBT from the conduction or valence band edgers high concentrations of carriers sensitively depend on a normalized Fermi energy which is independent of temperature. The effect of different stacking orders of graphene multilayers on the electric field induced band gap is studied. The gap for trilayer graphene with the ABC stacking is much larger than the corresponding gap for the ABA trilayer. The gap for the different types of stacking is much larger as compared to the case of Bernal stacking. A non-monotonic dependence of the true energy gap in trilayer graphene on the charge density is investigated along with the electronic low-energy band structure of ABC stacked multilayer graphene. The band structure of trilayer graphene systems in the presence of a perpendicular electric field is obtained using a tight-binding approach.

Rahmani, M.; Ahmadi, M. T.; Webb, J. F.; Shayesteh, N.; Mousavi, S. M.; Sadeghi, H.; Ismail, R.

2012-11-01

155

Review: Retinal degeneration: Focus on the unfolded protein response  

PubMed Central

Recently published literature has provided evidence that the unfolded protein response (UPR) is involved in the development of retinal degeneration. The scope of these studies encompassed diabetic retinopathy, retinopathy of prematurity, glaucoma, retinal detachment, light-induced retinal degeneration, age-related macular degeneration, and inherited retinal degeneration. Subsequent studies investigating the role of individual UPR markers in retinal pathogenesis and examining the therapeutic potential of reprogramming the UPR as a method for modulating the rate of retinal degeneration have been initiated. Manipulation of UPR markers has been made possible by the use of knockout mice, pharmacological agents, and viral vector-mediated augmentation of gene expression. Future research will aim at identifying specific inhibitors and/or inducers of UPR regulatory markers as well as expand the list of UPR-related animal models. Additionally, adeno-associated virus-mediated gene delivery is a safe and effective method for modulating gene expression, and thus is a useful research tool for manipulating individual UPR markers in affected retinas and a promising delivery vector for gene therapy in retinal degenerative disorders. PMID:24068865

Gorbatyuk, Oleg

2013-01-01

156

Electrostatic Solitary Structures in a Relativistic Degenerate Multispecies Plasma  

NASA Astrophysics Data System (ADS)

The nonlinear propagation of cylindrical and spherical modified ion-acoustic (mIA) waves in an unmagnetized, collisionless, relativistic, degenerate multispecies plasma has been investigated theoretically. This plasma system is assumed to contain both relativistic degenerate electron and positron fluids, nonrelativistic degenerate positive and negative ions, and positively charged static heavy ions. The restoring force is provided by the degenerate pressures of the electrons and positrons, whereas the inertia is provided by the mass of positive and negative ions. The positively charged static heavy ions participate only in maintaining the quasi-neutrality condition at equilibrium. The nonplanar K-dV and mK-dV equations are derived by using reductive perturbation technique and numerically analyzed to identify the basic features (speed, amplitude, width, etc.) of mIA solitary structures. The basic characteristics of mIA solitary waves are found to be significantly modified by the effects of degenerate pressures of electron, positron, and ion fluids, their number densities, and various charge states of heavy ions. The implications of our results to dense plasmas in astrophysical compact objects (e.g., nonrotating white dwarfs, neutron stars, etc.) are briefly mentioned.

Hossen, M. R.; Mamun, A. A.

2014-12-01

157

Electrostatic Solitary Structures in a Relativistic Degenerate Multispecies Plasma  

NASA Astrophysics Data System (ADS)

The nonlinear propagation of cylindrical and spherical modified ion-acoustic (mIA) waves in an unmagnetized, collisionless, relativistic, degenerate multispecies plasma has been investigated theoretically. This plasma system is assumed to contain both relativistic degenerate electron and positron fluids, nonrelativistic degenerate positive and negative ions, and positively charged static heavy ions. The restoring force is provided by the degenerate pressures of the electrons and positrons, whereas the inertia is provided by the mass of positive and negative ions. The positively charged static heavy ions participate only in maintaining the quasi-neutrality condition at equilibrium. The nonplanar K-dV and mK-dV equations are derived by using reductive perturbation technique and numerically analyzed to identify the basic features (speed, amplitude, width, etc.) of mIA solitary structures. The basic characteristics of mIA solitary waves are found to be significantly modified by the effects of degenerate pressures of electron, positron, and ion fluids, their number densities, and various charge states of heavy ions. The implications of our results to dense plasmas in astrophysical compact objects (e.g., nonrotating white dwarfs, neutron stars, etc.) are briefly mentioned.

Hossen, M. R.; Mamun, A. A.

2014-08-01

158

Biologic Treatment of Mild and Moderate Intervertebral Disc Degeneration  

PubMed Central

Disc degeneration is the most common cause of back pain in adults and has enormous socioeconomic implications. Conservative management is ineffective in most cases, and results of surgical treatment have not yet reached desirable standards. Biologic treatment options are an alternative to the above conventional management and have become very attractive in recent years. The present review highlights the currently available biologic treatment options in mild and moderate disc degeneration, where a potential for regeneration still exists. Biologic treatment options include protein-based and cell-based therapies. Protein-based therapies involve administration of biologic factors into the intervertebral disc to enhance matrix synthesis, delay degeneration or impede inflammation. These factors can be delivered by an intradiscal injection, alone or in combination with cells or tissue scaffolds and by gene therapy. Cell-based therapies comprise treatment strategies that aim to either replace necrotic or apoptotic cells, or minimize cell death. Cell-based therapies are more appropriate in moderate stages of degenerated disc disease, when cell population is diminished; therefore, the effect of administration of growth factors would be insufficient. Although clinical application of biologic treatments is far from being an everyday practice, the existing studies demonstrate promising results that will allow the future design of more sophisticated methods of biologic intervention to treat intervertebral disc degeneration. PMID:25171110

Vasiliadis, Elias S; Pneumaticos, Spyros G; Evangelopoulos, Demitrios S; Papavassiliou, Athanasios G

2014-01-01

159

Wallerian degeneration: an emerging axon death pathway linking injury and disease.  

PubMed

Axon degeneration is a prominent early feature of most neurodegenerative disorders and can also be induced directly by nerve injury in a process known as Wallerian degeneration. The discovery of genetic mutations that delay Wallerian degeneration has provided insight into mechanisms underlying axon degeneration in disease. Rapid Wallerian degeneration requires the pro-degenerative molecules SARM1 and PHR1. Nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2) is essential for axon growth and survival. Its loss from injured axons may activate Wallerian degeneration, whereas NMNAT overexpression rescues axons from degeneration. Here, we discuss the roles of these and other proposed regulators of Wallerian degeneration, new opportunities for understanding disease mechanisms and intriguing links between Wallerian degeneration, innate immunity, synaptic growth and cell death. PMID:24840802

Conforti, Laura; Gilley, Jonathan; Coleman, Michael P

2014-06-01

160

The multilevel pairing Hamiltonian versus the degenerate case  

SciTech Connect

We study the pairing Hamiltonian in a set of non-degenerate levels. First, we review in the path integral framework the spontaneous breaking of the U(1) symmetry occurring in such a system for the degenerate situation. Then the behaviors with the coupling constant of the ground state energy in the multilevel and in the degenerate case are compared. Next we discuss, in the multilevel case, an exact strong coupling expansion for the ground state energy which introduces the moments of the single particle level distribution. The domain of validity of the expansion, which is known in the macroscopic limit, is explored for finite systems and its implications for the energy of the latter is discussed. Finally the seniority and Gaudin excitations of the pairing Hamiltonian are addressed and shown to display the same gap in leading order.

Barbaro, M.B. [Dipartimento di Fisica Teorica, Universita di Torino, Via P. Giuria 1, I-10125 Torino (Italy); INFN, Sez. di Torino, Torino (Italy)], E-mail: barbaro@to.infn.it; Cenni, R. [Istituto Nazionale di Fisica Nucleare, Sez. di Genova, Genova (Italy); Chiacchiera, S.; Molinari, A. [Dipartimento di Fisica Teorica, Universita di Torino, Via P. Giuria 1, I-10125 Torino (Italy); INFN, Sez. di Torino, Torino (Italy); Palumbo, F. [INFN - Laboratori Nazionali di Frascati, Frascati (Italy)

2007-11-15

161

Radiative generation of neutrino mixing: degenerate masses and threshold corrections  

E-print Network

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.

Hollik, Wolfgang Gregor

2014-01-01

162

Fundus autofluorescence imaging in age-related macular degeneration.  

PubMed

Abstract Fundus autofluorescence (FAF) is a noninvasive imaging technology that provides information on the distribution of lipofuscin within the retinal pigment epithelial cells. Progressive accumulation of lipofuscin within retinal pigment epithelial cells is involved in the pathogenesis of age-related macular degeneration (AMD). Fundus autofluorescence imaging using a confocal scanning laser ophthalmoscope is a useful technique to identify high-risk characteristics in patients with nonexudative AMD. It gives also some valuable knowledge and clues in differantial diagnosis of exudative age-related macular degeneration. This review comprises an introduction to fundus autofluorescence, a review of FAF imaging in AMD, and the recent classification of geographic atrophy (GA) and early AMD phenotypes by the Fundus Autofluorescence in Age-related Macular Degeneration Study. The association of phenotype and atrophy progression and choroidal neovascularization development are also summarized. PMID:23952079

Bat?o?lu, Figen; Demirel, Sibel; Ozmert, Emin

2015-01-01

163

Electromagnetic wave equations for relativistically degenerate quantum magnetoplasmas.  

PubMed

A generalized set of nonlinear electromagnetic quantum hydrodynamic (QHD) equations is derived for a magnetized quantum plasma, including collisional, electron spin- 1/2, and relativistically degenerate electron pressure effects that are relevant for dense astrophysical systems, such as white dwarfs. For illustrative purposes, linear dispersion relations are derived for one-dimensional magnetoacoustic waves for a collisionless nonrelativistic degenerate gas in the presence of the electron spin- 1/2 contribution and for magnetoacoustic waves in a plasma containing relativistically degenerate electrons. It is found that both the spin and relativistic degeneracy at high densities tend to slow down the magnetoacoustic wave due to the Pauli paramagnetic effect and relativistic electron mass increase. The present study outlines the theoretical framework for the investigation of linear and nonlinear behaviors of electromagnetic waves in dense astrophysical systems. The results are applied to calculate the magnetoacoustic speeds for both the nonrelativistic and relativistic electron degeneracy cases typical for white dwarf stars. PMID:20866534

Masood, Waqas; Eliasson, Bengt; Shukla, Padma K

2010-06-01

164

[Age-related macular degeneration (AMD): etiopathogenesis and therapeutic strategies].  

PubMed

Age-related macular degeneration (AMD) is a disease leading to severe visual loss and legal blindness in the population over 60 years of age. Its pathogenesis is likely multifactorial, involving a complex interaction of metabolic, functional, genetic, and environmental factors, and remains poorly understood. For these reasons, currently used therapeutic approaches are insufficiently effective. Although major abnormalities are seen in four functionally interrelated tissues, i.e. photoreceptors, retinal pigment epithelium (RPE), Bruch's membrane, and choriocapillaries, the impairment of RPE cell functions is an early and crucial event in the molecular pathways leading to clinical relevant AMD changes. The RPE progressively degenerates, which results in an irreversible degeneration of photoreceptors. Four processes: lipofuscinogenesis, drusogenesis, inflammation, and neovascularization, specifically contribute to the development of the disease. Two types of AMD are distinguished: the dry and the wet form. This paper briefly describes major molecular and cellular events leading to AMD, and presents currently used and new, forthcoming therapeutic strategies. PMID:17369776

Nowak, Jerzy Z; Bienias, Wojciech

2007-01-01

165

Ranibizumab in neovascular age-related macular degeneration.  

PubMed

Neovascular age-related macular degeneration (AMD) is a visually devastating condition resulting from choroidal neovascularization and secondary photoreceptor loss. Ranibizumab and bevacizumab are medications that target vascular endothelial growth factor (VEGF). While other therapies have demonstrated some ability to reduce the risk of losing vision from neovascular AMD, most patients continue to lose some degree of central visual acuity. There is growing evidence that intravitreal administration of ranibizumab and bevacizumab is effective in significantly improving the visual acuity in patients with neovascular age-related macular degeneration. PMID:18046922

Kenneth, T Eng; Kertes, Peter J

2006-01-01

166

Local tracking and stability for degenerate viscous shock waves  

NASA Astrophysics Data System (ADS)

We study the pointwise behavior of perturbed degenerate (sonic) shock waves for scalar conservation laws with nonconstant diffusion. Building on the pointwise Green's function approach of Zumbrun and Howard (Indiana U. Math. J. 47(3) (1998) 741) we extend the linear analysis to an equation with nonintegrable coefficients. In lieu of working with the integrated equation, we employ a tracking mechanism that we expect will allow degenerate waves to be incorporated into the general framework for nondegenerate systems (Indiana U. Math. J. 47(3) (1998) 741).

Howard, Peter

167

Selective rod degeneration and partial cone inactivation characterize an iodoacetic acid model of Swine retinal degeneration.  

PubMed

PURPOSE. Transgenic pigs carrying a mutant human rhodopsin transgene have been developed as a large animal model of retinitis pigmentosa (RP). This model displays some key features of human RP, but the time course of disease progression makes this model costly, time consuming, and difficult to study because of the size of the animals at end-stage disease. Here, the authors evaluate an iodoacetic acid (IAA) model of photoreceptor degeneration in the pig as an alternative model that shares features of the transgenic pig and human RP. METHODS. IAA blocks glycolysis, thereby inhibiting photoreceptor function. The effect of the intravenous injection of IAA on swine rod and cone photoreceptor viability and morphology was followed by histologic evaluation of different regions of the retina using hematoxylin and eosin and immunostaining. Rod and cone function was analyzed by full-field electroretinography and multifocal electroretinography. RESULTS. IAA led to specific loss of rods in a central-to-peripheral retinal gradient. Although cones were resistant, they showed shortened outer segments, loss of bipolar cell synaptic connections, and a diminished flicker ERG, hallmarks of transition to cone dysfunction in RP patients. CONCLUSIONS. IAA provides an alternative rod-dominant model of retinal damage that shares a surprising number of features with the pig transgenic model of RP and with human RP. This IAA model is cost-effective and rapid, ensuring that the size of the animals does not become prohibitive for end-stage evaluation or therapeutic intervention. PMID:21896868

Wang, Wei; Fernandez de Castro, Juan; Vukmanic, Eric; Zhou, Liang; Emery, Douglas; Demarco, Paul J; Kaplan, Henry J; Dean, Douglas C

2011-01-01

168

Cerebellar degeneration in the Niemann-Pick type C mouse  

Microsoft Academic Search

Chronological morphological changes and topographical distribution of degenerating Purkinje cells were studied in the murine model of Niemann-Pick disease type C (NPC mouse). Loss of Purkinje cells can be detected in the anterior vermis as early as 60 days of age, coinciding with early neurological signs, and progressed to total absence in the entire hemisphere and vermis with exception of

Y. Higashi; S. Murayama; P. G. Pentchev; K. Suzuki

1993-01-01

169

Factors associated with lumbar intervertebral disc degeneration in the elderly  

Microsoft Academic Search

Background contextLumbar intervertebral disc degeneration (DD) precedes degenerative diseases of the lumbar spine. Various factors in addition to normal aging are reported to be associated with DD, and recently atherosclerosis and risk factors for cardiovascular diseases (cardiovascular risk factors) have received much attention; however, the links between these risk factors and DD are unclear.

Mika Hangai; Koji Kaneoka; Shinya Kuno; Shiro Hinotsu; Masataka Sakane; Naotaka Mamizuka; Shinsuke Sakai; Naoyuki Ochiai

2008-01-01

170

Exact null controllability of degenerate evolution equations with scalar control  

SciTech Connect

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.

Fedorov, Vladimir E; Shklyar, Benzion

2012-12-31

171

Nerve conduction during Wallerian degeneration in the baboon  

Microsoft Academic Search

Conduction in the lateral popliteal nerve of the baboon was studied during the course of Wallerian degeneration. Six nerves were examined. In each case the muscle response to nerve stimulation and the ascending nerve action potential were recorded daily until the nerve became inexcitable. The muscle response to nerve stimulation disappeared after four to five days, but ascending nerve action

R. W. Gilliatt; R. J. Hjorth

1972-01-01

172

Magnetic resonance imaging of meniscal degeneration in asymptomatic knees.  

PubMed

Histopathological studies have suggested that spontaneous degeneration of knee menisci predisposes to symptomatic tears. We used magnetic resonance (MR) imaging to study noninvasively 20 patients with documented meniscal tears in one knee but asymptomatic contralateral knees, 18 normal controls, and 15 patients with symptomatic nonmeniscal knee disorders. A scoring system for MR signal changes was developed, and differences between the three groups were tested for significance by a multivariate analysis of covariance. MR signal changes in the menisci begin at around 30 years of age, progress with age, occur in both men and women, and occur in subjects who are inactive as well as those who undergo habitual knee stress exercises. Most subjects with documented meniscal tears in one knee have MR signals in the asymptomatic contralateral knee that reflect a more advanced degree of meniscal degeneration than in age-comparable normal controls or patients with nonmeniscal knee disorders. After adjustment for potential confounding variables, weight, and sex, the mean scores in the asymptomatic knee of patients with meniscal disease are significantly higher than those of normal controls (p = 0.021) and nonmeniscal disease patients (p = 0.019). These results document the occurrence of age-dependent degeneration within knee menisci, and support the hypothesis that a segment of the population has pre-existing meniscal degeneration predisposing them to traumatic or spontaneous meniscal tears. PMID:2324849

Negendank, W G; Fernandez-Madrid, F R; Heilbrun, L K; Teitge, R A

1990-05-01

173

Cesare Lombroso: an anthropologist between evolution and degeneration  

PubMed Central

Summary 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. PMID:21729591

Mazzarello, Paolo

174

Subacute combined degeneration: clinical, electrophysiological, and magnetic resonance imaging findings  

Microsoft Academic Search

OBJECTIVEVitamin B12 deficiency is a systemic disease that often affects the nervous system. One of the most prevalent manifestations is subacute combined degeneration (SCD) of the spinal cord. To access the clinical, electrophysiological, and structural abnormalities associated with SCD, a study was conducted in nine patients.METHODSClinical, electrophysiological (electroneurography, somatosensory and motor evoked potentials), and MRI evaluations were performed in patients

B Hemmer; F X Glocker; M Schumacher; G Deuschl; C H Lücking

1998-01-01

175

Blood Flow Magnetic Resonance Imaging of Retinal Degeneration  

E-print Network

Blood Flow Magnetic Resonance Imaging of Retinal Degeneration Yingxia Li,1 Haiying Cheng,1 Qiang. Duong1,2,3,4,5,6,7 PURPOSE. This study aims to investigate quantitative basal blood flow as well as hypercapnia- and hyperoxia-induced blood flow changes in the retinas of the Royal College of Surgeons (RCS

Duong, Timothy Q.

176

Advancing Research and Treatment for Frontotemporal Lobar Degeneration (ARTFL)  

ClinicalTrials.gov

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)

2015-02-11

177

Adaptive evolution of eye degeneration in the Mexican blind cavefish.  

PubMed

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. PMID:15653557

Jeffery, W R

2005-01-01

178

Cesare Lombroso: an anthropologist between evolution and degeneration.  

PubMed

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. PMID:21729591

Mazzarello, Paolo

2011-01-01

179

Linear harmonic oscillator in spaces with degenerate metrics  

E-print Network

With the help of contraction method we study the harmonic oscillator in spaces with degenerate metrics, namely, on Galilei plane and in the flat 3D Cayley-Klein spaces $R_3(j_2,j_3).$ It is shown that the inner degrees of freedom are appeared which physical dimensions are different from the dimension of the space.

N. A. Gromov

2006-03-02

180

Longitudinal Magnetoacoustic Phenomena in Degenerate Semiconductors and Semimetals  

Microsoft Academic Search

The effects of parabolic and nonparabolic band structures on the propagation of ultrasound in a degenerate semiconductor like SrTiO3 in the presence of a dc longitudinal magnetic field are investigated. The major interaction between the conduction electrons and the ultrasound is via deformation potential coupling. It is found that the absorption coefficient and sound velocity for ultrasound propagating parallel to

Chhi-Chong Wu; Jensan Tsai

1972-01-01

181

Environmental Hydrocarbons Produce Degeneration in Cat Hypothalamus and Optic Tract  

Microsoft Academic Search

2,5-Hexanedione, the principal neurotoxic metabolite of the industrial solvents n-hexane and methyl n-butyl ketone causes axonal degeneration in the mammillary body and visual nuclei of cats. Prolonged, low-level exposure to hydrocarbons in the environment may cause premature deterioration in areas of the human brain vital for perception and behavior.

Herbert H. Schaumburg; Peter S. Spencer

1978-01-01

182

Hedgehog signalling controls eye degeneration in blind cavefish  

Microsoft Academic Search

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

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

2004-01-01

183

Local tracking and stability for degenerate viscous shock waves  

Microsoft Academic Search

We study the pointwise behavior of perturbed degenerate (sonic) shock waves for scalar conservation laws with nonconstant diffusion. Building on the pointwise Green's function approach of Zumbrun and Howard (Indiana U. Math. J. 47(3) (1998) 741) we extend the linear analysis to an equation with nonintegrable coefficients. In lieu of working with the integrated equation, we employ a tracking mechanism

Peter Howard

2002-01-01

184

Genetic factors of age-related macular degeneration  

Microsoft Academic Search

Age-related macular degeneration (AMD) is a leading cause of blindness in the United States and developed countries. Although the etiology and pathogenesis of AMD remain unknown, a complex interaction of genetic and environmental factors is thought to exist. The incidence and progression of all of the features of AMD are known to increase significantly with age. The tendency for familial

Jingsheng Tuo; Christine M. Bojanowski; Chi-Chao Chan

2004-01-01

185

Urocortin 2 treatment is protective in excitotoxic retinal degeneration.  

PubMed

Urocortin 2 (Ucn 2) is a corticotrop releasing factor paralog peptide with many physiological functions and it has widespread distribution. There are some data on the cytoprotective effects of Ucn 2, but less is known about its neuro- and retinoprotective actions. We have previously shown that Ucn 2 is protective in ischemia-induced retinal degeneration. The aim of the present study was to examine the protective potential of Ucn 2 in monosodium-glutamate (MSG)-induced retinal degeneration by routine histology and to investigate cell-type specific effects by immunohistochemistry. Rat pups received MSG applied on postnatal days 1, 5 and 9 and Ucn 2 was injected intravitreally into one eye. Retinas were processed for histology and immunocytochemistry after 3 weeks. Immunolabeling was determined for glial fibrillary acidic protein, vesicular glutamate transporter 1, protein kinase C?, calbindin, parvalbumin and calretinin. Retinal tissue from animals treated with MSG showed severe degeneration compared to normal retinas, but intravitreal Ucn 2 treatment resulted in a retained retinal structure both at histological and neurochemical levels: distinct inner retinal layers and rescued inner retinal cells (different types of amacrine and rod bipolar cells) could be observed. These findings support the neuroprotective function of Ucn 2 in MSG-induced retinal degeneration. PMID:24311224

Szabadfi, K; Kiss, P; Reglodi, D; Fekete, E M; Tamas, A; Danyadi, B; Atlasz, T; Gabriel, R

2014-03-01

186

Speech and Language Findings Associated with Paraneoplastic Cerebellar Degeneration  

ERIC Educational Resources Information Center

Paraneoplastic cerebellar degeneration (PCD) is an autoimmune disease that can be associated with cancer of the breast, lung, and ovary. The clinical presentation of PCD commonly includes ataxia, visual disturbances, and dysarthria. The speech disturbances associated with PCD have not been well characterized, despite general acceptance that…

Paslawski, Teresa; Duffy, Joseph R.; Vernino, Steven

2005-01-01

187

Nutritional modulation of age-related macular degeneration  

Technology Transfer Automated Retrieval System (TEKTRAN)

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly worldwide. It affects 30-50 million individuals and clinical hallmarks of AMD are observed in at least one third of persons over the age of 75 in industrialized countries (Gehrs et al., 2006). Costs associated wi...

188

Remarks on Cyclotomic and Degenerate Cyclotomic BMW Algebras  

E-print Network

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.

Goodman, Frederick M

2010-01-01

189

Episodic memory and regional atrophy in frontotemporal lobar degeneration  

Microsoft Academic Search

It has been unclear to what extent memory is affected in frontotemporal lobar degeneration (FTLD). Since patients usually have atrophy in regions implicated in memory function, the frontal and\\/or temporal lobes, one would expect some memory impairment, and that the degree of atrophy in these regions would be inversely related to memory function. The purposes of this study were (1)

Hedvig Söderlund; Sandra E. Black; Bruce L. Miller; Morris Freedman; Brian Levine

2008-01-01

190

Joint incongruity and meniscal degeneration: an electron microscopic examination  

Microsoft Academic Search

Conclusion  The menisci play an important role in stress shielding the joint surfaces of the knee following intra-articular fractures\\u000a and other conditions that might increase trans-articular pressure. The effect of such shielding, however, results in significant\\u000a wear and degeneration of the meniscus itself.

S. Morris; D. Cottell; D. Me Cormack

2002-01-01

191

Longitudinal dielectric permeability of the quantum degenerate collisional plasmas  

E-print Network

Dielectric permeability of the degenerate electronic gas for the collisional plasmas is found. The kinetic equation of Wigner -- Vlasov -- Boltzmann with integral of collisions in relaxation form in coordinate space is used. We will notice that dielectric permeability with using of the relaxation equation in the momentum space has been received by Mermin.

Anatoly V. Latyshev; Alexander Yushkanov

2010-01-22

192

CONTINUOUS DEPENDENCE ESTIMATES FOR VISCOSITY SOLUTIONS OF FULLY NONLINEAR DEGENERATE PARABOLIC EQUATIONS  

E-print Network

CONTINUOUS DEPENDENCE ESTIMATES FOR VISCOSITY SOLUTIONS OF FULLY NONLINEAR DEGENERATE PARABOLIC for viscosity solutions of fully nonlinear degenerate parabolic equations with time and space dependent for the vanishing viscosity method. Finally, we illustrate the results (i) { (iii) on the Hamilton

Soatto, Stefano

193

Retinal Oxygenation and Oxygen Metabolism in Abyssinian Cats with a Hereditary Retinal Degeneration  

E-print Network

Retinal Oxygenation and Oxygen Metabolism in Abyssinian Cats with a Hereditary Retinal Degeneration circulation in hereditary photoreceptor degenerations. METHODS. Seven adult Abyssinian cats affected- phic) one as well. In the present study, we further examined the hypothesis that oxygen from

Linsenmeier, Robert

194

Viruses associated with ovarian degeneration in Apis mellifera L. queens.  

PubMed

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. PMID:21283547

Gauthier, Laurent; Ravallec, Marc; Tournaire, Magali; Cousserans, François; Bergoin, Max; Dainat, Benjamin; de Miranda, Joachim R

2011-01-01

195

Viruses Associated with Ovarian Degeneration in Apis mellifera L. Queens  

PubMed Central

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. PMID:21283547

Gauthier, Laurent; Ravallec, Marc; Tournaire, Magali; Cousserans, François; Bergoin, Max; Dainat, Benjamin; de Miranda, Joachim R.

2011-01-01

196

Membrane protein oxidation determines neuronal degeneration.  

PubMed

Oxidative stress is an early hallmark in neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. However, the critical biochemical effector mechanisms of oxidative neurotoxicity have remained surprisingly elusive. In screening various peroxides and potential substrates of oxidation for their effect on neuronal survival, we observed that intramembrane compounds were significantly more active than aqueous or amphiphilic compounds. To better understand this result, we synthesized a series of competitive and site-specific membrane protein oxidation inhibitors termed aminoacyllipids, whose structures were designed on the basis of amino acids frequently found at the protein-lipid interface of synaptic membrane proteins. Investigating the aminoacyllipids in primary neuronal culture, we found that the targeted protection of transmembrane tyrosine and tryptophan residues was sufficient to prevent neurotoxicity evoked by hydroperoxides, kainic acid, glutathione-depleting drugs, and certain amyloidogenic peptides, but ineffective against non-oxidative inducers of apoptosis such as sphingosine or Akt kinase inhibitors. Thus, the oxidative component of different neurotoxins appears to converge on neuronal membrane proteins, irrespective of the primary mechanism of cellular oxidant generation. Our results indicate the existence of a one-electron redox cycle and its functional relevance to membrane protein aromatic surface amino acids, whose disturbance or overload leads to excessive membrane protein oxidation and neuronal death. This article is protected by copyright. All rights reserved. PMID:25393523

Hajieva, Parvana; Bayatti, Nadhim; Granold, Matthias; Behl, Christian; Moosmann, Bernd

2014-11-13

197

Blow-up dynamics for the aggregation equation with degenerate , Andrea L. Bertozzia  

E-print Network

Blow-up dynamics for the aggregation equation with degenerate diffusion Yao Yaoa , Andrea L-similarity, aggregation, degenerate diffusion 1. Introduction 1.1. Background Aggregation-diffusion type equations arise-law degenerate diffusion. In the absence of the diffusion term um , (1.1) becomes the aggregation equation, which

Bertozzi, Andrea L.

198

Simple Colorimetric Method for Detecting Degenerate Strains of the Cultivated Basidiomycete Flammulina velutipes (Enokitake)  

Microsoft Academic Search

The primary objective of this study was to develop a simple method for detecting degenerate Flammulina velutipes (Eno- kitake) cultures. Cultural degeneration of cultivated strains of Enokitake similar to the degeneration observed for Agaricus bisporus (1, 2) has become a serious problem in Japan. Previ- ous efforts to evaluate the fruiting potential of Enokitake have been made using isozyme electrophoresis

Yumi Magae; Kobun Akahane; Kimiyoshi Nakamura; Shigeyuki Tsunoda

2005-01-01

199

ON DEGENERATE HAMBURGER MOMENT PROBLEM AND EXTENSIONS OF POSITIVE SEMIDEFINITE HANKEL BLOCK MATRICES  

E-print Network

ON DEGENERATE HAMBURGER MOMENT PROBLEM AND EXTENSIONS OF POSITIVE SEMIDEFINITE HANKEL BLOCK semidefinite Hankel block­matrices and associated degenerate truncated matrix Hamburger moment problems. The description of all solutions of a degenerate matrix Hamburger moment problem is given in terms of a linear

Bolotnikov, Vladimir

200

Experimental analysis of degenerate vector phase-sensitive amplification.  

PubMed

We comprehensively investigate a degenerate vector phase-sensitive amplifier (PSA). We determine the gain dependence on the relative phase and polarization angle between the pumps and the degenerate signal wave. The vector PSA is experimentally shown to be sensitive to the pump states of polarization (SOP) due to polarization mode dispersion in the fiber. However, the scheme performance agrees well with theory under specific pump SOPs and we achieve an on-off gain over 10 dB with a small deviation from the theoretically expected results. In comparison to the scalar scheme, the proposed vector scheme has larger tolerance for pump depletion due to four-wave mixing between pumps and generation of higher-order idlers. PMID:25321564

Lorences-Riesgo, Abel; Chiarello, Fabrizio; Lundström, Carl; Karlsson, Magnus; Andrekson, Peter A

2014-09-01

201

Accreting neutron stars, black holes, and degenerate dwarf stars  

NASA Astrophysics Data System (ADS)

During the past 8 years, extended temporal and broadband spectroscopic studies carried out by X-ray astronomical satellites have led to the identification of specific compact X-ray sources as accreting neutron stars, black holes, and degenerate dwarf stars in close binary systems. Such sources provide a unique opportunity to study matter under extreme conditions not accessible in the terrestrial laboratory. Quantitative theoretical models have been developed which demonstrate that detailed studies of these sources will lead to a greatly increased understanding of dense and superdense hadron matter, hadron superfluidity, high-temperature plasma in superstrong magnetic fields, and physical processes in strong gravitational fields. Through a combination of theory and observation such studies will make possible the determination of the mass, radius, magnetic field, and structure of neutron stars and degenerate dwarf stars and the identification of further candidate black holes, and will contribute appreciably to our understanding of the physics of accretion by compact astronomical objects.

Pines, D.

1980-02-01

202

Current-Drive Efficiency in a Degenerate Plasma  

SciTech Connect

a degenerate plasma, the rates of electron processes are much smaller than the classical model would predict, affecting the efficiencies of current generation by external non-inductive means, such as by electromagnetic radiation or intense ion beams. For electron-based mechanisms, the current-drive efficiency is higher than the classical prediction by more than a factor of 6 in a degenerate hydrogen plasma, mainly because the electron-electron collisions do not quickly slow down fast electrons. Moreover, electrons much faster than thermal speeds are more readily excited without exciting thermal electrons. In ion-based mechanisms of current drive, the efficiency is likewise enhanced due to the degeneracy effects, since the electron stopping power on slow ion beams is significantly reduced.

S. Son and N.J. Fisch

2005-11-01

203

Generation and degeneration of long internal waves in lakes  

NASA Astrophysics Data System (ADS)

The nonlinear evolution, generation and degeneration of wind-driven, basin-scale internal waves in lakes are investigated employing weakly-nonlinear, weakly-dispersive evolution models. The models studied are based on rational, asymptotic approximations of the hydrodynamic equations of motion, and include a two-layer model, a multi-modal model, and a large-lake model with the effect of earth's rotation. It is found that nonlinearity, in conjunction with the dispersive nature of the fluid medium, plays a principle role in (i) the early stage of degeneration of basin-scale waves through nonlinear steepening and subsequent generation of oscillatory waves; and (ii) the transfer of energy among multiple vertical modes in the internal field. Strong dependence of these nonlinear processes on the background stratification, the lake geometry, the horizontal extent of a lake, and the spatio-temporal wind stress function are demonstrated and quantified through a series of numerical simulations of the different models.

Sakai, Takahiro

2008-12-01

204

Resistive collimation of electron beams in relativistic and degenerate plasma  

NASA Astrophysics Data System (ADS)

The purpose of this research is the study of the effects of plasma state and fiber on collimating relativistic electron beam in fast ignition. In this paper, for collimating relativistic electrons produced at the laser plasma interaction, a thin fiber of aluminum, lithium or CH either in the classical, degenerate or relativistic plasma states is considered. The fast electron beam could be collimated down to radii of 10 ?m, in that case, the best results are achieved when there is a sharp transition in resistance. This ensures that the correct magnetic growth rate is used for hot electrons at different energy levels. Calculations show that the resistivity of the material surrounding the CH fiber in the degenerate plasma is smaller than that for classical and relativistic plasma.

Mahdavi, M.; Khodadadi Azadboni, F.

2014-09-01

205

Structure of nearly degenerate dipole bands in 108Ag  

NASA Astrophysics Data System (ADS)

The high spin negative parity states of 108Ag have been investigated with the 11B + 100Mo reaction at 39 MeV beam energy using the INGA facility at TIFR, Mumbai. From the ?-? 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 108Ag 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.

Sethi, J.; Palit, R.; Saha, S.; Trivedi, T.; Bhat, G. H.; Sheikh, J. A.; Datta, P.; Carroll, J. J.; Chattopadhyay, S.; Donthi, R.; Garg, U.; Jadhav, S.; Jain, H. C.; Karamian, S.; Kumar, S.; Litz, M. S.; Mehta, D.; Naidu, B. S.; Naik, Z.; Sihotra, S.; Walker, P. M.

2013-08-01

206

On degenerate plasma diagnostics based on ?-ray measurement  

NASA Astrophysics Data System (ADS)

The potentiality of electron degeneracy diagnostics based on ?-ray measurement is discussed. For this purpose, the nuclear reactions D (?, ?)6Li and T (?, ?)7Li are considered. These reactions are induced in DT plasma by fusion-born energetic ?-particles and proceed through the excited nuclei 6Li* and 7Li* emitting monochromatic ?-quanta with 2.186-MeV and 0.478-MeV energies, respectively, in their decay to the ground state. If the plasma is being highly compressed and the electrons are in degenerate state, then the stopping range of the ?-particles is lengthened compared with the case of non-degenerate electron plasma. As a result, the probability that a fusion-born ?-particle will undergo D (?, ?) or T(?, ?) reaction during slowing down would be enhanced. In this paper we will discuss the feasibility of detecting the 2.186-MeV and 0.478-MeV ?-ray in ICF environment.

Senmyo, N.; Nakao, Y.; Voronchev, V. T.; Johzaki, T.

