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1

A clustering property of highly-degenerate transcription factor binding sites in  

E-print Network

-wide analysis of TFBS-like sequences for the transcriptional repressor, RE1 Silencing Transcription Factor (RESTA clustering property of highly-degenerate transcription factor binding sites in the mammalian Transcription factor binding sites (TFBSs) are short DNA sequences interacting with transcription factors (TFs

2

Degenerate target sites mediate rapid primed CRISPR adaptation.  

PubMed

Prokaryotes encode adaptive immune systems, called CRISPR-Cas (clustered regularly interspaced short palindromic repeats-CRISPR associated), to provide resistance against mobile invaders, such as viruses and plasmids. Host immunity is based on incorporation of invader DNA sequences in a memory locus (CRISPR), the formation of guide RNAs from this locus, and the degradation of cognate invader DNA (protospacer). Invaders can escape type I-E CRISPR-Cas immunity in Escherichia coli K12 by making point mutations in the seed region of the protospacer or its adjacent motif (PAM), but hosts quickly restore immunity by integrating new spacers in a positive-feedback process termed "priming." Here, by using a randomized protospacer and PAM library and high-throughput plasmid loss assays, we provide a systematic analysis of the constraints of both direct interference and subsequent priming in E. coli. We have defined a high-resolution genetic map of direct interference by Cascade and Cas3, which includes five positions of the protospacer at 6-nt intervals that readily tolerate mutations. Importantly, we show that priming is an extremely robust process capable of using degenerate target regions, with up to 13 mutations throughout the PAM and protospacer region. Priming is influenced by the number of mismatches, their position, and is nucleotide dependent. Our findings imply that even outdated spacers containing many mismatches can induce a rapid primed CRISPR response against diversified or related invaders, giving microbes an advantage in the coevolutionary arms race with their invaders. PMID:24711427

Fineran, Peter C; Gerritzen, Matthias J H; Suárez-Diez, María; Künne, Tim; Boekhorst, Jos; van Hijum, Sacha A F T; Staals, Raymond H J; Brouns, Stan J J

2014-04-22

3

Chondrocyte clusters adjacent to sites of cartilage degeneration have characteristics of progenitor cells.  

PubMed

The purpose of this study was to investigate the site-specific characteristics and roles of chondrocyte clusters in human knee osteoarthritis. Cartilage explants were obtained from 45 knees undergoing total knee replacement surgery. The explants were taken from 4 locations in the knee: the medial femoral condyle, the medial posterior femoral condyle (MPC), the lateral femoral condyle, and the lateral posterior femoral condyle (LPC). Cartilage degeneration, cell density, and cell arrangement were compared histologically. A live/dead cell viability assay and immunohistochemical analyses using antibodies against STRO-1, FGF2, and Ki-67 were performed. Cell proliferation and cartilaginous nodule production in MPC and LPC explants in monolayer culture were compared. Finally, MPC cartilage explants were cultured to observe histological changes. The cell density of the MPC explants was higher than that of the LPC because of clustering. MPC explants contained more live cells than the LPC did, and the expression of IHC markers in MPC explants was higher than that in LPC. Chondrocytes from MPC proliferated faster and produced more nodules in monolayer culture than those from the LPC and MPC explants were repaired during organ culture. In conclusion, chondrocyte clusters adjacent to severe cartilage degeneration have specific characteristics, with progenitor and proliferative potential. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:548-555, 2015. PMID:25691232

Hoshiyama, Yoshiaki; Otsuki, Shuhei; Oda, Shuhei; Kurokawa, Yoshitaka; Nakajima, Mikio; Jotoku, Tsuyoshi; Tamura, Ryuichi; Okamoto, Yoshinori; Lotz, Martin K; Neo, Masashi

2015-04-01

4

Another late complication after endovascular aneurysm repair: aneurysmal degeneration at the iliac artery landing site.  

PubMed

The purpose of this article is to describe a hitherto underreported late complication of infrarenal endovascular aneurysm repair (EVAR), namely type Ib endoleakage resulting from aneurysmal degeneration at the iliac artery landing site. In a prospectively recorded audit, between 1994 and 2007, 297 patients underwent EVAR. All cases that developed iliac artery aneurysm (IAA) were studied. Ten cases of IAA in seven patients (2.4% of the cohort) developed 5 to 9 years after EVAR. Eight of the 10 involved the lower landing site of the stent graft. Landing site diameter before EVAR was 12 mm (range 10-15 mm). Three IAAs presented as emergencies with rapidly expanding sacs and impending rupture. All cases underwent further endovascular intervention with no < 30-day mortality. Iliac artery landing site aneurysm formation after EVAR occurs uncommonly after 5 or more years. It should be regarded as an indication for intervention prior to type Ib endoleakage development. The need for lifelong surveillance is highlighted. PMID:19344588

Agu, Obekieze; Boardley, Dee; Adiseshiah, Mohan

2008-01-01

5

Kinases and phosphatases and tau sites involved in Alzheimer neurofibrillary degeneration  

PubMed Central

Microtubule associated protein (MAP) tau is abnormally hyperphosphorylated in Alzheimer’s disease (AD) and related tauopathies; in this form it is the major protein subunit of paired helical filaments (PHF)/neurofibrillary tangles. However, the nature of protein kinases and phosphatases and tau sites involved in this lesion has been elusive. We investigated self-assembly and microtubule assembly promoting activities of hyperphosphorylated tau isolated from Alzheimer disease brain cytosol, the AD abnormally hyperphosphorylated tau (AD P-tau) before and after dephosphorylation by phosphoseryl/phosphothreonyl protein phosphatase-2A (PP-2A), and then rephosphorylation by cyclic AMP-dependent protein kinase (PKA), calcium, calmodulin-dependent protein kinase II (CaMKII), glycogen synthase kinase-3? (GSK-3?) and cyclin-dependent protein kinase 5 (cdk5) in different kinase combinations. We found that (i) dephosphorylation of AD P-tau by PP-2A inhibits its polymerization into PHF/straight filaments (SF) and restores its binding and ability to promote assembly of tubulin into microtubules; (ii) rephosphorylation of PP-2A-dephosphorylated AD P-tau by sequential phosphorylation by PKA, CaMKII and GSK-3? or cdk5, and as well as by cdk5 and GSK-3?, promotes its self-assembly into tangles of PHF similar to those seen in Alzheimer brain, and (iii) phosphorylation of tau sites required for this pathology are Thr231 and Ser262, along with several sites flanking the microtubule binding repeat region. Phosphorylation of recombinant human brain tau441 yielded similar results as the PP-2A dephosphorylated AD P-tau, except that mostly SF were formed. The conditions for the abnormal hyperphosphorylation of tau that promoted its self-assembly also induced the microtubule assembly inhibitory activity. These findings suggest that activation of PP-2A or inhibition of either both GSK-3? and cdk5 or one of these two kinases plus PKA or CaMKII might be required to inhibit Alzheimer neurofibrillary degeneration. PMID:17241267

Wang, Jian-Zhi; Grundke-Iqbal, Inge; Iqbal, Khalid

2011-01-01

6

Patterns of nucleotide composition at fourfold degenerate sites of animal mitochondrial genomes  

Microsoft Academic Search

Three statistics (%GC, GC-skew, and AT-skew) can be used to describe the overall patterns of nucleotide composition in DNA sequences. Fourfold degenerate third codon positions from 16 animal mitochondrial genomes were analyzed. The overall composition, as measured by %GC, varies from 3.6 %GC in the honeybee to 47.2 %GC in human mtDNA. Compositional differences between strands of the mitochondrial genome

Nicole T. Perna; Thomas D. Kocher

1995-01-01

7

Patterns of nucleotide composition at fourfold degenerate sites of animal mitochondrial genomes.  

PubMed

Three statistics (%GC, GC-skew, and AT-skew) can be used to describe the overall patterns of nucleotide composition in DNA sequences. Fourfold degenerate third codon positions from 16 animal mitochondrial genomes were analyzed. The overall composition, as measured by %GC, varies from 3.6 %GC in the honeybee to 47.2 %GC in human mtDNA. Compositional differences between strands of the mitochondrial genome were quantified using the two skew statistics presented in this paper. Strand-specific distribution of bases varies among animal taxa independently of overall %GC. Compositional patterns reflect the substitution process. Description of these patterns may aid in the formation of hypotheses about substitutional mechanisms. PMID:7563121

Perna, N T; Kocher, T D

1995-09-01

8

Single-site resolved studies of a bilayer quantum degenerate gas  

NASA Astrophysics Data System (ADS)

Ultracold atoms in optical lattices are a versatile platform for quantum many-body simulation with the promise of insights into quantum magnetism, superconductivity, and superfluidity. In recent years, quantum gas microscopes with single-site resolution have opened the door to local observation and manipulation of strongly correlated two-dimensional quantum gases. Here we present techniques for extending study to two tunnel-coupled planes. Using an axial superlattice we prepare a bilayer system, with full control of the inter-plane tunnel coupling and detuning. We observe coherent inter-plane population transfer with single-site resolution in both planes. A collisional energy blockade in the bilayer system allows us to go beyond parity imaging and unambiguously identify site occupations from zero to three atoms. We have obtained site-resolved images of the ``wedding-cake'' Mott insulator structure and antiferromagnetic ordering in a quantum Ising model. Further applications include spin-dependent readout and in situ phase imaging.

Ma, Ruichao; Preiss, Philipp; Tai, Ming; Bakr, Waseem; Simon, Jonathan; Greiner, Markus

2012-06-01

9

Cerebellar Degeneration  

MedlinePLUS

... Degeneration? Cerebellar degeneration is a process in which neurons in the cerebellum - the area of the brain ... proteins that are necessary for the survival of neurons. Associated diseases: Diseases that are specific to the ...

10

Striatonigral Degeneration  

MedlinePLUS

... However, unlike Parkinson's disease, striatonigral degeneration is not responsive to levodopa. Dopamine and anticholinergics provide some benefit. ... or the NIH is appreciated. Last updated December 5, 2013 National Institute of Neurological Disorders and Stroke ...

11

Corticobasal Degeneration  

Microsoft Academic Search

Corticobasal degeneration (CBG) is an increasingly recognized neurodegenerative disease with both motor and cognitive dysfunction. The diagnosis is probably underesti- mated because of the heterogeneity of clinical features, overlap with symptoms, and patho- logic findings of other neurodegenerative diseases. The most characteristic initial motor symptoms are akinesia, rigidity, and apraxia. Dystonia and alien limb phenomena are fre- quently observed. There

Natividad P. Stover; Ray L. Watts

2001-01-01

12

The Alzheimer's A beta -peptide is deposited at sites of complement activation in pathologic deposits associated with aging and age-related macular degeneration.  

PubMed

Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in older individuals worldwide. The disease is characterized by abnormal extracellular deposits, known as drusen, that accumulate along the basal surface of the retinal pigmented epithelium. Although drusen deposition is common in older individuals, large numbers of drusen and/or extensive areas of confluent drusen represent a significant risk factor for AMD. Widespread drusen deposition is associated with retinal pigmented epithelial cell dysfunction and degeneration of the photoreceptor cells of the neural retina. Recent studies have shown that drusen contain a variety of immunomodulatory molecules, suggesting that the process of drusen formation involves local inflammatory events, including activation of the complement cascade. Similar observations in Alzheimer's disease (AD) have lead to the hypothesis that chronic localized inflammation is an important element of AD pathogenesis, with significant neurodegenerative consequences. Accordingly, the amyloid beta (A beta) peptide, a major constituent of neuritic plaques in AD, has been implicated as a primary activator of complement in AD. Here we show that A beta is associated with a substructural vesicular component within drusen. A beta colocalizes with activated complement components in these "amyloid vesicles," thereby identifying them as potential primary sites of complement activation. Thus, A beta deposition could be an important component of the local inflammatory events that contribute to atrophy of the retinal pigmented epithelium, drusen biogenesis, and the pathogenesis of AMD. PMID:12189211

Johnson, Lincoln V; Leitner, William P; Rivest, Alexander J; Staples, Michelle K; Radeke, Monte J; Anderson, Don H

2002-09-01

13

The Alzheimer's A?-peptide is deposited at sites of complement activation in pathologic deposits associated with aging and age-related macular degeneration  

PubMed Central

Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in older individuals worldwide. The disease is characterized by abnormal extracellular deposits, known as drusen, that accumulate along the basal surface of the retinal pigmented epithelium. Although drusen deposition is common in older individuals, large numbers of drusen and/or extensive areas of confluent drusen represent a significant risk factor for AMD. Widespread drusen deposition is associated with retinal pigmented epithelial cell dysfunction and degeneration of the photoreceptor cells of the neural retina. Recent studies have shown that drusen contain a variety of immunomodulatory molecules, suggesting that the process of drusen formation involves local inflammatory events, including activation of the complement cascade. Similar observations in Alzheimer's disease (AD) have lead to the hypothesis that chronic localized inflammation is an important element of AD pathogenesis, with significant neurodegenerative consequences. Accordingly, the amyloid beta (A?) peptide, a major constituent of neuritic plaques in AD, has been implicated as a primary activator of complement in AD. Here we show that A? is associated with a substructural vesicular component within drusen. A? colocalizes with activated complement components in these “amyloid vesicles,” thereby identifying them as potential primary sites of complement activation. Thus, A? deposition could be an important component of the local inflammatory events that contribute to atrophy of the retinal pigmented epithelium, drusen biogenesis, and the pathogenesis of AMD. PMID:12189211

Johnson, Lincoln V.; Leitner, William P.; Rivest, Alexander J.; Staples, Michelle K.; Radeke, Monte J.; Anderson, Don H.