2008-05-01

207

Clinical diagnostic criteria and classification controversies in frontotemporal lobar degeneration  

PubMed Central

Frontotemporal lobar degeneration (FTLD) can manifest as a spectrum of clinical syndromes, ranging from behavioural impairment to language or motor dysfunction. Recently, revised diagnostic criteria have been proposed for the behavioural and progressive aphasia syndromes associated with frontotemporal degeneration. The present review will summarize these diagnostic guidelines and highlight some lingering controversies in the classification of FTLD clinical syndromes. We will discuss common tools and methods used to identify the insidious changes of behavioural variant frontotemporal dementia (bvFTD), the value of new, patient-based tasks of orbitofrontal function, and the issue of a benign or ‘phenocopy’ variant of bvFTD. With regard to primary progressive aphasia (PPA), we will discuss the scope of the semantic disorder in semantic-variant PPA, the nature of the speech disorder in non-fluent, agrammatic PPA, and the preliminary utility of a logopenic PPA classification. PMID:23611345

RASCOVSKY, KATYA; GROSSMAN, MURRAY

2014-01-01

208

Protein Gq Modulates Termination of Phototransduction and Prevents Retinal Degeneration*  

PubMed Central

Appropriate termination of the phototransduction cascade is critical for photoreceptors to achieve high temporal resolution and to prevent excessive Ca2+-induced cell toxicity. Using a genetic screen to identify defective photoresponse mutants in Drosophila, we isolated and identified a novel G?q mutant allele, which has defects in both activation and deactivation. We revealed that Gq modulates the termination of the light response and that metarhodopsin/Gq interaction affects subsequent arrestin-rhodopsin (Arr2-Rh1) binding, which mediates the deactivation of metarhodopsin. We further showed that the G?q mutant undergoes light-dependent retinal degeneration, which is due to the slow accumulation of stable Arr2-Rh1 complexes. Our study revealed the roles of Gq in mediating photoresponse termination and in preventing retinal degeneration. This pathway may represent a general rapid feedback regulation of G protein-coupled receptor signaling. PMID:22389492

Hu, Wen; Wan, Didi; Yu, Xiaoming; Cao, Jinguo; Guo, Peiyi; Li, Hong-sheng; Han, Junhai

2012-01-01

209

Follistatin Alleviates Synovitis and Articular Cartilage Degeneration Induced by Carrageenan  

PubMed Central

Activins are proinflammatory cytokines which belong to the TGF? superfamily. Follistatin is an extracellular decoy receptor for activins. Since both activins and follistatin are expressed in articular cartilage, we hypothesized that activin-follistatin signaling participates in the process of joint inflammation and cartilage degeneration. To test this hypothesis, we examined the effects of follistatin in a carrageenan-induced mouse arthritis model. Synovitis induced by intra-articular injection of carrageenan was significantly alleviated by preinjection with follistatin. Macrophage infiltration into the synovial membrane was significantly reduced in the presence of follistatin. In addition, follistatin inhibited proteoglycan erosion induced by carrageenan in articular cartilage. These data indicate that activin-follistatin signaling is involved in joint inflammation and cartilage homeostasis. Our data suggest that follistatin can be a new therapeutic target for inflammation-induced articular cartilage degeneration. PMID:25574420

Yamada, Jun; Abula, Kahaer; Inoue, Makiko; Sekiya, Ichiro; Muneta, Takeshi

2014-01-01

210

Suppression of Density Fluctuations in a Quantum Degenerate Fermi Gas  

SciTech Connect

We study density profiles of an ideal Fermi gas and observe Pauli suppression of density fluctuations (atom shot noise) for cold clouds deep in the quantum degenerate regime. Strong suppression is observed for probe volumes containing more than 10 000 atoms. Measuring the level of suppression provides sensitive thermometry at low temperatures. After this method of sensitive noise measurements has been validated with an ideal Fermi gas, it can now be applied to characterize phase transitions in strongly correlated many-body systems.

Sanner, Christian; Su, Edward J.; Keshet, Aviv; Gommers, Ralf; Shin, Yong-il; Huang Wujie; Ketterle, Wolfgang [MIT-Harvard Center for Ultracold Atoms, Research Laboratory of Electronics, and Department of Physics, Massachusetts Institute of Technology, Cambridge Massachusetts 02139 (United States)

2010-07-23

211

Simulating 4D Simplicial Gravity including Degenerate Triangulations  

E-print Network

We extend simulations of simplicial gravity in four dimensions to include {\\it degenerate} triangulations and demonstrate that using this ensemble the geometric finite-size effects are much reduced. We provide strong numerical evidence for the existence of an exponential bound on the entropy of the model and establish that the phase structure is identical to that of a corresponding model restricted to an ensemble of combinatorial triangulations.

S. Bilke; G. Thorleifsson

1998-09-15

212

A novel classification system of lumbar disc degeneration.  

PubMed

The Pfirrmann and modified Pfirrmann grading systems are currently used to classify lumbar disc degeneration. These systems, however, do not incorporate variables that have been associated with lumbar disc degeneration, including Modic changes, a high intensity zone, and a significant reduction in disc height. A system that incorporates these variables that is easy to apply may be useful for research and clinical purposes. A grading system was developed that incorporates disc structure and brightness, presence or absence of Modic changes, presence or absence of a high intensity zone, and reduction in disc height (disc height less than 5mm). MRI of 300 lumbar discs in 60 patients were analyzed twice by two neurosurgeons. Intra and inter-observer reliabilities were assessed by calculating Cohen's ? values. There were 156 grade zero ("normal"), 50 grade one, 57 grade two, 26 grade three, 10 grade four, and one grade five ("worst") discs. Inter-observer reliability was substantial (?=0.66 to 0.77) for disc brightness/structure, Modic changes, and disc height. Inter-observer reliability was moderate (?=0.41) for high intensity zone. Intra-observer reliability was moderate to excellent (?=0.53 to 0.94) in all categories. Agreement on the total grade between reviewers occurred 71% of the time and a difference of one grade occurred in an additional 25% of cases. Lumbar disc degeneration can be graded reliably by this novel system. The advantage of this system is that it incorporates disc brightness/structure, Modic changes, high intensity zone, and a rigid definition of loss of disc height. This system might be useful in research studies evaluating disc degeneration. Further studies are required to demonstrate possible clinical utility in predicting outcomes after spinal treatments such as fusion. PMID:25443079

Riesenburger, Ron I; Safain, Mina G; Ogbuji, Richard; Hayes, Jackson; Hwang, Steven W

2015-02-01

213

Geriatric vision loss due to cataracts, macular degeneration, and glaucoma.  

PubMed

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 elderly. PMID:22499498

Eichenbaum, Joseph W

2012-01-01

214

Circadian photoreception in the retinally degenerate mouse ( rd\\/rd )  

Microsoft Academic Search

We have examined the effects of light on circadian locomotor rhythms in retinally degenerate mice (C57BL\\/6J mice homozygous for the rd allele: rd\\/rd). The sensitivity of circadian photoreception in these mice was determined by varying the irradiance of a 15 min light pulse (515 nm) given at circadian time 16 and meauring the magnitude of the phase shift of the

R. G. Foster; I. Provencio; D. Hudson; S. Fiske; W. Grip; M. Menaker

1991-01-01

215

"Slow" wave of zero-sound in degenerate Fermi gas  

NASA Astrophysics Data System (ADS)

The dynamic Hartree-Fock theory with point-like interaction is used to calculate the speed of sound and damping factor of a zero-sound wave propagating in a degenerate Fermi gas. This wave propagates slower than Fermi velocity. It is shown, that if the interaction is weak and density is small, then the damping of such a wave can be small. A possibility of discovering such waves in ultracold Fermi gases is discussed.

Poluektov, Yuri; Savchenko, Volodymyr

2014-09-01

216

Remarks on Cyclotomic and Degenerate Cyclotomic BMW Algebras  

Microsoft Academic Search

We relate the structure of cyclotomic and degenerate cyclotomic BMW algebras,\\u000afor arbitrary parameter values, to that for admissible parameter values. In\\u000aparticular, we show that these algebras are cellular. We characterize those\\u000aparameter sets for affine BMW algebras over an algebraically closed field that\\u000apermit the algebras to have non--trivial cyclotomic quotients.

Frederick M. Goodman

2010-01-01

217

Magnetic susceptibility and Landau diamagnetism of quantum collisional degenerate plasmas  

E-print Network

With the use of correct expression of the electric conductivity of quantum collisional degenerate plasmas (A. V. Latyshev and A. A. Yushkanov, Transverse electrical conductivity of a quantum collisional plasma in the Mermin approach, - Theor. and Math. Phys., {\\bf 175}(1): 559-569 (2013)) the kinetic description of a magnetic susceptibility is obtained and the formula for calculation of Landau diamagnetism is deduced.

A. V. Latyshev; A. A. Yushkanov

2013-05-21

218

Membrane-shaping disorders: a common pathway in axon degeneration.  

PubMed

Neurons with long projections are particularly liable to damage, which is reflected by a large group of hereditary neurodegenerative disorders that primarily affect these neurons. In the group of hereditary spastic paraplegias motor axons of the central nervous system degenerate, while distal pure motor neuropathies, Charcot-Marie-Tooth disorders and the group of hereditary sensory and autonomic neuropathies are characterized by degeneration of peripheral nerve fibres. Because the underlying pathologies share many parallels, the disorders are also referred to as axonopathies. A large number of genes has been associated with axonopathies and one of the emerging subgroups encodes membrane-shaping proteins with a central reticulon homology domain. Association of these proteins with lipid bilayers induces positive membrane curvature and influences the architecture of cellular organelles. Membrane-shaping proteins closely cooperate and directly interact with each other, but their structural features and localization to distinct subdomains of organelles suggests mutually exclusive roles. In some individuals a mutation in a shaping protein can result in upper motor neuron dysfunction, whereas in other patients it can lead to a degeneration of peripheral neurons. This suggests that membrane-shaping disorders might be considered as a continuous disease-spectrum of the axon. PMID:25281866

Hübner, Christian A; Kurth, Ingo

2014-12-01

219

Production of quantum degenerate strontium gases: Larger, better, faster, colder  

E-print Network

We report on an improved scheme to generate Bose-Einstein condensates (BECs) and degenerate Fermi gases of strontium. This scheme allows us to create quantum gases with higher atom number, a shorter time of the experimental cycle, or deeper quantum degeneracy than before. We create a BEC of 84-Sr exceeding 10^7 atoms, which is a 30-fold improvement over previously reported experiments. We increase the atom number of 86-Sr BECs to 2.5x10^4 (a fivefold improvement), and refine the generation of attractively interacting 88-Sr BECs. We present a scheme to generate 84-Sr BECs with a cycle time of 2s, which, to the best of our knowledge, is the shortest cycle time of BEC experiments ever reported. We create deeply-degenerate 87-Sr Fermi gases with T/T_F as low as 0.10(1), where the number of populated nuclear spin states can be set to any value between one and ten. Furthermore, we report on a total of five different double-degenerate Bose-Bose and Bose-Fermi mixtures. These studies prepare an excellent starting poi...

Stellmer, Simon; Schreck, Florian

2012-01-01

220

Electrostatic rogue-waves in relativistically degenerate plasmas  

SciTech Connect

In this paper, we investigate the modulational instability and the possibility of electrostatic rogue-wave propagations in a completely degenerate plasma with arbitrary degree of degeneracy, i.e., relativistically degenerate plasma, ranging from solid density to the astrophysical compact stars. The hydrodynamic approach along with the perturbation method is used to reduce the governing equations to the nonlinear Schrödinger equation from which the modulational instability, the growth rate of envelope excitations and the occurrence of rogue as well as super-rogue waves in the plasma, is evaluated. It is observed that the modulational instability in a fully degenerate plasma can be quite sensitive to the plasma number-density and the wavenumber of envelop excitations. It is further revealed that the relativistically degeneracy plasmas (R{sub 0}?>?1) are almost always modulationally unstable. It is found, however, that the highly energetic sharply localized electrostatic rogue as well as super-rogue waves can exist in the astrophysical compact objects like white dwarfs and neutron star crusts. The later may provide a link to understand many physical processes in such stars and it may lead us to the origin of the random-localized intense short gamma-ray bursts, which “appear from nowhere and disappear without a trace” quite similar to oceanic rogue structures.

Akbari-Moghanjoughi, M. [Department of Physics, Faculty of Sciences, Azarbaijan Shahid Madani University, 51745-406 Tabriz, Iran and International Centre for Advanced Studies in Physical Sciences and Institute for Theoretical Physics, Ruhr University Bochum, D-44780 Bochum (Germany)

2014-10-15

221

Quantum degenerate mixture of ytterbium and lithium atoms  

SciTech Connect

We have produced a quantum degenerate mixture of fermionic alkali-metal {sup 6}Li and bosonic spin-singlet {sup 174}Yb gases. This was achieved using sympathetic cooling of lithium atoms by evaporatively cooled ytterbium atoms in a far-off-resonant optical dipole trap. We observe the coexistence of Bose-condensed (T/T{sub c}{approx_equal}0.8) {sup 174}Yb with 2.3x10{sup 4} atoms and Fermi degenerate (T/T{sub F}{approx_equal}0.3) {sup 6}Li with 1.2x10{sup 4} atoms. Quasipure Bose-Einstein condensates of up to 3x10{sup 4} {sup 174}Yb atoms can be produced in single-species experiments. Our results mark a significant step toward studies of few- and many-body physics with mixtures of alkali-metal and alkaline-earth-metal-like atoms, and for the production of paramagnetic polar molecules in the quantum regime. Our methods also establish a convenient scheme for producing quantum degenerate ytterbium atoms in a 1064 nm optical dipole trap.

Hansen, Anders H.; Khramov, Alexander; Dowd, William H.; Jamison, Alan O.; Ivanov, Vladyslav V.; Gupta, Subhadeep [Department of Physics, University of Washington, Seattle, Washington 98195 (United States)

2011-07-15

222

Exact nonlinear excitations in double-degenerate plasmas  

SciTech Connect

In this work, we use the conventional hydrodynamics formalism and incorporate the Chew-Goldberger-Low double-adiabatic theory to evaluate the nonlinear electrostatic ion excitations in double-degenerate (electron spin-orbit degenerate) magnetized quantum plasmas. Based on the Sagdeev pseudopotential method, an exact general pseudopotential is calculated which leads to the allowed Mach-number range criteria for such localized density structures in an anisotropic magnetized plasma. We employ the criteria on the Mach-number range for diverse magnetized quantum plasma with different equations of state. It is remarked that various plasma fractional parameters such as the system dimensionality, ion-temperature, relativistic-degeneracy, Zeeman-energy, and plasma composition are involved in the stability of an obliquely propagating nonlinear ion-acoustic wave in a double-degenerate quantum plasma. Current study is most appropriate for nonlinear wave analysis in dense astrophysical magnetized plasma environments such as white-dwarfs and neutron-star crusts where the strong magnetic fields can be present.

Akbari-Moghanjoughi, M. [Department of Physics, Faculty of Sciences, Azarbaijan University of Tarbiat Moallem, 51745-406 Tabriz (Iran, Islamic Republic of)

2012-06-15

223

Spinal inhibitory circuits and their role in motor neuron degeneration.  

PubMed

In the spinal cord neuronal activity is controlled by the balance between excitatory and inhibitory neurotransmission, mediated mainly by the neurotransmitters glutamate and GABA/glycine, respectively. Alterations of this equilibrium have been associated with spinal motor neuron hyperexcitability and degeneration, which can be induced by excitotoxicity or by decreasing inhibitory neurotransmission. Here we review the ventral horn neuronal network and the possible involvement of inhibitory circuits in the mechanisms of degeneration of motor neurons characteristic of amyotrophic lateral sclerosis (ALS). Whereas glutamate mediated excitotoxicity seems to be an important factor, recent experimental and histopathological evidence argue in favor of a decreased activity of the inhibitory circuits controlling motor neuron excitability, mainly the recurrent inhibition exerted by Renshaw cells. A decreased Renshaw cell activity may be caused by cell loss or by a reduction of its inhibitory action secondary to a decreased excitation from cholinergic interneurons. Ultimately, inhibitory failure by either mechanism might lead to motor neuron degeneration, and this suggests inhibitory circuits and Renshaw cells as pharmacologic targets for ALS treatment. PMID:24157492

Ramírez-Jarquín, Uri Nimrod; Lazo-Gómez, Rafael; Tovar-Y-Romo, Luis B; Tapia, Ricardo

2014-07-01

224

The lumbar intervertebral disc: from embryonic development to degeneration.  

PubMed

Lumbar intervertebral discs (IVDs) are prone to degeneration upon skeletal maturity. In fact, this process could explain approximately 40% of the cases of low back pain in humans. Despite the efficiency of pain-relieving treatments, the scientific community seeks to develop innovative therapeutic approaches that might limit the use of invasive surgical procedures (e.g., spine fusion and arthroplasty). As a prerequisite to the development of these strategies, we must improve our fundamental knowledge regarding IVD pathophysiology. Recently, several studies have demonstrated that there is a singular phenotype associated with Nucleus pulposus (NP) cells, which is distinct from that of articular chondrocytes. In parallel, recent studies concerning the origin and development of NP cells, as well as their role in intervertebral tissue homeostasis, have yielded new insights into the complex mechanisms involved in disc degeneration. This review summarizes our current understanding of IVD physiology and the complex cell-mediated processes that contribute to IVD degeneration. Collectively, these recent advances could inspire the scientific community to explore new biotherapeutic strategies. PMID:23932724

Colombier, Pauline; Clouet, Johann; Hamel, Olivier; Lescaudron, Laurent; Guicheux, Jérôme

2014-03-01

225

Degeneration Modulates Retinal Response to Transient Exogenous Oxidative Injury  

PubMed Central

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 may confer such relative protection from oxidative injury. PMID:24586289

Lederman, Michal; Hagbi-Levi, Shira; Grunin, Michelle; Obolensky, Alexey; Berenshtein, Eduard; Banin, Eyal; Chevion, Mordechai; Chowers, Itay

2014-01-01

226

Genome-wide analysis of pain-, nerve- and neurotrophin -related gene expression in the degenerating human annulus  

PubMed Central

Background In spite of its high clinical relevance, the relationship between disc degeneration and low back pain is still not well understood. Recent studies have shown that genome-wide gene expression studies utilizing ontology searches provide an efficient and valuable methodology for identification of clinically relevant genes. Here we use this approach in analysis of pain-, nerve-, and neurotrophin-related gene expression patterns in specimens of human disc tissue. Control, non-herniated clinical, and herniated clinical specimens of human annulus tissue were studied following Institutional Review Board approval. Results Analyses were performed on more generated (Thompson grade IV and V) discs vs. less degenerated discs (grades I-III), on surgically operated discs vs. control discs, and on herniated vs. control discs. Analyses of more degenerated vs. less degenerated discs identified significant upregulation of well-recognized pain-related genes (bradykinin receptor B1, calcitonin gene-related peptide and catechol-0-methyltransferase). Nerve growth factor was significantly upregulated in surgical vs. control and in herniated vs. control discs. All three analyses also found significant changes in numerous proinflammatory cytokine- and chemokine-related genes. Nerve, neurotrophin and pain-ontology searches identified many matrix, signaling and functional genes which have known importance in the disc. Immunohistochemistry was utilized to confirm the presence of calcitonin gene-related peptide, catechol-0-methyltransferase and bradykinin receptor B1 at the protein level in the human annulus. Conclusions Findings point to the utility of microarray analyses in identification of pain-, neurotrophin and nerve-related genes in the disc, and point to the importance of future work exploring functional interactions between nerve and disc cells in vitro and in vivo. Nerve, pain and neurotrophin ontology searches identified numerous changes in proinflammatory cytokines and chemokines which also have significant relevance to disc biology. Since the degenerating human disc is primarily an avascular tissue site into which disc cells have contributed high levels of proinflammatory cytokines, these substances are not cleared from the tissue and remain there over time. We hypothesize that as nerves grow into the human annulus, they encounter a proinflammatory cytokine-rich milieu which may sensitize nociceptors and exacerbate pain production. PMID:22963171

2012-01-01

227

Subconjunctival Palomid 529 in the treatment of neovascular age-related macular degeneration  

PubMed Central

Background Recent evidence suggests that neovascular age-related macular degeneration (AMD) may have an immune mediated component. Palomid 529, an investigational medication involving the immune Akt/mTOR pathway, is unique in dissociating both targets of rapamycin complexes TORC1 and TORC2. This small short-term pilot study assesses the safety of subconjunctival Palomid 529 in the treatment of neovascular AMD, with some limited efficacy information. Methods In this 12-week phase I open-label prospective pilot study, five participants with neovascular age-related macular degeneration that were refractory to intravitreal anti-vascular endothelial growth factor (VEGF) received three serial monthly subconjunctival doses of 1.9 mg Palomid 529. All participants were also offered concomitant monthly intravitreal anti-VEGF injections. Safety was monitored via adverse events recording. Additional outcome measures included visual acuity, optical coherence tomography, fluorescein angiography, indocyanine green angiography and fundus photography. Results The study drug was well-tolerated by all participants. There were no drug-related adverse events and no serious adverse events. A depot formed at the injection site, which persisted at the end of the study. In these anti-VEGF refractory patients, no clinically important changes in best-corrected visual acuity, fluorescein leakage pattern, choroidal neovascularization size on indocyanine green angiography, or autofluorescence pattern on fundus autofluorescence were observed compared to baseline. The fluid status, assessed with optical coherence tomography showed that central retinal thickness and macular volume remained stable in three participants, while the other two participants clinically progressed. Conclusions Serial subconjunctival injections of Palomid 529 were well-tolerated and resulted in depot formation. There were no concerns for any ocular or systemic toxicity during this small short-term study. Larger randomized studies are required to determine efficacy. PMID:23689994

Dalal, Monica; Jacobs-El, Naima; Nicholson, Benjamin; Tuo, Jingsheng; Chew, Emily; Chan, Chi-Chao; Nussenblatt, Robert; Ferris, Frederick

2014-01-01

228

A structural and functional analysis of Nna1 in Purkinje cell degeneration (pcd) mice  

PubMed Central

The axotomy-inducible enzyme Nna1 defines a subfamily of M14 metallocarboxypeptidases, and its mutation underlies the Purkinje cell degeneration (pcd) mouse. However, the relationship among its catalytic activity, substrate specificities, and the critical processes of neurodegeneration/axon regeneration is incompletely understood. Here we used a transgenic rescue strategy targeting expression of modified forms of Nna1 to Purkinje cells in pcd mice to determine structure-activity relationships for neuronal survival and in parallel characterized the enzymatic properties of purified recombinant Nna1. The Nna1 subfamily uniquely shares conserved substrate-determining residues with aspartoacylase that, when mutated, cause Canavan disease. Homologous mutations (D1007E and R1078E) inactivate Nna1 in vivo, as does mutation of its catalytic glutamate (E1094A), which implies that metabolism of acidic substrates is essential for neuronal survival. Consistent with reports that Nna1 is a tubulin glutamylase, recombinant Nna1—but not the catalytic mutants—removes glutamate from tubulin. Recombinant Nna1 metabolizes synthetic substrates with 2 or more C-terminal glutamate (but not aspartate) residues (Vmax for 3 glutamates is ?7-fold higher than 2 glutamates although KM is similar). Catalysis is not ATP/GTP dependent, and mutating the ATP/GTP binding site of Nna1 has no effect in vivo. Nna1 is a monomeric enzyme essential for neuronal survival through hydrolysis of polyglutamate-containing substrates.—Wu, H.-Y., Wang, T., Li, L., Correia, K., Morgan, J. I. A structural and functional analysis of Nna1 in Purkinje cell degeneration (pcd) mice. PMID:22835831

Wu, Hui-Yuan; Wang, Taiyu; Li, Leyi; Correia, Kristen; Morgan, James I.

2012-01-01

229

Inhibition of polyisoprenylated methylated protein methyl esterase by synthetic musks induces cell degeneration.  

PubMed

Synthetic fragrances are persistent environmental pollutants that tend to bioaccumulate in animal tissues. They are widely used in personal care products and cleaning agents. Worldwide production of Galaxolide and Tonalide are in excess of 4500 tons annually. Because of their widespread production and use, they have been detected in surface waters and fish in the US and Europe. Consumption of contaminated water and fish from such sources leads to bioaccumulation and eventual toxicity. Since fragrances and flavors bear structural similarities to polyisoprenes, it was of interest to determine whether toxicity by Galaxolide and Tonalide may be linked with polyisoprenylated methylated protein methyl esterase (PMPMEase) inhibition. A concentration-dependent study of PMPMEase inhibition by Galaxolide and Tonalide as well as their effects on the degeneration of cultured cells were conducted. Galaxolide and Tonalide inhibited purified porcine liver PMPMEase with Ki values of 11 and 14 ?M, respectively. Galaxolide and Tonalide also induced human cancer cell degeneration with EC50 values of 26 and 98 ?M (neuroblastoma SH-SY5Y cells) and 58 and 14 ?M (lung cancer A549 cells), respectively. The effects on cell viability correlate well with the inhibition of PMPMEase activity in the cultured cells. Molecular docking analysis revealed that the binding interactions are most likely between the fragrance molecules and hydrophobic amino acids in the active site of the enzyme. These results appear to suggest that the reported neurotoxicity of these compounds may be associated with their inhibition of PMPMEase. Exposure to fragrances may pose a significant risk to individuals predisposed to developing degenerative disorders. PMID:22489002

Ayuk-Takem, Lambert; Amissah, Felix; Aguilar, Byron J; Lamango, Nazarius S

2014-04-01

230

CREB1/ATF1 Activation in Photoreceptor Degeneration and Protection  

PubMed Central

Purpose. The cAMP response element binding protein 1 (CREB1) and activating transcription factor 1 (ATF1) are closely related members of the bZIP superfamily of transcription factors. Both are activated in response to a wide array of stimuli, including cellular stress. This study was conducted to assess the CREB1/ATF1 pathway in photoreceptor disease and protection. Methods. The expression levels of p-CREB1, CREB1, and ATF1 were examined by immunoblot and immunohistochemistry in normal canine retina and retinas of several canine models of retinal degeneration (rcd1, rcd2, erd, prcd, XLPRA1, XLPRA2, T4R RHO). Humans retinas affected with age-related macular degeneration (AMD) were also examined. p-CREB1/ATF1 immunolabeling was assessed in normal and rcd1 dogs treated with ciliary neurotrophic factor (CNTF), to examine the effect of a neuroprotective stimulus on activation of CREB1/ATF1. Results. Native CREB1 and ATF1 as well as phosphorylated CREB1/ATF1 was examined in normal canine retina by immunoblot. The p-CREB1 antibody identified phosphorylated CREB1 and ATF1 and labeled the inner retina only in normal dogs. In degenerate canine and human retinas, strong immunolabeling appeared in rod and cone photoreceptors, indicating increased expression of native CREB1 and ATF1, as well as increased phosphorylation of these proteins. Retinal protection by CNTF in rcd1 dogs was accompanied by a significant increase in the number of p-CREB1/ATF1-labeled photoreceptor nuclei. Conclusions. Positive association of CREB1/ATF1 phosphorylation with photoreceptor protection suggests that it may contribute to an innate protective response. These data identify a signaling mechanism in rods and cones of potential importance for therapies of RP and AMD. PMID:19643965

Beltran, William A.; Allore, Heather G.; Johnson, Elizabeth; Towle, Virginia; Tao, Weng; Acland, Gregory M.; Aguirre, Gustavo D.

2009-01-01

231

Decreased Proteasomal Activity Causes Photoreceptor Degeneration in Mice  

PubMed Central

Purpose. To study the retinal degeneration caused by decreased proteasomal activity in ?5t transgenic (?5t-Tg) mice, an animal model of senescence acceleration. Methods. ?5t-Tg mice and age-matched littermate control (WT) mice were used. Proteasomal activities and protein level of poly-ubiquitinated protein in retinal extracts were quantified. Fundus images of ?5t-Tg mice were taken and their features were assessed. For histologic evaluation, the thicknesses of inner nuclear layer (INL), outer nuclear layer (ONL), and photoreceptor outer segment (OS) were measured. For functional analysis, ERG was recorded under scotopic and photopic illumination conditions. Immunofluorescence (IF) staining and TUNEL were performed to investigate the mechanism of photoreceptor degeneration. Results. Chymotrypsin-like activity was partially suppressed in retinal tissues of ?5t-Tg mice. Retinal degenerative changes with arterial attenuation were present in ?5t-Tg, but not in WT mice. Inner nuclear layer thickness showed no significant change between ?5t-Tg and WT mice at 1, 3, 6, and 9 months of age. By contrast, thicknesses of ONL and OS in ?5t-Tg mice were significantly decreased at 3, 6, and 9 months compared with those in WT mice. Electroretinograms showed decrease of scotopic a-wave amplitude in ?5t-Tg mice. The number of TUNEL-positive cells in ONL were significantly increased in ?5t-Tg mice and colocalized with apoptosis-inducing factor, but not with cleaved caspase-3 and -9, indicating that the photoreceptor cell death was induced via a caspase-independent pathway. Conclusions. The current data showed that impaired proteasomal function causes photoreceptor degeneration. PMID:24994871

Ando, Ryo; Noda, Kousuke; Tomaru, Utano; Kamoshita, Mamoru; Ozawa, Yoko; Notomi, Shoji; Hisatomi, Toshio; Noda, Mika; Kanda, Atsuhiro; Ishibashi, Tatsuro; Kasahara, Masanori; Ishida, Susumu

2014-01-01

232

Activity Dependent Degeneration Explains Hub Vulnerability in Alzheimer's Disease  

PubMed Central

Brain connectivity studies have revealed that highly connected ‘hub’ regions are particularly vulnerable to Alzheimer pathology: they show marked amyloid-? deposition at an early stage. Recently, excessive local neuronal activity has been shown to increase amyloid deposition. In this study we use a computational model to test the hypothesis that hub regions possess the highest level of activity and that hub vulnerability in Alzheimer's disease is due to this feature. Cortical brain regions were modeled as neural masses, each describing the average activity (spike density and spectral power) of a large number of interconnected excitatory and inhibitory neurons. The large-scale network consisted of 78 neural masses, connected according to a human DTI-based cortical topology. Spike density and spectral power were positively correlated with structural and functional node degrees, confirming the high activity of hub regions, also offering a possible explanation for high resting state Default Mode Network activity. ‘Activity dependent degeneration’ (ADD) was simulated by lowering synaptic strength as a function of the spike density of the main excitatory neurons, and compared to random degeneration. Resulting structural and functional network changes were assessed with graph theoretical analysis. Effects of ADD included oscillatory slowing, loss of spectral power and long-range synchronization, hub vulnerability, and disrupted functional network topology. Observed transient increases in spike density and functional connectivity match reports in Mild Cognitive Impairment (MCI) patients, and may not be compensatory but pathological. In conclusion, the assumption of excessive neuronal activity leading to degeneration provides a possible explanation for hub vulnerability in Alzheimer's disease, supported by the observed relation between connectivity and activity and the reproduction of several neurophysiologic hallmarks. The insight that neuronal activity might play a causal role in Alzheimer's disease can have implications for early detection and interventional strategies. PMID:22915996

de Haan, Willem; Mott, Katherine; van Straaten, Elisabeth C. W.; Scheltens, Philip; Stam, Cornelis J.

2012-01-01

233

The effects of claudin 14 during early Wallerian degeneration after sciatic nerve injury  

PubMed Central

Claudin 14 has been shown to promote nerve repair and regeneration in the early stages of Wallerian degeneration (0–4 days) in rats with sciatic nerve injury, but the mechanism underlying this process remains poorly understood. This study reported the effects of claudin 14 on nerve degeneration and regeneration during early Wallerian degeneration. Claudin 14 expression was up-regulated in sciatic nerve 4 days after Wallerian degeneration. The altered expression of claudin 14 in Schwann cells resulted in expression changes of cytokines in vitro. Expression of claudin 14 affected c-Jun, but not Akt and ERK1/2 pathways. Further studies revealed that enhanced expression of claudin 14 could promote Schwann cell proliferation and migration. Silencing of claudin 14 expression resulted in Schwann cell apoptosis and reduction in Schwann cell proliferation. Our data revealed the role of claudin 14 in early Wallerian degeneration, which may provide new insights into the molecular mechanisms of Wallerian degeneration.

Gong, Leilei; Zhu, Yun; Xu, Xi; Li, Huaiqin; Guo, Weimin; Zhao, Qin; Yao, Dengbing

2014-01-01

234

Molecular chaperones protect against JNK- and Nmnat-regulated axon degeneration in Drosophila  

PubMed Central

Summary Axon degeneration is observed at the early stages of many neurodegenerative conditions and this often leads to subsequent neuronal loss. We previously showed that inactivating the c-Jun N-terminal kinase (JNK) pathway leads to axon degeneration in Drosophila mushroom body (MB) neurons. To understand this process, we screened candidate suppressor genes and found that the Wallerian degeneration slow (WldS) protein blocked JNK axonal degeneration. Although the nicotinamide mononucleotide adenylyltransferase (Nmnat1) portion of WldS is required, we found that its nicotinamide adenine dinucleotide (NAD+) enzyme activity and the WldS N-terminus (N70) are dispensable, unlike axotomy models of neurodegeneration. We suggest that WldS-Nmnat protects against axonal degeneration through chaperone activity. Furthermore, ectopically expressed heat shock proteins (Hsp26 and Hsp70) also protected against JNK and Nmnat degeneration phenotypes. These results suggest that molecular chaperones are key in JNK- and Nmnat-regulated axonal protective functions. PMID:23264732

Rallis, Andrew; Lu, Bingwei; Ng, Julian

2013-01-01

235

Genetic and Epigenetic Regulation in Age-related Macular Degeneration  

PubMed Central

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in the older population worldwide. While strong genetic risk factors have been associated with AMD etiology, environmental influences through epigenetic regulation are also likely to play a role. Recent advances in epigenetic studies have resulted in the development of numerous epigenetic drugs for the treatment of cancer and inflammation. Here, we review the current literature on the genetic and epigenetic mechanisms of AMD and suggest that understanding the cooperation of epigenetic and genetic mechanisms will greatly advance the clinical management of AMD. PMID:23997991

Wei, Lai; Chen, Ping; Lee, Joo Hyun; Nussenblatt, Robert B.

2013-01-01

236

Hydrodynamics in a Degenerate, Strongly Attractive Fermi Gas  

NASA Technical Reports Server (NTRS)

In summary, we use all-optical methods with evaporative cooling near a Feshbach resonance to produce a strongly interacting degenerate Fermi gas. We observe hydrodynamic behavior in the expansion dynamics. At low temperatures, collisions may not explain the expansion dynamics. We observe hydrodynamics in the trapped gas. Our observations include collisionally-damped excitation spectra at high temperature which were not discussed above. In addition, we observe weakly damped breathing modes at low temperature. The observed temperature dependence of the damping time and hydrodynamic frequency are not consistent with collisional dynamics nor with collisionless mean field interactions. These observations constitute the first evidence for superfluid hydrodynamics in a Fermi gas.

Thomas, John E.; Kinast, Joseph; Hemmer, Staci; Turlapov, Andrey; O'Hara, Ken; Gehm, Mike; Granade, Stephen

2004-01-01

237

An aggregation equation with degenerate diffusion: qualitative property of solutions  

E-print Network

We study a nonlocal aggregation equation with degenerate diffusion, set in a periodic domain. This equation represents the generalization to $m > 1$ of the McKean-Vlasov equation where here the "diffusive" portion of the dynamics are governed by Porous medium self-interactions. We focus primarily on $m\\in(1,2]$ with particular emphasis on $m = 2$. In general, we establish regularity properties and, for small interaction, exponential decay to the uniform stationary solution. For $m=2$, we obtain essentially sharp results on the rate of decay for the entire regime up to the (sharp) transitional value of the interaction parameter.

Chayes, Lincoln; Yao, Yao

2012-01-01

238

Degenerate quantum codes and the quantum Hamming bound  

E-print Network

The parameters of a nondegenerate quantum code must obey the Hamming bound. An important open problem in quantum coding theory is whether or not the parameters of a degenerate quantum code can violate this bound for nondegenerate quantum codes. In this paper we show that Calderbank-Shor-Steane (CSS) codes with alphabet $q\\geq 5$ cannot beat the quantum Hamming bound. We prove a quantum version of the Griesmer bound for the CSS codes which allows us to strengthen the Rains' bound that an $[[n,k,d

Pradeep Kiran Sarvepalli; Andreas Klappenecker

2009-11-21

239

Electron thermal conductivity owing to collisions between degenerate electrons  

E-print Network

We calculate the thermal conductivity of electrons produced by electron-electron Coulomb scattering in a strongly degenerate electron gas taking into account the Landau damping of transverse plasmons. The Landau damping strongly reduces this conductivity in the domain of ultrarelativistic electrons at temperatures below the electron plasma temperature. In the inner crust of a neutron star at temperatures T thermal conductivity completely dominates over the electron conductivity due to electron-ion (electron-phonon) scattering and becomes competitive with the the electron conductivity due to scattering of electrons by impurity ions.

P. S. Shternin; D. G. Yakovlev

2006-08-17

240

Peptide and steroid regulation of muscle degeneration in an insect.  

PubMed

Two types of cell death occur in the intersegmental muscles of the giant silkmoth Antheraea polyphemus. The first results from a slow atrophy of the fibers, and the second is a rapid, programmed dissolution of the muscle. Both types appear to be mediated by endocrine factors. The slow atrophy is brought about by the decline in the steroid molting hormone 20-hydroxyecdysone and can be prevented with exogenous steroid. The rapid degeneration is triggered by the peptide eclosion hormone, but the sensitivity of the muscle to the peptide depends on the history of exposure of the muscle to 20-hydroxyecdysone. PMID:6278594

Schwartz, L M; Truman, J W

1982-03-12

241

Aetiology of spheroidal degeneration of the cornea in Labrador.  

PubMed Central

To determine the aetiology of spheroidal degeneration of the cornea (Labrador keratopathy), total population surveys were conducted in 5 communities in coastal Labrador and northern Newfoundland. For 4 years records were also kept on all clinic patients aged 40 or more throughout the region. Both methods gave a peak prevalence at latitudes 55 degrees--56 degrees north. The greatest severity and earliest age of onset occurred around the same latitudes. Of the proposed environmental causative agents only ultraviolet radiation, reflected from ice and snow, explains the distribution of the disease. The high cumulative UV dosage is due to the unique geographical and climatic features of the region. Images PMID:7236572

Johnson, G J

1981-01-01

242

A Search for Unresolved Double Degenerates Using IUE Archives  

E-print Network

We present preliminary results of a study aimed at detecting double white dwarf systems using a method based on a comparison of optical and UV spectra for 141 DA stars drawn from the IUE archives. In particular, we are looking for dicrepancies between optical and UV temperatures. Even though known unresolved degenerate binaries stand out in this comparison, most temperature differences can probably be attributed to the presence of reddening, or the presence of heavy elements. We are in the process of securing additional optical spectroscopic observations to increase the number of stars in our analysis.

Charles-Philippe Lajoie; Pierre Bergeron

2005-03-08

243

Arthroscopic management of mucoid degeneration of anterior cruciate ligament  

PubMed Central

Background: Mucoid degeneration of the anterior cruciate ligament (ACL) is a less understood entity. The purpose of this study was to diagnose mucoid degeneration of anterior cruciate ligament and to assess the effectiveness of arthroscopic treatment in these patients. Materials and Methods: Between December 2007 and November 2011, 20 patients were diagnosed to be suffering from mucoid degeneration of anterior cruciate ligament (ACL) on the basis of magnetic resonance imaging (MRI), histopathology, and arthroscopy findings. 12 patients were males and 8 patients were females, with mean age of 42.2 years for males (range 28-52 years) and 39.4 years for females (range 30–54 years). They presented with pain on terminal extension (n=10) and on terminal flexion (n=2) without history of significant preceding trauma. MRI showed an increased signal in the substance of the ACL both in the T1- and T2-weighted images, with a mass-like configuration that was reported as a partial or complete tear of the ACL by the radiologist. At arthroscopy, the ACL was homogenous, bulbous, hypertrophied, and taut, occupying the entire intercondylar notch. A debulking of the ACL was performed by a judicious excision of the degenerated mucoid tissue, taking care to leave behind as much of the intact ACL as possible. Releasing it and performing a notchplasty treated impingement of the ACL to the roof and lateral wall. In one patient, we had to replace ACL due to insufficient tissue left behind to support the knee. Results: Good to excellent pain relief on terminal flexion–extension was obtained in 19 of 20 knees. The extension deficit was normalized in all knees. Lachman and anterior drawer test showed a firm endpoint in all, and 85% (n=17) showed good to excellent subjective satisfaction. Conclusions: Mucoid hypertrophy of the ACL should be suspected in elderly persons presenting pain on terminal extension or flexion without preceding trauma, especially when there is no associated meniscal lesion or ligamentous insufficiency. They respond well to a judicious arthroscopic release of the ACL with notchplasty. PMID:23162150

Chudasama, Chirag H; Chudasama, Vyoma C; Prabhakar, Mukund M

2012-01-01

244

The mass ratio distribution of short period double degenerate stars  

Microsoft Academic Search

Short period double degenerates (DDs) are close white dwarf - white dwarf\\u000abinary stars which are the result of the evolution of interacting binary stars.\\u000aWe present the first definitive measurements of the mass ratio for two DDs,\\u000aWD0136+768 and WD1204+450, and an improved measurement of the mass ratio for\\u000aWD0957-666. We compare the properties of the 6 known DDs

P. F. L. Maxted; T. R. Marsh; C. K. J. Moran

2002-01-01

245

Tissue engineering strategies to study cartilage development, degeneration and regeneration.  

PubMed

Cartilage tissue engineering has primarily focused on the generation of grafts to repair cartilage defects due to traumatic injury and disease. However engineered cartilage tissues have also a strong scientific value as advanced 3D culture models. Here we first describe key aspects of embryonic chondrogenesis and possible cell sources/culture systems for in vitro cartilage generation. We then review how a tissue engineering approach has been and could be further exploited to investigate different aspects of cartilage development and degeneration. The generated knowledge is expected to inform new cartilage regeneration strategies, beyond a classical tissue engineering paradigm. PMID:25174307

Bhattacharjee, Maumita; Coburn, Jeannine; Centola, Matteo; Murab, Sumit; Barbero, Andrea; Kaplan, David L; Martin, Ivan; Ghosh, Sourabh

2014-08-29

246

Malignant degeneration of a chondromyxoid fibroma in a child.  

PubMed

A 10-year-old boy was treated for a chondromyxoid fibroma of the left femur by curettage, and 2 months later complete healing was demonstrated radiographically. Three years after operation, radiographs revealed replacement of the ilium, ischium and upper femur, and destruction of the left hip by a soft-tissue and bony mass; a left hemipelvectomy was performed for what was shown to be a chondrosarcoma. Follow-up 10 years after the initial operation and 7 years after the hemipelvectomy has confirmed uneventful recovery in this rare case of malignant degeneration of a proven chondromyxoid fibroma of bone. PMID:1148963

Sehayik, S; Rosman, M A

1975-07-01

247

Imploding and exploding shocks in negative ion degenerate plasmas  

SciTech Connect

Imploding and exploding shocks are studied in nonplanar geometries for negative ion degenerate plasma. Deformed Korteweg de Vries Burgers (DKdVB) equation is derived by using reductive perturbation method. Two level finite difference scheme is used for numerical analysis of DKdVB. It is observed that compressive and rarefactive shocks are observed depending on the value of quantum parameter. The effects of temperature, kinematic viscosity, mass ratio of negative to positive ions and quantum parameter on diverging and converging shocks are presented.

Hussain, S.; Akhtar, N. [Theoretical Plasma Physics Division, PINSTECH, Nilore, Islamabad 44000 (Pakistan); Department of Physics and Applied Mathematics PIEAS, Nilore, Islamabad 44000 (Pakistan)

2011-08-15

248

Present and Possible Therapies for Age-Related Macular Degeneration  

PubMed Central

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 options for this condition remain substantially limited. In this review, we outline the existing arsenal of therapies available for AMD and discuss the additional role of further novel therapies currently under investigation for this debilitating disease. PMID:25097787

Kamal, Ahmed

2014-01-01

249

Functional and structural modifications during retinal degeneration in the rd10 mouse  

Microsoft Academic Search

Mouse models of retinal degeneration are useful tools to study therapeutic approaches for patients affected by hereditary retinal dystrophies. We have studied degeneration in the rd10 mice both by immunocytochemistry and TUNEL-labeling of retinal cells, and through electrophysiological recordings. The cell degeneration in the retina of rd10 mice produced appreciable morphological changes in rod and cone cells by P20. Retinal

R. Barhoum; G. Martínez-Navarrete; S. Corrochano; F. Germain; L. Fernandez-Sanchez; E. J. de la Rosa; P. de la Villa; N. Cuenca

2008-01-01

250

DICER1 deficit induces Alu RNA toxicity in age-related macular degeneration  

Microsoft Academic Search

Geographic atrophy (GA), an untreatable advanced form of age-related macular degeneration, results from retinal pigmented epithelium (RPE) cell degeneration. Here we show that the microRNA (miRNA)-processing enzyme DICER1 is reduced in the RPE of humans with GA, and that conditional ablation of Dicer1, but not seven other miRNA-processing enzymes, induces RPE degeneration in mice. DICER1 knockdown induces accumulation of Alu

Hiroki Kaneko; Sami Dridi; Valeria Tarallo; Bradley D. Gelfand; Benjamin J. Fowler; Won Gil Cho; Mark E. Kleinman; Steven L. Ponicsan; William W. Hauswirth; Vince A. Chiodo; Katalin Karikó; Jae Wook Yoo; Dong-Ki Lee; Majda Hadziahmetovic; Ying Song; Smita Misra; Gautam Chaudhuri; Frank W. Buaas; Robert E. Braun; David R. Hinton; Qing Zhang; Hans E. Grossniklaus; Jan M. Provis; Michele C. Madigan; Ann H. Milam; Nikki L. Justice; Romulo J. C. Albuquerque; Alexander D. Blandford; Sasha Bogdanovich; Yoshio Hirano; Jassir Witta; Elaine Fuchs; Dan R. Littman; Balamurali K. Ambati; Charles M. Rudin; Mark M. W. Chong; Patrick Provost; Jennifer F. Kugel; James A. Goodrich; Joshua L. Dunaief; Judit Z. Baffi; Jayakrishna Ambati

2011-01-01

251

Ablation of the X-Linked Retinitis Pigmentosa 2 (Rp2) Gene in Mice Results in Opsin Mislocalization and Photoreceptor Degeneration  

PubMed Central

Purpose. Mutations in the RP2 gene are associated with 10% to 15% of X-linked retinitis pigmentosa (XLRP), a debilitating disorder characterized by the degeneration of retinal rod and cone photoreceptors. The molecular mechanism of pathogenesis of photoreceptor degeneration in XLRP-RP2 has not been elucidated, and no treatment is currently available. This study was undertaken to investigate the pathogenesis of RP2-associated retinal degeneration. Methods. We introduced loxP sites that flank exon 2, a mutational hotspot in XLRP-RP2, in the mouse Rp2 gene. We then produced Rp2-null allele using transgenic mice that expressed Cre-recombinase under control of the ubiquitous CAG promoter. Electroretinography (ERG), histology, light microscopy, transmission electron microscopy, and immunofluorescence microscopy were performed to ascertain the effect of ablation of Rp2 on photoreceptor development, function, and protein trafficking. Results. Although no gross abnormalities were detected in the Rp2null mice, photopic (cone) and scotopic (rod) function as measured by ERG showed a gradual decline starting as early as 1 month of age. We also detected slow progressive degeneration of the photoreceptor membrane discs in the mutant retina. These defects were associated with mislocalization of cone opsins to the nuclear and synaptic layers and reduced rhodopsin content in the outer segment of mutant retina prior to the onset of photoreceptor degeneration. Conclusions. Our studies suggest that RP2 contributes to the maintenance of photoreceptor function and that cone opsin mislocalization represents an early step in XLRP caused by RP2 mutations. The Rp2null mice should serve as a useful preclinical model for testing gene- and cell-based therapies. PMID:23745007

Li, Linjing; Khan, Naheed; Hurd, Toby; Ghosh, Amiya Kumar; Cheng, Christiana; Molday, Robert; Heckenlively, John R.; Swaroop, Anand; Khanna, Hemant

2013-01-01

252

Intervertebral disc degeneration in the dog. Part 2: chondrodystrophic and non-chondrodystrophic breeds.  

PubMed

Dogs can be grouped into two distinct types of breed based on the predisposition to chondrodystrophy, namely, non-chondrodystrophic (NCD) and chondrodystrophic (CD). In addition to a different process of endochondral ossification, NCD and CD breeds have different characteristics of intravertebral disc (IVD) degeneration and IVD degenerative diseases. The anatomy, physiology, histopathology, and biochemical and biomechanical characteristics of the healthy and degenerated IVD are discussed in the first part of this two-part review. This second part describes the similarities and differences in the histopathological and biochemical characteristics of IVD degeneration in CD and NCD canine breeds and discusses relevant aetiological factors of IVD degeneration. PMID:23154070

Smolders, Lucas A; Bergknut, Niklas; Grinwis, Guy C M; Hagman, Ragnvi; Lagerstedt, Anne-Sofie; Hazewinkel, Herman A W; Tryfonidou, Marianna A; Meij, Björn P

2013-03-01

253

Axon degeneration is key component of neuronal death in amyloid - ? toxicity  

PubMed Central

Depending upon the stimulus, neuronal cell death can either be triggered from the cell body (soma) or the axon. We investigated the origin of the degeneration signal in amyloid ? (A?) induced neuronal cell death in cultured in vitro hippocampal neurons. We discovered that A?1–42 toxicity-induced axon degeneration precedes cell death in hippocampal neurons. Overexpression of Bcl-xl inhibited both axonal and cell body degeneration in the A?-42 treated neurons. Nicotinamide mononucleotide adenylyltransferase 1 (Nmnat1) blocks axon degeneration in a variety of paradigms, but it cannot block neuronal cell body death. Therefore, if the neuronal death signals in A?1–42 toxicity originate from degenerating axons, we should be able to block neuronal death by inhibiting axon degeneration. To explore this possibility we over-expressed Nmnat1 in hippocampal neurons. We found that inhibition of axon degeneration in A?1–42 treated neurons prevented neuronal cell death. Thus, we conclude that axon degeneration is the key component of A?1–42 induced neuronal degeneration, and therapies targeting axonal protection can be important in finding a treatment for Alzheimer’s disease. PMID:24083988

Alobuia, Wilson M.; Xia, Wei; Vohra, Bhupinder P. S.

2014-01-01

254

Three dimensional electrostatic solitary waves in a dense magnetoplasma with relativistically degenerate electrons  

SciTech Connect

In this paper, small but finite amplitude electrostatic solitary waves in a relativistic degenerate magnetoplasma, consisting of relativistically degenerate electrons and non-degenerate cold ions, are investigated. The Zakharov-Kuznetsov equation is derived employing the reductive perturbation technique and its solitary wave solution is analyzed. It is shown that only compressive electrostatic solitary structures can propagate in such a degenerate plasma system. The effects of plasma number density, ion cyclotron frequency, and direction cosines on the profiles of ion acoustic solitary waves are investigated and discussed at length. The relevance of the present investigation vis-a-vis pulsating white dwarfs is also pointed out.

Ata-ur-Rahman,; Qamar, A. [Institute of Physics and Electronics, University of Peshawar, Peshawar 25000 (Pakistan) [Institute of Physics and Electronics, University of Peshawar, Peshawar 25000 (Pakistan); National Centre for Physics, QAU Campus, Shahdrah Valley Road, Islamabad 44000 (Pakistan); Masood, W. [National Centre for Physics, QAU Campus, Shahdrah Valley Road, Islamabad 44000 (Pakistan) [National Centre for Physics, QAU Campus, Shahdrah Valley Road, Islamabad 44000 (Pakistan); COMSATS, Institute of Information Technology, Park Road, Chak Shahzad, Islamabad 44000 (Pakistan); Eliasson, B. [Physics Department, University of Strathclyde, Glasgow G4 0NG, Scotland (United Kingdom)] [Physics Department, University of Strathclyde, Glasgow G4 0NG, Scotland (United Kingdom)

2013-09-15

255

Some Remarks on Space-Time Decompositions, and Degenerate Metrics, in General Relativity  

NASA Astrophysics Data System (ADS)

Space-time decomposition of the Hilbert-Palatini action, written in a form which admits degenerate metrics, is considered. Simple numerology shows why D = 3 and 4 are singled out as admitting a simple phase space. The canonical structure of the degenerate sector turns out to be awkward. However, the real degenerate metrics obtained as solutions are the same as those that occur in Ashtekar's formulation of complex general relativity. An exact solution of Ashtekar's equations, with degenerate metric, shows that the manifestly four-dimensional form of the action, and its 3 + 1 form, are not quite equivalent.

Bengtsson, Ingemar

256

Three dimensional electrostatic solitary waves in a dense magnetoplasma with relativistically degenerate electrons  

NASA Astrophysics Data System (ADS)

In this paper, small but finite amplitude electrostatic solitary waves in a relativistic degenerate magnetoplasma, consisting of relativistically degenerate electrons and non-degenerate cold ions, are investigated. The Zakharov-Kuznetsov equation is derived employing the reductive perturbation technique and its solitary wave solution is analyzed. It is shown that only compressive electrostatic solitary structures can propagate in such a degenerate plasma system. The effects of plasma number density, ion cyclotron frequency, and direction cosines on the profiles of ion acoustic solitary waves are investigated and discussed at length. The relevance of the present investigation vis-a-vis pulsating white dwarfs is also pointed out.

Ata-ur-Rahman; Masood, W.; Eliasson, B.; Qamar, A.

2013-09-01

257

Testing the single degenerate channel for supernova Ia  

NASA Astrophysics Data System (ADS)

The progenitors of supernova Ia are close binaries containing white dwarfs. Of crucial importance to the evolution of these systems is how much material the white dwarf can stably accrete and hence grow in mass. This occurs during a short-lived intense phase of mass transfer known as the super soft source (SSS) phase. The short duration of this phase and large extinction to soft X-rays means that only a handful are known in our Galaxy. Far more can be learned from the underlying SSS progenitor population of close white dwarf plus FGK type binaries. Unfortunately, these systems are hard to find since the main-sequence stars completely outshine the white dwarfs at optical wavelengths. Because of this, there are currently no known close white dwarf binaries with F, G or early K type companions, making it impossible to determine the contribution of the single degenerate channel towards supernova Ia. Using the GALEX and RAVE surveys we have now identified the first large sample of FGK stars with UV excesses, a fraction of which are these illusive, close systems. Following an intense ground based spectroscopic investigation of these systems, we have identified 5 definite close binaries, with periods of less than a few days. Here we apply for COS spectroscopic observations to measure the mass and temperature of the white dwarfs in order to determine the future evolution of these systems. This will provide a crucial test for the single degenerate channel towards supernova Ia.

Parsons, Steven

2014-10-01

258

Rare earth nanoparticles prevent retinal degeneration induced by intracellular peroxides:  

NASA Astrophysics Data System (ADS)

Photoreceptor cells are incessantly bombarded with photons of light, which, along with the cells' high rate of oxygen metabolism, continuously exposes them to elevated levels of toxic reactive oxygen intermediates (ROIs). Vacancy-engineered mixed-valence-state cerium oxide nanoparticles (nanoceria particles) scavenge ROIs. Our data show that nanoceria particles prevent increases in the intracellular concentrations of ROIs in primary cell cultures of rat retina and, in vivo, prevent loss of vision due to light-induced degeneration of photoreceptor cells. These data indicate that the nanoceria particles may be effective in inhibiting the progression of ROI-induced cell death, which is thought to be involved in macular degeneration, retinitis pigmentosa and other blinding diseases, as well as the ROI-induced death of other cell types in diabetes, Alzheimer's disease, atherosclerosis, stroke and so on. The use of nanoceria particles as a direct therapy for multiple diseases represents a novel strategy and suggests that they may represent a unique platform technology.

Chen, Junping; Patil, Swanand; Seal, Sudipta; McGinnis, James F.

2006-11-01

259

Present and future treatment possibilities in macular degeneration  

NASA Astrophysics Data System (ADS)

Purpose: To discuss present and future treatment possibilities in different types of choroidal neovascularisation. Methods: Presented are angiographic- and OCT-findings in patients with macular degeneration of different origin. Choroidal neovascularisations, which are not likely to respond positively to established procedures like thermal laser coagulation or photodynamic therapy will be discussed. Results and conclusions: Present study-guidelines and new methods of pharmacological intervention are analysed in different patterns of macular degeneration. Conventional laser coagulation in the treatment of classic, extrafoveal CNV and photodynamic therapy of predominantly classic subfoveal CNV still represent a gold standard. There are new recommendations, loosening the tight criteria of the TAP and VIP-guidelines, which cover, for instance, wider visual acuity ranges and the treatment of juxtafoveally located choroidal neovascularisations. Positive findings in literature confirm the role of PDT in pathologic myopia and other non-AMD CNV. Studies about surgical procedures, like macula- or RPE-translocation after surgical removal or thermal laser destruction of the CNV are in progress and are expected to show promising results. Phase II/III studies will soon point out the effect of anti-VEGF agents. The application of intravitreal (triamcinolone) or peribulbar (anecortave acetat) steroids could be useful. The combination with surgical or laser techniques could bring further benefit to the patient.

Fisher, E.; Wegner, A.; Pfeiler, T.; Mertz, M.

2005-11-01

260

Pontocerebellar atrophy combined with vestibular-reticular degeneration.  

PubMed

A 41-year-old woman was hospitalized in 1939 with neurologic signs from which there was complete recovery over a two-year period. In 1965 she was readmitted because of increasing forgetfulness and inability to care for herself; there were no neurologic deficits. In June 1970 torticollis developed and persisted until her death 15 months later. No cerebellar signs were elicited, but increased muscle tone was prominent. The brain showed remarkable flattening of the inferior surface of the cerebellum; the pons was small. The medullary substance of the cerebellum and each branchium pontis appeared completely demyelinated. Transverse fibres were apparently absent in the central basis pontis. Microscopically in addition to the pontocerebellar atrophy there was degeneration of the vestibular system, reticular formation of the medulla oblongata and medial longitudinal fasciculi. The inferior olives showed only moderate neuronal degeneration in the caudal areas. Basal ganglia and thalamus showed some involvement in the pathological process. It is postulated that the vestibular-reticular system atrophy was the anatomic substrate for the torticollis, and apparently overshadowed cerebellar signs, which are ordinarily associated with pontocerebellar atrophy. PMID:300099

Neumann, M A

1977-01-01

261

The brain basis of musicophilia: evidence from frontotemporal lobar degeneration.  

PubMed

Musicophilia, or abnormal craving for music, is a poorly understood phenomenon that has been associated in particular with focal degeneration of the temporal lobes. Here we addressed the brain basis of musicophilia using voxel-based morphometry (VBM) on MR volumetric brain images in a retrospectively ascertained cohort of patients meeting clinical consensus criteria for frontotemporal lobar degeneration: of 37 cases ascertained, 12 had musicophilia, and 25 did not exhibit the phenomenon. The syndrome of semantic dementia was relatively over-represented among the musicophilic subgroup. A VBM analysis revealed significantly increased regional gray matter volume in left posterior hippocampus in the musicophilic subgroup relative to the non-musicophilic group (p < 0.05 corrected for regional comparisons); at a relaxed significance threshold (p < 0.001 uncorrected across the brain volume) musicophilia was associated with additional relative sparing of regional gray matter in other temporal lobe and prefrontal areas and atrophy of gray matter in posterior parietal and orbitofrontal areas. The present findings suggest a candidate brain substrate for musicophilia as a signature of distributed network damage that may reflect a shift of hedonic processing toward more abstract (non-social) stimuli, with some specificity for particular neurodegenerative pathologies. PMID:23801975

Fletcher, Phillip D; Downey, Laura E; Witoonpanich, Pirada; Warren, Jason D

2013-01-01

262

The brain basis of musicophilia: evidence from frontotemporal lobar degeneration  

PubMed Central

Musicophilia, or abnormal craving for music, is a poorly understood phenomenon that has been associated in particular with focal degeneration of the temporal lobes. Here we addressed the brain basis of musicophilia using voxel-based morphometry (VBM) on MR volumetric brain images in a retrospectively ascertained cohort of patients meeting clinical consensus criteria for frontotemporal lobar degeneration: of 37 cases ascertained, 12 had musicophilia, and 25 did not exhibit the phenomenon. The syndrome of semantic dementia was relatively over-represented among the musicophilic subgroup. A VBM analysis revealed significantly increased regional gray matter volume in left posterior hippocampus in the musicophilic subgroup relative to the non-musicophilic group (p < 0.05 corrected for regional comparisons); at a relaxed significance threshold (p < 0.001 uncorrected across the brain volume) musicophilia was associated with additional relative sparing of regional gray matter in other temporal lobe and prefrontal areas and atrophy of gray matter in posterior parietal and orbitofrontal areas. The present findings suggest a candidate brain substrate for musicophilia as a signature of distributed network damage that may reflect a shift of hedonic processing toward more abstract (non-social) stimuli, with some specificity for particular neurodegenerative pathologies. PMID:23801975

Fletcher, Phillip D.; Downey, Laura E.; Witoonpanich, Pirada; Warren, Jason D.

2013-01-01

263

Dwarf spheroidal galaxies as degenerate gas of free fermions  

NASA Astrophysics Data System (ADS)

In this paper we analyze a simple scenario in which Dark Matter (DM) consists of free fermions with mass mf. We assume that on galactic scales these fermions are capable of forming a degenerate Fermi gas, in which stability against gravitational collapse is ensured by the Pauli exclusion principle. The mass density of the resulting con figuration is governed by a non-relativistic Lane-Emden equation, thus leading to a universal cored profile that depends only on one free parameter in addition to mf. After reviewing the basic formalism, we test this scenario against experimental data describing the velocity dispersion of the eight classical dwarf spheroidal galaxies of the Milky Way. We find that, despite its extreme simplicity, the model exhibits a good fit to the data and realistic predictions for the size of DM halos providing that mfsimeq 200 eV. Furthermore, we show that in this setup larger galaxies correspond to the non-degenerate limit of the gas. We propose a concrete realization of this model in which DM is produced non-thermally via inflaton decay. We show that imposing the correct relic abundance and the bound on the free-streaming length constrains the inflation model in terms of inflaton mass, its branching ratio into DM and the reheating temperature.

Domcke, Valerie; Urbano, Alfredo

2015-01-01

264

Cannabinoid CB2 receptor (CB2R) stimulation delays rubrospinal mitochondrial-dependent degeneration and improves functional recovery after spinal cord hemisection by ERK1/2 inactivation.  

PubMed

Spinal cord injury (SCI) is a devastating condition of CNS that often results in severe functional impairments for which there are no restorative therapies. As in other CNS injuries, in addition to the effects that are related to the primary site of damage, these impairments are caused by degeneration of distal regions that are connected functionally to the primary lesion site. Modulation of the endocannabinoid system (ECS) counteracts this neurodegeneration, and pharmacological modulation of type-2 cannabinoid receptor (CB2R) is a promising therapeutic target for several CNS pathologies, including SCI. This study examined the effects of CB2R modulation on the fate of axotomized rubrospinal neurons (RSNs) and functional recovery in a model of spinal cord dorsal hemisection (SCH) at the cervical level in rats. SCH induced CB2R expression, severe atrophy, and cell death in contralateral RSNs. Furthermore, SCH affected molecular changes in the apoptotic cascade in RSNs - increased cytochrome c release, apoptosome formation, and caspase-3 activity. CB2R stimulation by its selective agonist JWH-015 significantly increased the bcl-2/bax ratio, reduced cytochrome c release, delayed atrophy and degeneration, and improved spontaneous functional recovery through ERK1/2 inactivation. These findings implicate the ECS, particularly CB2R, as part of the endogenous neuroprotective response that is triggered after SCI. Thus, CB2R modulation might represent a promising therapeutic target that lacks psychotropic effects and can be used to exploit ECS-based approaches to counteract neuronal degeneration. PMID:25188514

Latini, L; Bisicchia, E; Sasso, V; Chiurchiù, V; Cavallucci, V; Molinari, M; Maccarrone, M; Viscomi, M T

2014-01-01

265

Site Map  

Cancer.gov

Site Map Programs & Resources Research Groups Foundations of Prevention Biometry Publications Statistical Software About the Research Group Cancer Biomarkers Funding Opportunities Key Programs Meetings and Events Publications About

266

A new use for an old method: the Woelcke myelin stain for counting degenerating neurons in the brain of mice following status epilepticus.  

PubMed

The Woelcke method is classically used for myelin staining. Degenerating neurons can be revealed histologically by hemalun and phloxin (H&P) where they appear "eosinophilic". In the first 24 h following soman-induced status epilepticus, we observed that the Woelcke method also revealed condensed, dark blue/black cells (W+ cells) in the gray matter of brain regions known to be sites of seizure-related brain damage, marked by the presence of eosinophilic cells. In the present study, using adjacent brain sections alternately stained with either the Woelcke or the H&P method, we show that eosinophilic cells and W+ cells are the same degenerating cells. Moreover, we show that semi-automated quantitative evaluation of W+ cells through computerized image analysis is considerably easier and faster than that of eosinophilic cells. It is therefore concluded that the Woelcke technique could be very useful, especially for quantifying acute brain cell damage following status epilepticus. PMID:22155333

Carpentier, Pierre; Foquin, Annie; Dorandeu, Frédéric

2012-08-01

267

Primary myxomatous degeneration of cardiac valves. Clinical, pathological, haemodynamic, and echocardiographic profile.  

PubMed Central

Four hundred and ninety-nine surgically excised valves were examined for pathological evidence of myxomatous degeneration. Thirty-six valves (7%) had myxomatous degeneration as a major pathological finding. Fourteen valves (3%) had significant myxomatous degeneration of the pars fibrosa, a finding which we define as "primary myxomatous degeneration". Echocardiographic findings and catheterisation results were correlated with the clinical course, surgical results, and follow-up in these 14 patients. Echocardiograms in 10 of the 11 patients who had them (91%) showed abnormalities suggesting the presence of primary myxomatous degeneration. Echocardiography was more helpful than angiography in diagnosis. The histological pattern of primary mitral myxomatous degeneration appears to be identical to that seen in patients with mitral valve prolapse and five of six patients with mitral lesions had echocardiographic evidence of prolapse. None of the patients with primary myxomatous degeneration of the aortic valve had syphilis of Marfan's syndrome. While the aetiology of primary myxomatous degeneration of cardiac valves is not known, a link to a more generalised disorder is suggested. Images PMID:7459145

Rippe, J; Fishbein, M C; Carabello, B; Angoff, G; Sloss, L; Collins, J J; Alpert, J S

1980-01-01

268

Intradiscal injection of simvastatin retards progression of intervertebral disc degeneration induced by stab injury  

Microsoft Academic Search

INTRODUCTION: Earlier work indicates that the cholesterol-lowering drug, simvastatin, is anabolic to chondrogenic expression of rat intervertebral disc (IVD) cells, which suggests a potential role for simvastatin in IVD regeneration. In this study, we expand on our earlier work to test the effectiveness of simvastatin on disc degeneration utilizing a rat tail disc degeneration model. METHODS: 30 rats that underwent

Huina Zhang; Lin Wang; Jun Beom Park; Paul Park; Victor C Yang; Scott J Hollister; Frank La Marca; Chia-Ying Lin

2009-01-01

269

EXISTENCE AND UNIQUENESS OF SOLUTIONS TO AN AGGREGATION EQUATION WITH DEGENERATE DIFFUSION  

E-print Network

EXISTENCE AND UNIQUENESS OF SOLUTIONS TO AN AGGREGATION EQUATION WITH DEGENERATE DIFFUSION ANDREA L- ness of solutions of a nonlocal aggregation equation with degenerate diffusion. The equation we study is relevant to models of biological aggregation. 1. Introduction A number of nonlocal continuum models have

Soatto, Stefano

270

JOURNAL OF MOLECULAR SPECTROSCOPY 103, 147-159 (1984) Reduced Effective Hamiltonians for Degenerate Vibrational States  

E-print Network

JOURNAL OF MOLECULAR SPECTROSCOPY 103, 147-159 (1984) Reduced Effective Hamiltonians for Degenerate Vibrational States of Methane-Type Molecules' V. I. PEREVALOV,*VL. G. TYUTEREV,* AND B. I. ZHILINSKII, I 17234, USSR The ambiguity of effective Hamiltonians for the fundamental degenerate states

Zhilinskií, Boris

271

Relationship between Frontotemporal Dementia and Corticobasal Degeneration\\/Progressive Supranuclear Palsy  

Microsoft Academic Search

Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) were described as separate entities, but prior to that an extrapyramidal variety of Pick’s disease was recognized. Subsequently a pathological overlap between these conditions and clinical overlap between frontotemporal dementia, primary progressive aphasia, corticobasal degeneration syndrome and more recently PSP was recognized. Initially only the movement disorder had been emphasized, but now

Andrew Kertesz; David Munoz

2004-01-01

272

The periodic table of n-categories for low dimensions I: degenerate categories and  

E-print Network

The periodic table of n-categories for low dimensions I: degenerate categories and degenerate-mail: eugenia@math.uchicago.edu, gurski@math.uchicago.edu July 2005 Abstract We examine the periodic table the first few entries in the "Periodic Table" of n- categories. This table was first described by Baez

Cheng, Eugenia

273

Polarization Switching of Light Interacting with a Degenerate Two-Level Optical Medium  

E-print Network

Polarization Switching of Light Interacting with a Degenerate Two-Level Optical Medium Julie A 12180, USA Abstract Polarization switching of light in a degenerate two-level medium, known as the configuration, is described. The polarization dynamics of light pulses is investigated by means of the inverse

Kovacic, Gregor

274

Prematurely senescent ARPE-19 cells display features of age-related macular degeneration  

Microsoft Academic Search

The etiology of age-related macular degeneration (AMD), the leading cause of blindness in the developed world, remains poorly understood, but may be related to cumulative oxidative stress. The prime target of the disease is the retinal pigmented epithelium (RPE). To study the molecular mechanisms underlying RPE degeneration, we investigated whether repetitive oxidative stress induced premature senescence in RPE cells from

Anne-Lise Glotin; Florence Debacq-Chainiaux; Jean-Yves Brossas; Anne-Marie Faussat; Jacques Tréton; Anna Zubielewicz; Olivier Toussaint; Frédéric Mascarelli

2008-01-01

275

Degenerate U-and V -statistics under ergodicity: Asymptotics, bootstrap and applications in statistics  

E-print Network

Degenerate U- and V -statistics under ergodicity: Asymptotics, bootstrap and applications in statistics Anne Leucht Universit¨at Hamburg Fachbereich Mathematik, SPST Bundesstra�e 55 D-20146 Hamburg.neumann@uni-jena.de Abstract We derive the asymptotic distributions of degenerate U- and V -statistics of stationary

276

CONTINUOUS DEPENDENCE ESTIMATES FOR VISCOSITY SOLUTIONS OF FULLY NONLINEAR DEGENERATE ELLIPTIC EQUATIONS  

E-print Network

CONTINUOUS DEPENDENCE ESTIMATES FOR VISCOSITY SOLUTIONS OF FULLY NONLINEAR DEGENERATE ELLIPTIColder continuous viscosity solutions of fully nonlinear degenerate elliptic equations. Furthermore, we provide existence, uniqueness, and Holder continuity results for bounded viscosity solutions of such equations. Our

277

Genetic Linkage of Snowflake Vitreoretinal Degeneration to Chromosome 2q36  

Microsoft Academic Search

PURPOSE. To identify the chromosomal location of the gene causing snowflake vitreoretinal degeneration (SVD), an autoso- mal dominant retinal degeneration characterized by small yel- low-white dots in the retina, fibrillar anomaly of the vitreous humor, and retinal detachment. METHODS. Clinical data were collected on 31 family members by history and examination. Thirteen family members under- went prospective examination. Genotyping was

Xiaodong Jiao; Robert Ritter; J. Fielding Hejtmancik; Albert O. Edwards

2004-01-01

278

Asymptomatic snowflake degeneration in a polymethyl methacrylate (PMMA) intraocular lens implant.  

PubMed

Snowflake degeneration is a late complication of polymethyl methacrylate (PMMA) intraocular lens implants. We report a case of asymptomatic advanced snowflake opacification presenting 13 years after implantation who maintained a visual acuity of 6/6. This report serves to illustrate the variability of the clinical effects of snowflake degeneration, which do not necessarily correlate with slit-lamp appearances. PMID:19230357

Tan, Lee T; Shuttleworth, Garry N

2008-01-01

279

Degenerate nDoping of Few-Layer Transition Metal Dichalcogenides by Potassium  

E-print Network

Degenerate nDoping of Few-Layer Transition Metal Dichalcogenides by Potassium Hui Fang,,,§ Mahmut semiconductors by surface charge transfer using potassium. High-electron sheet densities of 1.0 � 1013 cm-2 and 2: Degenerate doping, few-layer, TMDCs, MoS2, WSe2, potassium, surface charge transfer The desire for enhanced

California at Irvine, University of

280

Simple colorimetric method for detecting degenerate strains of the cultivated basidiomycete Flammulina velutipes (Enokitake).  

PubMed

Degeneration of cultivated strains of Flammulina velutipes is a serious problem. We developed a simple colorimetric method to detect degenerate strains by using a liquid medium supplemented with bromothymol blue and lactose. The ability of a strain to develop normal mushrooms could be determined by the color of the medium. PMID:16204563

Magae, Yumi; Akahane, Kobun; Nakamura, Kimiyoshi; Tsunoda, Shigeyuki

2005-10-01

281

Identification of potyviruses using the polymerase chain reaction with degenerate primers  

Microsoft Academic Search

Local areas of conserved amino acid sequence in the replicase and coat proteins of potyviruses were used to select nucleotide sequences for use in the construction of sets of degenerate oligonucleotide primers for amplification of DNA fragments on potyvirus-specific templates in a combined assay of reverse transcription and the polymerase chain reaction (RT-PCR). Sequences selected for the construction of degenerate

Simon A. Langeveld; Jean-Michel Dore; Johan Memelink; Antonius F. L. M. Derks; Cornelia I. M. van der Vlugt; Cees J. Asjes; John F. Bol

1991-01-01

282

6.301 Solid State Circuits Recitation 7: Emitter Degeneration, and More on Multistage Amps  

E-print Network

." Look at the common emitter amplifier: RL gmV - + rV RS VS RL RS VS #12;6.301 Solid State Circuits6.301 Solid State Circuits Recitation 7: Emitter Degeneration, and More on Multistage Amps Prof;6.301 Solid State Circuits Recitation 7: Emitter Degeneration, and More on Multistage Amps Prof. Joel L

Goldwasser, Shafi

283

Cusp Points in the Parameter Space of Degenerate 3-RPR Planar Parallel Manipulators  

E-print Network

Cusp Points in the Parameter Space of Degenerate 3-RPR Planar Parallel Manipulators Montserrat of the cusp lo- cus for planar parallel manipulators. Cusp points make pos- sible non-singular assembly us to classify a family of degenerate 3-RPR manipulators. Keywords: kinematics, parallel manipulator

Paris-Sud XI, Université de

284

Universal dynamics of a degenerate unitary Bose gas  

NASA Astrophysics Data System (ADS)

From neutron stars to high-temperature superconductors, strongly interacting many-body systems at or near quantum degeneracy are a rich source of intriguing phenomena. The microscopic structure of the first-discovered quantum fluid, superfluid liquid helium, is difficult to access owing to limited experimental probes. Although an ultracold atomic Bose gas with tunable interactions (characterized by its scattering length, a) had been proposed as an alternative strongly interacting Bose system, experimental progress has been limited by its short lifetime. Here we present time-resolved measurements of the momentum distribution of a Bose-condensed gas that is suddenly jumped to unitarity, where . Contrary to expectation, we observe that the gas lives long enough to permit the momentum to evolve to a quasi-steady-state distribution, consistent with universality, while remaining degenerate. Investigations of the time evolution of this unitary Bose gas may lead to a deeper understanding of quantum many-body physics.

Makotyn, P.; Klauss, C. E.; Goldberger, D. L.; Cornell, E. A.; Jin, D. S.

2014-02-01

285

BA/ODE Correspondence for Degenerate Gaudin Models  

E-print Network

In this work, we generalize the numerical approach to Gaudin models developed earlier by us to degenerate systems showing that their treatment is surprisingly convenient from a numerical point of view. In fact, high degeneracies not only reduce the number of relevant states in the Hilbert space by a non negligible fraction, they also allow to write the relevant equations in the form of sparse matrix equations. Moreover, we introduce a new inversion method based on a basis of barycentric polynomials which leads to a more stable and efficient root extraction which most importantly avoids the necessity of working with arbitrary precision. As an example we show the results of our procedure applied to the Richardson model on a square lattice.

Araby, Omar El; Faribault, Alexandre

2012-01-01

286

Stem cells as tools in regenerative therapy for retinal degeneration  

PubMed Central

Objectives Regenerative medicine intends to provide therapies for severe injuries or chronic diseases where endogenous repair does not sufficiently restore the tissue. Pluripotent stem cells (SC), with their capacity to give rise to specialized cells, are the most promising candidates for clinical application. Despite encouraging results, a combination with up-to-date tissue engineering might be critical for ultimate success. Design The focus is on the use of SC for regeneration of retinal degenerations. Cell populations include embryonic, neural, and bone marrow-derived SC and engineered grafts will also be described. Results Experimental approaches have successfully replaced damaged photoreceptors and retinal pigment epithelium using endogenous and exogenous SC. Conclusions SC have the potential to significantly impact retinal regeneration. A combination with bioengineering may bear even greater promise. However, ethical and scientific issues have yet to be solved. PMID:19365041

Enzmann, Volker; Yolcu, Esma; Kaplan, Henry J.; Ildstad, Suzanne T.