2002-01-01

14

Macular Degeneration  

NSDL National Science Digital Library

This patient education program discusses age-related macular degeneration including the causes, risks, symptoms, diagnosis, treatment options, and management of the disease. It also reviews the anatomy of the eye and vision. This resource is a MedlinePlus Interactive Health Tutorial from the National Library of Medicine, designed and developed by the Patient Education Institute. NOTE: This tutorial requires a special Flash plug-in, version 4 or above. If you do not have Flash, you will be prompted to obtain a free download of the software before you start the tutorial. You will also need an Acrobat Reader, available as a free download, in order to view the Reference Summary.

Patient Education Institute

15

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

NASA Astrophysics Data System (ADS)

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.

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

2015-01-01

16

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 (R3) and tetragonal (I4?/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

17

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

18

The Alzheimer's A-peptide is deposited at sites of complement activation in pathologic deposits associated with aging and age-related macular degeneration  

Microsoft Academic Search

Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in older individuals worldwide. The disease is characterized by abnormal extracellular deposits, known as drusen, that accumulate along the basal surface of the retinal pigmented epithelium. Although drusen deposition is common in older individuals, large numbers of drusen and\\/or extensive areas of confluent drusen represent a significant risk

Lincoln V. Johnson; William P. Leitner; Alexander J. Rivest; Michelle K. Staples; Monte J. Radeke; Don H. Anderson

2002-01-01

19

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

20

The Pathophysiology of Cigarette Smoking and Age-Related Macular Degeneration  

Microsoft Academic Search

\\u000a Age-related macular degeneration (AMD) is the most common form of visual impairment, in people over 65, in the Western world.\\u000a AMD is a multifactorial disease with genetic and environmental factors influencing disease progression. Cigarette smoking\\u000a is the most significant environmental influence with an estimated increase in risk of 2- to 4-fold. Smoke-induced damage in\\u000a AMD is mediated through direct oxidation,

S. S. Ni Dhubhghaill; M. Campbell; L. Cassidy; M. M. Humphries; P. Humphries

21

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

22

Biomechanics of Disc Degeneration  

PubMed Central

Disc degeneration and associated disorders are among the most debated topics in the orthopedic literature over the past few decades. These may be attributed to interrelated mechanical, biochemical, and environmental factors. The treatment options vary from conservative approaches to surgery, depending on the severity of degeneration and response to conservative therapies. Spinal fusion is considered to be the “gold standard” in surgical methods till date. However, the association of adjacent level degeneration has led to the evolution of motion preservation technologies like spinal arthroplasty and posterior dynamic stabilization systems. These new technologies are aimed to address pain and preserve motion while maintaining a proper load sharing among various spinal elements. This paper provides an elaborative biomechanical review of the technologies aimed to address the disc degeneration and reiterates the point that biomechanical efficacy followed by long-term clinical success will allow these nonfusion technologies as alternatives to fusion, at least in certain patient population. PMID:22745914

Palepu, V.; Kodigudla, M.; Goel, V. K.

2012-01-01

23

Quantum degenerate systems  

SciTech Connect

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

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

2012-10-15

24

Frontotemporal Lobar Degeneration  

PubMed Central

Frontotemporal lobar degeneration (FTLD) is a clinically and pathologically heterogeneous syndrome, characterized by progressive decline in behaviour or language associated with degeneration of the frontal and anterior temporal lobes. While the seminal cases were described at the turn of the 20th century, FTLD has only recently been appreciated as a leading cause of dementia, particularly in patients presenting before the age of 65 years. Three distinct clinical variants of FTLD have been described: (i) behavioural-variant frontotemporal dementia, characterized by changes in behaviour and personality in association with frontal-predominant cortical degeneration; (ii) semantic dementia, a syndrome of progressive loss of knowledge about words and objects associated with anterior temporal neuronal loss; and (iii) progressive nonfluent aphasia, characterized by effortful language output, loss of grammar and motor speech deficits in the setting of left perisylvian cortical atrophy. The majority of pathologies associated with FTLD clinical syndromes include either tau-positive (FTLD-TAU) or TAR DNA-binding protein 43 (TDP-43)-positive (FTLD-TDP) inclusion bodies. FTLD overlaps clinically and pathologically with the atypical parkinsonian disorders corticobasal degeneration and progressive supranuclear palsy, and with amyotrophic lateral sclerosis. The majority of familial FTLD cases are caused by mutations in the genes encoding microtubule-associated protein tau (leading to FTLD-TAU) or progranulin (leading to FTLD-TDP). The clinical and pathologic heterogeneity of FTLD poses a significant diagnostic challenge, and in vivo prediction of underlying histopathology can be significantly improved by supplementing the clinical evaluation with genetic tests and emerging biological markers. Current pharmacotherapy for FTLD focuses on manipulating serotonergic or dopaminergic neurotransmitter systems to ameliorate behavioural or motor symptoms. However, recent advances in FTLD genetics and molecular pathology make the prospect of biologically driven, disease-specific therapies for FTLD seem closer than ever. PMID:20369906

Rabinovici, Gil D.; Miller, Bruce L.

2010-01-01

25

Alzheimer neurofibrillary degeneration  

Microsoft Academic Search

Neurofibrillary degeneration has primary and pivotal involvement in the pathogenesis of Alzheimer disease (AD) and other tauopathies.\\u000a The inhibition of this lesion offers a promising therapeutic approach. The microtubule-associated protein (MAP) tau is abnormally\\u000a hyperphosphorylated in the brain of patients with AD, and in this form it is the major protein subunit of paired helical filaments\\/neurofibrillary\\u000a tangles (PHF\\/NFT). The abnormal

Khalid Iqbal; Alejandra del C. Alonso; Ezzat El-Akkad; Cheng-Xin Gong; Niloufar Haque; Sabiha Khatoon; Jin-Jing Pei; Hitoshi Tanimukai; Ichiro Tsujio; Jian-Zhi Wang; Grundke-Iqbal Inge

2003-01-01

26

Local reactivity descriptors from degenerate frontier molecular orbitals  

NASA Astrophysics Data System (ADS)

Conceptual Density Functional Theory (DFT) has proposed a set of local descriptors to measure the reactivity on specific sites of a molecule, as an example dual descriptor has been successfully used in analyzing interesting systems to understand their local reactivity, however under the frozen orbital approximation (FOA), it is defined from non-degenerate frontier molecular orbitals (FMOs). In this work, the degeneration is taken into account to propose approximated expressions to obtain the dual descriptor, nucleophilic and electrophilic Fukui functions in closed-shell systems. The proposed expressions have been tested on molecules presenting degenerate FMOs.

Martínez, Jorge

2009-08-01

27

The degenerate gravitino scenario  

E-print Network

In this work, we explore the "degenerate gravitino" scenario where the mass difference between the gravitino and the lightest MSSM particle is much smaller than the gravitino mass itself. In this case, the energy released in the decay of the next to lightest sypersymmetric particle (NLSP) is reduced. Consequently the cosmological and astrophysical constraints on the gravitino abundance, and hence on the reheating temperature, become softer than in the usual case. On the other hand, such small mass splittings generically imply a much longer lifetime for the NLSP. We find that, in the constrained MSSM (CMSSM), for neutralino LSP or NLSP, reheating temperatures compatible with thermal leptogenesis are reached for small splittings of order 10^{-2} GeV. While for stau NLSP, temperatures of 4x10^9 GeV can be obtained even for splittings of order of tens of GeVs. This "degenerate gravitino" scenario offers a possible way out to the gravitino problem for thermal leptogenesis in supersymmetric theories.

Lotfi Boubekeur; Ki Young Choi; Roberto Ruiz de Austri; Oscar Vives

2010-04-07

28

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

29

Age-Related Macular Degeneration  

MedlinePLUS

... related Macular Degeneration: What is AMD? In This Topic What is AMD? Wet AMD Dry AMD Risk ... for More Information National Institute on Aging Related Topics Low Vision More Vision Topics The information in ...

30

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

31

Chondroadherin fragmentation mediated by the protease HTRA1 distinguishes human intervertebral disc degeneration from normal aging.  

PubMed

Chondroadherin, a member of the leucine-rich repeat family, has previously been demonstrated to be fragmented in some juveniles with idiopathic scoliosis. This observation led us to investigate adults with disc degeneration. Immunoblotting analysis demonstrated that non-degenerate discs from three different age groups show no chondroadherin fragmentation. Furthermore, the chondroadherin fragments in adult degenerate disc and the juvenile scoliotic disc were compared via immunoblot analysis and appeared to have a similar size. We then investigated whether or not chondroadherin fragmentation increases with the severity of disc degeneration. Three different samples with different severities were chosen from the same disc, and chondroadherin fragmentation was found to be more abundant with increasing severity of degeneration. This observation led us to the creation of a neoepitope antibody to the cleavage site observed. We then observed that the cleavage site in adult degenerate discs and juvenile scoliotic discs was identical as confirmed by the neoepitope antibody. Consequently, investigation of the protease capable of cleaving chondroadherin at this site was necessary. In vitro digests of disc tissue demonstrated that ADAMTS-4 and -5; cathepsins K, B, and L; and MMP-3, -7, -12, and -13 were incapable of cleavage of chondroadherin at this site and that HTRA1 was indeed the only protease capable. Furthermore, increased protein levels of the processed form of HTRA1 were demonstrated in degenerate disc tissues via immunoblotting. The results suggest that chondroadherin fragmentation can be used as a biomarker to distinguish the processes of disc degeneration from normal aging. PMID:23673665

Akhatib, Bashar; Onnerfjord, Patrik; Gawri, Rahul; Ouellet, Jean; Jarzem, Peter; Heinegård, Dick; Mort, John; Roughley, Peter; Haglund, Lisbet

2013-06-28

32

Frontotemporal lobar degeneration: current perspectives  

PubMed Central

The term frontotemporal lobar degeneration (FTLD) refers to a group of progressive brain diseases, which preferentially involve the frontal and temporal lobes. Depending on the primary site of atrophy, the clinical manifestation is dominated by behavior alterations or impairment of language. The onset of symptoms usually occurs before the age of 60 years, and the mean survival from diagnosis varies between 3 and 10 years. The prevalence is estimated at 15 per 100,000 in the population aged between 45 and 65 years, which is similar to the prevalence of Alzheimer’s disease in this age group. There are two major clinical subtypes, behavioral-variant frontotemporal dementia and primary progressive aphasia. The neuropathology underlying the clinical syndromes is also heterogeneous. A common feature is the accumulation of certain neuronal proteins. Of these, the microtubule-associated protein tau (MAPT), the transactive response DNA-binding protein, and the fused in sarcoma protein are most important. Approximately 10% to 30% of FTLD shows an autosomal dominant pattern of inheritance, with mutations in the genes for MAPT, progranulin (GRN), and in the chromosome 9 open reading frame 72 (C9orf72) accounting for more than 80% of familial cases. Although significant advances have been made in recent years regarding diagnostic criteria, clinical assessment instruments, neuropsychological tests, cerebrospinal fluid biomarkers, and brain imaging techniques, the clinical diagnosis remains a challenge. To date, there is no specific pharmacological treatment for FTLD. Some evidence has been provided for serotonin reuptake inhibitors to reduce behavioral disturbances. No large-scale or high-quality studies have been conducted to determine the efficacy of non-pharmacological treatment approaches in FTLD. In view of the limited treatment options, caregiver education and support is currently the most important component of the clinical management. PMID:24600223

Riedl, Lina; Mackenzie, Ian R; Förstl, Hans; Kurz, Alexander; Diehl-Schmid, Janine

2014-01-01

33

Age-related macular degeneration  

PubMed Central

Age-related macular degeneration is the leading cause of blindness in elderly populations of European descent. The most consistent risk factors associated with this ocular condition are increasing age and cigarette smoking. Genetic investigations have shown that complement factor H, a regulator of the alternative complement pathway, and LOC387715/HtrA1 are the most consistent genetic risk factors for age-related macular degeneration. Although the pathogenesis of this disease is unknown, oxidative stress might have an important role. Treatment with antioxidant vitamins and zinc can reduce the risk of developing advanced age-related macular degeneration by about a quarter in those at least at moderate risk. Intravitreal injections of ranibizumab, a monoclonal antibody that inhibits all forms of vascular endothelial growth factor, have been shown to stabilise loss of vision and, in some cases, improve vision in individuals with neovascular age-related macular degeneration. These findings, combined with assessments of possible environmental and genetic interactions and new approaches to modulate inflammatory pathways, will hopefully further expand our ability to understand and treat age-related macular degeneration. PMID:19027484

Coleman, Hanna R; Chan, Chi-Chao; Ferris, Frederick L; Chew, Emily Y

2008-01-01

34

Age-related macular degeneration.  

PubMed

Age-related macular degeneration is the leading cause of blindness in elderly populations of European descent. The most consistent risk factors associated with this ocular condition are increasing age and cigarette smoking. Genetic investigations have shown that complement factor H, a regulator of the alternative complement pathway, and LOC387715/HtrA1 are the most consistent genetic risk factors for age-related macular degeneration. Although the pathogenesis of this disease is unknown, oxidative stress might have an important role. Treatment with antioxidant vitamins and zinc can reduce the risk of developing advanced age-related macular degeneration by about a quarter in those at least at moderate risk. Intravitreal injections of ranibizumab, a monoclonal antibody that inhibits all forms of vascular endothelial growth factor, have been shown to stabilise loss of vision and, in some cases, improve vision in individuals with neovascular age-related macular degeneration. These findings, combined with assessments of possible environmental and genetic interactions and new approaches to modulate inflammatory pathways, will hopefully further expand our ability to understand and treat age-related macular degeneration. PMID:19027484

Coleman, Hanna R; Chan, Chi-Chao; Ferris, Frederick L; Chew, Emily Y

2008-11-22

35

Axonal degeneration as a self-destructive defense mechanism against neurotropic virus infection  

PubMed Central

Theiler's murine encephalomyelitis virus (TMEV) and other neurotropic virus infections result in degeneration of each component of the neuron: apoptosis of the cell body, axonal (Wallerian) degeneration, and dendritic and synaptic pathology. In general, axonal degeneration is detrimental for hosts. However, axonal degeneration can be beneficial in the case of infection with neurotropic viruses that spread in the CNS using axonal transport. C57BL/WldS (WldS, Wallerian degeneration slow mutant) mice are protected from axonal degeneration. WldS mice infected with the neurovirulent GDVII strain of TMEV are more resistant to virus infection than wild-type mice, suggesting that axonal preservation contributes to the resistance. By contrast, infection with the less virulent Daniels strain of TMEV results in high levels of virus propagation in the CNS, suggesting that prolonged survival of axons in WldS mice favors virus spread. Thus, axonal degeneration might be a beneficial self-destruct mechanism that limits the spread of neurotropic viruses, in the case of less virulent virus infection. We hypothesize that neurons use ‘built-in’ self-destruct protection machinery (compartmental neurodegeneration) against neurotropic virus infection, since the CNS is an immunologically privileged site. Early induction of apoptosis in the neuronal cell body limits virus replication. Wallerian degeneration of the axon prevents axonal transport of virus. Dendritic and synaptic degeneration blocks virus transmission at synapses. Thus, the balance between neurodegeneration and virus propagation may be taken into account in the future design of neuroprotective therapy. PMID:19079794

Tsunoda, Ikuo

2008-01-01

36

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

37

Degeneration of the intervertebral disc  

Microsoft Academic Search

The intervertebral disc is a cartilaginous structure that resembles articular cartilage in its biochemistry, but morphologically it is clearly different. It shows degenerative and ageing changes earlier than does any other connective tissue in the body. It is believed to be important clinically because there is an association of disc degeneration with back pain. Current treatments are predominantly conservative or,

Jill PG Urban; Sally Roberts

2003-01-01

38

Gribov ambiguity and degenerate systems  

NASA Astrophysics Data System (ADS)

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

Canfora, Fabrizio; de Micheli, Fiorenza; Salgado-Rebolledo, Patricio; Zanelli, Jorge

2014-08-01

39

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

40

Standing Electromagnetic Solitons in Degenerate Relativistic Plasmas  

E-print Network

The existence of standing high frequency electromagnetic (EM) solitons in a fully degenerate overdense electron plasma is studied applying relativistic hydrodynamics and Maxwell equations. The stable soliton solutions are found in both relativistic and nonrelativistic degenerate plasmas.

Mikaberidze, G

2015-01-01

41

What Is Age-Related Macular Degeneration?  

MedlinePLUS

... regimen for dry macular degeneration . Using an Amsler grid to test for macular degeneration If you have ... you should use a chart called an Amsler grid every day to monitor your vision, as dry ...

42

Age-related macular degeneration.  

PubMed

Age-related macular degeneration (AMD) is a common and painless eye condition that is the leading cause of vision loss for people older than 50 years. Occupational and environmental health nurses can aid in slowing the progression of AMD by encouraging workers to have periodic eye examinations, maintain good health practices, and notify health care professionals if they notice blurred vision or blind spots in central vision. PMID:25093372

Randolph, Susan A

2014-08-01

43

A porous 4-fold-interpenetrated chiral framework exhibiting vapochromism, single-crystal-to-single-crystal solvent exchange, gas sorption, and a poisoning effect.  

PubMed

The synthesis and characterization of a 4-fold-interpenetrated pseudodiamond metal-organic framework (MOF), Co(II)(pybz)2·2DMF [pybz = 4-(4-pyridyl)benzoate], are reported. N,N-Dimethylformamide (DMF) of the channels can be removed to give the porous framework, and it can also be exchanged for methanol, ethanol, benzene, and cyclohexane. It is a rare example of a stable MOF based on a single octahedral building unit. The single-crystal structures of Co(II)(pybz)2·2DMF, Co(II)(pybz)2, Co(II)(pybz)2·4MeOH, and Co(II)(pybz)2·2.5EtOH have been successfully determined. In all of them, the framework is marginally modified and contains a highly distorted and strained octahedral node of cobalt with two pyridine nitrogen atoms and two chelate carboxylate groups. In air, the crystals of Co(II)(pybz)2·2DMF readily change color from claret red to light pink. Thermogravimetric analysis and Raman spectroscopy indicate a change in coordination, where the carboxylate becomes monodentate and an additional two water molecules are coordinated to each cobalt atom. In a dry solvent, this transformation does not take place. Tests show that Co(II)(pybz)2 may be a more efficient drying agent than silica gel and anhydrous CuSO4. The desolvated Co(II)(pybz)2 can absorb several gases such as CO2, N2, H2, and CH4 and also vapors of methanol, ethanol, benzene, and cyclohexane. If Co(II)(pybz)2 is exposed to air and followed by reactivation, its sorption capacity is considerably reduced, which we associate with a poisoning effect. Because of the long distance between the cobalt atoms in the structure, the magnetic properties are those of a paramagnet. PMID:23398593

Zeng, Ming-Hua; Tan, Yan-Xi; He, Yan-Ping; Yin, Zheng; Chen, Qing; Kurmoo, Mohamedally

2013-03-01

44

General Pathophysiology in Retinal Degeneration  

PubMed Central

Retinal degeneration, including that seen in age-related macular degeneration and retinitis pigmentosa (RP), is the most common form of neural degenerative disease in the world. There is great genetic and allelic heterogeneity of the various retinal dystrophies. Classifications of these diseases can be ambiguous, as there are similar clinical presentations in retinal degenerations arising from different genetic mechanisms. As would be expected, alterations in the activity of the phototransduction cascade, such as changes affecting the renewal and shedding of the photoreceptor OS, visual transduction, and/ or retinol metabolism have a great impact on the health of the retina. Mutations within any of the molecules responsible for these visual processes cause several types of retinal and retinal pigment epithelium degenerative diseases. Apoptosis has been implicated in the rod cell loss seen in a mouse model of RP, but the precise mechanisms that connect the activation of these pathways to the loss of phosphodiesterase (PDE6?) function has yet to be defined. Additionally, the activation of apoptosis by CCAAT/-enhancer-binding protein homologous protein (CHOP), after activation of the unfolded protein response pathway, may be responsible for cell death, although the mechanism remains unknown. However, the mechanisms of cell death after loss of function of PDE6, which is a commonly studied mammalian model in research, may be generalizable to loss of function of different key proteins involved in the phototransduction cascade. PMID:24732759

Wert, Katherine J.; Lin, Jonathan H.; Tsang, Stephen H.

2015-01-01

45

Radial keratotomy associated endothelial degeneration  

PubMed Central

Purpose To describe the presentation and clinical course of eyes with a history of radial keratotomy (RK) and varying degrees of endothelial degeneration. Methods Retrospective case series were used. Results Thirteen eyes (seven patients) were identified with clinical findings of significant guttata and a prior history of RK. The mean age of presentation for cornea evaluation was 54.3 years (range: 38–72 years), averaging 18.7 years (range: 11–33 years) after RK. The presentation of guttata varied in degree from moderate to severe. Best corrected visual acuity (BCVA) ranged from 20/25 to 20/80. All patients had a history of bilateral RK, except one patient who did not develop any guttata in the eye without prior RK. No patients reported a family history of Fuch’s Dystrophy. One patient underwent a penetrating keratoplasty in one eye and a Descemet’s stripping automated endothelial keratoplasty (DSAEK) in the other eye. Conclusions RK may induce a spectrum of endothelial degeneration. In elderly patients, the findings of guttata may signify comorbid Fuch’s dystrophy in which RK incisions could potentially hasten endothelial decomposition. In these select patients with stable cornea topography and prior RK, DSAEK may successfully treat RK endothelial degeneration. PMID:22347792

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

2012-01-01

46

Light scattering of degenerate fermions  

NASA Astrophysics Data System (ADS)

We report on progress in measuring the suppression of resonant light scattering in a gas of degenerate fermions. A gas of trapped degenerate fermions is expected to exhibit narrower optical linewidths and longer excited state lifetimes than single atoms when the Fermi energy is larger than the photon recoil energy [1-3]. In this case, the number of available states into which a scattered atom can recoil is significantly reduced due to the filling of the Fermi sea. We produce a degenerate gas of 4x10^4 ultra-cold fermionic ^40K atoms by sympathetic cooling with bosonic ^87Rb in a micro-magnetic chip trap. The atoms can then be loaded into a tight dipole trap just above the surface of the chip and probed with a near resonance laser pulse. [1] Th. Busch, J. R. Anglin, J. I. Cirac, and P. Zoller, Europhys. Lett. 44, 1 (1998). [2] B. DeMarco and D. S. Jin, Phys. Rev. A 58, R4267 (1998). [3] J. Javanainen and J. Ruostekosky, Phys. Rev. A 52, 3033 (1995). Work supported by NSERC, CFI, OIT, Research Corporation, and PRO.

Aubin, S.; Leblanc, L. J.; Myrskog, S.; Extavour, M. H. T.; McKay, D.; Stummer, A.; Thywissen, J. H.

2006-05-01

47

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

48

Degeneration behaviour of the cochlear nerve  

Microsoft Academic Search

On the basis of the degeneration behaviour two different types of cochlear afferent neurons can be distinguished. About 95% of all cochlear neurons are of the common type I with large myelinated spiral ganglion cells. They show complete retrograde degeneration after transsection of the cochlear nerve and they are exclusively connected to the inner hair cells. The remaining 5% neurons

H. Spoendlin

1971-01-01

49

Degenerate Adiabatic Perturbation Theory: Foundations and Applications  

E-print Network

We present details and expand on the framework leading to the recently introduced degenerate adiabatic perturbation theory [Phys. Rev. Lett. 104, 170406 (2010)], and on the formulation of the degenerate adiabatic theorem, along with its necessary and sufficient conditions given in [Phys. Rev. A 85, 062111 (2012)]. 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 non-exactly-solvable Hamiltonians whose solutions are numerically computed.