2011-01-01

287

p62/SQSTM1 analysis in frontotemporal lobar degeneration.  

PubMed

Mutations in the gene p62/SQSTM1 have been reported as a relatively rare cause of frontotemporal lobar degeneration (FTLD). To establish whether this was the case for cases of FTLD from the United Kingdom, we sequenced the sequenced the entire open reading frame of this gene in a large cohort of patients. We identified 3 novel mutations in p62/SQSTM1 in 4 patients. One of these was a premature stop codon that removed the last 101 amino acids of the protein that presumably has a negative effect on protein function. Another mutation was also found in a case with a repeat expansion mutation in C9orf72 confirmed by Southern blot. These findings confirm a role of p62/SQSTM1 as a cause of FTLD. PMID:25433461

Miller, Louise; Rollinson, Sara; Callister, Janis Bennion; Young, Kate; Harris, Jenny; Gerhard, Alex; Neary, David; Richardson, Anna; Snowden, Julie; Mann, David M A; Pickering-Brown, Stuart M

2014-10-18

288

Complement factor H polymorphism in age-related macular degeneration.  

PubMed

Age-related macular degeneration (AMD) is a major cause of blindness in the elderly. We report a genome-wide screen of 96 cases and 50 controls for polymorphisms associated with AMD. Among 116,204 single-nucleotide polymorphisms genotyped, an intronic and common variant in the complement factor H gene (CFH) is strongly associated with AMD (nominal P value <10(-7)). In individuals homozygous for the risk allele, the likelihood of AMD is increased by a factor of 7.4 (95% confidence interval 2.9 to 19). Resequencing revealed a polymorphism in linkage disequilibrium with the risk allele representing a tyrosine-histidine change at amino acid 402. This polymorphism is in a region of CFH that binds heparin and C-reactive protein. The CFH gene is located on chromosome 1 in a region repeatedly linked to AMD in family-based studies. PMID:15761122

Klein, Robert J; Zeiss, Caroline; Chew, Emily Y; Tsai, Jen-Yue; Sackler, Richard S; Haynes, Chad; Henning, Alice K; SanGiovanni, John Paul; Mane, Shrikant M; Mayne, Susan T; Bracken, Michael B; Ferris, Frederick L; Ott, Jurg; Barnstable, Colin; Hoh, Josephine

2005-04-15

289

Genetic factors of age-related macular degeneration  

PubMed Central

Age-related macular degeneration (AMD) is a leading cause of blindness in the United States and developed countries. Although the etiology and pathogenesis of AMD remain unknown, a complex interaction of genetic and environmental factors is thought to exist. The incidence and progression of all of the features of AMD are known to increase significantly with age. The tendency for familial aggregation and the findings of gene variation association studies implicate a significant genetic component in the development of AMD. This review summarizes in detail the AMD-related genes identified by studies on genetically engineered and spontaneously gene-mutated (naturally mutated) animals, AMD chromosomal loci identified by linkage studies, AMD-related genes identified through studies of monogenic degenerative retinal diseases, and AMD-related gene variation identified by association studies. PMID:15094132

Tuo, Jingsheng; Bojanowski, Christine M.; Chan, Chi-Chao

2007-01-01

290

AMO Teledioptric System for age-related macular degeneration  

NASA Astrophysics Data System (ADS)

A 2.5 X magnification system consisting of a two-zone intraocular implant and a spectacle was developed, tested, and clinically tried by fifty patients with cataract ad age-related macular degeneration. Optical bench testing results and clinical data confirmed that the field of view of the system was 2.6 times wider than an equivalent external telescope. The study also demonstrated that the implant itself was clinically equivalent to a standard monofocal intraocular lens for cataract. The clinical study indicated that higher magnification without compromising the compactness and optical quality was needed as the disease progressed. Also, a sound vision rehabilitation process is important to provide patients the full benefits of the system.

Chou, Jim-Son; Ting, Albert C.

1994-05-01

291

Age-related macular degeneration – clinical review and genetics update  

PubMed Central

Age-related macular degeneration (AMD) is the leading cause of central vision impairment in persons over the age of 50 years in developed countries. Both genetic and non-genetic (environmental) factors play major roles in AMD etiology, and multiple gene variants and lifestyle factors such as smoking have been associated with the disease. While dissecting the basic etiology of the disease remains a major challenge, current genetic knowledge has provided opportunities for improved risk assessment, molecular diagnosis and clinical testing of genetic variants in AMD treatment and management. This review addresses the potential of translating the wealth of genetic findings for improved risk prediction and therapeutic intervention in AMD patients. Finally, we discuss the recent advancement in genetics and genomics and the future prospective of personalized medicine in AMD patients. PMID:23713713

Ratnapriya, R; Chew, E Y

2013-01-01

292

Harmonic entanglement in a degenerate parametric down conversion  

E-print Network

We study the harmonic entanglement and squeezing in a two-mode radiation produced in a degenerate parametric down conversion process coupled to a two-mode vacuum reservoir employing the linearization procedure. It is found that there is a quadrature entanglement between the harmonically related fundamental and second-harmonic modes and the superimposed radiation exhibits a significant two-mode squeezing. The entanglement exits even when there is no two-mode squeezing, since the correlation leading to these phenomena are essentially different. In addition, the more the external coherent light is down converted, the more stronger the entanglement and mean photon number of the two-mode radiation would be which is not generally true for squeezing.

Sintayehu Tesfa

2007-07-25

293

Wave functions of hot excitons in semiconductors with degenerate bands  

SciTech Connect

Hot excitons in direct-gap cubic semiconductors with a degenerate valence band are considered. Corrections to the model of independent excitonic branches in terms of the small parameter {Dirac_h}/Ka{sub B}, where K is the exciton momentum and a{sub B} is the Bohr radius, are determined. The corrections take into account the internal motion of particles in the exciton. It is shown that the internal motion mixes the states of light and heavy holes in the exciton wave function. As a result, the processes of forward scattering of excitons with transitions between different excitonic branches become allowed. The consideration is concerned with the region of kinetic energies no higher than the spin-orbit splitting in the valence band. The dispersion relation for holes is described in the spherical Kohn-Luttinger model (the 4 x 4 matrix)

Efanov, A. V. [Russian Academy of Sciences, Institute of Semiconductor Physics, Siberian Branch (Russian Federation)], E-mail: efanov@isp.nsc.ru

2008-06-15

294

Ovarian cancer revealed by paraneoplastic cerebellar degeneration: a case report  

PubMed Central

The prevalence of paraneoplastic cerebellar degeneration (PCD) associated with gynecological cancer is rare. Here, we reported the first case of ovarian cancer revealed by PCD in our institute. we describe a 80- year –old Moroccan female presented with subacute vestibular and cerebellar syndromes, she had an inguinal lymphadenopathy,with high levels of Anti-YO. Rapid progression and absence of known etiologies point towards a probable paraneoplastic origin of the syndrome in this patient. The exact incidence of PNS among those diagnosed with cancer remains uncertain, it is important to report this cases in the literature to help early diagnosis and appropriate treatment, which are able to stabilize the neurological symptoms. PMID:25360186

Elomrani, Fadwa; Ouziane, Imane; Boutayeb, Saber; Bensouda, Youssef; Mrabti, Hind; Errihani, Hassan

2014-01-01

295

Radiation Therapy for Neovascular Age-related Macular Degeneration  

SciTech Connect

In the enormity of the public health burden imposed by age-related macular degeneration (ARMD), much effort has been directed toward identifying effective and efficient treatments. Currently, anti-vascular endothelial growth factor (VEGF) injections have demonstrated considerably efficacy in treating neovascular ARMD, but patients require frequent treatment to fully benefit. Here, we review the rationale and evidence for radiation therapy of ARMD. The results of early photon external beam radiation therapy are included to provide a framework for the sequential discussion of evidence for the usage of stereotactic radiation therapy, proton therapy, and brachytherapy. The evidence suggests that these 3 modern modalities can provide a dose-dependent benefit in the treatment of ARMD. Most importantly, preliminary data suggest that all 3 can be used in conjunction with anti-VEGF therapeutics, thereby reducing the frequency of anti-VEGF injections required to maintain visual acuity.

Kishan, Amar U. [Harvard Medical School, Boston, Massachusetts (United States)] [Harvard Medical School, Boston, Massachusetts (United States); Modjtahedi, Bobeck S.; Morse, Lawrence S. [Department of Ophthalmology and Vision Sciences, University of California, Davis, Sacramento, California (United States)] [Department of Ophthalmology and Vision Sciences, University of California, Davis, Sacramento, California (United States); Lee, Percy, E-mail: percylee@mednet.ucla.edu [Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, California (United States)] [Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, California (United States)

2013-03-01

296

Androgen receptor function in motor neuron survival and degeneration.  

PubMed

Polyglutamine repeat expansion in the androgen receptor is responsible for the motor neuron degeneration in X-linked spinal and bulbar muscular atrophy (SBMA; Kennedy's disease). This mutation, like the other polyglutamine repeat expansions, has proven to be toxic itself by a gain-of-function effect; however, a growing body of evidence indicates that loss of androgen receptor normal function simultaneously contributes to SBMA disease pathology, and, conversely, that normal androgen receptor signaling mediates important trophic effects upon motor neurons. This review considers the trophic requirements of motor neurons, focusing upon the role of known neurotrophic factors in motor neuron disease natural history, and the interactions of androgen receptor signaling pathways with motor neuron disease pathogenesis and progression. A thorough understanding of androgen receptor signaling in motor neurons should provide important inroads toward the development of effective treatments for a variety of devastating motor neuron diseases. PMID:18625411

Cary, Gregory A; La Spada, Albert R

2008-08-01

297

Age-related macular degeneration and the aging eye  

PubMed Central

Age-related macular degeneration (AMD) is an ocular disease that causes damage to the retinal macula, mostly in the elderly. Normal aging processes can lead to structural and blood flow changes that can predispose patients to AMD, although advanced age does not inevitably cause AMD. In this review, we describe changes that occur in the macular structure, such as the retinal pigment epithelium and Bruch’s membrane, with advancing age and in AMD. The role of genetics in AMD and age-related changes in ocular blood flow that may play a role in the pathogenesis of AMD are also discussed. Understanding the pathophysiology of AMD development can help guide future research to further comprehend this disease and to develop better treatments to prevent its irreversible central vision loss in the elderly. PMID:18982917

Ehrlich, Rita; Harris, Alon; Kheradiya, Nisha S; Winston, Diana M; Ciulla, Thomas A; Wirostko, Barbara

2008-01-01

298

Intravitreal aflibercept for neovascular age-related macular degeneration.  

PubMed

Neovascular age-related macular degeneration (AMD) is the leading cause of legal blindness in patients over the age of 50 in the western world. Intravitreally administered anti-VEGF drugs have been developed to halt neovascular growth in AMD. Randomized trials have demonstrated the excellent safety profile and significant benefit of anti-VEGF therapy in maintaining vision. Aflibercept (Eylea(®); Regeneron, NY, USA) is a soluble decoy receptor against VEGF that offers greater potency and binding affinity than other anti-VEGF drugs. Having received US FDA approval for neovascular AMD in November 2011, aflibercept given every 8 weeks after a loading dose was 'clinically equivalent' and statistically noninferior to the current FDA-approved therapy ranibizumab (Lucentis(®); Genentech, CA, USA), given every 4 weeks. This article discusses the clinical background of AMD, development of aflibercept, results of the clinical trials and the future role of aflibercept in ocular neovascular diseases. PMID:23413903

Xu, David; Kaiser, Peter K

2013-02-01

299

Protecting facet joints post-lumbar discectomy: Barricaid annular closure device reduces risk of facet degeneration.  

PubMed

Lumbar discectomy is an effective treatment for lumbar disc herniation (LDH). Although the majority of patients experience successful outcomes, a significant fraction will experience a recurrence of their back pain due to facet joint degeneration. Facet joint degeneration after discectomy may be the result of excessive nuclear removal, disc space narrowing, and annular injury. This study investigated whether implantation with the Barricaid annular closure device (ACD) during discectomy reduced the rate of facet degeneration. Inclusion criteria were primary lumbar disc herniation failing conservative treatment, Visual Analog Scale (VAS) Leg?40/100, Oswestry Disability Index (ODI)?40/100 and defects that were ?60 mm2 (Barricaid arm only), and patient age 18-75. CT interpretations were collected preoperatively and 12 months post-discectomy. Patients implanted with Barricaid had significantly reduced rates and grades of facet degeneration than patients without Barricaid. Reinforcing the annulus fibrosus with Barricaid during lumbar discectomy may slow the progression of facet joint degeneration. PMID:23473658

Trummer, Martin; Eustacchio, Sandro; Barth, Martin; Klassen, Peter Douglas; Stein, Shlomit

2013-08-01

300

Axonal degeneration in an Alzheimer mouse model is PS1 gene dose dependent and linked to intraneuronal A? accumulation  

PubMed Central

Abnormalities and impairments in axonal transport are suggested to strongly contribute to the pathological alterations underlying AD. The exact mechanisms leading to axonopathy are currently unclear, but it was recently suggested that APP expression itself triggers axonal degeneration. We used APP transgenic mice and crossed them on a hemi- or homozygous PS1 knock-in background (APP/PS1KI). Depending on the mutant PS1 dosage, we demonstrate a clear aggravation in both plaque-associated and plaque-distant axonal degeneration, despite of an unchanged APP expression level. Amyloid-? (A?) peptides were found to accumulate in axonal swellings as well as in axons and apical dendrites proximate to neurons accumulating intraneuronal A? in their cell bodies. This suggests that A? can be transported within neurites thereby contributing to axonal deficits. In addition, diffuse extracellular A? deposits were observed in the close vicinity of axonal spheroids accumulating intracellular A?, which might be indicative of a local A? release from sites of axonal damage. PMID:25018730

Christensen, Ditte Z.; Huettenrauch, Melanie; Mitkovski, Miso; Pradier, Laurent; Wirths, Oliver

2014-01-01

301

Lubricin Protects the Temporomandibular Joint Surfaces from Degeneration  

PubMed Central

The temporomandibular joint (TMJ) is a specialized synovial joint essential for the mobility and function of the mammalian jaw. The TMJ is composed of the mandibular condyle, the glenoid fossa of the temporal bone, and a fibrocartilagenous disc interposed between these bones. A fibrous capsule, lined on the luminal surface by the synovial membrane, links these bones and retains synovial fluid within the cavity. The major component of synovial fluid is lubricin, a glycoprotein encoded by the gene proteoglycan 4 (Prg4), which is synthesized by chondrocytes at the surface of the articular cartilage and by synovial lining cells. We previously showed that in the knee joint, Prg4 is crucial for maintenance of cartilage surfaces and for regulating proliferation of the intimal cells in the synovium. Consequently, the objective of this study was to determine the role of lubricin in the maintenance of the TMJ. We found that mice lacking lubricin have a normal TMJ at birth, but develop degeneration resembling TMJ osteoarthritis by 2 months, increasing in severity over time. Disease progression in Prg4?/? mice results in synovial hyperplasia, deterioration of cartilage in the condyle, disc and fossa with an increase in chondrocyte number and their redistribution in clusters with loss of superficial zone chondrocytes. All articular surfaces of the joint had a prominent layer of protein deposition. Compared to the knee joint, the osteoarthritis-like phenotype was more severe and manifested earlier in the TMJ. Taken together, the lack of lubricin in the TMJ causes osteoarthritis-like degeneration that affects the articular cartilage as well as the integrity of multiple joint tissues. Our results provide the first molecular evidence of the role of lubricin in the TMJ and suggest that Prg4?/? mice might provide a valuable new animal model for the study of the early events of TMJ osteoarthritis. PMID:25188282

Purcell, Patricia

2014-01-01

302

Polyethylene glycol induced mouse model of retinal degeneration.  

PubMed

Age-related macular degeneration (AMD) is a leading cause of irreversible blindness. This study was done to characterize dry AMD-like changes in mouse retinal pigment epithelium (RPE) and retina after polyethylene glycol (PEG) treatment. We injected male C57BL/6 mice subretinally with PBS, 0.025, 0.25, 0.5 and 1.0 mg of PEG-400 and the animals were sacrificed on day 5. Eyes were harvested and processed for histological analysis. In all other experiments 0.5 mg PEG was injected and animals were sacrificed on days 1, 3, 5 or 14. Paraffin, 5 ?m and plastic, 1 ?m and 80 nm sections were used for further analysis. Subretinal injection of 0.5 mg PEG induced a 32% reduction of outer nuclear layer (ONL) thickness, 61% decrease of photoreceptor outer and inner segment length, 49% decrease of nuclear density in the ONL and 31% increase of RPE cell density by day 5 after injection. The maximum level of TUNEL positive nuclei in the ONL (6.8 + 1.99%) was detected at day 5 after PEG injection and co-localized with Casp3act. Histological signs of apoptosis were observed in the ONL by light or electron microscopy. Degeneration of RPE cells was found in PEG injected eyes. Gene expression data identified several genes reported to be involved in human AMD. C3, Cfi, Serping1, Mmp9, Htra1 and Lpl were up-regulated in PEG injected eyes compared to PBS controls. PEG leads to morphological and gene expression changes in RPE and retina consistent with dry AMD. This model will be useful to investigate dry AMD pathogenesis and treatment. PMID:25088354

Lyzogubov, Valeriy V; Bora, Nalini S; Tytarenko, Ruslana G; Bora, Puran S

2014-10-01

303

Site selection  

SciTech Connect

The conditions and criteria for selecting a site for a nuclear weapons test at the Nevada Test Site are summarized. Factors considered are: (1) scheduling of drill rigs, (2) scheduling of site preparation (dirt work, auger hole, surface casing, cementing), (3) schedule of event (when are drill hole data needed), (4) depth range of proposed W.P., (5) geologic structure (faults, Pz contact, etc.), (6) stratigraphy (alluvium, location of Grouse Canyon Tuff, etc.), (7) material properties (particularly montmorillonite and CO/sub 2/ content), (8) water table depth, (9) potential drilling problems (caving), (10) adjacent collapse craters and chimneys, (11) adjacent expended but uncollapsed sites, (12) adjacent post-shot or other small diameter holes, (13) adjacent stockpile emplacement holes, (14) adjacent planned events (including LANL), (15) projected needs of Test Program for various DOB's and operational separations, and (16) optimal use of NTS real estate.

Olsen, C.W.

1983-07-01

304

Site Documentation  

Microsoft Academic Search

The focus of this paper will be student\\/researcher needs, vis-á-vis the documentation of building sites. In addition to explaining why architectural students need certain types of visual documentation, the paper will present a case study.

Barbara Opar

1994-01-01

305

Site Map  

Cancer.gov

Search:  Site Map Whats New NBIA Application Collaborators NCI Cancer Imaging Program (CIP) Cancer Therapy Evaluation Program (CTEP) Division of Cancer Prevention(DCP) QUICK LINKS National Cancer Institute cancer Biomedical Informatics Grid (caBIG) NCI

306

Recent Patents on Emerging Therapeutics for the Treatment of Glaucoma, Age Related Macular Degeneration and Uveitis  

PubMed Central

Advancements in the field and rising interest among pharmaceutical researchers have led to the development of new molecules with enhanced therapeutic activity. Design of new drugs which can target a particular pathway and/or explore novel targets is of immense interest to ocular pharmacologists worldwide. Delivery of suitable pharmacologically active agents at proper dose (within the therapeutic window) to the target tissues without any toxicity to the healthy ocular tissues still remain an elusive task. Moreover, the presence of static and dynamic barriers to drug absorption including the corneal epithelium (lipophilic), corneal and scleral stroma (hydrophilic), conjunctival lymphatics, choroidal vasculature and the blood-ocular barriers also pose a significant challenge for achieving therapeutic drug concentrations at the target site. Although many agents are currently available, new compounds are being introduced for treating various ocular diseases. Deeper understanding of the etiology and complex mechanisms associated with the disease condition would aid in the development of potential therapeutic candidates. Novel small molecules as well as complex biotechnology derived macromolecules with superior efficacy, safety and tolerability are being developed. Therefore, this review article provides an overview of existing drugs, treatment options, advances in emerging therapeutics and related recent patents for the treatment of ocular disorders such as glaucoma, age related macular degeneration (AMD) and uveitis. PMID:25414810

Vadlapudi, Aswani Dutt; Patel, Ashaben; Cholkar, Kishore; Mitra, Ashim K.

2014-01-01

307

Lumbar disc degeneration is linked to a carbohydrate sulfotransferase 3 variant  

PubMed Central

Lumbar disc degeneration (LDD) is associated with both genetic and environmental factors and affects many people worldwide. A hallmark of LDD is loss of proteoglycan and water content in the nucleus pulposus of intervertebral discs. While some genetic determinants have been reported, the etiology of LDD is largely unknown. Here we report the findings from linkage and association studies on a total of 32,642 subjects consisting of 4,043 LDD cases and 28,599 control subjects. We identified carbohydrate sulfotransferase 3 (CHST3), an enzyme that catalyzes proteoglycan sulfation, as a susceptibility gene for LDD. The strongest genome-wide linkage peak encompassed CHST3 from a Southern Chinese family–based data set, while a genome-wide association was observed at rs4148941 in the gene in a meta-analysis using multiethnic population cohorts. rs4148941 lies within a potential microRNA-513a-5p (miR-513a-5p) binding site. Interaction between miR-513a-5p and mRNA transcribed from the susceptibility allele (A allele) of rs4148941 was enhanced in vitro compared with transcripts from other alleles. Additionally, expression of CHST3 mRNA was significantly reduced in the intervertebral disc cells of human subjects carrying the A allele of rs4148941. Together, our data provide new insights into the etiology of LDD, implicating an interplay between genetic risk factors and miRNA. PMID:24216480

Song, You-Qiang; Karasugi, Tatsuki; Cheung, Kenneth M.C.; Chiba, Kazuhiro; Ho, Daniel W.H.; Miyake, Atsushi; Kao, Patrick Y.P.; Sze, Kit Ling; Yee, Anita; Takahashi, Atsushi; Kawaguchi, Yoshiharu; Mikami, Yasuo; Matsumoto, Morio; Togawa, Daisuke; Kanayama, Masahiro; Shi, Dongquan; Dai, Jin; Jiang, Qing; Wu, Chengai; Tian, Wei; Wang, Na; Leong, John C.Y.; Luk, Keith D.K.; Yip, Shea-ping; Cherny, Stacey S.; Wang, Junwen; Mundlos, Stefan; Kelempisioti, Anthi; Eskola, Pasi J.; Männikkö, Minna; Mäkelä, Pirkka; Karppinen, Jaro; Järvelin, Marjo-Riitta; O’Reilly, Paul F.; Kubo, Michiaki; Kimura, Tomoatsu; Kubo, Toshikazu; Toyama, Yoshiaki; Mizuta, Hiroshi; Cheah, Kathryn S.E.; Tsunoda, Tatsuhiko; Sham, Pak-Chung; Ikegawa, Shiro; Chan, Danny

2013-01-01

308

A plant Y chromosome-STS marker encoding a degenerate retrotransposon.  

PubMed

The dioecious plant Silene latifolia has both X and Y sex chromosomes. Male-specific random amplified polymorphic DNA (RAPD) fragments were analyzed to identify Y-chromosome-linked sequences. One of the RAPD fragments, MS4, was converted into a more reliable and reproducible sequence-tagged site (STS) marker. A set of MS4 STS primers was used to amplify two genomic DNA fragments (MS4a and MS4b) from a male plant and one (MS4a) from a female plant, which indicates that MS4b is located on the Y chromosome. Sequence analysis revealed that MS4a encoded a gag protein of a Ty3-gypsy-like retrotransposon. A 147-bp region from the middle of MS4a was deleted in MS4b. The MS4b sequence was not detected in the most closely related dioecious species, S. dioica. This suggests that a retrotransposon with the MS4b sequence has degenerated recently on the Y chromosome. PMID:12589074

Obara, Mari; Matsunaga, Sachihiro; Nakao, Shunsuke; Kawano, Shigeyuki

2002-12-01

309

CX3CL1 (Fractalkine) Protein Expression in Normal and Degenerating Mouse Retina: In Vivo Studies  

PubMed Central

We aimed to investigate fractalkine (CX3CL1) protein expression in wild type (wt) retina and its alterations during retinal degeneration in mouse model (rd10) of retinitis pigmentosa. Forms of retinal protein CX3CL1, total protein and mRNA levels of CX3CL1 were analyzed at postnatal days (P) 5, 10, 14, 22, 30, 45, and 60 by Western blotting and real-time PCR. Cellular sources of CX3CL1 were investigated by in situ hybridization histochemistry (ISH) and using transgenic (CX3CL1cherry) mice. The immunoblots revealed that in both, wt and rd10 retinas, a membrane integrated ?100 kDa CX3CL1 form and a cleaved ?85 kDa CX3CL1 form were present at P5. At P10, accumulation of another presumably intra-neuronal ?95 kDa form and a decrease in the ?85-kDa form were observed. From P14, a ?95 kDa form became principal in wt retina, while in rd10 retinas a soluble ?85 kDa form increased at P45 and P60. In comparison, retinas of rd10 mice had significantly lower levels of total CX3CL1 protein (from P10 onwards) and lower CX3CL1 mRNA levels (from P14), even before the onset of primary rod degeneration. ISH and mCherry reporter fluorescence showed neurons in the inner retina layers as principal sites of CX3CL1 synthesis both in wt and rd10 retinas. In conclusion, our results demonstrate that CX3CL1 has a distinctive course of expression and functional regulation in rd10 retina starting at P10. The biological activity of CX3CL1 is regulated by conversion of a membrane integrated to a soluble form during neurogenesis and in response to pathologic changes in the adult retinal milieu. Viable mature neurons in the inner retina likely exhibit a dynamic intracellular storage depot of CX3CL1. PMID:25191897

Zieger, Marina; Ahnelt, Peter K.; Uhrin, Pavel

2014-01-01

310

dnc-1/dynactin 1 Knockdown Disrupts Transport of Autophagosomes and Induces Motor Neuron Degeneration  

PubMed Central

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neurons. We previously showed that the expression of dynactin 1, an axon motor protein regulating retrograde transport, is markedly reduced in spinal motor neurons of sporadic ALS patients, although the mechanisms by which decreased dynactin 1 levels cause neurodegeneration have yet to be elucidated. The accumulation of autophagosomes in degenerated motor neurons is another key pathological feature of sporadic ALS. Since autophagosomes are cargo of dynein/dynactin complexes and play a crucial role in the turnover of several organelles and proteins, we hypothesized that the quantitative loss of dynactin 1 disrupts the transport of autophagosomes and induces the degeneration of motor neuron. In the present study, we generated a Caenorhabditis elegans model in which the expression of DNC-1, the homolog of dynactin 1, is specifically knocked down in motor neurons. This model exhibited severe motor defects together with axonal and neuronal degeneration. We also observed impaired movement and increased number of autophagosomes in the degenerated neurons. Furthermore, the combination of rapamycin, an activator of autophagy, and trichostatin which facilitates axonal transport dramatically ameliorated the motor phenotype and axonal degeneration of this model. Thus, our results suggest that decreased expression of dynactin 1 induces motor neuron degeneration and that the transport of autophagosomes is a novel and substantial therapeutic target for motor neuron degeneration. PMID:23408943

Ikenaka, Kensuke; Kawai, Kaori; Katsuno, Masahisa; Huang, Zhe; Jiang, Yue-Mei; Iguchi, Yohei; Kobayashi, Kyogo; Kimata, Tsubasa; Waza, Masahiro; Tanaka, Fumiaki; Mori, Ikue; Sobue, Gen

2013-01-01

311

Altered Knee Joint Mechanics in Simple Compression Associated with Early Cartilage Degeneration  

PubMed Central

The progression of osteoarthritis can be accompanied by depth-dependent changes in the properties of articular cartilage. The objective of the present study was to determine the subsequent alteration in the fluid pressurization in the human knee using a three-dimensional computer model. Only a small compression in the femur-tibia direction was applied to avoid numerical difficulties. The material model for articular cartilages and menisci included fluid, fibrillar and nonfibrillar matrices as distinct constituents. The knee model consisted of distal femur, femoral cartilage, menisci, tibial cartilage, and proximal tibia. Cartilage degeneration was modeled in the high load-bearing region of the medial condyle of the femur with reduced fibrillar and nonfibrillar elastic properties and increased hydraulic permeability. Three case studies were implemented to simulate (1) the onset of cartilage degeneration from the superficial zone, (2) the progression of cartilage degeneration to the middle zone, and (3) the progression of cartilage degeneration to the deep zone. As compared with a normal knee of the same compression, reduced fluid pressurization was observed in the degenerated knee. Furthermore, faster reduction in fluid pressure was observed with the onset of cartilage degeneration in the superficial zone and progression to the middle zone, as compared to progression to the deep zone. On the other hand, cartilage degeneration in any zone would reduce the fluid pressure in all three zones. The shear strains at the cartilage-bone interface were increased when cartilage degeneration was eventually advanced to the deep zone. The present study revealed, at the joint level, altered fluid pressurization and strains with the depth-wise cartilage degeneration. The results also indicated redistribution of stresses within the tissue and relocation of the loading between the tissue matrix and fluid pressure. These results may only be qualitatively interesting due to the small compression considered. PMID:23424607

Dabiri, Y.; Li, L. P.

2013-01-01

312

Altered knee joint mechanics in simple compression associated with early cartilage degeneration.  

PubMed

The progression of osteoarthritis can be accompanied by depth-dependent changes in the properties of articular cartilage. The objective of the present study was to determine the subsequent alteration in the fluid pressurization in the human knee using a three-dimensional computer model. Only a small compression in the femur-tibia direction was applied to avoid numerical difficulties. The material model for articular cartilages and menisci included fluid, fibrillar and nonfibrillar matrices as distinct constituents. The knee model consisted of distal femur, femoral cartilage, menisci, tibial cartilage, and proximal tibia. Cartilage degeneration was modeled in the high load-bearing region of the medial condyle of the femur with reduced fibrillar and nonfibrillar elastic properties and increased hydraulic permeability. Three case studies were implemented to simulate (1) the onset of cartilage degeneration from the superficial zone, (2) the progression of cartilage degeneration to the middle zone, and (3) the progression of cartilage degeneration to the deep zone. As compared with a normal knee of the same compression, reduced fluid pressurization was observed in the degenerated knee. Furthermore, faster reduction in fluid pressure was observed with the onset of cartilage degeneration in the superficial zone and progression to the middle zone, as compared to progression to the deep zone. On the other hand, cartilage degeneration in any zone would reduce the fluid pressure in all three zones. The shear strains at the cartilage-bone interface were increased when cartilage degeneration was eventually advanced to the deep zone. The present study revealed, at the joint level, altered fluid pressurization and strains with the depth-wise cartilage degeneration. The results also indicated redistribution of stresses within the tissue and relocation of the loading between the tissue matrix and fluid pressure. These results may only be qualitatively interesting due to the small compression considered. PMID:23424607

Dabiri, Y; Li, L P

2013-01-01

313

Influence of Alendronate and Endplate Degeneration to Single Level Posterior Lumbar Spinal Interbody Fusion  

PubMed Central

Objective Using alendronate after spinal fusion is a controversial issue due to the inhibition of osteoclast mediated bone resorption. In addition, there are an increasing number of reports that the endplate degeneration influences the lumbar spinal fusion. The object of this retrospective controlled study was to evaluate how the endplate degeneration and the bisphosphonate medication influence the spinal fusion through radiographic evaluation. Methods In this study, 44 patients who underwent single-level posterior lumbar interbody fusion (PLIF) using cage were examined from April 2007 to March 2009. All patients had been diagnosed as osteoporosis and would be recommended for alendronate medication. Endplate degeneration is categorized by the Modic changes. The solid fusion is defined if there was bridging bone between the vertebral bodies, either within or external to the cage on the plain X-ray and if there is less than 5° of angular difference in dynamic X-ray. Results In alendronate group, fusion was achieved in 66.7% compared to 73.9% in control group (no medication). Alendronate did not influence the fusion rate of PLIF. However, there was the statistical difference of fusion rate between the endplate degeneration group and the group without endplate degeneration. A total of 52.4% of fusion rate was seen in the endplate degeneration group compared to 91.3% in the group without endplate degeneration. The endplate degeneration suppresses the fusion process of PLIF. Conclusion Alendronate does not influence the fusion process in osteoporotic patients. The endplate degeneration decreases the fusion rate. PMID:25620981

Rhee, Wootack; Ha, Seongil; Lim, Jae Hyeon; Jang, Il Tae

2014-01-01

314

Initial evolution of supports of solutions of quasilinear parabolic equations with degenerate absorption potential  

SciTech Connect

The propagation of supports of solutions of second-order quasilinear parabolic equations is studied; the equations are of the type of nonstationary diffusion, having semilinear absorption with an absorption potential which degenerates on the initial plane. We find sufficient conditions, which are sharp in a certain sense, on the relationship between the boundary regime and the type of degeneration of the potential to ensure the strong localization of solutions. We also establish a weak localization of solutions for an arbitrary potential which degenerates only on the initial plane. Bibliography: 12 titles.

Stepanova, Ekaterina V; Shishkov, Andrey E

2013-03-31

315

Glycogen synthase kinase-3 is associated with neuronal and glial hyperphosphorylated tau deposits in Alzheimer's disease, Pick's disease, progressive supranuclear palsy and corticobasal degeneration  

Microsoft Academic Search

Tau phosphorylation was examined in Alzheimer's disease (AD), Pick's disease (PiD), progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) using phospho-specific tau antibodies recognizing the phosphorylated form of Ser202, Ser214 and Ser 396, and antibodies to non-phosphorylated glycogen synthase kinase-3!\\/# (GSK-3!\\/#), which regulates phosphorylation at these specific sites on tau and phosphorylated GSK-3#Ser9 (GSK-3#-P); this antibody is directed to the

I. Ferrer; M. Barrachina; B. Puig

2002-01-01

316

Imaging Polarimetry in Age-Related Macular Degeneration  

PubMed Central

PURPOSE To evaluate the birefringence properties of eyes with age-related macular degeneration (AMD). To compare the information from two techniques—scanning laser polarimetry (GDx) and polarization-sensitive spectral-domain optical coherence tomography (OCT)—and investigate how they complement each other. METHODS The authors prospectively examined the eyes of two healthy subjects and 13 patients with exudative AMD. Using scanning laser polarimetry, they computed phase-retardation maps, average reflectance images, and depolarized light images. To obtain polarimetry information with improved axial resolution, they developed a fiber-based, polarization-sensitive, spectral-domain OCT system and measured the phase retardation associated with birefringence in the same eyes. RESULTS Both GDx and polarization-sensitive spectral-domain optical coherence tomography detected abnormal birefringence at the locus of exudative lesions. Polarization-sensitive, spectral-domain OCT showed that in the old lesions with fibrosis, phase-retardation values were significantly larger than in the new lesions (P = 0.020). Increased scattered light and altered polarization scramble were associated with portions of the lesions. CONCLUSIONS GDx and polarization-sensitive spectral-domain OCT are complementary in probing birefringence properties in exudative AMD. Polarimetry findings in exudative AMD emphasized different features and were related to the progression of the disease, potentially providing a noninvasive tool for microstructure in exudative AMD. PMID:18515594

Miura, Masahiro; Yamanari, Masahiro; Iwasaki, Takuya; Elsner, Ann E.; Makita, Shuichi; Yatagai, Toyohiko; Yasuno, Yoshiaki

2010-01-01

317

Seven new loci associated with age-related macular degeneration.  