Gustavo Rigolin; Gerardo Ortiz

2014-08-07

50

Degenerate scale for multiply connected Laplace problems  

Microsoft Academic Search

The degenerate scale in the boundary integral equation (BIE) or boundary element method (BEM) solution of multiply connected problem is studied in this paper. For the mathematical analysis, we use the null-field integral equation, degenerate kernels and Fourier series to examine the solvability of BIE for multiply connected problem in the discrete system. Two treatments, the method of adding a

Jeng-Tzong Chen; Wen-Cheng Shen

2007-01-01

51

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

52

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

53

Molecular Therapy for Disk Degeneration and Pain  

PubMed Central

The nucleus pulposus of the intervertebral disk contains high amounts of the proteoglycan aggrecan, which confers the disk with a remarkable ability to resist compression. Other molecules such as collagens and noncollagenous proteins in the extracellular matrix are also essential for function. During disk degeneration, aggrecan and other molecules are lost due to proteolysis. This can result in loss of disk height, which can ultimately lead to pain. Biological therapy of intervertebral disk degeneration aims at preventing or restoring primarily aggrecan content and other molecules using therapeutic molecules. The purpose of the article is to review recent advances in biological repair of degenerate disks and pain. PMID:24436869

Mwale, Fackson

2013-01-01

54

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

55

Malignant degeneration in burn scars.  

PubMed

The malignant potential of burn scars has been recognized since Marjolin's classical description of cancer arising in several types of post-traumatic scars. With improved burn therapy since the last war, there has been a higher survival rate of severe burns with proportionate increase in cancer associated with burn scars. This will create increasing problems of permanent disability and compensation. The younger the patient at the time of the burn, the longer the time required for the cancer to develop. Acute cancer development in burn scars has been reported after a four-week interval. Cancer may develop from six weeks to fifty years or more. The etiology of cancer in burn scars is not known. The most important clinical finding is the fact that most of the burn cancers occur in areas which were not grafted. The most common type of cancer encountered in burn scars is squamous cell carcinoma, which forms in Marjolin ulcers. Basal cell carcinoma may develop in the most superficial of burn scars.Treatment should be directed primarily to prompt and adequate skin grafting in all deep burns in order to prevent malignant degeneration of the burn scars. Once it has developed the treatment is the same as for other malignancies which are not associated with burns. Wide surgical excision with block dissection of the regional lymph nodes when they are involved is the treatment of choice. The prognosis of burn scar cancer is poor, once the process has extended because of early and distant metastasis. PMID:13691372

CASTANARES, S

1961-03-01

56

[Spongiform encephalopathy and multisystemic degeneration].  

PubMed

Onset of a neurological disease was coincidental in two members of a family. The mother died at the age of 57 and her daughter at the age of 27 years. Clinically the disease was manifested by cerebellar ataxia, visual disturbances, dystonic movements and intellectual impairment which appeared very later in the course of the disease in the younger patient. Myoclonus was only observed in the mother. The EEG examination revealed non-specific abnormalities. CT scans disclosed severe cerebellar atrophy and reduced size of the pons in the daughter. The duration of the disease was 7 months in the mother and 3 years in her daughter. The neuropathological examination showed degeneration of the thalamus, substantia nigra and inferior olives, together with loss of Purkinje cells and axonal torpedos in the granular layer of the mother. Olivopontocerebellar atrophy, atrophy of the thalamus and substantia nigra, associated to typical spongiform encephalopathy of the cerebral cortex, amygdaloid complex and striatum occurred in the daughter. These observations let us to comment whether multisystemic atrophies may be fortuitously associated to different prion-induced encephalopathies, or may be found in the context of spongiform encephalopathies. PMID:1863455

Ferrer, I; Saracibar, N; González, G

1991-01-01

57

Mouse models for cone degeneration.  

PubMed

Loss of cone vision has devastating effects on everyday life. Even though much effort has been made to understand cone physiology and pathophysiology, no successful therapies are available for patients suffering from cone disorders. As complex retinal interactions cannot be studied in vitro, utilization of different animal models is inevitable. Due to recent advances in transgenesis, mice became the most popular animal model to study human diseases, also in ophthalmology. While there are similarities in retinal anatomy and pathophysiology between mice and humans, there are also differences, most importantly the lack of a cone-rich macula in mice. Instead, cones in mice are rare and distributed over the whole retina, which makes the analysis of cone pathophysiology very difficult in these animals. This hindrance is one of the reasons why our understanding of rod pathophysiological processes is much more advanced. Recently, however, the sparseness of cones was overcome by the generation of the Nrl (- / -) mouse that expresses only cone photoreceptors in the retina. This paper will give a brief overview of some of the known mouse models to study cone degeneration and discuss the current knowledge gained from the analysis of these models. PMID:24664745

Samardzija, Marijana; Grimm, Christian

2014-01-01

58

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

59

fREDUCE: Detection of degenerate regulatory elements using correlation with expression  

PubMed Central

Background The precision of transcriptional regulation is made possible by the specificity of physical interactions between transcription factors and their cognate binding sites on DNA. A major challenge is to decipher transcription factor binding sites from sequence and functional genomic data using computational means. While current methods can detect strong binding sites, they are less sensitive to degenerate motifs. Results We present fREDUCE, a computational method specialized for the detection of weak or degenerate binding motifs from gene expression or ChIP-chip data. fREDUCE is built upon the widely applied program REDUCE, which elicits motifs by global statistical correlation of motif counts with expression data. fREDUCE introduces several algorithmic refinements that allow efficient exhaustive searches of oligonucleotides with a specified number of degenerate IUPAC symbols. On yeast ChIP-chip benchmarks, fREDUCE correctly identified motifs and their degeneracies with accuracies greater than its predecessor REDUCE as well as other known motif-finding programs. We have also used fREDUCE to make novel motif predictions for transcription factors with poorly characterized binding sites. Conclusion We demonstrate that fREDUCE is a valuable tool for the prediction of degenerate transcription factor binding sites, especially from array datasets with weak signals that may elude other motif detection methods. PMID:17941998

Wu, Randy Z; Chaivorapol, Christina; Zheng, Jiashun; Li, Hao; Liang, Shoudan

2007-01-01

60

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

61

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

62

Mucoid degeneration of the anterior cruciate ligament  

Microsoft Academic Search

Mucoid degeneration of the anterior cruciate ligament (ACL) is a rare cause of knee pain. We report a case of a patient with\\u000a mucoid degeneration of the ACL, presenting with posterior knee pain and no history of a major knee trauma. On clinical examination,\\u000a the active range of motion showed a flexion deficit. The posterior knee pain was induced by

Robrecht Motmans; Frank Verheyden

2009-01-01

63

MALIGNANT DEGENERATION IN BURN SCARS  

PubMed Central

The malignant potential of burn scars has been recognized since Marjolin's classical description of cancer arising in several types of post-traumatic scars. With improved burn therapy since the last war, there has been a higher survival rate of severe burns with proportionate increase in cancer associated with burn scars. This will create increasing problems of permanent disability and compensation. The younger the patient at the time of the burn, the longer the time required for the cancer to develop. Acute cancer development in burn scars has been reported after a four-week interval. Cancer may develop from six weeks to fifty years or more. The etiology of cancer in burn scars is not known. The most important clinical finding is the fact that most of the burn cancers occur in areas which were not grafted. The most common type of cancer encountered in burn scars is squamous cell carcinoma, which forms in Marjolin ulcers. Basal cell carcinoma may develop in the most superficial of burn scars. Treatment should be directed primarily to prompt and adequate skin grafting in all deep burns in order to prevent malignant degeneration of the burn scars. Once it has developed the treatment is the same as for other malignancies which are not associated with burns. Wide surgical excision with block dissection of the regional lymph nodes when they are involved is the treatment of choice. The prognosis of burn scar cancer is poor, once the process has extended because of early and distant metastasis. ImagesFigure 1.Figure 2.Figure 2.Figure 3.Figure 3.Figure 4. PMID:13691372

Castañares, Salvador

1961-01-01

64

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

65

Analytical study and numerical experiments for degenerate scale problems in boundary element method using degenerate kernels and circulants  

Microsoft Academic Search

For a potential problem, the boundary integral equation approach has been shown to yield a nonunique solution when the geometry is equal to a degenerate scale. In this paper, the degenerate scale problem in boundary element method (BEM) is analytically studied using the degenerate kernels and circulants. For the circular domain problem, the singular problem of the degenerate scale with

J. T. Chen; J. H. Lin; S. R. Kuo; Y. P. Chiu

2001-01-01

66

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

67

Optic pathway degeneration in Japanese black cattle  

PubMed Central

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

2014-01-01

68

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

69

A Caspase Cascade Regulating Developmental Axon Degeneration  

PubMed Central

Axon degeneration initiated by trophic factor withdrawal shares many features with programmed cell death, but many prior studies discounted a role for caspases in this process, particularly Caspase-3. Recently, Caspase-6 was implicated based on pharmacological and knockdown evidence, and we report here that genetic deletion of Caspase-6 indeed provides partial protection from degeneration. However, we find at a biochemical level that Caspase-6 is activated effectively only by Caspase-3 but not other “upstream” caspases, prompting us to revisit the role of Caspase-3. In vitro, we show that genetic deletion of Caspase-3 is fully protective against sensory axon degeneration initiated by trophic factor withdrawal, but not injury-induced Wallerian degeneration, and we define a biochemical cascade from pro-survival Bcl2 family regulators to Caspase-9, then Caspase-3, and then Caspase-6. Only low levels of active Caspase-3 appear to be required, helping explain why its critical role has been obscured in prior studies. In vivo, Caspase-3 and Caspase-6 knockout mice show a delay in developmental pruning of retinocollicular axons, thereby implicating both Caspase-3 and Caspase-6 in axon degeneration that occurs as a part of normal development. PMID:23223278

Simon, David J.; Weimer, Robby M.; McLaughlin, Todd; Kallop, Dara; Stanger, Karen; Yang, Jing; O’Leary, Dennis D.M.; Hannoush, Rami N.; Tessier-Lavigne, Marc

2012-01-01

70

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

2015-03-01

71

Perineurial permeability to sodium during Wallerian degeneration in rat sciatic nerve.  

PubMed

In rat sciatic nerves, the effect of Wallerian degeneration on the rate of transperineurial passage of sodium between the endoneurium and the epineurial extracellular space was investigated. In nerves transected and ligated at the sciatic notch, an in situ technique was used to measure the permeability coefficient-surface area product (PS) of the mid-thigh portion of the perineurium to 22Na. Sampling times ranged from one day to sixteen weeks after the lesion. Additionally, endoneurial water content (an indicator of nerve edema) was also measured in transected, degenerating nerves at the same sampling times. Endoneurial water content increased significantly by the fourth day after transection, peaked at four weeks, and then remained elevated through 16 weeks of post-lesion measurement. The PS of the perineurium to 22Na on the 4th day after transection was significantly greater than that of control animals. This increase then declined to normal levels through the 2nd week, and finally increased to values that were 3-fold to 4-fold of control values for the remainder of the observation period. The earlier, short lasting increase in perineurial PS is probably associated with the inflammatory response to nerve section, and proliferation of perineurial layers and cells. The later increase in perineurial permeability is proposed to play a role in the dissipation of endoneurial hydrostatic pressure and clearance of myelin debris from the endoneurium. In view of the complex changes in perineurial permeability described herein, it would seem inappropriate to consider these phenomena merely as passive breakdowns of the barrier properties of the perineurium. PMID:1466671

Weerasuriya, A; Hockman, C H

1992-05-29

72

Malignant degeneration of multilevel monostotic Paget's disease involving the thoracic spine: an unusual presentation.  

PubMed

Paget's disease is the second most common metabolic bone disease after osteoporosis and is characterized by abnormal bone turnover and remodeling that can lead to pain, pathological fracture, bony deformity and nerve compression syndromes. The lumbar region is the most commonly affected site within the spine followed by the thoracic and cervical spine. Even though the spine is affected very commonly in Paget's disease, malignant degeneration is exceptionally rare. Multilevel monostotic spine involvement due to Paget's disease is very uncommon. An unusual clinico-radiological manifestation of multilevel thoracic Paget's disease with sarcomatous degeneration presenting as a neurosurgical emergency is reported with a pertinent review of the literature. PMID:24411323

Tan, Lee A; Kasliwal, Manish K; Harbhajanka, Aparna; Miller, Ira J; Deutsch, Harel

2014-07-01

73

Retinal degeneration and local oxygen metabolism.  

PubMed

Vision loss due to various forms of outer retinal degeneration remains a major problem in clinical ophthalmology. Most retinal degenerations are precipitated by genetic mutations affecting the retinal pigment epithelium and sensory retina, but it is becoming increasingly evident that resultant metabolic changes within the retina may also contribute to the further progression of photoreceptor cell loss. In particular, a role for the local oxygen environment within the retina has been proposed. The correct balance between retinal oxygen supply and oxygen consumption in the retina is essential for retinal homeostasis, and disruption of this balance is a factor in many retinal diseases. In animal models of photoreceptor degeneration, manipulation of environmental oxygen levels has been reported to be able to modulate the rate of photoreceptor degeneration. Clinically, hyperbaric oxygen therapy has already been used in retinitis pigmentosa patients and other types of oxygen therapy have been proposed. It therefore seems appropriate to review our current understanding of the oxygen environment in the normal and degenerating retina, and to build a clearer picture of how the retinal oxygen environment can be modulated. We focus on techniques that have been, or may be, applied clinically, such as modulation of systemic oxygen levels and modulation of retinal oxygen metabolism by light deprivation. Data from direct measurements of intraretinal oxygen distribution in rat models at different stages of photoreceptor degeneration will be reviewed. These models include the Royal College of Surgeons (RCS) rat, and the P23H rat model of outer retinal degeneration. Microelectrode based techniques have allowed the intraretinal oxygen distribution to be measured as a function of retinal depth under well-controlled systemic conditions at different stages of the degeneration process. Both models showed changes in the intraretinal oxygen distribution during the degenerative period, with the changes reflecting the gradual loss of oxygen metabolism of the degenerating photoreceptors. This results in higher than normal oxygen levels in the remaining outer retina and a significant alteration in the oxygen flux from the choroid to the inner retina. The maintenance of normal oxygen levels in the inner retina implies that inner retinal oxygen uptake is well preserved, and that there is also reduced oxygen input from the deeper capillary layer of the retinal circulation. Choroidal oxygen tension and the oxygen tension in the pre-retinal vitreous were unaffected at any of the time periods studied prior to, and during, the degeneration process. It is well known that both hypoxia and hyperoxia can cause neural cell stress and damage. Logically, any therapeutic intervention based on oxygen therapy should attempt to restore the oxygen environment of the remaining retinal cells to within the physiological range. Before any oxygen based therapies for the treatment of retinal degeneration should be seriously considered, the oxygen environment in the degenerating retina should be determined, along with clinically usable methods to restore the oxygen environment to the critical cell layers. PMID:15939030

Yu, Dao-Yi; Cringle, Stephen J

2005-06-01

74

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

2006-12-23

75

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

76

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

77

Ion acoustic shock waves in degenerate plasmas  

SciTech Connect

Korteweg de Vries Burgers equation for negative ion degenerate dissipative plasma has been derived using reductive perturbation technique. The quantum hydrodynamic model is used to study the quantum ion acoustic shock waves. The effects of different parameters on quantum ion acoustic shock waves are studied. It is found that quantum parameter, electrons Fermi temperature, temperature of positive and negative ions, mass ratio of positive to negative ions, viscosity, and density ratio have significant impact on the shock wave structure in negative ion degenerate plasma.

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

2011-07-15

78

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

79

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

80

Further studies of degenerative hip disease; antitrochanteric degeneration in turkeys and broiler type chickens.  

PubMed

Postmortem examination revealed antitrochanteric degeneration in turkeys (8 male, 2 female) and broiler type chickens (5 male, 1 female). Antitrochanteric degeneration was detected in birds aged 20 weeks or older but histological examination identified lesions in others with grossly normal antitrochanters. Normal and abnormal antitrochanteric development was studied in male, skeletally immature, turkeys and broilers. Differential subchondral bone growth occurred, with relatively delayed ilial bone development. As a result, hyaline cartilage was retained dorsally and persisted even in adult birds. Retained hyaline, and in younger birds growth plate, cartilage was prone to osteochondrosis. When cartilage flap formation involved fissures traversing retained hyaline cartilage, the term osteochondrosis dissecans was appropriate. In other cases of antitrochanteric degeneration, changes typical of osteoarthrosis were present with, in some instances, no evidence of pre-existing osteochondrosis. Certain sites of antitrochanteric cartilage may be susceptible to fatigue failure in these cases. PMID:3973105

Duff, S R

1985-01-01

81

Alzheimer neurofibrillary degeneration: significance, etiopathogenesis, therapeutics and prevention  

PubMed Central

Alzheimer disease (AD) is multi-factorial and heterogeneous. Independent of the aetiology, this disease is characterized clinically by chronic and progressive dementia and histopathologically by neurofibrillary degeneration of abnormally hyperphosphorylated tau seen as intraneuronal neurofibrillary tangles, neuropil threads and dystrophic neurites, and by neuritic (senile) plaques of ?-amyloid. The neurofibrillary degeneration is apparently required for the clinical expression of AD, and in related tauopathies it leads to dementia in the absence of amyloid plaques. While normal tau promotes assembly and stabilizes microtubules, the abnormally hyperphosphorylated tau sequesters normal tau, MAP1 and MAP2, and disrupts microtubules. The abnormal hyperphosphorylation of tau also promotes its self-assembly into tangles of paired helical and or straight filaments. Tau is phosphorylated by a number of protein kinases. Glycogen synthase kinase-3 (GSK-3) and cyclin dependent protein kinase 5 (cdk5) are among the kinases most implicated in the abnormal hyperphosphorylation of tau. Among the phosphatases which regulate the phosphorylation of tau, protein phosphatase-2A (PP-2A), the activity of which is down-regulated in AD brain, is by far the major enzyme. The inhibition of abnormal hyperphosphorylation of tau is one of the most promising therapeutic targets for the development of disease modifying drugs. A great advantage of inhibiting neurofibrillary degeneration is that it can be monitored by evaluating the levels of total tau and tau phosphorylated at various known abnormally hyperphosphorylated sites in the cerebrospinal fluid of patients, obtained by lumbar puncture. There are at least five subgroups of AD, each is probably caused by a different etiopathogenic mechanism. The AD subgroup identification of patients can help increase the success of clinical trials and the development of specific and potent disease modifying drugs. PMID:18194444

Iqbal, K.; Grundke-Iqbal, I.

2011-01-01

82

Cellular localization of cerebellar muscarinic receptors: an autoradiographic analysis of weaver, reeler, Purkinje cell degeneration and staggerer mice  

SciTech Connect

Light microscopic autoradiography of (/sup 3/H)quinuclidinyl benzilate binding sites was used to study the distribution of muscarinic cholinergic receptors in mouse mutants which have abnormalities affecting specific cerebellar cell types. In the normal C57BL/6J mouse, binding sites were distributed throughout the cerebellar cortex, with the highest levels in the granule cell layer and deep cerebellar nuclei. Normal binding site density was observed in the cerebellum of the weaver mutant in which the majority of granule cells had degenerated. The density of (/sup 3/H)quinuclidinyl benzilate binding sites was elevated in the cortex of the reeler, despite a reduction in the number of granule cells. The concentration of binding sites was also high over the Purkinje cell masses where granule cells were largely absent. No significant reduction in cortical (/sup 3/H)quinuclidinyl benzilate binding site density was detected in the Purkinje cell degeneration mutant, in which essentially all Purkinje cells had degenerated. In contrast, receptor binding in the deep cerebellar nuclei of this mutant was significantly increased. A substantial increase in labeling was observed in the cortex and deep nuclei of the staggerer cerebellum in which a large fraction of Golgi II cells, Purkinje cells, granule cells and mossy fibers have degenerated. We discuss the possibility that the persistence of (/sup 3/H)quinuclidinyl benzilate binding sites in all four mutants may imply a non-neuronal localization for a large proportion of muscarinic receptors in the mouse cerebellar cortex.

Neustadt, A.; Frostholm, A.; Rotter, A.

1988-02-01

83

Superfluid regimes in degenerate atomic Fermi gases  

SciTech Connect

We give a brief overview of recent studies of quantum degenerate regimes in ultracold Fermi gases. The attention is focused on the regime of Bose-Einstein condensation of weakly bound molecules of fermionic atoms, formed at a large positive scattering length for the interspecies atom-atom interaction. We analyze remarkable collisional stability of these molecules and draw prospects for future studies.

Shlyapnikov, G.V. [Laboratoire Physique Theorique et Modeles Statistique, Universite Paris Sud, Bat. 100, 91405 Orsay (France); Van der Waals-Zeeman Institute, University of Amsterdam, Valckenierstraat 65/67, 1018 XEAmsterdam (Netherlands)

2005-05-05

84

Depression in Age-Related Macular Degeneration  

ERIC Educational Resources Information Center

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

Casten, Robin; Rovner, Barry

2008-01-01

85

Degenerate Monge-Ampere equations over projective manifolds  

E-print Network

In this thesis, we study degenerate Monge-Ampere equations over projective manifolds. The main degeneration is on the cohomology class which is Kähler in classic cases. Our main results concern the case when this class is ...

Zhang, Zhou, Ph. D. Massachusetts Institute of Technology

2006-01-01

86

Time course of degeneration of short and long postganglionic sympathetic nerve fibres and effect of pentobarbitone and colchicine on degeneration  

PubMed Central

1 The time-course of degeneration of sympathetic nerves was investigated by measurement of the endogenous noradrenaline content of the rat vas deferens, submandibular gland and spleen following sympathectomy. 2 Extirpation of the hypogastric plexus, superior cervical ganglion and coeliac plexus under pentobarbitone anaesthesia caused 50% depletion of the noradrenaline content of the vas deferens, submandibular gland and spleen in approximately 16, 19 and 21 h, respectively. 3 Under pentobarbitone anaesthesia, proximal sympathectomy (i.e., close to the end organ) produced depletion of the noradrenaline content of the submandibular gland 8 h earlier than that caused by distal sympathectomy. Under ether anaesthesia, the time difference in obtaining the same degree of depletion after the two procedures of sympathectomy was only 2 hours. 4 Removal of the superior cervical ganglion under ether anaesthesia resulted in almost complete depletion of noradrenaline content of the submandibular gland in 17 h, whereas when a similar operation was performed under pentobarbitone anaesthesia, nearly 24 h were required for the same degree of depletion. Similarly, the noradrenaline content of the spleen was depleted 4 h earlier if the coeliac plexus was ablated under ether as compared to pentobarbitone anaesthesia. 5 Local application of colchicine (10 mg/ml, 30 min) to postganglionic sympathetic nerve axons had no effect on the noradrenaline content of the submandibular gland up to 24 hours. However, removal of the superior ganglion following colchicine application considerably slowed the depletion of the noradrenaline content of the submandibular gland (at 17 and 20 h after ganglionectomy, 10 and 20% depletion, respectively, in the experimental gland, as compared to 70 and 80%, respectively, in the control gland). 6 To explain the results, it is proposed that injury to the sympathetic nerves at the site of sectioning triggers a signal (messenger substance) which travels down to the nerve endings to produce degeneration. Thus, the length of the extrinsic nerve fibre influences the time course of degeneration by changing the rate of transport of the messenger substance, whereas pentobarbitone and colchicine alter the synthesis and/or transport of the messenger substance to modify the time-course of degeneration. PMID:656699

Wakade, Arun R.