PubMed

Age-related macular degeneration (AMD) is a common cause of blindness in older individuals. To accelerate the understanding of AMD biology and help design new therapies, we executed a collaborative genome-wide association study, including >17,100 advanced AMD cases and >60,000 controls of European and Asian ancestry. We identified 19 loci associated at P < 5 × 10(-8). These loci show enrichment for genes involved in the regulation of complement activity, lipid metabolism, extracellular matrix remodeling and angiogenesis. Our results include seven loci with associations reaching P < 5 × 10(-8) for the first time, near the genes COL8A1-FILIP1L, IER3-DDR1, SLC16A8, TGFBR1, RAD51B, ADAMTS9 and B3GALTL. A genetic risk score combining SNP genotypes from all loci showed similar ability to distinguish cases and controls in all samples examined. Our findings provide new directions for biological, genetic and therapeutic studies of AMD. PMID:23455636

Fritsche, Lars G; Chen, Wei; Schu, Matthew; Yaspan, Brian L; Yu, Yi; Thorleifsson, Gudmar; Zack, Donald J; Arakawa, Satoshi; Cipriani, Valentina; Ripke, Stephan; Igo, Robert P; Buitendijk, Gabriëlle H S; Sim, Xueling; Weeks, Daniel E; Guymer, Robyn H; Merriam, Joanna E; Francis, Peter J; Hannum, Gregory; Agarwal, Anita; Armbrecht, Ana Maria; Audo, Isabelle; Aung, Tin; Barile, Gaetano R; Benchaboune, Mustapha; Bird, Alan C; Bishop, Paul N; Branham, Kari E; Brooks, Matthew; Brucker, Alexander J; Cade, William H; Cain, Melinda S; Campochiaro, Peter A; Chan, Chi-Chao; Cheng, Ching-Yu; Chew, Emily Y; Chin, Kimberly A; Chowers, Itay; Clayton, David G; Cojocaru, Radu; Conley, Yvette P; Cornes, Belinda K; Daly, Mark J; Dhillon, Baljean; Edwards, Albert O; Evangelou, Evangelos; Fagerness, Jesen; Ferreyra, Henry A; Friedman, James S; Geirsdottir, Asbjorg; George, Ronnie J; Gieger, Christian; Gupta, Neel; Hagstrom, Stephanie A; Harding, Simon P; Haritoglou, Christos; Heckenlively, John R; Holz, Frank G; Hughes, Guy; Ioannidis, John P A; Ishibashi, Tatsuro; Joseph, Peronne; Jun, Gyungah; Kamatani, Yoichiro; Katsanis, Nicholas; N Keilhauer, Claudia; Khan, Jane C; Kim, Ivana K; Kiyohara, Yutaka; Klein, Barbara E K; Klein, Ronald; Kovach, Jaclyn L; Kozak, Igor; Lee, Clara J; Lee, Kristine E; Lichtner, Peter; Lotery, Andrew J; Meitinger, Thomas; Mitchell, Paul; Mohand-Saïd, Saddek; Moore, Anthony T; Morgan, Denise J; Morrison, Margaux A; Myers, Chelsea E; Naj, Adam C; Nakamura, Yusuke; Okada, Yukinori; Orlin, Anton; Ortube, M Carolina; Othman, Mohammad I; Pappas, Chris; Park, Kyu Hyung; Pauer, Gayle J T; Peachey, Neal S; Poch, Olivier; Priya, Rinki Ratna; Reynolds, Robyn; Richardson, Andrea J; Ripp, Raymond; Rudolph, Guenther; Ryu, Euijung; Sahel, José-Alain; Schaumberg, Debra A; Scholl, Hendrik P N; Schwartz, Stephen G; Scott, William K; Shahid, Humma; Sigurdsson, Haraldur; Silvestri, Giuliana; Sivakumaran, Theru A; Smith, R Theodore; Sobrin, Lucia; Souied, Eric H; Stambolian, Dwight E; Stefansson, Hreinn; Sturgill-Short, Gwen M; Takahashi, Atsushi; Tosakulwong, Nirubol; Truitt, Barbara J; Tsironi, Evangelia E; Uitterlinden, André G; van Duijn, Cornelia M; Vijaya, Lingam; Vingerling, Johannes R; Vithana, Eranga N; Webster, Andrew R; Wichmann, H-Erich; Winkler, Thomas W; Wong, Tien Y; Wright, Alan F; Zelenika, Diana; Zhang, Ming; Zhao, Ling; Zhang, Kang; Klein, Michael L; Hageman, Gregory S; Lathrop, G Mark; Stefansson, Kari; Allikmets, Rando; Baird, Paul N; Gorin, Michael B; Wang, Jie Jin; Klaver, Caroline C W; Seddon, Johanna M; Pericak-Vance, Margaret A; Iyengar, Sudha K; Yates, John R W; Swaroop, Anand; Weber, Bernhard H F; Kubo, Michiaki; Deangelis, Margaret M; Léveillard, Thierry; Thorsteinsdottir, Unnur; Haines, Jonathan L; Farrer, Lindsay A; Heid, Iris M; Abecasis, Gonçalo R

2013-04-01

318

Selective neuronal degeneration induced by soluble oligomeric amyloid beta protein.  

PubMed

The prevailing amyloid hypothesis for Alzheimer's disease (AD) holds that amyloid beta-protein (Abeta) causes neuronal degeneration by forming neurotoxic fibrillar structures. Yet, many aspects of AD pathology and symptoms are not well explained by this hypothesis. Here, we present evidence that neurotoxicity of soluble oligomeric Abeta closely corresponds to the selective neurodegeneration so distinctly manifest in AD. Selectivity was first observed in vitro, where only the human central nervous system neuronal cells were susceptible to soluble oligomeric Abeta. Furthermore, in mouse cerebral slice treated with soluble oligomeric Abeta, selective regiospecific toxicity was evident in the hippocampal CA1, a division important for memory, but not in the CA3 subfield. The fibrillar Abeta, however, killed neurons in all regions of the cerebral slice cultures and also in cerebellar slices. Remarkably, even at the highest soluble oligomeric Abeta concentrations, cerebellar neurons were completely spared, consistent with one of the hallmark features of AD pathology. Our observation of the selective neurodegeneration of soluble oligomeric Abeta to neurons involved in cognitive function may provide a new opportunity for the development of an effective AD therapy as well as elucidating the pathological mechanism of AD. PMID:12424218

Kim, Hyeon-Jin; Chae, Soo-Cheon; Lee, Dae-Kwon; Chromy, Brett; Lee, Sam Cheol; Park, Yeong-Chul; Klein, William L; Krafft, Grant A; Hong, Seong-Tshool

2003-01-01

319

Terrien’s Marginal Degeneration Accompanied by Latticed Stromal Opacities  

PubMed Central

ABSTRACT Purpose We report a case of Terrien’s marginal degeneration (TMD) with a unilaterally typical narrow band of peripheral corneal stroma thinning, accompanied by the presence of an unusual network of opacities diffusing throughout the anterior stroma layers. Case Report A 43-year-old woman presented with superior nasal peripheral corneal thinning and an unusual network of polygonal stromal opacities in the anterior corneal stroma of the right eye. Latticed corneal changes were unusually extensive and distributed diffusely in the stroma. No abnormalities were found in the corneal epithelium and in the basal epithelial cells. No noticeable changes were found in the left eye. Because of a progressively worse ocular irritation of the right eye, a diagnosis of TMD was made for this patient. Conclusions This case of TMD accompanied by keratopathy was unusual. The branching stromal lattice pattern of the corneal opacities was difficult to distinguish from lattice corneal dystrophy. In this case, the polygonal stromal opacities were located in the anterior corneal stroma and therefore were distinguished from a similar manifestation in posterior crocodile shagreen. PMID:24681833

Zhang, Yibing; Jia, Hui

2014-01-01

320

Mechanism of Inflammation in Age-Related Macular Degeneration  

PubMed Central

Age-related macular degeneration (AMD) is a multifactorial disease that represents the most common cause of irreversible visual impairment among people over the age of 50 in Europe, the United States, and Australia, accounting for up to 50% of all cases of central blindness. Risk factors of AMD are heterogeneous, mainly including increasing age and different genetic predispositions, together with several environmental/epigenetic factors, that is, cigarette smoking, dietary habits, and phototoxic exposure. In the aging retina, free radicals and oxidized lipoproteins are considered to be major causes of tissue stress resulting in local triggers for parainflammation, a chronic status which contributes to initiation and/or progression of many human neurodegenerative diseases such as AMD. Experimental and clinical evidences strongly indicate the pathogenetic role of immunologic processes in AMD occurrence, consisting of production of inflammatory related molecules, recruitment of macrophages, complement activation, microglial activation and accumulation within those structures that compose an essential area of the retina known as macula lutea. This paper reviews some attractive aspects of the literature about the mechanisms of inflammation in AMD, especially focusing on those findings or arguments more directly translatable to improve the clinical management of patients with AMD and to prevent the severe vision loss caused by this disease. PMID:23209345

Parmeggiani, Francesco; Romano, Mario R.; Costagliola, Ciro; Semeraro, Francesco; Incorvaia, Carlo; D'Angelo, Sergio; Perri, Paolo; De Palma, Paolo; De Nadai, Katia; Sebastiani, Adolfo

2012-01-01

321

Ocular surface temperature in age-related macular degeneration.  

PubMed

Background. The aim of this study is to investigate the ocular thermographic profiles in age-related macular degeneration (AMD) eyes and age-matched controls to detect possible hemodynamic abnormalities, which could be involved in the pathogenesis of the disease. Methods. 32 eyes with early AMD, 37 eyes with atrophic AMD, 30 eyes affected by untreated neovascular AMD, and 43 eyes with fibrotic AMD were included. The control group consisted of 44 healthy eyes. Exclusion criteria were represented by any other ocular diseases other than AMD, tear film abnormalities, systemic cardiovascular abnormalities, diabetes mellitus, and a body temperature higher than 37.5°C. A total of 186 eyes without pupil dilation were investigated by infrared thermography (FLIR A320). The ocular surface temperature (OST) of three ocular points was calculated by means of an image processing technique from the infrared images. Two-sample t-test and one-way analysis of variance (ANOVA) test were used for statistical analyses. Results. ANOVA analyses showed no significant differences among AMD groups (P value?>0.272). OST in AMD patients was significantly lower than in controls (P > 0.05). Conclusions. Considering the possible relationship between ocular blood flow and OST, these findings might support the central role of ischemia in the pathogenesis of AMD. PMID:25436140

Sodi, Andrea; Matteoli, Sara; Giacomelli, Giovanni; Finocchio, Lucia; Corvi, Andrea; Menchini, Ugo

2014-01-01

322

Frequency tunable non-degenerate Josephson amplifier for qubit readout  

NASA Astrophysics Data System (ADS)

We have developed a new ultra low noise microwave amplifier based on the Josephson parametric converter (JPC), which overcomes a practical weakness of devices of previous generations: having sufficient frequency tunability to easily match the qubit readout frequency. The JPC consists of two superconducting microwave resonators that are coupled to each other through a ring of four Josephson junctions, threaded by a magnetic flux and providing the non-linearity for the amplification process. The non-linearity is of the trilinear form involving the minimal number of modes, and allows ideal non-degenerate parametric amplification at the quantum limit of noise. In our new tunable version, the junctions responsible for amplification are shunted by a cross of four larger junctions, which for our purpose can be regarded as linear inductors, as in the work of Roch et al.[1]. The JPC has now a unique bias point at any applied flux and is tunable over more than half a gigahertz. We are currently using this amplifier in conjunction with a quantum non-demolition measurement of a transmon qubit and have observed quantum jumps with fidelity larger than 90%. [1] N. Roch, E. Flurin, F. Nguyen, P. Morfin, P. Campagne-Ibarcq, M. H. Devoret, and B. Huard, in preparation.

Schackert, Flavius; Hatridge, Michael; Sliwa, Katrina; Abdo, Baleegh; Frunzio, Luigi; Devoret, Michel

2012-02-01

323

Therapeutic Modalities of Exudative Age-related Macular Degeneration  

PubMed Central

Introduction: Age-related macular degeneration (AMD) is a leading cause of irreversible serious vision damage in persons over 50 years of age. In treating AMD many medicaments are applied such as inhibitors of vascular endothelial growth factor (VEGF), have been very carefully included over the last few years after a series of study research. Aims: To analyze the past methods of treatment, discuss emerging therapies which could advance the treatment of exudative AMD. The past anti-VEGF therapies require frequent repetitions of administration, with uncertain visual acuity recovery, as not all patients react to anti-VEGF therapy. Consequently, there is a need to find out additional therapies which could improve the treatment of exudative AMD. The real aim in the treating of AMD is to prevent CNV development. Methods: A survey of the current clinical research and results in the field of the present and future treatments of exudative AMD. Results: There are many areas of research into new methods of the exudative AMD treatment. Conclusion: The future therapies for exudative AMD treatment have a potential not only to reduce the frequency of administration and follow-up visits, but also to improve effects of treatment by targeting additional ways of CNV development, increasing the aptitude of target binding and extending durability of treatment. PMID:25568535

Mavija, Milka; Alimanovic, Emina; Jaksic, Vesna; Kasumovic, Sanja Sefic; Cekic, Sonja; Stamenkovic, Miroslav

2014-01-01

324

Non-Fluent Speech in Frontotemporal Lobar Degeneration  

PubMed Central

We investigated the cognitive and neural bases of impaired speech fluency, a central feature of primary progressive aphasia. Speech fluency was assessed in 35 patients with frontotemporal lobar degeneration (FTLD) who presented with progressive non-fluent aphasia (PNFA, n=11), semantic dementia (SemD, n=12), or a social and executive disorder without aphasia (SOC/EXEC, n=12). Fluency was quantified as the number of words per minute in an extended, semi-structured speech sample. This was related to language characteristics of the speech sample and to neuropsychological measures. PNFA patients were significantly less fluent than controls and other FTLD patients. Fluency correlated with grammatical expression but not with speech errors or executive difficulty. SemD and SOC/EXEC patients were also less fluent than controls. In SemD, fluency was associated with semantically limited content. In SOC/EXEC, fluency was associated with executive limitations. Voxel-based morphometry analyses of high-resolution MRI related fluency to gray matter volume in left inferior frontal, insula, and superior temporal regions for the entire cohort of FTLD patients. This region overlapped partially distinct atrophic areas in each FTLD subgroup. It thus appears to play a crucial role in speech fluency, which can be interrupted in different ways in different FTLD subgroups. PMID:22180700

Ash, Sharon; Moore, Peachie; Vesely, Luisa; Gunawardena, Delani; McMillan, Corey; Anderson, Chivon; Avants, Brian; Grossman, Murray

2011-01-01

325

Late degeneration in rabbit tissues after irradiation by heavy ions  

NASA Technical Reports Server (NTRS)

Results are presented for investigations of the late effects of heavy-ion irradiation on rabbit tissues which were undertaken to assess the hazards associated with the long-term exposure of humans to heavy ions in space during such activities as the construction of solar power stations or voyages to Mars. White rabbits approximately six weeks old were exposed to various doses of collimated beams of 400-MeV/n Ne ions, 570 MeV/n Ar ions and Co-60 gamma rays directed through both eyes, and the responses of the various tissues (hair follicles, skin, cornea, lens, retina, Harderian glands, bone and forebrain) were examined. Proliferating tissues are found to exhibit high damage levels in the early and late periods following irradiation, while terminally differentiating tissues repond to radiation most intensely in the late period, years after irradiation, with no intermediate recovery. The results obtained from rabbits are used to predict the occurrence of late tissue degeneration in the central nervous system, terminally differentiating systems and stem cells of humans one or more decades following exposure to radiation levels anticipated during long-duration space flights. The studies also indicate that tissues may be prematurely aged in the sense that tissue life spans may be shortened without the development of malignancies.

Lett, J. T.; Cox, A. B.; Keng, P. C.; Lee, A. C.; Su, C. M.; Bergtold, D. S.

1980-01-01

326

Alpers syndrome: progressive neuronal degeneration of children with liver disease.  

PubMed

Alpers syndrome was not clearly defined until the link between brain and liver disease was described. Alpers syndrome can now be clearly established as a disorder of oxidative metabolism related to mitochondrial dysfunction, and in most instances with an autosomal mode of inheritance. The symptoms and signs are discussed. The illness occurs in the first years of life with the sudden onset of intractable seizures associated with developmental delay, hypotonia, ataxia, cortical blindness, and hepatic failure, and death occurs within a short time. Treating the seizures with valproic acid can cause the rapid onset of liver failure and must be avoided. To establish a definite diagnosis, liver and muscle biopsies may be needed. The former shows bile duct proliferation with the evidence of cirrhosis, and the latter may support the involvement of the mitochondrial respiratory chain if there are ragged-red fibres. Genetic studies can show an association with mitochondrial DNA depletion and mutations in the polymerase gene. Cytochrome c oxidase deficiency has been demonstrated in some patients. Useful diagnostic tests include liver function tests, lactic acid levels in the blood and cerebrospinal fluid, electroencephalograms, computed tomography, and magnetic resonance imaging. The differential diagnosis will be from other forms of neuronal degeneration and disorders of mitochondrial function. There is no specific treatment, which must await further research into causes. PMID:17109792

Gordon, Neil

2006-12-01

327

Donor and acceptor concentrations in degenerate InN  

SciTech Connect

A formalism is presented to determine donor (N{sub D}) and acceptor (N{sub A}) concentrations in wurtzitic InN characterized by degenerate carrier concentration (n) and mobility ({mu}). The theory includes scattering not only by charged point defects and impurities, but also by charged threading dislocations, of concentration N{sub dis}. For an 0.45-{micro}m-thick InN layer grown on Al{sub 2}O{sub 3} by molecular beam epitaxy, having N{sub dis} = 5 x 10{sup 10} cm{sup -2}, determined by transmission electron microscopy, n(20 K) = 3.5 x 10{sup 18} cm{sup -3}, and {mu}(20 K) = 1055 cm{sup 2}/V-s, determined by Hall-effect measurements, the fitted values are N{sub D} = 4.7 x 10{sup 18} cm{sup -3} and N{sub A} = 1.2 x 10{sup 18} cm{sup -3}. The identities of the donors and acceptors are not known, although a comparison of N{sub D} with analytical data, and also with calculations of defect formation energies, suggests that a potential candidate for the dominant donor is H.

Look, D.C.; Lu, H.; Schaff, W.J.; Jasinski, J.; Liliental-Weber, Z.

2002-01-28

328

Heavy-fermion instability in double-degenerate plasmas  

SciTech Connect

In this work, we study the propagations of normal frequency modes for quantum hydrodynamic waves in the linear limit and introduce a new kind of instability in a double-degenerate plasma. Three different regimes, namely, low, intermediate, and high magnetic field strengths are considered which span the applicability of the work to a wide variety of environments. Distinct behavior is observed for different regimes, for instance, in the laboratory-scale field regime no frequency-mode instability occurs unlike those of intermediate and high magnetic-field strength regimes. It is also found that the instability of this kind is due to the heavy-fermions which appear below a critical effective-mass parameter ({mu}{sub cr}={radical}(3)) and that the responses of the two (lower and upper frequency) modes to fractional effective-mass change in different effective-mass parameter ranges (below and above the critical value) are quite opposite to each other. It is shown that the heavy-fermion instability due to extremely high magnetic field such as that encountered for a neutron-star crust can lead to confinement of stable propagations in both lower and upper frequency modes to the magnetic poles. Current study can have important implications for linear wave dynamics in both laboratory and astrophysical environments possessing high magnetic fields.

Akbari-Moghanjoughi, M. [Department of Physics, Faculty of Sciences, Azarbaijan University of Tarbiat Moallem, 51745-406 Tabriz (Iran, Islamic Republic of)

2012-07-15

329

Mucoid degeneration of the anterior cruciate ligament: Management and outcome  

PubMed Central

Background: Mucoid degeneration (MD) is a rare pathological affection of the anterior cruciate ligament (ACL). Mucinous material within the substance of ACL produces pain and limited motion in the knee. This series describes the clinicoradiological presentation of patients with mucoid ACL, partial arthroscopic debridement of ACL and outcomes. Materials and Methods: During a period of 3 years, 11 patients were included based upon the clinical suspicion, magnetic resonance imaging (MRI) findings, arthroscopic features and histopathologic confirmation of MD of ACL. Result: Six patients were male and five were female with median age of 40 years (range 21-59 years). All patients complained of knee pain with median duration of 5 months (range 1-24 months). All patients had painful deep flexion with 63.6% (N = 7) reporting trivial trauma before the onset of symptoms. MRI revealed MD of ACL in all with associated cyst in three patients. Partial debridement of ACL was done in ten and complete in one patient. None of them required notchplasty. Histopathology confirmed the diagnosis in all of them. At the mean followup of 13.81 months (range 6-28 months), all patients regained complete flexion and none complained of instability. Conclusion: Prior knowledge of condition with high index of suspicion and careful interpretation of MRI can establish the diagnosis preoperatively. It responds well to partial debridement of ACL and mucinous material without development of instability. PMID:24741143

Pandey, Vivek; Suman, CPS; Sharma, Swati; Rao, Sripathi P; Kiran Acharya, KV; Sambaji, Charudutt

2014-01-01

330

SINGLE-DEGENERATE TYPE Ia SUPERNOVAE WITHOUT HYDROGEN CONTAMINATION  

SciTech Connect

The lack of hydrogen in spectra of type Ia supernovae (SNe Ia) is often seen as troublesome for single-degenerate (SD) progenitor models. We argue that, since continued accretion of angular momentum can prevent explosion of the white dwarf, it may be natural for the donor stars in SD progenitors of SNe Ia to exhaust their envelopes and shrink rapidly before the explosion. This outcome seems most likely for SD SN Ia progenitors where mass transfer begins from a giant donor star and might extend to other SD systems. Not only is the amount of hydrogen left in such a system below the current detection limit, but the donor star is typically orders of magnitude smaller than its Roche lobe by the point when an SD SN Ia occurs, in which case attempts to observe collisions between SN shocks and giant donor stars seem unlikely to succeed. We consider the constraints on this model from the circumstellar structures seen in spectra of SN 2006X and suggest a novel explanation for the origin of this material.

Justham, Stephen, E-mail: sjustham@pku.edu.cn [Kavli Institute for Astronomy and Astrophysics, Peking University, Beijing (China)

2011-04-01

331

New Approaches to the Treatment of Frontotemporal Lobar Degeneration  

PubMed Central

Purpose of review Treatment approaches for frontotemporal lobar degeneration (FTLD) are rapidly evolving with improved understanding of the disease. This brief review highlights recent advances. Recent findings Early-onset dementia has a devastating impact on families and rids its victims of their most productive and rewarding years. Over the past ten years, FTLD has emerged as the commonest cause of dementia under the age of 60 years, outstripping even Alzheimer’s disease in prevalence. Remarkable progress has occurred in our understanding of FTLD both as a set of distinctive clinical syndromes and as a set of disorders with unique genetic and pathological profiles. While there are no Food and Drug Administration approved medications for FTLD, new evidence of specific genetic and neurochemical defects are beginning to provide a strong rationale for pharmacological treatment. Summary Behavioral changes, which are common in behavioral variant FTD and semantic dementia, often respond to treatment with selective serotonin inhibitors. Memantine also holds promise to treat neuropsychiatric symptoms, but more prospective trials are needed. With better understanding of pathogenic molecular pathways involving microtubule associated protein tau, progranulin and TDP-43, potential disease-modifying therapies are being studied in animal models and approaching human trials. PMID:18989117

Vossel, Keith A.; Miller, Bruce L

2009-01-01

332

Age-related macular degeneration: linking clinical presentation to pathology.  

PubMed

Age-related macular degeneration (AMD) is one of the leading causes of blindness worldwide in the elderly population. Optometrists, as primary eye health care providers, require the skills and knowledge to accurately diagnose and manage AMD patients. There is an overwhelming body of research related to the clinical presentation, etiology, epidemiology, and pathology of this disease. Additionally, the evolution of new imaging modalities creates new opportunities to clinically detect and analyze previously uncharacterized and earlier changes in the retina. The challenge for optometrists is to combine all this information into an applicable knowledge base for use in everyday clinical assessment of AMD so that timely and accurate referrals can be made to retinal specialists. This review attempts to address this issue by linking the clinical presentation of AMD with the underlying disease biology. We emphasize the contribution of recent noninvasive imaging technologies to the clinical assessment of early and more advanced AMD including optical coherence tomography, fundus autofluorescence, and infrared reflectance. PMID:24879089

Nivison-Smith, Lisa; Milston, Rebecca; Madigan, Michele; Kalloniatis, Michael

2014-08-01

333

Nutritional supplements for age-related macular degeneration  

PubMed Central

Purpose of review Age-related macular degeneration, a leading cause of visual loss in older adults, has limited therapeutic options. This review describes the current literature on the role of nutritional supplementation in primary and secondary prevention of AMD. Recent findings Many observational studies have explored the association between diet, nutrient intake, and AMD. In particular, high dietary intakes of omega 3 fatty acids, and macular xanthophylls lutein and zeaxanthin have been associated with a lower risk of prevalent and incident AMD. However, the Age-Related Eye Disease Study (AREDS) is the only large-scale randomized controlled clinical trial to show a 25% beneficial effect of nutritional supplementation in reducing the risk progression to advanced AMD in patients with intermediate AMD or with advanced AMD in one eye at 5 years of follow-up. Based on the results of AREDS, these patients are recommended to take AREDS formulation of vitamins C, E, beta-carotene, and zinc with copper. Summary At the present time, there is insufficient evidence in the literature to recommend routine nutritional supplementation in healthy adults for primary prevention of AMD. However, patients with intermediate risk of AMD or advanced AMD in one eye should consider taking AREDS-type supplements. Observational studies have also suggested benefit from increased dietary intake of macular xanthophylls and omega-3 fatty acids. These are currently being evaluated prospectively in a randomized controlled clinical trial, the Age-Related Eye Disease Study 2 (AREDS2). PMID:20216418

Krishnadev, Nupura; Meleth, Annal D.; Chew, Emily Y.

2010-01-01

334

Genetic markers and biomarkers for age-related macular degeneration  

PubMed Central

Age-related macular degeneration (AMD) is the leading cause of visual impairment and blindness in the USA. Although the treatment of AMD has evolved to include laser photocoagulation, photodynamic therapy, surgical macular translocation and antiangiogenesis agents, treatment options for advanced AMD are limited. Furthermore, the dry form of AMD, albeit less devastating than the wet form, has even fewer viable treatment options. This review summarizes the various biomarkers of AMD and analyzes whether or not they may one day be exploited to determine risks of disease onset, measure progression of disease or even assess the effects of treatment of AMD. Potential biomarkers are important to identify since some might be utilized to reflect the disease state of a particular patient and to individualize therapy. Although studies have yielded promising results for nutrient and inflammatory biomarkers, these results have been inconsistent. At present, the best available markers of AMD risk are single nucleotide polymorphisms (SNPs). SNPs in complement factor H (CFH) and PLEKHA1/ARMS2/HtrA1 capture a substantial fraction of AMD risk and permit the identification of individuals at high risk of developing AMD. PMID:17917691

Ross, Robert J; Verma, Varun; Rosenberg, Kevin I; Chan, Chi-Chao; Tuo, Jingsheng

2007-01-01

335

Review of nutrient actions on age-related macular degeneration.  

PubMed

The actions of nutrients and related compounds on age-related macular degeneration (AMD) are explained in this review. The findings from 80 studies published since 2003 on the association between diet and supplements in AMD were reviewed. Antioxidants and other nutrients with an effect on AMD susceptibility include carotenoids (lutein and zeaxanthin, ?-carotene), vitamins (vitamin A, E, C, D, B), mineral supplements (zinc, copper, selenium), dietary fatty acids [monounsaturated fatty acids, polyunsaturated fatty acids (PUFA both omega-3 PUFA and omega-6 PUFA), saturated fatty acids and cholesterol], and dietary carbohydrates. The literature revealed that many of these antioxidants and nutrients exert a protective role by functioning synergistically. Specifically, the use of dietary supplements with targeted actions can provide minimal benefits on the onset or progression of AMD; however, this does not appear to be particularly beneficial in healthy people. Furthermore, some supplements or nutrients have demonstrated discordant effects on AMD in some studies. Since intake of dietary supplements, as well as exposure to damaging environmental factors, is largely dependent on population habits (including dietary practices) and geographical localization, an overall healthy diet appears to be the best strategy in reducing the risk of developing AMD. As of now, the precise mechanism of action of certain nutrients in AMD prevention remains unclear. Thus, future studies are required to examine the effects that nutrients have on AMD and to determine which factors are most strongly correlated with reducing the risk of AMD or preventing its progression. PMID:24461310

Zampatti, Stefania; Ricci, Federico; Cusumano, Andrea; Marsella, Luigi Tonino; Novelli, Giuseppe; Giardina, Emiliano

2014-02-01

336

Mitochondrial pathology and apoptotic muscle degeneration in Drosophila parkin mutants.  

PubMed

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by loss of dopaminergic neurons in the substantia nigra. Several lines of evidence strongly implicate mitochondrial dysfunction as a major causative factor in PD, although the molecular mechanisms responsible for mitochondrial dysfunction are poorly understood. Recently, loss-of-function mutations in the parkin gene, which encodes a ubiquitin-protein ligase, were found to underlie a familial form of PD known as autosomal recessive juvenile parkinsonism (AR-JP). To gain insight into the molecular mechanism responsible for selective cell death in AR-JP, we have created a Drosophila model of this disorder. Drosophila parkin null mutants exhibit reduced lifespan, locomotor defects, and male sterility. The locomotor defects derive from apoptotic cell death of muscle subsets, whereas the male sterile phenotype derives from a spermatid individualization defect at a late stage of spermatogenesis. Mitochondrial pathology is the earliest manifestation of muscle degeneration and a prominent characteristic of individualizing spermatids in parkin mutants. These results indicate that the tissue-specific phenotypes observed in Drosophila parkin mutants result from mitochondrial dysfunction and raise the possibility that similar mitochondrial impairment triggers the selective cell loss observed in AR-JP. PMID:12642658

Greene, Jessica C; Whitworth, Alexander J; Kuo, Isabella; Andrews, Laurie A; Feany, Mel B; Pallanck, Leo J

2003-04-01

337

Epidemiological Survey of Frontotemporal Lobar Degeneration in Tottori Prefecture, Japan  

PubMed Central

Background The prevalence of frontotemporal lobar degeneration (FTLD) in Japan is unknown. An epidemiological survey study of FTLD was undertaken in Tottori Prefecture, a district in the western region of Japan. Methods Hospitals in Tottori Prefecture were surveyed by a two-step questionnaire in 2010, and the prevalence of FTLD per 100,000 inhabitants was calculated using the actual number of patients and inhabitants in Tottori Prefecture on the prevalence day of October 1, 2010. Results In this survey, 66 patients were diagnosed with FTLD. The subtypes of FTLD were as follows: 62 cases of frontotemporal dementia (FTD), 3 cases of progressive nonfluent aphasia, and 1 case of semantic dementia. Among the FTD cases, 5 cases were FTD with motor neuron disease and 1 case was FTD with parkinsonism linked to chromosome 17. The prevalence of FTD in the total population of Tottori Prefecture was 11.2 per 100,000 inhabitants. Based on these results, the prevalence of FTLD in Japan in 2008 was estimated to be 9.5 per 100,000 individuals. Conclusions Our epidemiological survey results suggest that there are at least 12,000 FTLD patients in Japan, indicating that FTLD is not a rare disease. PMID:23300493

Wada-Isoe, Kenji; Ito, Satoru; Adachi, Tadashi; Yamawaki, Mika; Nakashita, Satoko; Kusumi, Masayoshi; Hiroe, Yu; Takada, Teruo; Watanabe, Ken; Hikasa, Chikanori; Nakashima, Kenji

2012-01-01

338

Genetic and neuroanatomic associations in sporadic frontotemporal lobar degeneration.  

PubMed

Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) that are sensitive for tau or TDP-43 pathology in frontotemporal lobar degeneration (FTLD). Neuroimaging analyses have revealed distinct distributions of disease in FTLD patients with genetic mutations. However, genetic influences on neuroanatomic structure in sporadic FTLD have not been assessed. In this report, we use novel multivariate tools, Eigenanatomy, and sparse canonical correlation analysis to identify associations between SNPs and neuroanatomic structure in sporadic FTLD. Magnetic resonance imaging analyses revealed that rs8070723 (MAPT) was associated with gray matter variance in the temporal cortex. Diffusion tensor imaging analyses revealed that rs1768208 (MOBP), rs646776 (near SORT1), and rs5848 (PGRN) were associated with white matter variance in the midbrain and superior longitudinal fasciculus. In an independent autopsy series, we observed that rs8070723 and rs1768208 conferred significant risk of tau pathology relative to TDP-43, and rs646776 conferred increased risk of TDP-43 pathology relative to tau. Identified brain regions and SNPs may help provide an in vivo screen for underlying pathology in FTLD and contribute to our understanding of sporadic FTLD. PMID:24373676

McMillan, Corey T; Toledo, Jon B; Avants, Brian B; Cook, Philip A; Wood, Elisabeth M; Suh, Eunran; Irwin, David J; Powers, John; Olm, Christopher; Elman, Lauren; McCluskey, Leo; Schellenberg, Gerard D; Lee, Virginia M-Y; Trojanowski, John Q; Van Deerlin, Vivianna M; Grossman, Murray

2014-06-01

339

Inflammatory priming predisposes mice to age-related retinal degeneration  

PubMed Central

Disruption of cellular processes affected by multiple genes and accumulation of numerous insults throughout life dictate the progression of age-related disorders, but their complex etiology is poorly understood. Postmitotic neurons, such as photoreceptor cells in the retina and epithelial cells in the adjacent retinal pigmented epithelium, are especially susceptible to cellular senescence, which contributes to age-related retinal degeneration (ARD). The multigenic and complex etiology of ARD in humans is reflected by the relative paucity of effective compounds for its early prevention and treatment. To understand the genetic differences that drive ARD pathogenesis, we studied A/J mice, which develop ARD more pronounced than that in other inbred mouse models. Although our investigation of consomic strains failed to identify a chromosome associated with the observed retinal deterioration, pathway analysis of RNA-Seq data from young mice prior to retinal pathological changes revealed that increased vulnerability to ARD in A/J mice was due to initially high levels of inflammatory factors and low levels of homeostatic neuroprotective factors. The genetic signatures of an uncompensated preinflammatory state and ARD progression identified here aid in understanding the susceptible genetic loci that underlie pathogenic mechanisms of age-associated disorders, including several human blinding diseases. PMID:22797304

Mustafi, Debarshi; Maeda, Tadao; Kohno, Hideo; Nadeau, Joseph H.; Palczewski, Krzysztof

2012-01-01

340

Degenerate four-wave mixing in triply resonant Kerr cavities  

SciTech Connect

We demonstrate theoretical conditions for highly efficient degenerate four-wave mixing in triply resonant nonlinear (Kerr) cavities. We employ a general and accurate temporal coupled-mode analysis in which the interaction of light in arbitrary microcavities is expressed in terms of a set of coupling coefficients that we rigorously derive from the full Maxwell equations. Using the coupled-mode theory, we show that light consisting of an input signal of frequency {omega}{sub 0}-{Delta}{omega} can, in the presence of pump light at {omega}{sub 0}, be converted with quantum-limited efficiency into an output shifted signal of frequency {omega}{sub 0}+{Delta}{omega}, and we derive expressions for the critical input powers at which this occurs. We find the critical powers in the order of 10 mW, assuming very conservative cavity parameters (modal volumes {approx}10 cubic wavelengths and quality factors {approx}1000). The standard Manley-Rowe efficiency limits are obtained from the solution of the classical coupled-mode equations, although we also derive them from simple photon-counting 'quantum' arguments. Finally, using a linear stability analysis, we demonstrate that maximal conversion efficiency can be retained even in the presence of self- and cross-phase modulation effects that generally act to disrupt the resonance condition.

Ramirez, David M.; Joannopoulos, J. D.; Soljacic, Marin [Department of Physics, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Rodriguez, Alejandro W. [Department of Mathematics, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); School of Science and Engineering, Harvard University, Cambridge, MA 02139 (United States); Hashemi, Hila; Johnson, Steven G. [Department of Mathematics, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States)

2011-03-15

341

[Age-related macular degeneration--a complex genetic disease].  

PubMed

Age-related macular degeneration (AMD,) is the most common cause of severe visual loss and blindness in the population over 60 years old, especially in the developed world. Two types of AMD are distinguished: the dry (non-exudative or atrophic) and the wet (exudative or neovascular) form. Family and twins studies have shown that the susceptibility for this disease is genetically influenced and the heritability has been estimated to be up to 75%. Until now, many of the candidate-genes associated with AMD have been discovered using studies on genetically engineered and naturally mutated animals, linkage studies, studies of monogenic degenerative retinal diseases and association studies. Recently genes have been described that significantly contribute to the etiopathogenesis of AMD: CFH, PLEKHA1/LOC387715/HTRA1 and C2/BF genes. AMD is considered to be a genetic complex disease in which multiple genes and environmental factors play a role in pathogenesis. Identification of other genes involved in development of AMD will improve our knowledge about new pathways and pathological mechanisms of the disease, as well as avenues for novel more effective treatments. The aim of this article is to survey published data on genetic aspect of AMD, with emphasis of several recently discovered genes described to be particularly important in the pathogenesis of AMD, and /or somehow associated with the occurrence of the disease. PMID:18655465

Antoniak, Katarzyna; Bienias, Wojciech; Nowak, Jerzy Z

2008-01-01

342

White matter degeneration in schizophrenia: a comparative diffusion tensor analysis  

NASA Astrophysics Data System (ADS)

Schizophrenia is a serious and disabling mental disorder. Diffusion tensor imaging (DTI) studies performed on schizophrenia have demonstrated white matter degeneration either due to loss of myelination or deterioration of fiber tracts although the areas where the changes occur are variable across studies. Most of the population based studies analyze the changes in schizophrenia using scalar indices computed from the diffusion tensor such as fractional anisotropy (FA) and relative anisotropy (RA). The scalar measures may not capture the complete information from the diffusion tensor. In this paper we have applied the RADTI method on a group of 9 controls and 9 patients with schizophrenia. The RADTI method converts the tensors to log-Euclidean space where a linear regression model is applied and hypothesis testing is performed between the control and patient groups. Results show that there is a significant difference in the anisotropy between patients and controls especially in the parts of forceps minor, superior corona radiata, anterior limb of internal capsule and genu of corpus callosum. To check if the tensor analysis gives a better idea of the changes in anisotropy, we compared the results with voxelwise FA analysis as well as voxelwise geodesic anisotropy (GA) analysis.

Ingalhalikar, Madhura A.; Andreasen, Nancy C.; Kim, Jinsuh; Alexander, Andrew L.; Magnotta, Vincent A.

2010-03-01

343

Submacular haemorrhages associated with neovascular age-related macular degeneration.  

PubMed

The exact incidence of submacular haemorrhage (SMH) in patients with neovascular age-related macular degeneration (nAMD) is unknown, and risk factors for its occurrence ill defined. It is known, however, to be a relatively common problem and important because the visual prognosis of these patients is poor. Unfortunately, patients with significant SMH were excluded from all the recent major randomised control trials for nAMD with antivascular endothelial growth factor (VEGF) agents and photodynamic therapy, and as such, the optimum management of patients is uncertain. SMH can present initially or during treatment of nAMD. The location, size, thickness and duration of SMH have an important bearing on treatment and outcomes. Thin or extrafoveal SMH are probably best treated with anti-VEGF agents alone. It has been proposed that patients with moderate-sized SMH, particularly thick haemorrhages, have an improved prognosis with surgical SMH displacement combined with treatment of CNVM if present. SMH drainage, macular translocation and RPE patch grafting are reserved for more severe extensive cases of SMH. Using these techniques, outcomes better than the natural history have been achieved. This review aims to summarise what is known about SMH in nAMD and will discuss a variety of therapeutic interventions. PMID:20813746

Steel, David Henry William; Sandhu, Sukhpal Singh

2011-08-01

344

Seven New Loci Associated with Age-Related Macular Degeneration  

PubMed Central

Age-related macular degeneration (AMD) is a common cause of blindness in older individuals. To accelerate understanding of AMD biology and help design new therapies, we executed a collaborative genomewide association study, examining >17,100 advanced AMD cases and >60,000 controls of European and Asian ancestry. We identified 19 genomic loci associated with AMD with p<5×10?8 and enriched for genes involved in regulation of complement activity, lipid metabolism, extracellular matrix remodeling and angiogenesis. Our results include 7 loci reaching p<5×10?8 for the first time, near the genes COL8A1/FILIP1L, IER3/DDR1, SLC16A8, TGFBR1, RAD51B, ADAMTS9/MIR548A2, and B3GALTL. A genetic risk score combining SNPs from all loci displayed similar good ability to distinguish cases and controls in all samples examined. Our findings provide new directions for biological, genetic and therapeutic studies of AMD. PMID:23455636

2013-01-01

345

Aflibercept for the treatment of age-related macular degeneration.  

PubMed

Aflibercept is a novel, recombinant, fusion protein that consists of portions of vascular endothelial growth factor (VEGF) receptor (R) 1 and VEGFR2 extracellular domains fused to the Fc portion of human immunoglobulin G1. It exhibits higher affinity for VEGF-A/-B and binds all the VEGF isoforms (VEGF-B and -C, placental growth factor). The efficacy of aflibercept was assessed in two randomized, double-masked, multicenter, active-controlled, clinical trials in patients with choroidal neovascularization due to exudative age-related macular degeneration (AMD) and compared it's efficacy to ranibizumab, which is already Food and Drug Administration (FDA)-approved for patients with wet AMD. In the two trials known as VIEW 1 and VIEW 2, aflibercept was as effective when dosed as 2 mg every 8 weeks after 3 monthly loading doses compared to monthly ranibizumab. Aflibercept was well tolerated with very rare systemic adverse events, including arterial thromboembolic events (ATEs). The incidence of ATEs was 1.8% during the first year of the clinical trials and included non-fatal strokes, non-fatal myocardial infarction, or death from vascular events or an unknown cause. In November 2011, aflibercept received FDA approval and is currently used in clinical practice for patients with wet AMD. PMID:25135809

Trichonas, George; Kaiser, Peter K

2013-12-01

346

Current therapeutic approaches in neovascular age-related macular degeneration.  

PubMed

Age-related macular degeneration (AMD) is the leading eye disease to cause visual impairment in the elderly. Neovascular AMD is a type of advanced AMD that is characterized by pathologic proliferation and leakage of abnormal blood vessels in the eye. While the pathogenesis of neovascular AMD is not completely known, one of the important milestones in neovascular AMD research was the identification of vascular endothelial growth factor (VEGF) as a major stimulus of abnormal angiogenesis that can be targeted for intravitreal treatment. Anti-VEGF therapies that neutralize or block the induction of angiogenesis by VEGF have recently revolutionized the therapeutic approach to neovascular AMD. The scientific literature regarding the efficacy and safety of anti-VEGF treatment has been hugely enriched with results from various recent randomized clinical trials involving the three most commonly utilized anti-VEGF pharmacologic agents--ranibizumab, bevacizumab, and aflibercept. The potential to stop and reverse the progressive loss of vision due to neovascular AMD is evident. Continued investigation into inhibiting VEGF as well as targeting other crucial factors that contribute to neovascular AMD is an active field of research that is expected to accelerate the progress of neovascular AMD therapy. PMID:23819948

Nguyen, Duy H; Luo, Jing; Zhang, Kang; Zhang, Ming

2013-06-01

347

Exponential Mixing of the 3D Stochastic Navier-Stokes Equations Driven by Mildly Degenerate Noises  

SciTech Connect

We prove the strong Feller property and exponential mixing for 3D stochastic Navier-Stokes equation driven by mildly degenerate noises (i.e. all but finitely many Fourier modes being forced) via a Kolmogorov equation approach.

Albeverio, Sergio [Bonn University, Department of Applied Mathematics (Germany); Debussche, Arnaud, E-mail: arnaud.debussche@bretagne.ens-cachan.fr [ENS Cachan Bretagne and IRMAR Campus de Ker Lann (France); Xu Lihu, E-mail: Lihu.Xu@brunel.ac.uk [Brunel University, Mathematics Department (United Kingdom)

2012-10-15

348

Equilibrium Fluctuations and Stability of the Condensate of a Degenerate Boson Fluid  

Microsoft Academic Search

A general theory is formulated for the fluctuations in the condensate of a degenerate boson fluid in homogeneous thermodynamic equilibrium. The point of view adopted is based on Bogoliubov's description of the condensate in terms of quasiaverages and on his \\

A. E. Glassgold; H. Sauermann

1969-01-01

349

Three Studies Point to Same Risk Gene for Age-Related Macular Degeneration  

MedlinePLUS

... and Jobs Three studies point to same risk gene for age-related macular degeneration Listen NIH-funded ... in Nature Genetics have converged on the same gene as a rare, but powerful risk factor for ...

350

The Retromer Complex Is Required for Rhodopsin Recycling and Its Loss Leads to Photoreceptor Degeneration  

PubMed Central

Rhodopsin mistrafficking can cause photoreceptor (PR) degeneration. Upon light exposure, activated rhodopsin 1 (Rh1) in Drosophila PRs is internalized via endocytosis and degraded in lysosomes. Whether internalized Rh1 can be recycled is unknown. Here, we show that the retromer complex is expressed in PRs where it is required for recycling endocytosed Rh1 upon light stimulation. In the absence of subunits of the retromer, Rh1 is processed in the endolysosomal pathway, leading to a dramatic increase in late endosomes, lysosomes, and light-dependent PR degeneration. Reducing Rh1 endocytosis or Rh1 levels in retromer mutants alleviates PR degeneration. In addition, increasing retromer abundance suppresses degenerative phenotypes of mutations that affect the endolysosomal system. Finally, expressing human Vps26 suppresses PR degeneration in Vps26 mutant PRs. We propose that the retromer plays a conserved role in recycling rhodopsins to maintain PR function and integrity. PMID:24781186

Wang, Shiuan; Tan, Kai Li; Agosto, Melina A.; Xiong, Bo; Yamamoto, Shinya; Sandoval, Hector; Jaiswal, Manish; Bayat, Vafa; Zhang, Ke; Charng, Wu-Lin; David, Gabriela; Duraine, Lita; Venkatachalam, Kartik; Wensel, Theodore G.; Bellen, Hugo J.

2014-01-01

351

Use of Immunosuppressive Agents for Treatment of Age-related Macular Degeneration (AMD) and Diabetic Retinopathy  

Cancer.gov

The National Eye Institute, Laboratory of Immunology is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize immunosuppressive agents for the treatment of age related macular degeneration.

352

Deficient Wnt signalling triggers striatal synaptic degeneration and impaired motor behaviour in adult mice  

PubMed Central

Synapse degeneration is an early and invariant feature of neurodegenerative diseases. Indeed, synapse loss occurs prior to neuronal degeneration and correlates with the symptom severity of these diseases. However, the molecular mechanisms that trigger synaptic loss remain poorly understood. Here we demonstrate that deficient Wnt signalling elicits synaptic degeneration in the adult striatum. Inducible expression of the secreted Wnt antagonist Dickkopf1 (Dkk1) in adult mice (iDkk1) decreases the number of cortico-striatal glutamatergic synapses and of D1 and D2 dopamine receptor clusters. Synapse loss occurs in the absence of axon retraction or cell death. The remaining excitatory terminals contain fewer synaptic vesicles and have a reduced probability of evoked transmitter release. IDkk1 mice show impaired motor coordination and are irresponsive to amphetamine. These studies identify Wnts as key endogenous regulators of synaptic maintenance and suggest that dysfunction in Wnt signalling contributes to synaptic degeneration at early stages in neurodegenerative diseases. PMID:25318560

Galli, Soledad; Lopes, Douglas M.; Ammari, Rachida; Kopra, Jaakko; Millar, Sarah E.; Gibb, Alasdair; Salinas, Patricia C.

2014-01-01

353

Investigating the genetic and molecular basis of age-related macular degeneration   

E-print Network

Age-related macular degeneration (AMD) is the leading cause of blindness worldwide, affecting an estimated 50 million individuals aged over 65 years. Environmental and genetic risk-factors contribute to the development ...

Stanton, Chloe May

2012-06-30

354

Alpha-Synuclein Disrupted Dopamine Homeostasis Leads to Dopaminergic Neuron Degeneration in Caenorhabditis elegans  

E-print Network

Disruption of dopamine homeostasis may lead to dopaminergic neuron degeneration, a proposed explanation for the specific vulnerability of dopaminergic neurons in Parkinson's disease. While expression of human ?-synuclein in C. elegans results...

Cao, Pengxiu; Yuan, Yiyuan; Pehek, Elizabeth A.; Moise, Alexander R.; Huang, Ying; Palczewski, Krzysztof; Feng, Zhaoyang

2010-02-19

355

Self-Representations: Alterations in Frontotemporal Lobar Degeneration and Correlates in the Brain.  

E-print Network

??Self-representations are multi-faceted and complex. Frontotemporal lobar degeneration (FTLD) is a neurodegenerative disease that selectively atrophies anterior brain regions (e.g., frontal pole, insula, anterior cingulate… (more)

Sturm, Virginia Emily

2009-01-01

356

Loss of MEC-17 Leads to Microtubule Instability and Axonal Degeneration  

PubMed Central

SUMMARY Axonal degeneration arises as a consequence of neuronal injury and is a common hallmark of a number of neurodegenerative diseases. However, the genetic causes and the cellular mechanisms that trigger this process are still largely unknown. Based on forward genetic screening in C. elegans, we have identified the ?-tubulin acetyltransferase gene mec-17 as causing spontaneous, adult-onset, and progressive axonal degeneration. Loss of MEC-17 leads to microtubule instability, a reduction in mitochondrial number, and disrupted axonal transport, with altered distribution of both mitochondria and synaptic components. Furthermore, mec-17-mediated axonal degeneration occurs independently from its acetyltransferase domain; is enhanced by mutation of coel-1, a tubulin-associated molecule; and correlates with the animal’s body length. This study therefore identifies a critical role for the conserved microtubule-associated protein MEC-17 in preserving axon integrity and preventing axonal degeneration. PMID:24373971

Neumann, Brent; Hilliard, Massimo A.

2014-01-01

357

EXISTENCE AND UNIQUENESS OF SOLUTIONS TO AN AGGREGATION EQUATION WITH DEGENERATE DIFFUSION  

Microsoft Academic Search

CEV‡ Abstract. We present an energy-methods-based proof of the existence and unique- ness of solutions of a nonlocal aggregation equation with degenerate diusion. The equation we study is relevant to models of biological aggregation.

ANDREA L. BERTOZZI; DEJAN SLEP

358

A disease-specific metabolic brain network associated with corticobasal degeneration.  

PubMed

Corticobasal degeneration is an uncommon parkinsonian variant condition that is diagnosed mainly on clinical examination. To facilitate the differential diagnosis of this disorder, we used metabolic brain imaging to characterize a specific network that can be used to discriminate corticobasal degeneration from other atypical parkinsonian syndromes. Ten non-demented patients (eight females/two males; age 73.9 ± 5.7 years) underwent metabolic brain imaging with (18)F-fluorodeoxyglucose positron emission tomography for atypical parkinsonism. These individuals were diagnosed clinically with probable corticobasal degeneration. This diagnosis was confirmed in the three subjects who additionally underwent post-mortem examination. Ten age-matched healthy subjects (five females/five males; age 71.7 ± 6.7 years) served as controls for the imaging studies. Spatial covariance analysis was applied to scan data from the combined group to identify a significant corticobasal degeneration-related metabolic pattern that discriminated (P < 0.001) the patients from the healthy control group. This pattern was characterized by bilateral, asymmetric metabolic reductions involving frontal and parietal cortex, thalamus, and caudate nucleus. These pattern-related changes were greater in magnitude in the cerebral hemisphere opposite the more clinically affected body side. The presence of this corticobasal degeneration-related metabolic topography was confirmed in two independent testing sets of patient and control scans, with elevated pattern expression (P < 0.001) in both disease groups relative to corresponding normal values. We next determined whether prospectively computed expression values for this pattern accurately discriminated corticobasal degeneration from multiple system atrophy and progressive supranuclear palsy (the two most common atypical parkinsonian syndromes) on a single case basis. Based upon this measure, corticobasal degeneration was successfully distinguished from multiple system atrophy (P < 0.001) but not progressive supranuclear palsy, presumably because of the overlap (? 24%) that existed between the corticobasal degeneration- and the progressive supranuclear palsy-related metabolic topographies. Nonetheless, excellent discrimination between these disease entities was achieved by computing hemispheric asymmetry scores for the corticobasal degeneration-related pattern on a prospective single scan basis. Indeed, a logistic algorithm based on the asymmetry scores combined with separately computed expression values for a previously validated progressive supranuclear palsy-related pattern provided excellent specificity (corticobasal degeneration: 92.7%; progressive supranuclear palsy: 94.1%) in classifying 58 testing subjects. In conclusion, corticobasal degeneration is associated with a reproducible disease-related metabolic covariance pattern that may help to distinguish this disorder from other atypical parkinsonian syndromes. PMID:25208922

Niethammer, Martin; Tang, Chris C; Feigin, Andrew; Allen, Patricia J; Heinen, Lisette; Hellwig, Sabine; Amtage, Florian; Hanspal, Era; Vonsattel, Jean Paul; Poston, Kathleen L; Meyer, Philipp T; Leenders, Klaus L; Eidelberg, David

2014-11-01

359

Scaffolds and stem cells: delivery of cell transplants for retinal degenerations  

PubMed Central

Retinal degenerations and optic neuropathies often lead to death of photoreceptors or retinal ganglion cells, respectively. Stem cell therapies are showing promise for these diseases in preclinical models and are beginning to transition into human trials, but cell delivery and integration remain major challenges. Focusing on photoreceptor- and progenitor-directed approaches, in this article, the authors review how advances in tissue engineering and cell scaffold design are enhancing cell therapies for retinal degeneration. PMID:23585772

Kador, Karl E; Goldberg, Jeffrey L

2013-01-01

360

Temperature jump in degenerate quantum gases in the presence of a Bose - Einstein condensate  

E-print Network

We construct a kinetic equation modeling the behavior of degenerate quantum Bose gases whose collision rate depends on the momentum of elementary excitations. We consider the case where the phonon component is the decisive factor in the elementary excitations. We analytically solve the half-space boundary value problem of the temperature jump at the boundary of the degenerate Bose gas in the presence of a Bose -- Einstein condensate.

A. V. Latyshev; A. A. Yushkanov

2010-01-04

361

Holmes' Tremor Associated with Bilateral Hypertrophic Olivary Degeneration Following Brain Stem Hemorrhage: A Case Report  

PubMed Central

Holmes' tremor is a condition characterized by a mixture of postural, rest, and action tremors due to midbrain lesions in the vicinity of the red nucleus. Hypertrophic olivary degeneration (HOD) is a rare type of neuronal degeneration involving the dento-rubro-olivary pathway and may present clinically as Holmes tremor. We report on a 59-year-old female patient who developed Holmes tremor in association with bilateral HOD, following brain stem hemorrhage. PMID:25340035

Kim, Min Kyu; Park, Se-Hyuck; Yoon, Dae Young

2014-01-01

362

The role of interleukin-1 in the pathogenesis of human Intervertebral disc degeneration  

Microsoft Academic Search

In this study, we investigated the hypotheses that in human intervertebral disc (IVD) degeneration there is local production of the cytokine IL-1, and that this locally produced cytokine can induce the cellular and matrix changes of IVD degeneration. Immunohistochemistry was used to localize five members of the IL-1 family (IL-1?, IL-1?, IL-1Ra (IL-1 receptor antagonist), IL-1RI (IL-1 receptor, type I),

Christine Lyn Le Maitre; Anthony J Freemont; Judith Alison Hoyland

2005-01-01

363

Does lumbar spinal degeneration begin with the anterior structures? A study of the observed epidemiology in a community-based population  

PubMed Central

Background- Prior studies that have concluded that disk degeneration uniformly precedes facet degeneration have been based on convenience samples of individuals with low back pain. We conducted a study to examine whether the view that spinal degeneration begins with the anterior spinal structures is supported by epidemiologic observations of degeneration in a community-based population. Methods- 361 participants from the Framingham Heart Study were included in this study. The prevalences of anterior vertebral structure degeneration (disk height loss) and posterior vertebral structure degeneration (facet joint osteoarthritis) were characterized by CT imaging. The cohort was divided into the structural subgroups of participants with 1) no degeneration, 2) isolated anterior degeneration (without posterior degeneration), 3) combined anterior and posterior degeneration, and 4) isolated posterior degeneration (without anterior structure degeneration). We determined the prevalence of each degeneration pattern by age group < 45, 45-54, 55-64, ?65. In multivariate analyses we examined the association between disk height loss and the response variable of facet joint osteoarthritis, while adjusting for age, sex, BMI, and smoking. Results- As the prevalence of the no degeneration and isolated anterior degeneration patterns decreased with increasing age group, the prevalence of the combined anterior/posterior degeneration pattern increased. 22% of individuals demonstrated isolated posterior degeneration, without an increase in prevalence by age group. Isolated posterior degeneration was most common at the L5-S1 and L4-L5 spinal levels. In multivariate analyses, disk height loss was independently associated with facet joint osteoarthritis, as were increased age (years), female sex, and increased BMI (kg/m2), but not smoking. Conclusions- The observed epidemiology of lumbar spinal degeneration in the community-based population is consistent with an ordered progression beginning in the anterior structures, for the majority of individuals. However, some individuals demonstrate atypical patterns of degeneration, beginning in the posterior joints. Increased age and BMI, and female sex may be related to the occurrence of isolated posterior degeneration in these individuals. PMID:21914197

2011-01-01

364

Sodium and Potassium Currents Influence Wallerian Degeneration of Injured Drosophila Axons  

PubMed Central

Axons degenerate after injury and in neuropathies and disease via a self-destruction program whose mechanism is poorly understood. Axons that have lost connection to their cell bodies have altered electrical and synaptic activities, but whether such changes play a role in the axonal degeneration process is not clear. We have used a Drosophila model to study the Wallerian degeneration of motoneuron axons and their neuromuscular junction synapses. We found that degeneration of the distal nerve stump after a nerve crush is greatly delayed when there is increased potassium channel activity (by overexpression of two different potassium channels, Kir2.1 and dORK?-C) or decreased voltage-gated sodium channel activity (using mutations in the para sodium channel). Conversely, degeneration is accelerated when potassium channel activity is decreased (by expressing a dominant-negative mutation of Shaker). Despite the effect of altering voltage-gated sodium and potassium channel activity, recordings made after nerve crush demonstrated that the distal stump does not fire action potentials. Rather, a variety of lines of evidence suggest that the sodium and potassium channels manifest their effects upon degeneration through changes in the resting membrane potential, which in turn regulates the level of intracellular free calcium within the isolated distal axon. PMID:24285879

Mishra, Bibhudatta; Carson, Ross; Hume, Richard I.

2013-01-01

365

High-resolution optical coherence tomography in mouse models of genetic and induced retinal degeneration  

NASA Astrophysics Data System (ADS)

For the study of disease mechanisms and the development of novel therapeutic strategies for retinal pathologies in human, rodent models play an important role. Nowadays, optical coherence tomography (OCT) allows three-dimensional investigation of retinal events over time. However, a detailed analysis of how different retinal degenerations are reflected in OCT images is still lacking in the biomedical field. Therefore, we use OCT to visualize retinal degeneration in specific mouse models in order to study disease progression in vivo and improve image interpretation of this noninvasive modality. We use a self-developed spectral domain OCT system for simultaneous dual-band imaging in the 0.8 ?m- and 1.3 ?m-wavelength range - the two most common spectral bands in biomedical OCT. A fiber-coupled ophthalmic scanning unit allows flexible imaging of the eye with a high axial resolution of 3 - 4 ?m in tissue. Four different mouse models consisting of one genetic (rhodopsin-deficient and three induced retinal degenerations (sodium iodate-induced damage, light-induced photoreceptor damage and Kainate neurotoxin damage) were investigated. OCT imaging was performed daily or weekly, depending on the specific degeneration model, over a time period of up to 9 weeks. Individual retinal layers that were affected by the specific degeneration could successfully be identified and monitored over the observation time period. Therefore, longitudinal OCT studies deliver reliable information about the retinal microstructure and the time course of retinal degeneration processes in vivo.

Cimalla, Peter; Carido, Madalena; Pran Babu, Sheik; Santos-Ferreira, Tiago; Gaertner, Maria; Kordowich, Simon; Wittig, Dierk; Ader, Marius; Karl, Mike; Koch, Edmund

2013-06-01

366

Noncell-autonomous photoreceptor degeneration in a zebrafish model of choroideremia.  

PubMed

Choroideremia is an X-linked hereditary retinal degeneration resulting from mutations in the Rab escort protein-1 (REP1). The Rep1 protein facilitates posttranslational modification of Rab proteins, which regulate intracellular trafficking in the retinal pigment epithelium (RPE) and photoreceptors and are likely involved in the removal of outer segment disk membranes by the RPE. A critical question for potential treatment of choroideremia is whether photoreceptor degeneration results from autonomous defects in opsin transport within the photoreceptor or as a nonautonomous and secondary consequence of RPE degeneration. To address this question, we have characterized the retinal pathology in zebrafish rep1 mutants, which carry a recessive nonsense mutation in the REP1 gene. Zebrafish rep1 mutants exhibit degeneration of the RPE and photoreceptors and complete loss of visual function as measured by electroretinograms. In the mutant RPE, photoreceptor outer segment material was not effectively eliminated, and large vacuoles were observed. However, opsin trafficking in photoreceptors occurred normally. Mosaic analysis revealed that photoreceptor degeneration was nonautonomous and required contact with the mutant RPE as mutant photoreceptors were rescued in wild-type hosts and wild-type photoreceptors degenerated in mutant hosts. We conclude that mutations in REP1 disrupt cellular processes in the RPE, which causes photoreceptor death as a secondary consequence. These results suggest that therapies that correct the RPE may successfully rescue photoreceptor loss in choroideremia. PMID:17360570

Krock, Bryan L; Bilotta, Joseph; Perkins, Brian D

2007-03-13

367

Early and sustained activation of autophagy in degenerating axons after spinal cord injury.  

PubMed

Axonal degeneration is one of the initial steps in many neurological disorders and has been associated with increased autophagic activity. Although there are increasing data on the regulation of autophagy proteins in the neuronal soma after spinal cord injury (SCI), their characterization in the axon is scarce. Here, we examined the regulation of autophagy during axonal degeneration in a rat model of SCI following a lesion at Th 8. We analyzed the morphological and ultrastructural changes in injured axons by immunohistochemical evaluation of autophagy-related proteins and electron microscopy at different time points following SCI. The expression of ULK1, Atg7 and Atg5 in damaged axons was rapidly upregulated within hours after SCI. The number of axonal LC3-positive autophagosomes was also rapidly increased after SCI and remained at an increased level for up to 6 weeks. Ultrastructural analysis showed early signs of axonal degeneration and increased autophagy. In conclusion, we show that autophagy is increased early and for a sustained period in degenerating axons after SCI and that it might be an important executive step involved in axonal degeneration. Therefore, autophagy may represent a promising target for future therapeutic interventions in the treatment of axonal degeneration in traumatic central nervous system disorders. PMID:25040536

Ribas, Vinicius Toledo; Schnepf, Bianca; Challagundla, Malleswari; Koch, Jan Christoph; Bähr, Mathias; Lingor, Paul

2015-03-01

368

Spatial distribution of fiber degeneration in acute hypoglycemic neuropathy in rat.  

PubMed

Hypoglycemia may cause axonal nerve fiber degeneration, but to do so it must be severe (less than 1.5 mmol/L) and of long duration (greater than or equal to 12 hours). Since in our previous study, systemic PO2, PCO2, pH, blood pressure, temperature, and hematocrit were maintained within physiologic limits, fiber degeneration cannot be attributed to systemic hypoxia. In this study the spatial distribution of axonal degeneration was assessed in transverse epoxy sections and teased fibers from different proximal-to-distal levels of nerves of the lower limb of the rats. Reactions in lumbar spinal motor neurons, spinal ganglia, and fasciculus gracilis were also studied. Axonal degeneration was the characteristic fiber alteration and it predominated in central fascicular distributions of distal sciatic, proximal tibial, and proximal peroneal nerves. This proximal-to-distal and central fascicular spatial distribution is not typical of distal polyneuropathy or of neuronal degeneration, but it is characteristic of a focal or multifocal nerve trunk neuropathy. Although local hypoxic-ischemic injury, possibly mediated by enhanced sympathetic tone, has not been excluded, we postulate a generalized deficiency of energy substrate manifesting itself by fiber degeneration at watershed zones of poorest perfusion. PMID:1660919

Yasaki, S; Dyck, P J

1991-11-01

369

Compressive strength of elderly vertebrae is reduced by disc degeneration and additional flexion.  

PubMed

Computer tomography (CT)-based finite element (FE) models assess vertebral strength better than dual energy X-ray absorptiometry. Osteoporotic vertebrae are usually loaded via degenerated intervertebral discs (IVD) and potentially at higher risk under forward bending, but the influences of the IVD and loading conditions are generally overlooked. Accordingly, magnetic resonance imaging was performed on 14 lumbar discs to generate FE models for the healthiest and most degenerated specimens. Compression, torsion, bending, flexion and extension conducted experimentally were used to calibrate both models. They were combined with CT-based FE models of 12 lumbar vertebral bodies to evaluate the effect of disc degeneration compared to a loading via endplates embedded in a stiff resin, the usual experimental paradigm. Compression and lifting were simulated, load and damage pattern were evaluated at failure. Adding flexion to the compression (lifting) and higher disc degeneration reduces the failure load (8-14%, 5-7%) and increases damage in the vertebrae. Under both loading scenarios, decreasing the disc height slightly increases the failure load; embedding and degenerated IVD provides respectively the highest and lowest failure load. Embedded vertebrae are more brittle, but failure loads induced via IVDs correlate highly with vertebral strength. In conclusion, osteoporotic vertebrae with degenerated IVDs are consistently weaker-especially under lifting, but clinical assessment of their strength is possible via FE analysis without extensive disc modelling, by extrapolating measures from the embedded situation. PMID:25460926

Maquer, Ghislain; Schwiedrzik, Jakob; Huber, Gerd; Morlock, Michael M; Zysset, Philippe K

2015-02-01

370

Genetic risk factors and age-related macular degeneration (AMD)  

PubMed Central

Age related macular degeneration (AMD) is the leading cause of blindness in individuals older than 65 years of age. It is a multifactorial disorder and identification of risk factors enables individuals to make lifestyle choices that may reduce the risk of disease. Collaboration between geneticists, ophthalmologists, and optometrists suggests that genetic risk factors play a more significant role in AMD than previously thought. The most important genes are associated with immune system modulation and the complement system, e.g., complement factor H (CFH), factor B (CFB), factor C3, and serpin peptidase inhibitor (SERPING1). Genes associated with membrane transport, e.g., ATP-binding cassette protein (ABCR) and voltage-dependent calcium channel gamma 3 (CACNG3), the vascular system, e.g., fibroblast growth factor 2 (FGF2), fibulin-5, lysyl oxidase-like gene (LOXL1) and selectin-P (SELP), and with lipid metabolism, e.g., apolipoprotein E (APOE) and hepatic lipase (LIPC) have also been implicated. In addition, several other genes exhibit some statistical association with AMD, e.g., age-related maculopathy susceptibility protein 2 (ARMS2) and DNA excision repair protein gene (ERCC6) but more research is needed to establish their significance. Modifiable risk factors for AMD should be discussed with patients whose lifestyle and/or family history place them in an increased risk category. Furthermore, calculation of AMD risk using current models should be recommended as a tool for patient education. It is likely that AMD management in future will be increasingly influenced by assessment of genetic risk as such screening methods become more widely available.

Mousavi, Maryam; Armstrong, Richard A.

2013-01-01

371

The WISE InfraRed Excesses around Degenerates (WIRED) Survey  

NASA Astrophysics Data System (ADS)

The Wide-field Infrared Survey Explorer (WISE) is a NASA medium class Explorer mission that was launched on 14 Dec 2009. WISE mapped the entire sky at 3.4, 4.6, 12, and 22 microns with 5-sigma point source sensitivities of approximately 0.08, 0.11, 1, and 6 mJy, respectively. Complete sky coverage was achieved in mid-July 2010. Prior to the first public release of WISE data planned for Spring 2011, several early science verification projects are being carried out by the WISE Science Team. The WISE InfraRed Excesses around Degenerates (WIRED) Survey has the goals of characterizing white dwarf (WD) stars in the WISE bands, confirming objects known to have IR excess from past observations (Spitzer, 2MASS, UKIDSS, etc.), and revealing new examples of WDs with IR excess that can be attributed to unresolved companions or debris disks. We are utilizing target lists drawn primarily from the Sloan Digital Sky Survey (SDSS) WD catalogs, as well as a separate sample from the McCook & Sion WD catalog. Preliminary results from the WIRED Survey utilizing 20% sky coverage with the SDSS Data Release 4 WD catalog yielded over 400 detections (S/N > 2) in at least one WISE band, and several new dust disk and WD+brown dwarf binary candidates. We will present an overview of the WIRED Survey results using the full WISE sky coverage with the SDSS Data Release 7 WD catalog (which contains over 18,000 targets). This work was supported in part by the NASA Postdoctoral Program (J.H.D.), and is based on data from: WISE, a joint project of UCLA and JPL/Caltech, funded by NASA; the UKIRT Infrared Deep Sky Survey; the Two Micron All Sky Survey, a joint project of the University of Massachusetts and IPAC/Caltech, funded by NASA and the NSF; and the Sloan Digital Sky Survey.

Hoard, D. W.; Debes, J. H.; Wachter, S.; Leisawitz, D. T.; Cohen, M.

2011-01-01

372

OBSERVATIONAL CONSTRAINTS ON THE DEGENERATE MASS-RADIUS RELATION  

SciTech Connect

The white dwarf mass-radius relationship is fundamental to modern astrophysics. It is central to routine estimation of DA white dwarf masses derived from spectroscopic temperatures and gravities. It is also the basis for observational determinations of the white dwarf initial-final-mass relation. Nevertheless, definitive and detailed observational confirmations of the mass-radius relation (MRR) remain elusive owing to a lack of sufficiently accurate white dwarf masses and radii. Current best estimates of masses and radii allow only broad conclusions about the expected inverse relation between masses and radii in degenerate stars. In this paper, we examine a restricted set of 12 DA white dwarf binary systems for which accurate (1) trigonometric parallaxes, (2) spectroscopic effective temperatures and gravities, and (3) gravitational redshifts are available. We consider these three independent constraints on mass and radius in comparison with an appropriate evolved MRR for each star. For the best-determined systems it is found that the DA white dwarfs conform to evolve theoretical MRRs at the 1{sigma} to 2{sigma} level. For the white dwarf 40 Eri B (WD 0413-077) we find strong evidence for the existence of a 'thin' hydrogen envelope. For other stars improved parallaxes will be necessary before meaningful comparisons are possible. For several systems current parallaxes approach the precision required for the state-of-the-art mass and radius determinations that will be obtained routinely from the Gaia mission. It is demonstrated here how these anticipated results can be used to firmly constrain details of theoretical mass-radius determinations.

Holberg, J. B. [Lunar and Planetary Laboratory, 1541 East University Boulevard, Sonett Space Sciences Building, University of Arizona, Tucson, AZ 85721 (United States); Oswalt, T. D. [Florida Institute of Technology, Melbourne, FL 32901 (United States); Barstow, M. A., E-mail: holberg@argus.lpl.arizona.edu, E-mail: toswalt@fit.edu, E-mail: mab@le.ac.uk [Department of Physics and Astronomy, University of Leicester, University Road, Leicester LE1 7RH (United Kingdom)

2012-03-15

373

Genome Degeneration and Adaptation in a Nascent Stage of Symbiosis  

PubMed Central

Symbiotic associations between animals and microbes are ubiquitous in nature, with an estimated 15% of all insect species harboring intracellular bacterial symbionts. Most bacterial symbionts share many genomic features including small genomes, nucleotide composition bias, high coding density, and a paucity of mobile DNA, consistent with long-term host association. In this study, we focus on the early stages of genome degeneration in a recently derived insect-bacterial mutualistic intracellular association. We present the complete genome sequence and annotation of Sitophilus oryzae primary endosymbiont (SOPE). We also present the finished genome sequence and annotation of strain HS, a close free-living relative of SOPE and other insect symbionts of the Sodalis-allied clade, whose gene inventory is expected to closely resemble the putative ancestor of this group. Structural, functional, and evolutionary analyses indicate that SOPE has undergone extensive adaptation toward an insect-associated lifestyle in a very short time period. The genome of SOPE is large in size when compared with many ancient bacterial symbionts; however, almost half of the protein-coding genes in SOPE are pseudogenes. There is also evidence for relaxed selection on the remaining intact protein-coding genes. Comparative analyses of the whole-genome sequence of strain HS and SOPE highlight numerous genomic rearrangements, duplications, and deletions facilitated by a recent expansion of insertions sequence elements, some of which appear to have catalyzed adaptive changes. Functional metabolic predictions suggest that SOPE has lost the ability to synthesize several essential amino acids and vitamins. Analyses of the bacterial cell envelope and genes encoding secretion systems suggest that these structures and elements have become simplified in the transition to a mutualistic association. PMID:24407854

Oakeson, Kelly F.; Gil, Rosario; Clayton, Adam L.; Dunn, Diane M.; von Niederhausern, Andrew C.; Hamil, Cindy; Aoyagi, Alex; Duval, Brett; Baca, Amanda; Silva, Francisco J.; Vallier, Agnès; Jackson, D. Grant; Latorre, Amparo; Weiss, Robert B.; Heddi, Abdelaziz; Moya, Andrés; Dale, Colin

2014-01-01

374

Genome degeneration and adaptation in a nascent stage of symbiosis.  

PubMed

Symbiotic associations between animals and microbes are ubiquitous in nature, with an estimated 15% of all insect species harboring intracellular bacterial symbionts. Most bacterial symbionts share many genomic features including small genomes, nucleotide composition bias, high coding density, and a paucity of mobile DNA, consistent with long-term host association. In this study, we focus on the early stages of genome degeneration in a recently derived insect-bacterial mutualistic intracellular association. We present the complete genome sequence and annotation of Sitophilus oryzae primary endosymbiont (SOPE). We also present the finished genome sequence and annotation of strain HS, a close free-living relative of SOPE and other insect symbionts of the Sodalis-allied clade, whose gene inventory is expected to closely resemble the putative ancestor of this group. Structural, functional, and evolutionary analyses indicate that SOPE has undergone extensive adaptation toward an insect-associated lifestyle in a very short time period. The genome of SOPE is large in size when compared with many ancient bacterial symbionts; however, almost half of the protein-coding genes in SOPE are pseudogenes. There is also evidence for relaxed selection on the remaining intact protein-coding genes. Comparative analyses of the whole-genome sequence of strain HS and SOPE highlight numerous genomic rearrangements, duplications, and deletions facilitated by a recent expansion of insertions sequence elements, some of which appear to have catalyzed adaptive changes. Functional metabolic predictions suggest that SOPE has lost the ability to synthesize several essential amino acids and vitamins. Analyses of the bacterial cell envelope and genes encoding secretion systems suggest that these structures and elements have become simplified in the transition to a mutualistic association. PMID:24407854

Oakeson, Kelly F; Gil, Rosario; Clayton, Adam L; Dunn, Diane M; von Niederhausern, Andrew C; Hamil, Cindy; Aoyagi, Alex; Duval, Brett; Baca, Amanda; Silva, Francisco J; Vallier, Agnès; Jackson, D Grant; Latorre, Amparo; Weiss, Robert B; Heddi, Abdelaziz; Moya, Andrés; Dale, Colin

2014-01-01

375

Nutritional Modulation of Age-Related Macular Degeneration  

PubMed Central

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly worldwide. It affects 30–50 million individuals and clinical hallmarks of AMD are observed in at least one third of persons over the age of 75 in industrialized countries (Gehrs et al., 2006). Costs associated with AMD are in excess of $340 billion US (American-Health-Assistance-Foundation, 2012). The majority of AMD patients in the United States are not eligible for clinical treatments (Biarnes et al., 2011; Klein et al., 2011). Preventive interventions through dietary modulation are attractive strategies because many studies suggest a benefit of micro and macronutrients with respect to AMD, as well as other age-related debilities, and with few, if any, adverse effects (Chiu, 2011). Preservation of vision would enhance quality of life for millions of elderly people, and alleviate the personal and public health financial burden of AMD (Frick et al., 2007; Wood et al., 2011). Observational studies indicate that maintaining adequate levels of omega-3 fatty acids (i.e. with 2 servings/wk of fish) or a low glycemic index diet may be particularly beneficial for early AMD and that higher levels of carotenoids may be protective, most probably, against neovascular AMD. Intervention trials are needed to better understand the full effect of these nutrients and/or combinations of nutrients on retinal health. Analyses that describe effects of a nutrient on onset and/or progress of AMD are valuable because they indicate the value of a nutrient to arrest AMD at the early stages. This comprehensive summary provides essential information about the value of nutrients with regard to diminishing risk for onset or progress of AMD and can serve as a guide until data from ongoing intervention trials are available. PMID:22503690

Weikel, Karen A; Taylor, Allen

2012-01-01

376

An intrinsic neural oscillator in the degenerating mouse retina.  