1978-01-01

87

The cell biology of intervertebral disc aging and degeneration  

Microsoft Academic Search

Intervertebral disc degeneration, which mimics disc aging but occurs at an accelerated rate, is considered to be related to neck or low back pain and disc herniation. Degenerated discs show breakdown of the extracellular matrix and thus fail to bear the daily loadings exerted on the spine. Rather than a passive process of wear and tear, disc degeneration is an

Chang-Qing Zhao; Li-Min Wang; Lei-Sheng Jiang; Li-Yang Dai

2007-01-01

88

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

89

Bounded search for de novo identification of degenerate cis-regulatory elements  

PubMed Central

Background The identification of statistically overrepresented sequences in the upstream regions of coregulated genes should theoretically permit the identification of potential cis-regulatory elements. However, in practice many cis-regulatory elements are highly degenerate, precluding the use of an exhaustive word-counting strategy for their identification. While numerous methods exist for inferring base distributions using a position weight matrix, recent studies suggest that the independence assumptions inherent in the model, as well as the inability to reach a global optimum, limit this approach. Results In this paper, we report PRISM, a degenerate motif finder that leverages the relationship between the statistical significance of a set of binding sites and that of the individual binding sites. PRISM first identifies overrepresented, non-degenerate consensus motifs, then iteratively relaxes each one into a high-scoring degenerate motif. This approach requires no tunable parameters, thereby lending itself to unbiased performance comparisons. We therefore compare PRISM's performance against nine popular motif finders on 28 well-characterized S. cerevisiae regulons. PRISM consistently outperforms all other programs. Finally, we use PRISM to predict the binding sites of uncharacterized regulons. Our results support a proposed mechanism of action for the yeast cell-cycle transcription factor Stb1, whose binding site has not been determined experimentally. Conclusion The relationship between statistical measures of the binding sites and the set as a whole leads to a simple means of identifying the diverse range of cis-regulatory elements to which a protein binds. This approach leverages the advantages of word-counting, in that position dependencies are implicitly accounted for and local optima are more easily avoided. While we sacrifice guaranteed optimality to prevent the exponential blowup of exhaustive search, we prove that the error is bounded and experimentally show that the performance is superior to other methods. A Java implementation of this algorithm can be downloaded from our web server at . PMID:16700920

Carlson, Jonathan M; Chakravarty, Arijit; Khetani, Radhika S; Gross, Robert H

2006-01-01

90

Inflammation in intervertebral disc degeneration and regeneration  

PubMed Central

Intervertebral disc (IVD) degeneration is one of the major causes of low back pain, a problem with a heavy economic burden, which has been increasing in prevalence as populations age. Deeper knowledge of the complex spatial and temporal orchestration of cellular interactions and extracellular matrix remodelling is critical to improve current IVD therapies, which have so far proved unsatisfactory. Inflammation has been correlated with degenerative disc disease but its role in discogenic pain and hernia regression remains controversial. The inflammatory response may be involved in the onset of disease, but it is also crucial in maintaining tissue homeostasis. Furthermore, if properly balanced it may contribute to tissue repair/regeneration as has already been demonstrated in other tissues. In this review, we focus on how inflammation has been associated with IVD degeneration by describing observational and in vitro studies as well as in vivo animal models. Finally, we provide an overview of IVD regenerative therapies that target key inflammatory players. PMID:25673296

Molinos, Maria; Almeida, Catarina R.; Caldeira, Joana; Cunha, Carla; Gonçalves, Raquel M.; Barbosa, Mário A.

2015-01-01

91

Macular degeneration in an arc welder.  

PubMed

A male welder who had been working in an industrial machine plant for more than 20 years experienced acute intense pain in his left eye with continuous lacrimation while performing arc welding in 1997. Later in 1997, at the age of 39 yr, macular edema was found in his left eye. He was diagnosed with macular degeneration (MD) of the left eye in 2002, and with right eye MD in 2004. Radiation in the visible and near infrared (IR) spectra penetrates the eye and is absorbed by the retina, possibly causing thermal or photochemical damage. Such retinal damage may be permanent and, therefore, sight-threatening. The young age and history of an acute painful eye injury are not consistent with age related macular degeneration (AMD) but rather is likely maculopathy caused by welding arc exposure. PMID:17485886

Kim, Eun A; Kim, Byung-Gyu; Yi, Cheol-Ho; Kim, Il Gon; Chae, Chang-Ho; Kang, Seong-Kyu

2007-04-01

92

Inflammation in intervertebral disc degeneration and regeneration.  

PubMed

Intervertebral disc (IVD) degeneration is one of the major causes of low back pain, a problem with a heavy economic burden, which has been increasing in prevalence as populations age. Deeper knowledge of the complex spatial and temporal orchestration of cellular interactions and extracellular matrix remodelling is critical to improve current IVD therapies, which have so far proved unsatisfactory. Inflammation has been correlated with degenerative disc disease but its role in discogenic pain and hernia regression remains controversial. The inflammatory response may be involved in the onset of disease, but it is also crucial in maintaining tissue homeostasis. Furthermore, if properly balanced it may contribute to tissue repair/regeneration as has already been demonstrated in other tissues. In this review, we focus on how inflammation has been associated with IVD degeneration by describing observational and in vitro studies as well as in vivo animal models. Finally, we provide an overview of IVD regenerative therapies that target key inflammatory players. PMID:25673296

Molinos, Maria; Almeida, Catarina R; Caldeira, Joana; Cunha, Carla; Gonçalves, Raquel M; Barbosa, Mário A

2015-03-01

93

Paraneoplastic cerebellar degeneration heralding fallopian tube adenocarcinoma.  

PubMed

The objective of this paper is to describe an 81-year-old woman with subacute cerebellar degeneration due to fallopian tube adenocarcinoma. Serum anti-Yo antibodies were used to screen for pelvic malignancy. Their presence led to a meticulous search, which included bilateral salpingoophorectomy. Subsequently an occult fallopian tube adenocarcinoma was discovered. This case report highlights the diagnostic value of antineuroneal antibodies in females with subacute neurologic impairment in the form of paraneoplastic syndrome. PMID:11328418

Levite, R; Fishman, A; Kesler, A; Altaras, M; Gadoth, N

2001-01-01

94

Tunable Interactions in Quantum Degenerate Lithium  

NASA Astrophysics Data System (ADS)

Quantum degenerate gases provide an ideal environment for studying fundamental physics. In these systems, a Feshbach resonance can be utilized to tune the interactions between certain colliding pairs of atoms, yielding control over both the magnitude and sign of the interactions. This has opened the doorway to a new area in which the underlying physics of non-linear optical phenomena and many solid-state effects can be explored in the ideal environment of a quantum degenerate gas. We will first discuss the experimental realization of a quantum degenerate Bose-Fermi mixture via sympathetic cooling [truscott01]. By confining this quantum degenerate gas in an all optical potential, the atom-atom interactions of the bosons can be manipulated to produce bright matter-wave solitons [strecker02] which are individual Bose-Einstein condensates (BEC) that we have observed to propagate for over 3 seconds without dispersion. Further, a highly interacting Fermi gas can be produced near a Feshbach resonance, and through manipulation of the external magnetic field, long lived ultra-cold bosonic molecules can be formed from the Fermi gas [strecker03]. The unexpected long lifetime of these vibrationally excited (v' = 38) molecules enables them to be evaporatively cooled to a molecular BEC. We use a pure molecular condensate as a probe of the BEC/BCS crossover region within the broad Feshbach resonance. Using an interrogation laser tuned to a bound-bound molecular resonance, the deeply bound molecular component of the gas is measured as a function of magnetic field, probing the fundamental many-body physics of a strongly interacting Fermi gas. [truscott01] A. G. Truscott, K. E. Strecker, W. I. McAlexander, G. B. Patridge, and R. G. Hulet, Science 291, 2570 (2001). [strecker02] K. E. Strecker, G. B. Partridge, A. G. Truscott, and R.G Hulet, Nature 417, 150 (2002). [strecker03] K. E. Strecker, G. B. Partridge and R. G. Hulet, Phys Rev. Lett. 91, 080406 (2003).

Strecker, Kevin

2005-05-01

95

Recombination-generation currents in degenerate semiconductors  

NASA Technical Reports Server (NTRS)

The classical Shockley-Read-Hall theory of free carrier recombination and generation via traps is extended to degenerate semiconductors. A concise and simple expression is found which avoids completely the concept of a Fermi level, a concept which is alien to nonequilibrium situations. Assumptions made in deriving the recombination generation current are carefully delineated and are found to be basically identical to those made in the original theory applicable to nondegenerate semiconductors.

Von Roos, O.

1978-01-01

96

Effect of trapping in degenerate quantum plasmas  

SciTech Connect

In the present work we consider the effect of trapping as a microscopic process in a plasma consisting of quantum electrons and nondegenerate ions. The formation of solitary structures is investigated in two cases: first when the electrons are fully degenerate and second when small temperature effects are taken into account. It is seen that not only rarefactive but coupled rarefactive and compressive solitons are obtained under different temperature conditions.

Shah, H. A.; Qureshi, M. N. S. [Department of Physics, GC University, Lahore 54000 (Pakistan); Tsintsadze, N. [Department of Physics, GC University, Lahore 54000 (Pakistan); Salam Chair, GC University, Lahore 54000 (Pakistan)

2010-03-15

97

Mechanism of neurofibrillary degeneration in Alzheimer's disease  

Microsoft Academic Search

Neurofibrillary degeneration associated with the formation of intraneuronal neurofibrillary tangles of paired helical filaments\\u000a (PHF) and 2.1 nm ? filaments is one of the most characteristic brain lesions of Alzheimer's disease. The major polypeptides\\u000a of PHF are the microtubule associated protein, ?. ?, in PHF is present in abnormally phosphorylated forms. In addition to\\u000a the PHF, the abnormal ? is

Khalid Iqbal; Alejandra del C. Alonso; Cheng-Xin Gong; Sabiha Khatoon; Toolsee J. Singh; Inge Grundke-Iqbal

1994-01-01

98

Confirmation of Substellar and Degenerate Companion Candidates  

NASA Astrophysics Data System (ADS)

With the AO-equipped NIRI instrument, we propose to obtain follow-up confirmation imaging of candidate substellar and degenerate companions to young, nearby A-stars discovered as a part of the two large-scale surveys: the IDPS (International Deep Planet Search) and VAST (Volume-limited A-STar) Surveys. The candidate substellar companions have masses covering the planet/brown dwarf transition (7 - 45 45 Mjup) at well-determined young ages between 30 and 400 Myrs and confirmed objects will serve as important benchmarks against which theoretical evolutionary and atmospheric models can be tested. Any confirmed substellar companions would cover either important intermediate ages or particularly low masses compared to isolated field brown dwarfs. The final target has an unusual pair of candidate co-moving objects that are potential white dwarfs, and would present a unique system of a quadruple composed of an A-star binary surrounded by a circumbinary debris disk with a wide pair of exceptionally young white dwarfs. This degenerate system would be another example of a Sirius B-type system, though unusual in containing two degenerate objects and a debris disk. In summary, the proposed observations are the critical follow-up measurements require to: estimate the frequency of wide orbit planetary mass and brown dwarf companions, and confirm the nature of a unique young quadruple system with a pair of white dwarfs.

Patience, Jennifer; De Rosa, Robert; Vigan, Arthur

2013-02-01

99

Exome Sequencing in Familial Corticobasal Degeneration  

PubMed Central

Background Corticobasal degeneration (CBD) is a neurodegenerative, sporadic disorder of unknown cause. Few familial cases have been described. Objective We aim to characterize the clinical, imaging, pathological and genetic features of two familial cases of CBD. Methods We describe two first cousins with CBD associated with atypical MRI findings. We performed exome sequencing in both subjects and in an unaffected first cousin of similar age. Results The cases include a 79-year-old woman and a 72-year-old man of Native American and British origin. The onset of the neurological manifestations was 74 and 68 years respectively. Both patients presented with a combination of asymmetric parkinsonism, apraxia, myoclonic tremor, cortical sensory syndrome, and gait disturbance. The female subject developed left side fixed dystonia. The manifestations were unresponsive to high doses of levodopa in both cases. Extensive bilateral T1-W hyperintensities and T2-W hypointensities in basal ganglia and thalamus were observed in the female patient; whereas these findings were more subtle in the male subject. Postmortem examination of both patients was consistent with corticobasal degeneration; the female patient had additional findings consistent with mild Alzheimer’s disease. No Lewy bodies were found in either case. Exome sequencing showed mutations leading to possible structural changes in MRS2 and ZHX2 genes, which appear to have the same upstream regulator miR-4277. Conclusions Corticobasal degeneration can have a familial presentation; the role of MRS2 and ZHX2 gene products in CBD should be further investigated. PMID:23867865

Fekete, Robert; Bainbridge, Matthew; Baizabal-Carvallo, Jose Fidel; Rivera, Andreana; Miller, Bradley; Du, Peicheng; Kholodovich, Vladyslav; Powell, Suzanne; Ondo, William

2014-01-01

100

[New drug therapy for retinal degeneration].  