PubMed

The loss of photoreceptors during retinal degeneration (RD) is known to lead to an increase in basal activity in remnant neural networks. To identify the source of activity, we combined two-photon imaging with patch-clamp techniques to examine the physiological properties of morphologically identified retinal neurons in a mouse model of RD (rd1). Analysis of activity in rd1 ganglion cells revealed sustained oscillatory (?10 Hz) synaptic activity in ?30% of all classes of cells. Oscillatory activity persisted after putative inputs from residual photoreceptor, rod bipolar cell, and inhibitory amacrine cell synapses were pharmacologically blocked, suggesting that presynaptic cone bipolar cells were intrinsically active. Examination of presynaptic rd1 ON and OFF bipolar cells indicated that they rested at relatively negative potentials (less than -50 mV). However, in approximately half the cone bipolar cells, low-amplitude membrane oscillation (?5 mV, ?10 Hz) were apparent. Such oscillations were also observed in AII amacrine cells. Oscillations in ON cone bipolar and AII amacrine cells exhibited a weak apparent voltage dependence and were resistant to blockade of synaptic receptors, suggesting that, as in wild-type retina, they form an electrically coupled network. In addition, oscillations were insensitive to blockers of voltage-gated Ca(2+) channels (0.5 mm Cd(2+) and 0.5 mm Ni(2+)), ruling out known mechanisms that underlie oscillatory behavior in bipolar cells. Together, these results indicate that an electrically coupled network of ON cone bipolar/AII amacrine cells constitutes an intrinsic oscillator in the rd1 retina that is likely to drive synaptic activity in downstream circuits. PMID:21451038

Borowska, Joanna; Trenholm, Stuart; Awatramani, Gautam B

2011-03-30

377

Deep anterior lamellar keratoplasty for pellucid marginal degeneration***  

PubMed Central

Purpose To present the surgical outcomes of deep anterior lamellar keratoplasty (DALK) for pellucid marginal degeneration (PMD). Methods A retrospective review was performed in 16 eyes of 16 patients who underwent DALK at the King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia between January 1, 2006 and December 30, 2009. Baring of Descemet’s membrane (DM) during DALK was achieved in 8 (50%) eyes; residual stroma was left intraoperatively in the remaining 8 (50%) eyes. The big bubble technique was performed in 10 (62.5%) eyes and manual dissection was performed in the remaining 6 (37.5%) eyes. Visual acuity (LogMAR notation), intraocular pressure, intraoperative complications and postoperative graft status were assessed. Results The mean follow up was 14.6 ± 8.2 months (range 6–35 months). The mean overall age was 31.4 ± 9.6 years (range, 19–50 years). Visual acuity increased statistically significantly from 0.9 ± 0.3 (range 0.5–1.6) preoperatively to 0.4 ± 0.2 (range 0.0–0.7) at last follow-up (p < 0.0001). There was a statistically significant improvement in postoperative sphere, cylinder, and spherical equivalent (p < 0.035, p < 0.001, and p < 0.02, respectively) compared to preoperative. Postoperative visual acuity was not statistically significantly related to gender, type of surgical technique, and baring or perforation of DM. The main graft-related complication was graft–host vascularization (2/16 eyes). Conclusion DALK reduces severe corneal astigmatism and results in good visual and refractive outcomes and is an effective alternative for patients with PMD. PMID:23964180

Al-Torbak, Abdullah A.

2012-01-01

378

TYPE Ia SINGLE DEGENERATE SURVIVORS MUST BE OVERLUMINOUS  

SciTech Connect

In the single-degenerate (SD) channel of a Type Ia supernovae (SNe Ia) explosion, a main-sequence (MS) donor star survives the explosion but it is stripped of mass and shock heated. An essentially unavoidable consequence of mass loss during the explosion is that the companion must have an overextended envelope after the explosion. While this has been noted previously, it has not been strongly emphasized as an inevitable consequence. We calculate the future evolution of the companion by injecting 2-6 Multiplication-Sign 10{sup 47} erg into the stellar evolution model of a 1 M{sub Sun} donor star based on the post-explosion progenitors seen in simulations. We find that, due to the Kelvin-Helmholtz collapse of the envelope, the companion must become significantly more luminous (10-10{sup 3} L{sub Sun }) for a long period of time (10{sup 3}-10{sup 4} yr). The lack of such a luminous ''leftover'' star in the LMC supernova remnant SNR 0609-67.5 provides another piece of evidence against the SD scenario. We also show that none of the stars proposed as the survivors of the Tycho supernova, including Tycho G, could plausibly be the donor star. Additionally, luminous donors closer than {approx}10 Mpc should be observable with the Hubble Space Telescope starting {approx}2 yr post-peak. Such systems include SN 1937C, SN 1972E, SN 1986G, and SN 2011fe. Thus, the SD channel is already ruled out for at least two nearby SNe Ia and can easily be tested for a number of additional ones. We also discuss similar implications for the companions of core-collapse SNe.

Shappee, Benjamin J.; Kochanek, C. S.; Stanek, K. Z., E-mail: shappee@astronomy.ohio-state.edu, E-mail: ckochanek@astronomy.ohio-state.edu, E-mail: kstanek@astronomy.ohio-state.edu [Department of Astronomy, Ohio State University, Columbus, OH 43210 (United States)

2013-03-10

379

VAGINAL DEGENERATION FOLLOWING IMPLANTATION OF SYNTHETIC MESH WITH INCREASED STIFFNESS  

PubMed Central

Objective To compare the impact of the prototype prolapse mesh Gynemesh PS to that of two new generation lower stiffness meshes, UltraPro and SmartMesh, on vaginal morphology and structural composition. Design A mechanistic study employing a non-human primate (NHP) model. Setting Magee-Womens Research Institute at the University of Pittsburgh. Population Parous rhesus macaques, with similar age, weight, parity and POP-Q scores. Methods Following IACUC approval, 50 rhesus macaques were implanted with Gynemesh PS (n=12), UltraPro with its blue line perpendicular to the longitudinal axis of vagina (n=10), UltraPro with its blue line parallel to the longitudinal axis of vagina (n=8) and SmartMesh (n=8) via sacrocolpopexy following hysterectomy. Sham operated animals (n=12) served as controls. Main Outcome Measures The mesh-vagina complex (MVC) was removed after 12 weeks and analyzed for histomorphology, in situ cell apoptosis, total collagen, elastin, glycosaminoglycan content and total collagenase activity. Appropriate statistics and correlation analyses were performed accordingly. Results Relative to sham and the two lower stiffness meshes, Gynemesh PS had the greatest negative impact on vaginal histomorphology and composition. Compared to sham, implantation with Gynemesh PS caused substantial thinning of the smooth muscle layer (1557 ± 499?m vs 866 ± 210 ?m, P=0.02), increased apoptosis particularly in the area of the mesh fibers (P=0.01), decreased collagen and elastin content (20% (P=0.03) and 43% (P=0.02), respectively) and increased total collagenase activity (135% (P=0.01)). GAG (glycosaminoglycan), a marker of tissue injury, was the highest with Gynemesh PS compared to sham and other meshes (P=0.01). Conclusion Mesh implantation with the stiffer mesh Gynemesh PS induced a maladaptive remodeling response consistent with vaginal degeneration. PMID:23240802

Liang, Rui; Abramowitch, Steven; Knight, Katrina; Palcsey, Stacy; Nolfi, Alexis; Feola, Andrew; Stein, Susan; Moalli, Pamela A.

2012-01-01

380

Diversity of reductive dehalogenase genes from environmental samples and enrichment cultures identified with degenerate primer PCR screens  

PubMed Central

Reductive dehalogenases are the critical enzymes for anaerobic organohalide respiration, a microbial metabolic process that has been harnessed for bioremediation efforts to resolve chlorinated solvent contamination in groundwater and is implicated in the global halogen cycle. Reductive dehalogenase sequence diversity is informative for the dechlorination potential of the site or enrichment culture. A suite of degenerate PCR primers targeting a comprehensive curated set of reductive dehalogenase genes was designed and applied to 12 DNA samples extracted from contaminated and pristine sites, as well as six enrichment cultures capable of reducing chlorinated compounds to non-toxic end-products. The amplified gene products from four environmental sites and two enrichment cultures were sequenced using Illumina HiSeq, and the reductive dehalogenase complement of each sample determined. The results indicate that the diversity of the reductive dehalogenase gene family is much deeper than is currently accounted for: one-third of the translated proteins have less than 70% pairwise amino acid identity to database sequences. Approximately 60% of the sequenced reductive dehalogenase genes were broadly distributed, being identified in four or more samples, and often in previously sequenced genomes as well. In contrast, 17% of the sequenced reductive dehalogenases were unique, present in only a single sample and bearing less than 90% pairwise amino acid identity to any previously identified proteins. Many of the broadly distributed reductive dehalogenases are uncharacterized in terms of their substrate specificity, making these intriguing targets for further biochemical experimentation. Finally, comparison of samples from a contaminated site and an enrichment culture derived from the same site 8 years prior allowed examination of the effect of the enrichment process. PMID:24312087

Hug, Laura A.; Edwards, Elizabeth A.

2013-01-01

381

Magnetotransport in epitaxial films of the degenerate semiconductor Zn(1-x)Co(x)O.  

PubMed

Magnetotransport measurements are performed over a broad range of temperature (T) and magnetic field (H) on highly degenerate n-type Zn(1-x)Co(x)O [Formula: see text] epitaxial films. The cobalt-free samples are characterized by a metallic resistivity ?(T) down to 2 K, a negative and predominantly isotropic magnetoresistance (MR) and optical transmission above 85% in the visible range of the electromagnetic spectrum. X-ray diffraction measurements show that while for [Formula: see text], all cobalt atoms occupy the tetrahedral sites of the wurtzite structure of ZnO, a phase separation into CoO is seen for x>0.2. In the solution phase, we do not observe any signatures of a spontaneous ordering of the cobalt spins despite a large concentration of mobile electrons (>10(20) cm(-3)). The absence of anomalous Hall resistance is consistent with this observation. The carrier concentration (n) over the entire range of x remains above the Mott limit for the insulator-to-metal transition in a doped semiconductor. However, while the Co-free samples are metallic (T>2 K), we see a resistivity (?) minimum followed by lnT divergence of ?(T) at low temperatures with increasing x. The magnetoresistance of these samples is negative and predominantly isotropic. Moreover, the MR tends to follow a logH behaviour at high fields. These observations, including the Kondo-like minimum in the resistivity, suggest s-d exchange dominated transport in these dilute magnetic semiconductors. PMID:21690670

Budhani, R C; Pant, Prita; Rakshit, R K; Senapati, K; Mandal, S; Pandey, N K; Jitendra Kumar

2005-01-12

382

Dorsal column sensory axons degenerate due to impaired microvascular perfusion after spinal cord injury in rats  

PubMed Central

The mechanisms contributing to axon loss after spinal cord injury (SCI) are largely unknown but may involve microvascular loss as we have previously suggested. Here, we used a mild contusive injury (120 kdyn IH impactor) at T9 in rats focusing on ascending primary sensory dorsal column axons, anterogradely traced from the sciatic nerves. The injury caused a rapid and progressive loss of dorsal column microvasculature and oligodendrocytes at the injury site and penumbra and a ~70% loss of the sensory axons, by 24 hours. To model the microvascular loss, focal ischemia of the T9 dorsal columns was achieved via phototoxic activation of intravenously injected rose bengal. This caused an ~53% loss of sensory axons and an ~80% loss of dorsal column oligodendrocytes by 24 hours. Axon loss correlated with the extent and axial length of microvessel and oligodendrocyte loss along the dorsal column. To determine if oligodendrocyte loss contributes to axon loss, the glial toxin ethidium bromide (EB; 0.3 µg/µl) was microinjected into the T9 dorsal columns, and resulted in an ~88% loss of dorsal column oligodendrocytes and an ~56% loss of sensory axons after 72 hours. EB also caused an ~72% loss of microvessels. Lower concentrations of EB resulted in less axon, oligodendrocyte and microvessel loss, which were highly correlated (R2 = 0.81). These data suggest that focal spinal cord ischemia causes both oligodendrocyte and axon degeneration, which are perhaps linked. Importantly, they highlight the need of limiting the penumbral spread of ischemia and oligodendrocyte loss after SCI in order to protect axons. PMID:23978615

Muradov, Johongir M.; Ewan, Eric E.; Hagg, Theo

2013-01-01

383

[Novel approach for management of age-related macular degeneration--antiangiogenic therapy and retinal regenerative therapy].  

PubMed

Age-related macular degeneration (AMD) is a leading cause of legal blindness in developed countries. Even with the recent advent of several treatment options, treatment of exudative AMD, characterized by choroidal neovascularization (CNV), remains difficult. Thus, in this review article, we report on the investigation of novel approaches for the management of AMD, antiangiogenic therapy for CNV, and retinal regenerative therapy. Polyion complex(PIC) micelles have a range in size of several tens of nanometers formed through an electrostatic interaction, and accumulate in solid tumors through an enhanced permeability and retention(EPR) effect. In this study, we examined the distribution of the PIC micelles which encapsulate fluorescein isothiocyanate-labeled poly-L-lysine{FITC-P(Lys)} in experimental CNV in rats, to investigate whether PIC micelles can be used for the treatment of CNV. We demonstrated that PIC micelles accumulate in the CNV lesions and are retained in the lesions for as long as 168 hours after intravenous administration. These results raise the possibility that PIC micelles can be used for achieving an effective drug delivery system against CNV. Although photodynamic therapy (PDT) is a very promising treatment for AMD, most patients require repeated treatments. For effective PDT against AMD, the selective delivery of a photosensitizer to the CNV lesions and an effective photochemical reaction at the CNV site are necessary. The characteristic dendritic structure of the photosensitizer prevents aggregation of its core sensitizer, thereby inducing a highly effective photochemical reaction. We present an effective PDT for AMD employing a supramolecular nanomedical device, i.e., a novel dendritic photosensitizer encapsulated in a polymeric micelle formulation. With its highly selective accumulation in CNV lesions, this treatment resulted in a remarkably efficacious CNV occlusion with minimal unfavorable phototoxicity. Our results will provide a basis for an effective approach to PDT for AMD. Spatial control of gene transfection in the body is a core issue in the gene therapy for ocular diseases including AMD. Photochemical internalization (PCI) is a technology that effects light-induced delivery of DNA directly inside cells. PCI usually requires that a photosensitizer be added to the drug-delivery system to photochemically destabilize the endosomal membrane. We have developed a ternary complex composed of a core containing DNA packaged with cationic peptides and enveloped in the anionic dendrimer, phthalocyanine, which provides the photosensitizing action. Subconjunctival injection of the ternary complex followed by laser irradiation resulted in transgene expression only in the laser-irradiated site in rats. This PCI-mediated gene delivery system is potentially useful in gene therapy for ophthalmic diseases. Accumulation of lipofuscin is related to an increased risk of AMD. We report that a major lipofuscin component, A2E(N-retinyledin-N-retinylethanolamin), activates the retinoic acid receptor (RAR). In vivo experiments suggest that A2E accumulation results in the pro-angiogenic conversion of retinal pigment epithelial(RPE) cell phenotype. This physiological consequence of A2E accumulation may be related to a novel potential therapeutic target for CNV. To recover visual function damaged by AMD, retinal regenerative therapy is essential. We investigated whether subretinal transplantation of bone marrow mesenchymal stem cells(MSCs) promotes photoreceptor survival in a rat model of retinal degeneration. Morphological and functional studies in vivo, including histological analysis and electrophysiological studies, indicate that the subretinal transplantation of MSCs delays retinal degeneration and preserves retinal function. These results suggest that MSC is a useful cell source for cell-transplantation therapy for retinal degeneration. In order to elucidate the molecular mechanisms of development of the fovea, which is composed mainly of cone photoreceptors and is susceptible to injury from AMD, we performed a co

Tamaki, Yasuhiro

2007-03-01

384

THE AFTERCLAP OF DEGENERATE CARBON IGNITION REVISITED Abstract.-Whether the degenerate C-0 cores, with develop in the heart of 4-8 II  

E-print Network

, with develop in the heart of 4-8 II stars, get fully disrupted or implode into neutron stars depends critically the effects of burning and cause the implosion of the core. 1.Introduction.- Stars in the 4-8 H& range form electron-degenerate carbon/oxygen cores, which then grow as the double shell burning of hydrogen and helium

Boyer, Edmond

385

An ex vivo laser-induced spinal cord injury model to assess mechanisms of axonal degeneration in real-time.  

PubMed

Injured CNS axons fail to regenerate and often retract away from the injury site. Axons spared from the initial injury may later undergo secondary axonal degeneration. Lack of growth cone formation, regeneration, and loss of additional myelinated axonal projections within the spinal cord greatly limits neurological recovery following injury. To assess how central myelinated axons of the spinal cord respond to injury, we developed an ex vivo living spinal cord model utilizing transgenic mice that express yellow fluorescent protein in axons and a focal and highly reproducible laser-induced spinal cord injury to document the fate of axons and myelin (lipophilic fluorescent dye Nile Red) over time using two-photon excitation time-lapse microscopy. Dynamic processes such as acute axonal injury, axonal retraction, and myelin degeneration are best studied in real-time. However, the non-focal nature of contusion-based injuries and movement artifacts encountered during in vivo spinal cord imaging make differentiating primary and secondary axonal injury responses using high resolution microscopy challenging. The ex vivo spinal cord model described here mimics several aspects of clinically relevant contusion/compression-induced axonal pathologies including axonal swelling, spheroid formation, axonal transection, and peri-axonal swelling providing a useful model to study these dynamic processes in real-time. Major advantages of this model are excellent spatiotemporal resolution that allows differentiation between the primary insult that directly injures axons and secondary injury mechanisms; controlled infusion of reagents directly to the perfusate bathing the cord; precise alterations of the environmental milieu (e.g., calcium, sodium ions, known contributors to axonal injury, but near impossible to manipulate in vivo); and murine models also offer an advantage as they provide an opportunity to visualize and manipulate genetically identified cell populations and subcellular structures. Here, we describe how to isolate and image the living spinal cord from mice to capture dynamics of acute axonal injury. PMID:25490396

Okada, Starlyn L M; Stivers, Nicole S; Stys, Peter K; Stirling, David P

2014-01-01

386

Degenerate MAGGY elements in a subgroup of Pyricularia grisea: a possible example of successful capture of a genetic invader by a fungal genome.  

PubMed

The LTR-retrotransposon MAGGY is found sporadically in isolates of Pyricularia grisea (Magnaporthe grisea). Based on a dendrogram constructed by RFLP analysis of rDNA, isolates that carry MAGGY elements were classified into a single cluster that comprised four rDNA types. However, in a few members of this cluster, exemplified by isolates from common millet (Panicum miliaceum), the MAGGY element has distinct features. Southern analysis suggested that these isolates possessed a single copy of a MAGGY-related sequence whose restriction map differed from that of MAGGY itself. Sequence analysis revealed that the MAGGY-related sequence was a degenerate form of MAGGY, characterized by numerous C:G to T:A transitions, which have often been reported to result from RIP (Repeat-induced point mutation) or RIP-like processes. However, the favored target site for C:G to T:A transitions in this fungus, determined by examining a total of 501 sites, was (A/T)pCp(A/T), which differs from that for the RIP process originally reported in Neurospora (CpA), and from that reported in Aspergillus (CpG). The fact that certain members of the cluster of MAGGY carriers retain a single copy of a degenerate MAGGY element implies that the ancestor of these isolates successfully "captured" the invading MAGGY element. PMID:10485287

Nakayashiki, H; Nishimoto, N; Ikeda, K; Tosa, Y; Mayama, S

1999-07-01

387

The Oral Iron Chelator Deferiprone Protects Against Retinal Degeneration Induced through Diverse Mechanisms  

PubMed Central

Purpose To investigate the effect of the iron chelator deferiprone (DFP) on sodium iodate (NaIO3)–induced retinal degeneration and on the hereditary retinal degeneration caused by the rd6 mutation. Methods Retinas from NaIO3-treated C57BL/6J mice, with or without DFP cotreatment, were analyzed by histology, immunofluorescence, and quantitative PCR to investigate the effect of DFP on retinal degeneration. To facilitate photoreceptor quantification, we developed a new function of MATLAB to perform this task in a semiautomated fashion. Additionally, rd6 mice treated with or without DFP were analyzed by histology to assess possible protection. Results In NaIO3-treated mice, DFP protected against retinal degeneration and significantly decreased expression of the oxidative stress–related gene heme oxygenase-1 and the complement gene C3. DFP treatment partially protected against NaIO3-induced reduction in the levels of mRNAs encoded by visual cycle genes rhodopsin (Rho) and retinal pigment epithelium–specific 65 kDa protein (Rpe65), consistent with the morphological data indicating preservation of photoreceptors and RPE, respectively. DFP treatment also protected photoreceptors in rd6 mice. Conclusions The oral iron chelator DFP provides significant protection against retinal degeneration induced through different modalities. This suggests that iron chelation could be useful as a treatment for retinal degeneration even when the main etiology does not appear to be iron dysregulation. Translational Relevance These data provide proof of principle that the oral iron chelator DFP can protect the retina against diverse insults. Further testing of DFP in additional animal retinal degeneration models at a range of doses is warranted. PMID:24049707

Hadziahmetovic, Majda; Pajic, Miroslav; Grieco, Steven; Song, Ying; Song, Delu; Li, Yafeng; Cwanger, Alyssa; Iacovelli, Jared; Chu, Sally; Ying, Gui-shuang; Connelly, John; Spino, Michael; Dunaief, Joshua L.

2012-01-01

388

The Oral Iron Chelator Deferiprone Protects Against Retinal Degeneration Induced through Diverse Mechanisms  

PubMed Central

Purpose To investigate the effect of the iron chelator deferiprone (DFP) on sodium iodate (NaIO3)–induced retinal degeneration and on the hereditary retinal degeneration caused by the rd6 mutation. Methods Retinas from NaIO3-treated C57BL/6J mice, with or without DFP cotreatment, were analyzed by histology, immunofluorescence, and quantitative PCR to investigate the effect of DFP on retinal degeneration. To facilitate photoreceptor quantification, we developed a new function of MATLAB to perform this task in a semiautomated fashion. Additionally, rd6 mice treated with or without DFP were analyzed by histology to assess possible protection. Results In NaIO3-treated mice, DFP protected against retinal degeneration and significantly decreased expression of the oxidative stress–related gene heme oxygenase-1 and the complement gene C3. DFP treatment partially protected against NaIO3-induced reduction in the levels of mRNAs encoded by visual cycle genes rhodopsin (Rho) and retinal pigment epithelium–specific 65 kDa protein (Rpe65), consistent with the morphological data indicating preservation of photoreceptors and RPE, respectively. DFP treatment also protected photoreceptors in rd6 mice. Conclusions The oral iron chelator DFP provides significant protection against retinal degeneration induced through different modalities. This suggests that iron chelation could be useful as a treatment for retinal degeneration even when the main etiology does not appear to be iron dysregulation. Translational Relevance These data provide proof of principle that the oral iron chelator DFP can protect the retina against diverse insults. Further testing of DFP in additional animal retinal degeneration models at a range of doses is warranted. PMID:24049709

Hadziahmetovic, Majda; Pajic, Miroslav; Grieco, Steven; Song, Ying; Song, Delu; Li, Yafeng; Cwanger, Alyssa; Iacovelli, Jared; Chu, Sally; Ying, Gui-shuang; Connelly, John; Spino, Michael; Dunaief, Joshua L

2012-01-01

389

Gene expression profiling of the rat sciatic nerve in early Wallerian degeneration after injury?  

PubMed Central

Wallerian degeneration is an important area of research in modern neuroscience. A large number of genes are differentially regulated in the various stages of Wallerian degeneration, especially during the early response. In this study, we analyzed gene expression in early Wallerian degeneration of the distal nerve stump at 0, 0.5, 1, 6, 12 and 24 hours after rat sciatic nerve injury using gene chip microarrays. We screened for differentially-expressed genes and gene expression patterns. We examined the data for Gene Ontology, and explored the Kyoto Encyclopedia of Genes and Genomes Pathway. This allowed us to identify key regulatory factors and recurrent network motifs. We identified 1 546 differentially-expressed genes and 21 distinct patterns of gene expression in early Wallerian degeneration, and an enrichment of genes associated with the immune response, acute inflammation, apoptosis, cell adhesion, ion transport and the extracellular matrix. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed components involved in the Jak-STAT, ErbB, transforming growth factor-?, T cell receptor and calcium signaling pathways. Key factors included interleukin-6, interleukin-1, integrin, c-sarcoma, carcinoembryonic antigen-related cell adhesion molecules, chemokine (C-C motif) ligand, matrix metalloproteinase, BH3 interacting domain death agonist, baculoviral IAP repeat-containing 3 and Rac. The data were validated with real-time quantitative PCR. This study provides a global view of gene expression profiles in early Wallerian degeneration of the rat sciatic nerve. Our findings provide insight into the molecular mechanisms underlying early Wallerian degeneration, and the regulation of nerve degeneration and regeneration.

Yao, Dengbing; Li, Meiyuan; Shen, Dingding; Ding, Fei; Lu, Shibi; Zhao, Qin; Gu, Xiaosong

2012-01-01

390

A Novel Catechol-O-Methyltransferase Variant Associated with Human Disc Degeneration  

PubMed Central

Background: Disc degeneration and its associated low back pain are a major health care concern causing disability with a prominent role in this country's medical, social and economic structure. Low back pain is devastating and influences the quality of life for millions. Low back pain lifetime prevalence approximates 80% with an estimated direct cost burden of $86 billion per year. Back pain patients incur higher costs, greater health care utilization, and greater work loss than patients without back pain. Methods: Research was performed following approval of our Institutional Review Board. DNA was isolated, processed and amplified using routine techniques. Amplified DNA was hybridized to Affymetrix Genome-Wide Human SNP Arrays. Quality control and genotyping analysis were performed using Affymetrix Genotyping Console. The Birdseed v2 algorithm was used for genotyping analysis. 2589 SNPs were selected a priori to enter statistical analysis using lotistic regression in SAS. Results: Our objective was to search for novel single nucleotide polymorphisms (SNPs) associated with disc degeneration. Four SNPs were found to have a significant relationship to disc degeneration; three are novel. Rs165656, a new SNP found to be associated with disc degeneration, was in catechol-O-methyltransferase (COMT), a gene with well-recognized pain involvement, especially in female subjects (p=0.01). Analysis confirmed the previously association between COMT SNP rs4633 and disc degeneration. We also report two novel disc degeneration-related SNPs (rs2095019 and rs470859) located in intergenic regions upstream to thrombospondin 2. Conclusions: Findings contribute to the challenging field of disc degeneration and pain, and are important in light of the high clinical relevance of low back pain and the need for improved understanding of its fundamental basis. PMID:24904231

Gruber, Helen E.; Sha, Wei; Brouwer, Cory R.; Steuerwald, Nury; Hoelscher, Gretchen L.; Hanley, Edward N. Jr.

2014-01-01

391

Sarm1-Mediated Axon Degeneration Requires Both SAM and TIR Interactions  

PubMed Central

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 ?-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 ? 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. PMID:23946415

Gerdts, Josiah; Summers, Daniel W.; Sasaki, Yo; DiAntonio, Aaron

2013-01-01

392

Complement factor I and age-related macular degeneration  

PubMed Central

Purpose The complement system has been implicated in the pathogenesis of age-related macular degeneration (AMD). Complement factor I (CFI) is a serum protease that inhibits all complement pathways. A previous multicenter study identified a single missense CFI mutation (p.Gly119Arg) in 20/3,567 (0.56%) of AMD cases versus 1/3,937 (0.025%) of controls, thus suggesting that this mutation confers a high risk of AMD. A second CFI mutation, p.Gly188Ala, was identified in one patient with AMD. Methods We screened 521 unrelated AMD cases and 627 controls for the p.Gly119Arg and p.Gly188Ala variants. All participants were Caucasian and >55 years, and recruited through Southampton Eye Unit or research clinics in Guernsey. All participants underwent dilated fundal examination by an experienced retinal specialist. SNP assays were performed using KASP™ biochemistry. Results The p.Gly119Arg mutation was identified in 7/521 AMD cases compared to 1/627 age-matched controls (odds ratio [OR] = 8.47, confidence interval [CI] = 1.04–69.00, p = 0.027). There was a varied phenotype among the seven cases with the mutation, which was present in 4/254 (1.6%) cases with active or end-stage wet AMD and 3/267 dry AMD cases (1.1%). The p.Gly188Ala substitution was identified in 1/521 cases and 1/627 controls. Conclusions Our results identified a much higher frequency of heterozygosity for p.Gly119Arg in both cases and controls than in previous studies. Of note is that our sub-cohort from Guernsey had a particularly high frequency of p.Gly119Arg heterozygosity in affected individuals (4%) compared to our sub-cohort from the mainland (0.71%). Although these data support the conclusions of van de Ven et al. that the p.Gly119Arg substitution confers a high risk of AMD, our data suggest that this missense mutation is not as rare or as highly penetrant as previously reported. There was no difference in frequency for a second CFI variant, p.Gly188Ala, between the cases and the controls. PMID:25352734

Alexander, Philip; Gibson, Jane; Cree, Angela J.; Ennis, Sarah

2014-01-01

393

A twin study on age-related macular degeneration.  

PubMed Central

A prospective twin study on age-related macular degeneration (AMD) recruited 83 monozygotic pairs, 28 dizygotic pairs, and one triplet set from 1986 through 1993. Zygosity was determined by genetic testing of red cell markers, HLA antigens, or specific DNA loci. There were no twin pairs in which I collected data on only one twin. To decrease ascertainment bias, after 1991 the recruitment notice did not mention AMD, and I did not ask about a history of eye disease before the eye examination. Because of this, twin pairs recruited from 1986 through 1991 were statistically analyzed separately from those after January 1, 1992. From 1986 through 1991, 23 twin pairs were recruited; 11 monozygotic and 2 dizygotic pairs had nonAMD retinal changes or no retinal abnormalities, 9 monozygotic pairs with AMD were all concordant, and 1 dizygotic pair was discordant for basal laminar drusen. The concordance rate of AMD did not differ significantly between monozygotic and dizygotic twin pairs (P = .10) for 1986 through 1991. In 1992 and 1993, 88 twin pairs and one triplet set were recruited; 49 monozygotic and 19 dizygotic pairs had nonAMD retinal changes or no retinal abnormalities, 14 monozygotic pairs with AMD were all concordant, and 2 of 7 dizygotic pairs were concordant for AMD. The nonidentical triplets (1 with and 2 without AMD) were categorized as one of the discordant dizygotic pairs in the statistical evaluation. In nontwin age-matched (within 2 or 5 years of age) or age- and sex-matched sibling pairs the concordance rate of AMD ranged from 16% to 25%. The concordance rate of AMD was significantly higher in monozygotic than in dizygotic twins (P = .001) for 1992 and 1993. The concordance rate was higher for monozygotic twin pairs recruited in 1992 and 1993 than in any of the four subsets of nontwin age-method or age- and sex-matched sibling pairs (P < .0001). Overall, from 1986 through 1993, 23 of 23 monozygotic and 2 of 8 dizygotic twin pairs were concordant for AMD; this included the one dizygotic pair which was discordant for basal laminar drusen. The data of this study strongly suggest a genetic predisposition to AMD. Images FIGURE 1 FIGURE 1 (cont.) FIGURE 2 FIGURE 2 (cont.) FIGURE 2 (cont.) FIGURE 3 FIGURE 3 (cont.) FIGURE 3 (cont.) FIGURE 3 (cont.) FIGURE 4 FIGURE 4 (cont.) FIGURE 5 FIGURE 5 (cont.) FIGURE 5 (cont.) FIGURE 6 FIGURE 6 (cont.) FIGURE 7 FIGURE 7 (cont.) FIGURE 8 FIGURE 8 (cont.) FIGURE 9 FIGURE 9 (cont.) FIGURE 9 (cont.) FIGURE 10 FIGURE 10 (cont.) FIGURE 11 FIGURE 11 (cont.) FIGURE 11 (cont.) FIGURE 12 FIGURE 12 (cont.) FIGURE 12 (cont.) PMID:7886884

Meyers, S M

1994-01-01

394

Race, iris color, and age-related macular degeneration.  

PubMed Central

PURPOSE: While most observers agree that age-related macular degeneration (AMD) is much more common in white persons than in persons of black African ancestry, the influence of iris color has been more controversial. We reexamined relationships between race, iris color, and AMD in a series of patients from our retina clinic. METHODS: We evaluated, in masked fashion, stereoscopic photographs of the retinas and irides in 306 sequential patients 60 years of age or older from our retina clinics. Four readers judged whether AMD was present, absent, or questionable in the retinal photographs and labeled iris color as blue, hazel, or brown. Presence or absence of AMD and presence and severity of the various macular lesions were determined by "majority vote" of the readers. We evaluated inter-rater agreement using the kappa statistic. We compared the prevalence of AMD and of specific AMD lesions as a function of race, sex, and iris color by contingency table analysis. RESULTS: The kappa statistic showed good inter-observer agreement, being 0.466 (P < 10(-6)) for definite or questionable AMD and ranging from 0.185 to 0.522 (P = 0.0047 to P < 10(-6)) for most lesions. We found significantly more AMD in white patients than in black patients (X2 = 27.54, P < 10(-4)). There was no significant difference in AMD prevalence by sex. In white patients, AMD was significantly more prevalent in individuals with blue or hazel irides than in those with brown irides (X2 = 15.04, P = .02). CONCLUSIONS: We confirm previous findings of a higher prevalence of AMD in white persons than in black persons. We also agree with those observers who claim that white subjects with light-colored irides have a higher prevalence of AMD than those with dark-colored irides. We suggest that differences in the association between iris pigmentation and AMD in different studies using different research methods may reflect genetic difference in the groups being studied. PMID:11190014

Frank, R N; Puklin, J E; Stock, C; Canter, L A

2000-01-01

395

Increased expression of matrix metalloproteinase-10, nerve growth factor and substance P in the painful degenerate intervertebral disc  

PubMed Central

Introduction Matrix metalloproteinases (MMPs) are known to be involved in the degradation of the nucleus pulposus (NP) during intervertebral disc (IVD) degeneration. This study investigated MMP-10 (stromelysin-2) expression in the NP during IVD degeneration and correlated its expression with pro-inflammatory cytokines and molecules involved in innervation and nociception during degeneration which results in low back pain (LBP). Methods Human NP tissue was obtained at postmortem (PM) from patients without a history of back pain and graded as histologically normal or degenerate. Symptomatic degenerate NP samples were also obtained at surgery for LBP. Expression of MMP-10 mRNA and protein was analysed using real-time polymerase chain reaction and immunohistochemistry. Gene expression for pro-inflammatory cytokines interleukin-1 (IL-1) and tumour necrosis factor-alpha (TNF-?), nerve growth factor (NGF) and the pain-associated neuropeptide substance P were also analysed. Correlations between MMP-10 and IL-1, TNF-? and NGF were assessed along with NGF with substance P. Results MMP-10 mRNA was significantly increased in surgical degenerate NP when compared to PM normal and PM degenerate samples. MMP-10 protein was also significantly higher in degenerate surgical NP samples compared to PM normal. IL-1 and MMP-10 mRNA demonstrated a significant correlation in surgical degenerate samples, while TNF-? was not correlated with MMP-10 mRNA. NGF was significantly correlated with both MMP-10 and substance P mRNA in surgical degenerate NP samples. Conclusions MMP-10 expression is increased in the symptomatic degenerate IVD, where it may contribute to matrix degradation and initiation of nociception. Importantly, this study suggests differences in the pathways involved in matrix degradation between painful and pain-free IVD degeneration. PMID:19695094

Richardson, Stephen M; Doyle, Paul; Minogue, Ben M; Gnanalingham, Kanna; Hoyland, Judith A

2009-01-01

396

Uterine type II estrogen-binding sites are not of eosinophil origin  

SciTech Connect

A recent report suggested that nuclear type II sites in the rat uterus are of eosinophil origin and may represent (/sup 3/H)estradiol binding to eosinophil peroxidase. To further evaluate this hypothesis the authors examined the response of nuclear type II sites to estrogen under conditions where eosinophils are not present. Results of the experiments show that physiological levels of estradiol-17..beta.. (10 nM for 72 h) will stimulate nuclear type II sites in highly purified cultures of rat uterine stromal and myometrial cells. The magnitude of the response of type II sites to estradiol in these stromal (4-fold) and myometrial (80-fold) cell cultures was essentially identical to that observed in the uterine cell types following in vivo estrogen treatment. Since these highly purified cultures of uterine cells were prepared from the uterus of a 21-day ovariectomized rat which is devoid of eosinophils, it was concluded that estradiol stimulation of nuclear type II sites is a direct intracellular response to estrogen which occurs independent of eosinophil accumulation. Furthermore, it was found that type II sites in the rat uterus are not peroxidase. Stimulation of cytosol and nuclear type II sites by estrogen in the rat uterus is a direct intracellular response to the hormone unrelated to eosinophil accumulation and/or peroxidase activity.

Not Available

1986-01-05

397

Axonal degeneration in Alzheimer’s disease: When signaling abnormalities meet the axonal transport system  

PubMed Central

Alzheimer’s disease (AD) is characterized by progressive, age-dependent degeneration of neurons in the central nervous system. A large body of evidence indicates that neurons affected in AD follow a dying-back pattern of degeneration, where abnormalities in synaptic function and axonal connectivity long precede somatic cell death. Mechanisms underlying dying-back degeneration of neurons in AD remain elusive but several have been proposed, including deficits in fast axonal transport (FAT). Accordingly, genetic evidence linked alterations in FAT to dying-back degeneration of neurons, and FAT defects have been widely documented in various AD models. In light of these findings, we discuss experimental evidence linking several AD-related pathogenic polypeptides to aberrant activation of signaling pathways involved in the phosphoregulation of microtubule-based motor proteins. While each pathway appears to affect FAT in a unique manner, in the context of AD, many of these pathways might work synergistically to compromise the delivery of molecular components critical for the maintenance and function of synapses and axons. Therapeutic approaches aimed at preventing FAT deficits by normalizing the activity of specific protein kinases may help prevent degeneration of vulnerable neurons in AD. PMID:22721767

Kanaan, Nicholas M.; Pigino, Gustavo F.; Brady, Scott T.; Lazarov, Orly; Binder, Lester I.; Morfini, Gerardo A.

2012-01-01

398

Effect of disc degeneration on the muscle recruitment pattern in upright posture: a computational analysis.  

PubMed

Based on the sensor driving control mechanism model, the effect of disc degeneration on the trunk muscle recruitment (TMR) pattern was analysed in erect standing posture. A previously developed computational model was used for this analysis, with modifications incorporating the T12-L1 motion segment and additional muscle fascicles. To generate disc degeneration at three different levels (L3-L4, L4-L5, or L5-S1), the material properties of the ground matrix of the annulus and bulk modulus of the nucleus were reduced. The finite element method combined with an optimization technique was applied to calculate the muscle forces. Minimization of deviations in the averaged tensile stress in the annulus fibres at the outermost layer in the five discs was selected for muscle force calculations. The results indicated that the disc degeneration noticeably increased the activation of the superficial muscle (IT and R) even though there was no clear change in the longissimus thoracis. Unlike some of the superficial muscles, activation in the deep muscles (multifidus (ML, MS, MT), LL and Q) was decreased. The change in TMR pattern generated an intervertebral disc angle difference and nucleus pressure increased in the upper level. These differences are expected to be functional in that they reduce the stress at the degenerated disc by changing the muscle activation, which slows down the progress of disc degeneration. PMID:25025614

Kim, Young Eun; Choi, Hae Won

2015-11-01

399

Genetic degeneration of old and young Y chromosomes in the flowering plant Rumex hastatulus  

PubMed Central

Heteromorphic sex chromosomes have originated independently in many species, and a common feature of their evolution is the degeneration of the Y chromosome, characterized by a loss of gene content and function. Despite being of broad significance to our understanding of sex chromosome evolution, the genetic changes that occur during the early stages of Y-chromosome degeneration are poorly understood, especially in plants. Here, we investigate sex chromosome evolution in the dioecious plant Rumex hastatulus, in which X and Y chromosomes have evolved relatively recently and occur in two distinct systems: an ancestral XX/XY system and a derived XX/XY1Y2 system. This polymorphism provides a unique opportunity to investigate the effect of sex chromosome age on patterns of divergence and gene degeneration within a species. Despite recent suppression of recombination and low X-Y divergence in both systems, we find evidence that Y-linked genes have started to undergo gene loss, causing ?28% and ?8% hemizygosity of the ancestral and derived X chromosomes, respectively. Furthermore, genes remaining on Y chromosomes have accumulated more amino acid replacements, contain more unpreferred changes in codon use, and exhibit significantly reduced gene expression compared with their X-linked alleles, with the magnitude of these effects being greatest for older sex-linked genes. Our results provide evidence for reduced selection efficiency and ongoing Y-chromosome degeneration in a flowering plant, and indicate that Y degeneration can occur soon after recombination suppression between sex chromosomes. PMID:24825885

Hough, Josh; Hollister, Jesse D.; Wang, Wei; Barrett, Spencer C. H.; Wright, Stephen I.

2014-01-01

400

A murine RP1 missense mutation causes protein mislocalization and slowly progressive photoreceptor degeneration.  

PubMed

Mutations in the RP1 gene can cause retinitis pigmentosa. We identified a spontaneous L66P mutation caused by two adjacent point mutations in the Rp1 gene in a colony of C57BL/6J mice. Mice homozygous for the L66P mutation exhibited slow, progressive photoreceptor degeneration throughout their lifespan. Optical coherence tomography imaging found abnormal photoreceptor reflectivity at 1 month of age. Histology found shortening and disorganization of the photoreceptor inner and outer segments and progressive thinning of the outer nuclear layer. Electroretinogram a- and b-wave amplitudes were decreased with age. Western blot analysis found that the quantity and size of the mutated retinitis pigmentosa 1 (RP1) protein were normal. However, immunohistochemistry found that the mutant Rp1 protein partially mislocalized to the transition zone of the shortened axonemes. This mutation disrupted colocalization with cytoplasmic microtubules in vitro. In conclusion, the L66P mutation in the first doublecortin domain of the Rp1 gene impairs Rp1 protein localization and function, leading to abnormalities in photoreceptor outer segment structure and progressive photoreceptor degeneration. This is the first missense mutation in Rp1 shown to cause retinal degeneration. It provides a unique, slowly progressive photoreceptor degeneration model that mirrors the slow degeneration kinetics in most patients with retinitis pigmentosa. PMID:25088982

Song, Delu; Grieco, Steve; Li, Yafeng; Hunter, Allan; Chu, Sally; Zhao, Liangliang; Song, Ying; DeAngelis, Robert A; Shi, Lan-Ying; Liu, Qin; Pierce, Eric A; Nishina, Patsy M; Lambris, John D; Dunaief, Joshua L

2014-10-01

401

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

PubMed

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. PMID:23226106

Xiong, Xin; Hao, Yan; Sun, Kan; Li, Jiaxing; Li, Xia; Mishra, Bibhudatta; Soppina, Pushpanjali; Wu, Chunlai; Hume, Richard I; Collins, Catherine A

2012-01-01

402

Wallerian degeneration of zebrafish trigeminal axons in the skin is required for regeneration and developmental pruning  

PubMed Central

Fragments of injured axons that detach from their cell body break down by the molecularly regulated process of Wallerian degeneration (WD). Although WD resembles local axon degeneration, a common mechanism for refining neuronal structure, several previously examined instances of developmental pruning were unaffected by WD pathways. We used laser axotomy and time-lapse confocal imaging to characterize and compare peripheral sensory axon WD and developmental pruning in live zebrafish larvae. Detached fragments of single injured axon arbors underwent three stereotyped phases of WD: a lag phase, a fragmentation phase and clearance. The lag phase was developmentally regulated, becoming shorter as embryos aged, while the length of the clearance phase increased with the amount of axon debris. Both cell-specific inhibition of ubiquitylation and overexpression of the Wallerian degeneration slow protein (WldS) lengthened the lag phase dramatically, but neither affected fragmentation. Persistent WldS-expressing axon fragments directly repelled regenerating axon branches of their parent arbor, similar to self-repulsion among sister branches of intact arbors. Expression of WldS also disrupted naturally occurring local axon pruning and axon degeneration in spontaneously dying trigeminal neurons: although pieces of WldS-expressing axons were pruned, and some WldS-expressing cells still died during development, in both cases detached axon fragments failed to degenerate. We propose that spontaneously pruned fragments of peripheral sensory axons must be removed by a WD-like mechanism to permit efficient innervation of the epidermis. PMID:21041367

Martin, Seanna M.; O'Brien, Georgeann S.; Portera-Cailliau, Carlos; Sagasti, Alvaro

2010-01-01

403

Genetic degeneration of old and young Y chromosomes in the flowering plant Rumex hastatulus.  

PubMed

Heteromorphic sex chromosomes have originated independently in many species, and a common feature of their evolution is the degeneration of the Y chromosome, characterized by a loss of gene content and function. Despite being of broad significance to our understanding of sex chromosome evolution, the genetic changes that occur during the early stages of Y-chromosome degeneration are poorly understood, especially in plants. Here, we investigate sex chromosome evolution in the dioecious plant Rumex hastatulus, in which X and Y chromosomes have evolved relatively recently and occur in two distinct systems: an ancestral XX/XY system and a derived XX/XY1Y2 system. This polymorphism provides a unique opportunity to investigate the effect of sex chromosome age on patterns of divergence and gene degeneration within a species. Despite recent suppression of recombination and low X-Y divergence in both systems, we find evidence that Y-linked genes have started to undergo gene loss, causing ? 28% and ? 8% hemizygosity of the ancestral and derived X chromosomes, respectively. Furthermore, genes remaining on Y chromosomes have accumulated more amino acid replacements, contain more unpreferred changes in codon use, and exhibit significantly reduced gene expression compared with their X-linked alleles, with the magnitude of these effects being greatest for older sex-linked genes. Our results provide evidence for reduced selection efficiency and ongoing Y-chromosome degeneration in a flowering plant, and indicate that Y degeneration can occur soon after recombination suppression between sex chromosomes. PMID:24825885

Hough, Josh; Hollister, Jesse D; Wang, Wei; Barrett, Spencer C H; Wright, Stephen I

2014-05-27

404

DICER1 deficit induces Alu RNA toxicity in age-related macular degeneration  

PubMed Central

Geographic atrophy (GA), an untreatable advanced form of age-related macular degeneration, results from retinal pigmented epithelium (RPE) cell death. Here we show that the microRNA (miRNA)-processing enzyme DICER1 is reduced in the RPE of humans with GA, and that conditional ablation of Dicer1, but not seven other miRNA-processing enzymes, induces RPE degeneration in mice. DICER1 knockdown induces accumulation of Alu RNA in human RPE cells and Alu-like B1 and B2 RNAs in mouse RPE. Alu RNA is increased in the RPE of humans with GA, and this pathogenic RNA induces human RPE cytotoxicity and RPE degeneration in mice. Antisense oligonucleotides targeting Alu/B1/B2 RNAs prevent DICER1 depletion-induced RPE degeneration despite global miRNA downregulation. DICER1 degrades Alu RNA, and this digested Alu RNA cannot induce RPE degeneration in mice. These findings reveal a miRNA-independent cell survival function for DICER1 involving retrotransposon transcript degradation, show that Alu RNA can directly cause human pathology, and identify new targets for a major cause of blindness. PMID:21297615

Kaneko, Hiroki; Dridi, Sami; Tarallo, Valeria; Gelfand, Bradley D.; Fowler, Benjamin J.; Cho, Won Gil; Kleinman, Mark E.; Ponicsan, Steven L.; Hauswirth, William W.; Chiodo, Vince A.; Karikó, Katalin; Yoo, Jae Wook; Lee, Dong-ki; Hadziahmetovic, Majda; Song, Ying; Misra, Smita; Chaudhuri, Gautam; Buaas, Frank W.; Braun, Robert E.; Hinton, David R.; Zhang, Qing; Grossniklaus, Hans E.; Provis, Jan M.; Madigan, Michele C.; Milam, Ann H.; Justice, Nikki L.; Albuquerque, Romulo J.C.; Blandford, Alexander D.; Bogdanovich, Sasha; Hirano, Yoshio; Witta, Jassir; Fuchs, Elaine; Littman, Dan R.; Ambati, Balamurali K.; Rudin, Charles M.; Chong, Mark M.W.; Provost, Patrick; Kugel, Jennifer F.; Goodrich, James A.; Dunaief, Joshua L.; Baffi, Judit Z.; Ambati, Jayakrishna

2011-01-01

405

Nonplanar Shock Structures in a Relativistic Degenerate Multi-Species Plasma  

NASA Astrophysics Data System (ADS)

A nonlinear propagation of cylindrical and spherical modified ion-acoustic (mIA) waves in an unmagnetized, collisionless, relativistic, degenerate multi-species plasma has been investigated theoretically. This plasma system is assumed to contain non-relativistic degenerate light ions, both non-relativistic and ultra-relativistic degenerate electron and positron fluids, and arbitrarily charged static heavy ions. The restoring force is provided by the degenerate pressures of the electrons and positrons, whereas the inertia is provided by the mass of ions. The arbitrarily charged static heavy ions participate only in maintaining the quasi-neutrality condition at equilibrium. The modified Burgers (mB) equation is derived by using reductive perturbation technique and numerically analyzed to identify the basic features of mIA shock structures. The basic characteristics of mIA shock waves are found to be significantly modified by the effects of degenerate pressures of electron, positron, and ion fluids, their number densities, and various charge state of heavy ions. The implications of our results to dense plasmas in astrophysical compact objects (e.g., non-rotating white dwarfs, neutron stars, etc.) are briefly discussed.

M. R., Hossen; S. A., Ema; A. A., Mamun

2014-12-01

406

Diapause Formation and Downregulation of Insulin-Like Signaling via DAF-16/FOXO Delays Axonal Degeneration and Neuronal Loss  

PubMed Central

Axonal degeneration is a key event in the pathogenesis of neurodegenerative conditions. We show here that mec-4d triggered axonal degeneration of Caenorhabditis elegans neurons and mammalian axons share mechanistical similarities, as both are rescued by inhibition of calcium increase, mitochondrial dysfunction, and NMNAT overexpression. We then explore whether reactive oxygen species (ROS) participate in axonal degeneration and neuronal demise. C. elegans dauers have enhanced anti-ROS systems, and dauer mec-4d worms are completely protected from axonal degeneration and neuronal loss. Mechanistically, downregulation of the Insulin/IGF-1-like signaling (IIS) pathway protects neurons from degenerating in a DAF-16/FOXO–dependent manner and is related to superoxide dismutase and catalase-increased expression. Caloric restriction and systemic antioxidant treatment, which decrease oxidative damage, protect C. elegans axons from mec-4d-mediated degeneration and delay Wallerian degeneration in mice. In summary, we show that the IIS pathway is essential in maintaining neuronal homeostasis under pro-degenerative stimuli and identify ROS as a key intermediate of neuronal degeneration in vivo. Since axonal degeneration represents an early pathological event in neurodegeneration, our work identifies potential targets for therapeutic intervention in several conditions characterized by axonal loss and functional impairment. PMID:23300463

Calixto, Andrea; Jara, Juan S.; Court, Felipe A.

2012-01-01

407

Monte Carlo simulation of the hall effect in degenerate GaAs  

NASA Astrophysics Data System (ADS)

This paper describes a simulation of the Hall effect in GaAs using a single particle Monte Carlo method. The Pauli exclusion principle and Fermi-Dirac statistics are included in the simulation so that the calculations are extended to the case of transport in degenerate materials with electron concentrations up to 10 19 cm -3. Hall mobility and drift mobility for electrons in the low-field ohmic transport regime are calculated from the Monte Carlo results and compared with available typical experimental data. These results demonstrate the importance of including electron-electron interactions in Monte Carlo simulations for GaAs with carrier concentrations above 10 17 cm -3. They also suggest the need for an evaluation of current models for ionized impurity scattering applied to degenerate materials and an examination of the role of energy band structure details in Monte Carlos simulations in degenerate materials.

Williams, C. K.; Littlejohn, M. A.; Glisson, T. H.; Hauser, J. R.

408

Cartilage Degeneration at Symptomatic Persistent Olecranon Physis in Adolescent Baseball Players  

PubMed Central

Background. Elbow overuse injuries are common in adolescent baseball players, but symptomatic persistent olecranon physis is rare, and its pathogenesis remains unclear. Purpose. To examine the histopathological and imaging findings of advanced persistent olecranon physis. Methods. The olecranon physes of 2 baseball pitchers, aged 14 and 15 years, were examined by preoperative magnetic resonance imaging (MRI), and surgical specimens were examined histologically. Results. T2-weighted MRI revealed alterations in the intrachondral signal intensity possibly related to collagen degeneration and increased free water content. Histological findings of specimens stained with hematoxylin-eosin showed complete disorganization of the cartilage structure, hypocellularity, chondrocyte cluster formation, and moderately reduced staining. All these findings are hallmarks of osteoarthritis and are suggestive of cartilage degeneration. Conclusion. Growth plate degeneration was evident in advanced cases of symptomatic persistent olecranon physis. These findings contribute to understanding the pathogenesis of this disease. PMID:25580304

Enishi, Tetsuya; Matsuura, Tetsuya; Suzue, Naoto; Takahashi, Yoshinori; Sairyo, Koichi

2014-01-01

409

Safranal, a Saffron Constituent, Attenuates Retinal Degeneration in P23H Rats  

PubMed Central

Saffron, an extract from Crocus sativus, has been largely used in traditional medicine for its antiapoptotic and anticarcinogenic properties. In this work, we investigate the effects of safranal, a component of saffron stigmas, in attenuating retinal degeneration in the P23H rat model of autosomal dominant retinitis pigmentosa. We demonstrate that administration of safranal to homozygous P23H line-3 rats preserves both photoreceptor morphology and number. Electroretinographic recordings showed higher a- and b-wave amplitudes under both photopic and scotopic conditions in safranal-treated versus non-treated animals. Furthermore, the capillary network in safranal-treated animals was preserved, unlike that found in untreated animals. Our findings indicate that dietary supplementation with safranal slows photoreceptor cell degeneration and ameliorates the loss of retinal function and vascular network disruption in P23H rats. This work also suggests that safranal could be potentially useful to retard retinal degeneration in patients with retinitis pigmentosa. PMID:22900092

Esquiva, Gema; Martín-Nieto, José; Pinilla, Isabel; Cuenca, Nicolás

2012-01-01

410

Cosmological constant in SUGRA models with Planck scale SUSY breaking and degenerate vacua  

NASA Astrophysics Data System (ADS)

The empirical mass of the Higgs boson suggests small to vanishing values of the quartic Higgs self-coupling and the corresponding beta function at the Planck scale, leading to degenerate vacua. This leads us to suggest that the measured value of the cosmological constant can originate from supergravity (SUGRA) models with degenerate vacua. This scenario is realised if there are at least three exactly degenerate vacua. In the first vacuum, associated with the physical one, local supersymmetry (SUSY) is broken near the Planck scale while the breakdown of the SU(2)W×U(1)Y symmetry takes place at the electroweak (EW) scale. In the second vacuum local SUSY breaking is induced by gaugino condensation at a scale which is just slightly lower than ?QCD in the physical vacuum. Finally, in the third vacuum local SUSY and EW symmetry are broken near the Planck scale.

Froggatt, C. D.; Nevzorov, R.; Nielsen, H. B.; Thomas, A. W.

2014-10-01

411

Mutations in PNPLA6 are linked to photoreceptor degeneration and various forms of childhood blindness.  

PubMed

Blindness due to retinal degeneration affects millions of people worldwide, but many disease-causing mutations remain unknown. PNPLA6 encodes the patatin-like phospholipase domain containing protein 6, also known as neuropathy target esterase (NTE), which is the target of toxic organophosphates that induce human paralysis due to severe axonopathy of large neurons. Mutations in PNPLA6 also cause human spastic paraplegia characterized by motor neuron degeneration. Here we identify PNPLA6 mutations in childhood blindness in seven families with retinal degeneration, including Leber congenital amaurosis and Oliver McFarlane syndrome. PNPLA6 localizes mostly at the inner segment plasma membrane in photoreceptors and mutations in Drosophila PNPLA6 lead to photoreceptor cell death. We also report that lysophosphatidylcholine and lysophosphatidic acid levels are elevated in mutant Drosophila. These findings show a role for PNPLA6 in photoreceptor survival and identify phospholipid metabolism as a potential therapeutic target for some forms of blindness. PMID:25574898

Kmoch, S; Majewski, J; Ramamurthy, V; Cao, S; Fahiminiya, S; Ren, H; MacDonald, I M; Lopez, I; Sun, V; Keser, V; Khan, A; Stránecký, V; Hartmannová, H; P?istoupilová, A; Hoda?ová, K; Piherová, L; Kucha?, L; Baxová, A; Chen, R; Barsottini, O G P; Pyle, A; Griffin, H; Splitt, M; Sallum, J; Tolmie, J L; Sampson, J R; Chinnery, P; Banin, E; Sharon, D; Dutta, S; Grebler, R; Helfrich-Foerster, C; Pedroso, J L; Kretzschmar, D; Cayouette, M; Koenekoop, R K

2015-01-01

412

Nearly degenerate heavy sterile neutrinos in cascade decay: Mixing and oscillations  

NASA Astrophysics Data System (ADS)

Some extensions beyond the Standard Model propose the existence of nearly degenerate heavy sterile neutrinos. If kinematically allowed these can be resonantly produced and decay in a cascade to common final states. The common decay channels lead to mixing of the heavy sterile neutrino states and interference effects. We implement nonperturbative methods to study the dynamics of the cascade decay to common final states, which features similarities but also noteworthy differences with the case of neutral meson mixing. We show that mixing and oscillations among the nearly degenerate sterile neutrinos can be detected as quantum beats in the distribution of final states produced from their decay. These oscillations would be a telltale signal of mixing between heavy sterile neutrinos. We study in detail the case of two nearly degenerate sterile neutrinos produced in the decay of pseudoscalar mesons and decaying into a purely leptonic "visible" channel: ?h?e+e-?a. Possible cosmological implications for the effective number of neutrinos Neff are discussed.

Boyanovsky, Daniel

2014-11-01

413

bcl-2 overexpression reduces apoptotic photoreceptor cell death in three different retinal degenerations.  

PubMed Central

Apoptosis of photoreceptors occurs infrequently in adult retina but can be triggered in inherited and environmentally induced retinal degenerations. The protooncogene bcl-2 is known to be a potent regulator of cell survival in neurons. We created lines of transgenic mice overexpressing bcl-2 to test for its ability to increase photoreceptor survival. Bcl-2 increased photoreceptor survival in mice with retinal degeneration caused by a defective opsin or cGMP phosphodiesterase. Overexpression of Bcl-2 in normal photoreceptors also decreased the damaging effects of constant light exposure. Apoptosis was induced in normal photoreceptors by very high levels of bcl-2. We conclude that bcl-2 is an important regulator of photoreceptor cell death in retinal degenerations. Images Fig. 1 Fig. 2 Fig. 3 Fig. 5 PMID:8692941

Chen, J; Flannery, J G; LaVail, M M; Steinberg, R H; Xu, J; Simon, M I

1996-01-01

414

Water induced relaxation of a degenerate vibration of guanidinium using 2D IR echo spectroscopy  

PubMed Central

The nearly degenerate asymmetric stretch vibrations near 1600 cm?1 of the guanidinium cation in D-glycerol/D2O mixtures having different viscosity were studied by 2D IR photon echo spectroscopy. The polarization dependent photon echo signal shows two separate frequency distributions in the 2D spectrum in D2O, even though only one band is evident from inspection of the linear FTIR spectrum. The split components are more clearly seen at higher viscosity. The interactions with solvent induce energy transfer between the degenerate component modes on the time scale of 0.5 ps. The energy transfer between modes is directly observed in 2D IR and distinguished by the waiting time dependence of the cross peaks from the transfers between threefold symmetric configurations of the distorted ion and solvent. The 2D IR analysis carried out for various polarization conditions required specification of frequency-frequency auto- and cross- correlation functions for the degenerate components. PMID:20143800

Vorobyev, Dmitriy Yu.; Kuo, Chun-Hung; Kuroda, Daniel G.; Scott, J. Nathan; Vanderkooi, Jane M.; Hochstrasser, Robin M.

2010-01-01

415

Ripple structure in degenerate electron gas-dominated stars with intense magnetic fields  

SciTech Connect

It is shown that the ripple structure observed in the variables of a degenerate electron gas in the laboratory under conditions of a strong magnetic field should also show up in stellar objects dominated by degenerate electron gases, in presence of an intense magnetic field. It is shown that ripple structures should be manifested as cusps in density profiles and mass versus central density plots of degenerate electron gas-dominated stars with intense enough magnetic fields, e.g., for a B field of the order of 10 to the 13th G, for typical white dwarf densities. Whether fields are intense enough in the known astrophysical bodies of this type is an open question. 27 refs.

Wilkes, J.M.; Ingraham, R.L. (New Mexico State Univ., Las Cruces (USA))

1989-09-01

416

The Olivocerebellar Projection Mediates Ibogaine-Induced Degeneration of Purkinje Cells: A Model of Indirect,  

E-print Network

Ibogaine, an indole alkaloid that causes hallucinations, tremor, and ataxia, produces cerebellar neurotoxicity in rats, manifested by degeneration of Purkinje cells aligned in narrow parasagittal bands that are coextensive with activated glial cells. Harmaline, a closely related alkaloid that excites inferior olivary neurons, causes the same pattern of Purkinje cell degeneration, providing a clue to the mechanism of toxicity. We have proposed that ibogaine, like harmaline, excites neurons in the inferior olive, leading to sustained release of glutamate at climbing fiber synapses on Purkinje cells. The objective of this study was to test the hypothesis that increased climbing fiber activity induced by ibogaine mediates excitotoxic Purkinje cell degeneration. The inferior olive was pharmacologically ablated in rats by a neurotoxic drug regimen using 3-acetylpyridine, and cerebellar damage attributed to subsequent administration of ibogaine was analyzed using immunocytochemical

Trans-synaptic Excitotoxicity; Mark E. Molliver

417

Effective cubic nonlinearity and cnoidal waves in the degenerate parametric frequency conversion  

SciTech Connect

It is shown that under the degenerate conditions (SHG and type-I degenerate parametric generation), the increase in the order of a system of truncated wave equations reduces the initial problem to the solution of two independent nonlinear Schroedinger equations, which allows one to write down the analytic solutions of the corresponding problems by using the standard methods for constructing the searched-for solutions in the form of cnoidal waves. It is established that in realising of cascade processes (quasi-synchronism), one of which is degenerate, this approach based on the introduction of the concept of the effective cascade cubic nonlinearity is not very convenient because the latter in the general case is no longer the Kerr one.

Petnikova, V M; Shuvalov, Vladimir V [International Laser Center, M. V. Lomonosov Moscow State University, Moscow (Russian Federation)

2010-05-26

418

Distinct MRI Atrophy Patterns in Autopsy-Proven Alzheimer’s Disease and Frontotemporal Lobar Degeneration  

PubMed Central

To better define the anatomic distinctions between Alzheimer’s disease (AD) and frontotemporal lobar degeneration (FTLD), we retrospectively applied voxel-based morphometry to the earliest magnetic resonance imaging scans of autopsy-proven AD (N=11), FTLD (N=18), and controls (N=40). Compared with controls, AD patients showed gray matter reductions in posterior temporoparietal and occipital cortex; FTLD patients showed atrophy in medial prefrontal and medial temporal cortex, insula, hippocampus, and amygdala; and patients with both disorders showed atrophy in dorsolateral and orbital prefrontal cortex and lateral temporal cortex (PFWE-corr < .05). Compared with FTLD, AD patients had decreased gray matter in posterior parietal and occipital cortex, whereas FTLD patients had selective atrophy in anterior cingulate, frontal insula, subcallosal gyrus, and striatum (P < .001, uncorrected). These findings suggest that AD and FTLD are anatomically distinct, with degeneration of a posterior parietal network in AD and degeneration of a paralimbic fronto-insular-striatal network in FTLD. PMID:18166607

Rabinovici, G. D.; Seeley, W. W.; Kim, E. J.; Gorno-Tempini, M. L.; Rascovsky, K.; Pagliaro, T. A.; Allison, S. C.; Halabi, C.; Kramer, J. H.; Johnson, J. K.; Weiner, M. W.; Forman, M. S.; Trojanowski, J. Q.; DeArmond, S. J.; Miller, B. L.; Rosen, H. J.

2008-01-01

419

Mitochondrial alarmins released by degenerating motor axon terminals activate perisynaptic Schwann cells  

PubMed Central

An acute and highly reproducible motor axon terminal degeneration followed by complete regeneration is induced by some animal presynaptic neurotoxins, representing an appropriate and controlled system to dissect the molecular mechanisms underlying degeneration and regeneration of peripheral nerve terminals. We have previously shown that nerve terminals exposed to spider or snake presynaptic neurotoxins degenerate as a result of calcium overload and mitochondrial failure. Here we show that toxin-treated primary neurons release signaling molecules derived from mitochondria: hydrogen peroxide, mitochondrial DNA, and cytochrome c. These molecules activate isolated primary Schwann cells, Schwann cells cocultured with neurons and at neuromuscular junction in vivo through the MAPK pathway. We propose that this inter- and intracellular signaling is involved in triggering the regeneration of peripheral nerve terminals affected by other forms of neurodegenerative diseases. PMID:25605902

Duregotti, Elisa; Negro, Samuele; Scorzeto, Michele; Zornetta, Irene; Dickinson, Bryan C.; Chang, Christopher J.; Montecucco, Cesare; Rigoni, Michela

2015-01-01

420

The effective density of randomly moving electrons and related characteristics of materials with degenerate electron gas  

NASA Astrophysics Data System (ADS)

Interpretation of the conductivity of metals, of superconductors in the normal state and of semiconductors with highly degenerate electron gas remains a significant issue if consideration is based on the classical statistics. This study is addressed to the characterization of the effective density of randomly moving electrons and to the evaluation of carrier diffusion coefficient, mobility, and other parameters by generalization of the widely published experimental results. The generalized expressions have been derived for various kinetic parameters attributed to the non-degenerate and degenerate electron gas, by analyzing a random motion of the single type carriers in homogeneous materials. The values of the most important kinetic parameters for different metals are also systematized and discussed. It has been proved that Einstein's relation between the diffusion coefficient and the drift mobility of electrons is held for any level of degeneracy if the effective density of randomly moving carriers is properly taken into account.

Palenskis, V.

2014-04-01

421

Second-order nonlinear Schrödinger equation breather solutions in the degenerate and rogue wave limits  

NASA Astrophysics Data System (ADS)

We present an explicit analytic form for the two-breather solution of the nonlinear Schrödinger equation with imaginary eigenvalues. It describes various nonlinear combinations of Akhmediev breathers and Kuznetsov-Ma solitons. The degenerate case, when the two eigenvalues coincide, is quite involved. The standard inverse scattering technique does not generally provide an answer to this scenario. We show here that the solution can still be found as a special limit of the general second-order expression and appears as a mixture of polynomials with trigonometric and hyperbolic functions. A further restriction of this particular case, where the two eigenvalues are equal to i, produces the second-order rogue wave with two free parameters considered as differential shifts. The illustrations reveal a precarious dependence of wave profile on the degenerate eigenvalues and differential shifts. Thus we establish a hierarchy of second-order solutions, revealing the interrelated nature of the general case, the rogue wave, and the degenerate breathers.

Kedziora, David J.; Ankiewicz, Adrian; Akhmediev, Nail

2012-06-01

422

Mitochondrial alarmins released by degenerating motor axon terminals activate perisynaptic Schwann cells.  

PubMed

An acute and highly reproducible motor axon terminal degeneration followed by complete regeneration is induced by some animal presynaptic neurotoxins, representing an appropriate and controlled system to dissect the molecular mechanisms underlying degeneration and regeneration of peripheral nerve terminals. We have previously shown that nerve terminals exposed to spider or snake presynaptic neurotoxins degenerate as a result of calcium overload and mitochondrial failure. Here we show that toxin-treated primary neurons release signaling molecules derived from mitochondria: hydrogen peroxide, mitochondrial DNA, and cytochrome c. These molecules activate isolated primary Schwann cells, Schwann cells cocultured with neurons and at neuromuscular junction in vivo through the MAPK pathway. We propose that this inter- and intracellular signaling is involved in triggering the regeneration of peripheral nerve terminals affected by other forms of neurodegenerative diseases. PMID:25605902

Duregotti, Elisa; Negro, Samuele; Scorzeto, Michele; Zornetta, Irene; Dickinson, Bryan C; Chang, Christopher J; Montecucco, Cesare; Rigoni, Michela

2015-02-01

423

THE PROGENITORS OF TYPE Ia SUPERNOVAE. II. ARE THEY DOUBLE-DEGENERATE BINARIES? THE SYMBIOTIC CHANNEL  

SciTech Connect

In order for a white dwarf (WD) to achieve the Chandrasekhar mass, M{sub C} , and explode as a Type Ia supernova (SNIa), it must interact with another star, either accreting matter from or merging with it. The failure to identify the class or classes of binaries which produce SNeIa is the long-standing 'progenitor problem'. Its solution is required if we are to utilize the full potential of SNeIa to elucidate basic cosmological and physical principles. In single-degenerate models, a WD accretes and burns matter at high rates. Nuclear-burning white dwarfs (NBWDs) with mass close to M{sub C} are hot and luminous, potentially detectable as supersoft X-ray sources (SSSs). In previous work, we showed that >90%-99% of the required number of progenitors do not appear as SSSs during most of the crucial phase of mass increase. The obvious implication might be that double-degenerate binaries form the main class of progenitors. We show in this paper, however, that many binaries that later become double degenerates must pass through a long-lived NBWD phase during which they are potentially detectable as SSSs. The paucity of SSSs is therefore not a strong argument in favor of double-degenerate models. Those NBWDs that are the progenitors of double-degenerate binaries are likely to appear as symbiotic binaries for intervals >10{sup 6} years. In fact, symbiotic pre-double-degenerates should be common, whether or not the WDs eventually produce SNeIa. The key to solving the Type Ia progenitor problem lies in understanding the appearance of NBWDs. Most of them do not appear as SSSs most of the time. We therefore consider the evolution of NBWDs to address the question of what their appearance may be and how we can hope to detect them.

Di Stefano, R. [Harvard-Smithsonian Center for Astrophysics, 60 Garden St. Cambridge, MA 02138 (United States)

2010-08-10

424

Non-erythropoietic erythropoietin derivatives protect from light-induced and genetic photoreceptor degeneration  

PubMed Central

Given the high genetic heterogeneity of inherited retinal degenerations (IRDs), a wide applicable treatment would be desirable to halt/slow progressive photoreceptor (PR) cell loss in a mutation-independent manner. In addition to its erythropoietic activity, erythropoietin (EPO) presents neurotrophic characteristics. We have previously shown that adeno-associated viral (AAV) vector-mediated systemic EPO delivery protects from PR degeneration. However, this is associated with an undesired hematocrit increase that could contribute to PR protection. Non-erythropoietic EPO derivatives (EPO-D) are available which allow us to dissect erythropoiesis's role in PR preservation and may be more versatile and safe than EPO as anti-apoptotic agents. We delivered in animal models of light-induced or genetic retinal degeneration either intramuscularly or subretinally AAV vectors encoding EPO or one of the three selected EPO-D: the mutant S100E, the helix A- and B-derived EPO-mimetic peptides. We observed that (i) systemic expression of S100E induces a significantly lower hematocrit increase than EPO and provides similar protection from PR degeneration, and (ii) intraocular expression of EPO-D protects PR from degeneration in the absence of significant hematocrit increase. On the basis of this, we conclude that erythropoiesis is not required for EPO-mediated PR protection. However, the lower efficacy observed when EPO or S100E is expressed intraocularly rather than systemically suggests that hormone systemic effects contribute to PR protection. Unlike S100E, EPO-mimetic peptides preserve PR only when given locally, suggesting that different EPO-D have a different potency or mode of action. In conclusion, our data show that subretinal delivery of AAV vectors encoding EPO-D protects from light-induced and genetic PR degeneration. PMID:21421996

Colella, Pasqualina; Iodice, Carolina; Di Vicino, Umberto; Annunziata, Ida; Surace, Enrico M.; Auricchio, Alberto

2011-01-01

425

Experimental investigation of amplitude and phase quantum correlations in a type II OPO above threshold: from the non-degenerate to the degenerate operation  

E-print Network

We describe a very stable type II optical parametric oscillator operated above threshold which provides 9.7 $\\pm$ 0.5 dB (89%) of quantum noise reduction on the intensity difference of the signal and idler modes. We also report the first experimental study by homodyne detection of the generated bright two-mode state in the case of frequency degenerate operation obtained by introducing a birefringent plate inside the optical cavity.

Julien Laurat; Thomas Coudreau; Laurent Longchambon; Claude Fabre

2004-12-14

426

The degenerate scenario in the NMSSM: Direct singlino-like neutralino searches with a gravitino LSP  

E-print Network

A two-component dark matter model is studied adopting the degenerate scenario in the R-parity conserving NMSSM. The gravitino LSP and the neutralino NLSP are extremely degenerate in mass, avoiding the BBN bounds and obtaining a high reheating temperature for thermal leptogenesis to work. In this model both gravitino (absolutely stable) and neutralino (quasi-stable) contribute to dark matter, and direct detection searches for neutralino are discussed. Points that survive all the constraints correspond to a singlino-like neutralino.

Grigoris Panotopoulos

2011-03-01

427

Complete quantum control of the population transfer branching ratio between two degenerate target states  

E-print Network

A five-level four-pulse phase-sensitive extended stimulated Raman adiabatic passage scheme is proposed to realize complete control of the population transfer branching ratio between two degenerate target states. The control is achieved via a three-node null eigenstate that can be correlated with an arbitrary superposition of the target states. Our results suggest that complete suppression of the yield of one of two degenerate product states, and therefore absolute selectivity in photochemistry, is achievable and predictable, even without studying the properties of the unwanted product state beforehand.

Jiangbin Gong; Stuart A. Rice

2004-05-12

428

Observation of Collective Atomic Recoil Motion in a Degenerate Fermion Gas  

SciTech Connect

We demonstrate collective atomic recoil motion with a dilute, ultracold, degenerate fermion gas in a single spin state. By utilizing an adiabatically decompressed magnetic trap with an aspect ratio different from that of the initial trap, a momentum-squeezed fermion cloud is achieved. With a single pump pulse of the proper polarization, we observe, for the first time, multiple wave-mixing processes that result in distinct collective atomic recoil motion modes in a degenerate fermion cloud. Contrary to the case with Bose condensates, no pump-laser detuning asymmetry is present.

Wang Pengjun; Fu Zhengkun; Chai Shijie; Zhang Jing [The State Key Laboratory of Quantum Optics and Quantum Optics Devices, Institute of Opto-Electronics, Shanxi University, Taiyuan 030006 (China); Deng, L. [Physical Measurements Laboratory, National Institute of Standards and Technology, Gaithersburg, Maryland 20899 (United States); Center for Cold Atom Physics and Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan 430071 (China); Hagley, E. W. [Physical Measurements Laboratory, National Institute of Standards and Technology, Gaithersburg, Maryland 20899 (United States)

2011-05-27

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Adenosine 5'-triphosphate (ATP) inhibits schwann cell demyelination during Wallerian degeneration.  

PubMed

Adenosine 5'-triphosphate (ATP) is implicated in intercellular communication as a neurotransmitter in the peripheral nervous system. In addition, ATP is known as lysosomal exocytosis activator. In this study, we investigated the role of extracellular ATP on demyelination during Wallerian degeneration (WD) using ex vivo and in vivo nerve degeneration models. We found that extracellular ATP inhibited myelin fragmentation and axonal degradation during WD. Furthermore, metformin and chlorpromazine, lysosomal exocytosis antagonists blocked the effect of ATP on the inhibition of demyelination. Thus, these findings indicate that ATP-induced-lysosomal exocytosis may be involved in demyelination during WD. PMID:24363123

Shin, Youn Ho; Chung, Hyung-Joo; Park, Chan; Jung, Junyang; Jeong, Na Young

2014-04-01

430

Prophylactic laser photocoagulation in hereditary snowflake vitreoretinal degeneration. A family report.  

PubMed

Examination of 37 members of a family revealed that 17 had snowflake vitreoretinal degeneration. All those affected showed some evidence of vitreous degeneration and 13 had retinal changes with differing degrees of severity. Vitreal changes may thus present as an early stage when hardly any retinal pathology is apparent. Peripheral retinal neovascularization was seen in four patients. Rhegmatogenous retinal detachment developed in two eyes and retinal breaks in six additional eyes. Because of the poor surgical prognosis in such cases, prophylactic treatment with argon laser photocoagulation is recommended for any type of retinal break. PMID:6626003

Pollack, A; Uchenik, D; Chemke, J; Oliver, M