PubMed

Retinitis pigmentosa (RP) is an inherited retinal degeneration characterized by nyctalopia, ring scotoma, and bone-spicule pigmentation of the retina. So far, no effective therapy has been found for RP. As a possible molecular etiology of RP, retina-specific gene deficits are most likely involved, but little has been identified in terms of intracellular mechanisms leading to retinal photoreceptor cell death at post-translational levels. In order to find an effective therapy for RP, we must look for underlying common mechanisms that are responsible for the development of RP, instead of designing a specific therapy for each of the RP types with different causes. Therefore, in the present study, several animal models with different causes of RP were studied, including (1)Royal College of Surgeons (RCS) rats with a deficit of retinal pigment epithelium (RPE) function caused by rhodopsin mutation; (2) P23H rats, (3) S334ter rats, (4) photo stress rats, (5) retinal degeneration (rd) mice with a deficit of phosphodiesterase(PDE) function; and (6) cancer-associated retinopathy (CAR) model rats with a deficit of recoverin-dependent photoreceptor adaptation function. In each of these models, the following assessments were made in order to elucidate common pathological mechanisms among the models: (1) retinal function assessed by electroretinogram (ERG), (2) retinal morphology, (3) retinoid analysis, (4) rhodopsin regeneration, (5) rhodopsin phosphorylation and dephosphorylation, and (6) cytosolic cGMP levels. We found that unregulated photoreceptor adaptation processes caused by an imbalance of rhodopsin phosphorylation and dephosphorylation caused retinal dysfunction leading to photoreceptor cell death. As possible candidate drugs for normalizing these retinal dysfunctions and stopping further retinal degeneration, nilvadipine, a Ca channel blocker, retinoid derivatives, and anthocyanine were chosen and tested to determine their effect on the above animal models with retinal degeneration. Nilvadipine showed beneficial effects against retinal degeneration in all models tested, but retinoid derivatives and anthocyanine showed these beneficial effects in only some models. Thus our present data allowed us to test the effectiveness of nilvadipine in the treatment of human RP patients. PMID:18240599

Ohguro, Hiroshi

2008-01-01

101

The development of melanopsin-containing retinal ganglion cells in mice with early retinal degeneration  

PubMed Central

In mammals, the neuronal pathways by which rod and cone photoreceptors mediate vision have been well documented. The roles that classical photoreceptors play in photoentrainment, however, have been less clear. In mammals, intrinsically photosensitive retinal ganglion cells (ipRGCs) that express the photopigment melanopsin project directly to the suprachiasmatic nucleus (SCN) of the hypothalamus, the site of the circadian clock, and thereby contribute to non-image forming responses to light. Classical photoreceptors are not necessary for photoentrainment since loss of rods and cones does not eliminate light entrainment. Conflicting evidence arose, however, when attenuated phase-shifting responses were observed in the retinal degenerate CBA/J mouse. In this study, we examined the time course of retinal degeneration in CBA/J mice and used these animals to determine if maturation of the outer retina regulates the morphology, number and distribution of ipRGCs. We also examined whether degeneration during the early development of the outer retina can alter the function of the adult circadian system. We report that dendritic stratification and distribution of ipRGCs was unaltered in mice with early retinal degeneration, suggesting that normal development of the outer retina was not necessary for these processes. We found, however, that adult CBA/J mice have greater numbers of ipRGCs than controls, implicating a role for the outer retinal photoreceptors in regulating developmental cell death of ipRGCs. PMID:19200239

Ruggiero, Linda; Allen, Charles N.; Brown, R. Lane; Robinson, David W.

2009-01-01

102

Relativistic Bernstein waves in a degenerate plasma  

SciTech Connect

Bernstein mode for a relativistic degenerate electron plasma is investigated. Using relativistic Vlasov-Maxwell equations, a general expression for the conductivity tensor is derived and then employing Fermi-Dirac distribution function a generalized dispersion relation for the Bernstein mode is obtained. Two limiting cases, i.e., non-relativistic and ultra-relativistic are discussed. The dispersion relations obtained are also graphically presented for some specific values of the parameters depicting how the propagation characteristics of Bernstein waves as well as the Upper Hybrid oscillations are modified with the increase in plasma number density.

Ali, Muddasir; Hussain, Azhar [Department of Physics, G.C. University, Lahore 54000 (Pakistan); Salam Chair in Physics, G.C. University, Lahore 54000 (Pakistan); Murtaza, G. [Salam Chair in Physics, G.C. University, Lahore 54000 (Pakistan)

2011-09-15

103

Spin susceptibility of degenerate quark matter  

NASA Astrophysics Data System (ADS)

The expression for spin susceptibility ? of degenerate quark matter is derived with corrections up to O(g4lng2). It is shown that, at low density, ?-1 changes sign and turns negative, indicating a ferromagnetic phase transition. To this order, we also calculate sound velocity c1 and incompressibility K with arbitrary spin polarization. The estimated values of c1 and K show that the equation of state of the polarized matter is stiffer than that of unpolarized matter. Finally, we determine the finite temperature corrections to the exchange energy and derive corresponding results for the spin susceptibility.

Pal, Kausik; Dutt-Mazumder, Abhee K.

2009-11-01

104

Aneutronic Fusion in a Degenerate Plasma  

SciTech Connect

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

S. Son; N.J. Fisch

2004-09-03

105

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

106

Cerebellar Degeneration Associated with Sjögren's Syndrome  

PubMed Central

Background Neurologic manifestations of primary Sjögren's syndrome (PSS) have been reported to vary from sensory polyneuropathy to encephalopathy or psychiatric problems. However, marked cerebellar degeneration associated with PSS has rarely been reported. Case Report We describe a patient with Sjögren's syndrome who exhibited rapidly progressive cerebellar ataxia, nystagmus, cognitive decline, and psychiatric problems. Brain magnetic resonance imaging revealed marked atrophy of the cerebellum, and 18F-fluorodeoxyglucose positron-emission tomography demonstrated glucose hypometabolism of the cerebellum. Conclusions Our PSS patient exhibited a progressive course of cerebellar syndrome, as evidenced by cerebellar atrophy on serial brain images. PMID:22787501

Kim, Mi Jung; Lee, Myoung Chong; Lee, Jae-Hong

2012-01-01

107

Quasilinear degenerate evolution equations in Banach spaces  

Microsoft Academic Search

.  The quasilinear degenerate evolution equation of parabolic type\\u000a$$\\\\frac{{d(Mv)}}\\u000a{{dt}} + L(Mv)v = F(Mv),$$ 0t$$\\\\frac{{du}}\\u000a{{dt}} + A(u)u \\\\mathrel\\\\backepsilon F(u),$$ 0t T, where A(u)=L(u)M–1 are multivalued linear operators in X for u K, K being a bounded ball ||u||ZR in another Banach space Z continuously embedded in X. Existence and uniqueness of the local solution for the related Cauchy problem

Angelo Favini; Atsushi Yagi

2004-01-01

108

Mechanisms of secondary degeneration after partial optic nerve transection  

PubMed Central

Secondary degeneration occurs commonly in the central nervous system after traumatic injuries and following acute and chronic diseases, including glaucoma. A constellation of mechanisms have been shown to be associated with secondary degeneration including apoptosis, necrosis, autophagy, oxidative stress, excitotoxicity, derangements in ionic homeostasis and calcium influx. Glial cells, such as microglia, astrocytes and oligodendrocytes, have also been demonstrated to take part in the process of secondary injury. Partial optic nerve transection is a useful model which was established about 13 years ago. The merit of this model compared with other optic nerve injury models used for glaucoma study, including complete optic nerve transection model and optic nerve crush model, is the possibility to separate primary degeneration from secondary degeneration in location. Therefore, it provides a good tool for the study of secondary degeneration. This review will focus on the research progress of the mechanisms of secondary degeneration using partial optic nerve transection model. PMID:25206855

Li, Hong-Ying; Ruan, Yi-Wen; Ren, Chao-Ran; Cui, Qi; So, Kwok-Fai

2014-01-01

109

MRI and MR tractography in bilateral hypertrophic olivary degeneration  

PubMed Central

Hypertrophic olivary degeneration is a trans-synaptic neuronal degeneration associated with hypertrophy of the inferior olivary nucleus due to a lesion in the triangle of Guillain-Mollaret. Familiarity with this entity on magnetic resonance imaging (MRI) is essential to avoid other erroneous ominous diagnoses. We present a case of bilateral hypertrophic olivary degeneration and discuss the etiopathogenesis and MRI findings in this entity. The contributory role of MR tractography in the diagnosis is also highlighted. PMID:25489133

Sen, Debraj; Gulati, Yoginder S.; Malik, Virender; Mohimen, Aneesh; Sibi, Eranki; Reddy, Deepak Chandra

2014-01-01

110

Stanniocalcin-1 Rescued Photoreceptor Degeneration in Two Rat Models of Inherited Retinal Degeneration  

PubMed Central

Oxidative stress and photoreceptor apoptosis are prominent features of many forms of retinal degeneration (RD) for which there are currently no effective therapies. We previously observed that mesenchymal stem/stromal cells reduce apoptosis by being activated to secrete stanniocalcin-1 (STC-1), a multifunctional protein that reduces oxidative stress by upregulating mitochondrial uncoupling protein-2 (UCP-2). Therefore, we tested the hypothesis that intravitreal injection of STC-1 can rescue photoreceptors. We first tested STC-1 in the rhodopsin transgenic rat characterized by rapid photoreceptor loss. Intravitreal STC-1 decreased the loss of photoreceptor nuclei and transcripts and resulted in measurable retinal function when none is otherwise present in this rapid degeneration. We then tested STC-1 in the Royal College of Surgeons (RCS) rat characterized by a slower photoreceptor degeneration. Intravitreal STC-1 reduced the number of pyknotic nuclei in photoreceptors, delayed the loss of photoreceptor transcripts, and improved function of rod photoreceptors. Additionally, STC-1 upregulated UCP-2 and decreased levels of two protein adducts generated by reactive oxygen species (ROS). Microarrays from the two models demonstrated that STC-1 upregulated expression of a similar profile of genes for retinal development and function. The results suggested that intravitreal STC-1 is a promising therapy for various forms of RD including retinitis pigmentosa and atrophic age-related macular degeneration (AMD). PMID:22294148

Roddy, Gavin W; Rosa Jr, Robert H; Youn Oh, Joo; Ylostalo, Joni H; Bartosh, Thomas J; Choi, Hosoon; Lee, Ryang Hwa; Yasumura, Douglas; Ahern, Kelly; Nielsen, Gregory; Matthes, Michael T; LaVail, Matthew M; Prockop, Darwin J

2012-01-01

111

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

112

Mucoid degeneration of the anterior cruciate Ligament: a case report  

PubMed Central

We report a case of mucoid degeneration of the anterior cruciate ligament (ACL). Mucoid degeneration of the ACL is a very rare cause of knee pain. There have been only some reported cases of mucoid degeneration of the ACL in the English literature. We reviewed previous reports and summarized clinical features and symptoms, including those found in our case. Magnetic Resonance Imaging is the most useful tool for differentiating mucoid degeneration of the ACL from an intraligamentous ganglion or other lesions in the knee joint. If this disease is considered preoperatively, it can be diagnosed easily based on characteristic findings. PMID:24147185

el Kadi, Khalid Ibn; Marcaillou, Florian; Blanc, Stephane; Salloum, Bassam; Dimontagliari, Cyril; Boutayeb, Fawzi

2013-01-01

113

Mucoid degeneration of the anterior cruciate ligament: a case report.  

PubMed

We report a case of mucoid degeneration of the anterior cruciate ligament (ACL). Mucoid degeneration of the ACL is a very rare cause of knee pain. There have been only some reported cases of mucoid degeneration of the ACL in the English literature. We reviewed previous reports and summarized clinical features and symptoms, including those found in our case. Magnetic Resonance Imaging is the most useful tool for differentiating mucoid degeneration of the ACL from an intraligamentous ganglion or other lesions in the knee joint. If this disease is considered preoperatively, it can be diagnosed easily based on characteristic findings. PMID:24147185

el Kadi, Khalid Ibn; Marcaillou, Florian; Blanc, Stephane; Salloum, Bassam; Dimontagliari, Cyril; Boutayeb, Fawzi

2013-01-01

114

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

115

Misregulation of rhodopsin phosphorylation and dephosphorylation found in P23H rat retinal degeneration.  

PubMed

To examine rhodopsin (Rho) functions in P23H rat, kinetics of Rho regeneration and dephosphorylation were investigated by spectrophotometric analysis and immunofluorescence labeling method using specific antibodies toward phosphorylated 334Ser or 338Ser site. Rho dephosphorylation at both sites was extremely delayed in P23H retina as compared to normal ones. Kinetics of Rho regeneration was not altered between normal and P23H rats under dark adaptation. Next, to study the effects of several Ca(2+)channel blockers on this model, retinal function and morphology were evaluated. Among them, nilvadipine showed a significant protective effect against P23H retinal degeneration. Neurotrophic factor, fibroblast growth factor-2 and Arc, known to suppress the apoptosis in the central nervous system, were significantly upregulated upon administration of nilvadipine. The present study indicates that misregulation of Rho phosphorylation may be involved as an important step in retinal degeneration of P23H and administration of nilvadipine may be a potential therapeutic agent for the retinal degenerations. PMID:19668436

Saito, Yoshiyuki; Ohguro, Hiroshi; Ohguro, Ikuyo; Sato, Noriyuki; Ishikawa, Futoshi; Yamazaki, Hitoshi; Metoki, Tomomi; Ito, Tadashi; Nakazawa, Mitsuru

2008-12-01

116

Overexpression of Dyrk1A contributes to neurofibrillary degeneration in Down syndrome  

PubMed Central

Adults with Down syndrome (DS) develop Alzheimer neurofibrillary degeneration in the brain, but the underlying molecular mechanism is unknown. Here, we report that the presence of an extra copy of the dual-specificity tyrosine-phosphorylated and regulated kinase 1A (Dyrk1A) gene due to trisomy 21 resulted in overexpression of Dyrk1A and elevated kinase activity in DS brain. Dyrk1A phosphorylated tau at several sites, and these sites were hyperphosphorylated in adult DS brains. Phosphorylation of tau by Dyrk1A primed its further phosphorylation by glycogen synthase kinase-3? (GSK-3?). Dyrk1A-induced tau phosphorylation inhibited tau’s biological activity and promoted its self-aggregation. In Ts65Dn mouse brain, an extra copy of the Dyrk1A gene caused increased expression and activity of Dyrk1A and resulted in increased tau phosphorylation. These findings strongly suggest a novel mechanism by which the overexpression of Dyrk1A in DS brain causes neurofibrillary degeneration via hyperphosphorylating tau. Liu, F., Liang, Z., Wegiel, J., Hwang, Y.-W., Iqbal, K., Grundke-Iqbal, I., Ramakrishna, N., Gong, C.-X. Overexpression of Dyrk1A contributes to neurofibrillary degeneration in Down syndrome. PMID:18509201

Liu, Fei; Liang, Zhihou; Wegiel, Jerzy; Hwang, Yu-Wen; Iqbal, Khalid; Grundke-Iqbal, Inge; Ramakrishna, Narayan; Gong, Cheng-Xin

2008-01-01

117

Age-related macular degeneration: what do patients find on the internet?  

PubMed Central

Objective To assess the quality of information and readability of the top internet sites for age-related macular degeneration (AMD). Design An examination of the technical information provision, quality and readability of websites found during an internet search for ‘age-related macular degeneration’. Setting Six internet search engines were used to find 26 unique sites on AMD. Main outcome measures Technical information and quality were assessed using a simple grading system. Readability was assessed using a Simple Measure Of Gobbledygook (SMOG) rating. Results Twelve organizational, seven academic and seven commercial sites were identified. The average technical scores were 82.3%, 67.9% and 65.2% for each type of site, respectively (P=0.097, one way ANOVA). The average quality scores were 62.2%, 62.6%, and 49.5% for each type of site, respectively (P=0.356, one-way ANOVA). The average SMOG ratings were 16.3, 16.1, and 16.2 for each type of site, respectively (P=0.983, one-way ANOVA). Fifteen of the sites provided details of new and emerging treatments, with seven providing a detailed discussion. Conclusions Many websites are now meeting the challenge of providing comprehensive information about AMD and its new treatments. Quality scores were disappointing, with sites needing to provide more evidence of authorship and attribution of information. The majority of sites had SMOG scores above 10, making them difficult for the average person to understand. As physicians we need to help design and direct patients to sites that provide high quality, current information. PMID:17911131

Rennie, Christina A; Hannan, Shabeeba; Maycock, Nick; Kang, Chee

2007-01-01

118

Study of degenerate parabolic system modeling the hydrogen displacement in a nuclear waste repository  

E-print Network

Our goal is the mathematical analysis of a two phase (liquid and gas) two components (water and hydrogen) system modeling the hydrogen displacement in a storage site for radioactive waste. We suppose that the water is only in the liquid phase and is incompressible. The hydrogen in the gas phase is supposed compressible and could be dissolved into the water with the Henry's law. The flow is described by the conservation of the mass of each components. The model is treated without simplified assumptions on the gas density. This model is degenerated due to vanishing terms. We establish an existence result for the nonlinear degenerate parabolic system based on new energy estimate on pressures.

Caro, Florian; Saad, Mazen

2012-01-01

119

Teaching NeuroImages: hemorrhagic cavernoma with secondary development of hypertrophic olivary degeneration.  

PubMed

Hypertrophic olivary degeneration (HOD) is secondary degeneration of the inferior olivary nucleus (ION) due to a primary lesion in the dento-rubro-olivary pathway. This pathway is known as the Guillain and Mollert triangle, containing the dentate nucleus and the contralateral red and inferior olivary nuclei (figure e-1 on the Neurology® Web site at www.neurology.org). The commonest presenting symptom is palatal myoclonus occurring 8-12 months after the primary insult. MRI of the ION initially has normal results (figure 1). Three phases of HOD exist on MRI: hyperintense signal change without hypertrophy, hyperintense signal change with hypertrophy (figure 2), and regression of hypertrophy with persistent hyperintense signal.(1.) PMID:23650241

Crosbie, Ian; McNally, Stephen; Brennan, Paul; Looby, Seamus

2013-05-01

120

Presumed immune-mediated cerebellar granuloprival degeneration in the Coton de Tuléar breed.  

PubMed

An unusual form of cerebellar granuloprival degeneration was observed in three male Coton de Tuléar puppies between 12 and 14 weeks of age from different litters showing progressive cerebellar signs beginning at 8 weeks after birth. Pathological examinations revealed a shrunken cerebellum. Histopathologically the granular cells were diminished or almost completely absent, some 'torpedos' of Purkinje cells were present. There was a marked gliosis, and occasionally small inflammatory foci were present. A marked diffuse T cell infiltration (CD3(+) cells) occurred in the lesions, B cells did not appear. CD18 staining showed an upregulation of microglial cells at the lesion site. Histopathologically the lesions resembled paraneoplastic cerebellar degeneration which is caused by an autoimmune mediated T cell reaction. This congenital condition in the Coton de Tuléar dog breed could be based on a genetically defined immune defect leading to autoimmune destruction of the granular cells. PMID:11024542

Tipold, A; Fatzer, R; Jaggy, A; Moore, P; Vandevelde, M

2000-10-01

121

Hypertrophic olivary degeneration - a report of two cases.  

PubMed

Hypertrophic olivary degeneration (HOD) is seen following lesions in the Guillain-Mollaret triangle. This is unique because the inferior olivary nucleus hypertrophies following degeneration unlike the typical atrophy seen in other structures. We report two cases of HOD in two different clinical scenarios. PMID:25806143

Sarawagi, Radha; Murugesan, Aravind

2015-01-01

122

A Family of Degenerate Codes for Depolarizing Channels  

NASA Astrophysics Data System (ADS)

Quantum degenerate code may improve the hashing bound of quantum capacity. We propose a family of quantum degenerate codes derived from two-colorable graphs. The coherent information of the codes is analytically obtained as a function of the channel noise for the depolarizing channel. We find a new code which has a higher noise threshold than that of the repetition code.

Chen, Xiao-Yu; Zhao, Jiang-Jun; Wang, Ting-Ting; Shou, Chao-Jun

2015-02-01

123

Degeneration of Acetabular Articular Cartilage to Bipolar Hemiarthroplasty  

PubMed Central

Purpose This study examined the rate of degeneration of acetabular cartilage by the bipolar head according to time, and also which clinical factors are related to the degeneration of acetabular cartilage. Materials and Methods Among 192 patients (226 hip joints) who received bipolar hemiarthroplasty from August 1996 to August 2002, 61 patients (65 hip joints) were enrolled in this study, who were followed up for more than 2 years and showed no signs of dislocation, infection, or functional problems. A modified form of a computer assisted vector wear analysis program was used to measure the rate of degeneration of the acetabular cartilage. The factors that appeared to affect the rate of acetabular degeneration in the two groups was evaluated. Results The average linear degenerative change in the acetabular cartilage and the volumetric degenerative change were 0.23 ± 0.107 mm/year and 114 ± 47.2 mm3/year, respectively. The result showed significant differences in activity and HHS between the 2 groups. The HHS showed a reverse relationship with the linear degeneration and volumetric degeneration, and the activity showed a correlation with the linear and volumetric degeneration. Conclusion The acetabular cartilage degenerates faster as the patient' activity increases, and slower with a higher HHS. When surgeons perform hip joint arthroplasty, it is strongly recommended that the life expectancy and the level of activity should be considered when deciding between a hemiarthroplasty and total hip arthroplasty. PMID:18972591

Kang, Jun Soon; Lee, Tong Joo; Lee, Sang Hyeop; Choi, Sung Wook; Won, Man Hee

2008-01-01

124

Hypertrophic Olivary Degeneration – A Report of Two Cases  

PubMed Central

Hypertrophic olivary degeneration (HOD) is seen following lesions in the Guillain–Mollaret triangle. This is unique because the inferior olivary nucleus hypertrophies following degeneration unlike the typical atrophy seen in other structures. We report two cases of HOD in two different clinical scenarios. PMID:25806143

Sarawagi, Radha; Murugesan, Aravind

2015-01-01

125

Frontal Lobe Degeneration of Non-Alzheimer Type Revisited  

Microsoft Academic Search

The neuropathology of frontal lobe degeneration of non-Alzheimer type was reevaluated on the basis of a new material of 13 cases against the background of experiences from earlier published 16 cases. The salient neuropathological feature was an unspecific neuronal degeneration of superficial cortical layers of the frontal and to some extent the temporal lobes without markers for Alzheimer's, Pick's or

Arne Brun

1993-01-01

126

Subacute combined degeneration of the spinal cord and air encephalography.  

PubMed

Subacute combined degeneration of the spinal cord is a rare complication of vitamin B12 deficiency and is seldom encountered today. A case of Addisonian pernicious anaemia is reported in which the classical signs of subacute combined degeneration developed suddenly after air encephalography had been performed. The patient made a complete recovery. PMID:1198219

Mendelsohn, G; Green, R; Skikne, B S; Scott, W F

1975-11-01

127

ELECTRON MICROSCOPIC AND HISTOCHEMICAL OBSERVATIONS OF MUSCLE DEGENERATION AFTER TOURNIQUET  

PubMed Central

As an experimental model for the different forms of muscle degeneration, injury caused by 2 hours' ischemia has been studied from 20 minutes to 16 hours after release of the tourniquet. Discoid degeneration developed in stretched fibers by dissolution of the I bands (Z substances and actin). The discs represented the Q bands (A-H-A). In fibers which passively maintained contraction lengths during degeneration, the Z substances were dissolved, but the continuity of the fibrils was preserved, since the filaments are continuous over all sarcomeres under these conditions. Mitochondria and the tubules of the endoplasmic reticulum swelled, ruptured, and disintegrated. Granular degeneration developed in fibers where mitochondria were abundant. Unstretched degenerating fibers with few mitochondria gave a homogeneous or hyaline appearance. The different forms of degeneration therefore were dependent on the status of stretch and the fiber type. The extent of degeneration was not a function of time after ischemia, there being both nearly normal and severely damaged fibers at 20 minutes and 16 hours after the release of tourniquets. When degeneration occurred, however, the basic alterations were the same in all fibers; there was mitochondrial and reticular swelling, dissolution of the Z substances, and finally disintegration of the contractile material. Some damage developed in the sarcolemmas and capillaries. The mitochondrial disintegration was not linked with inactivation of the succinic dehydrogenase system. PMID:13398442

Moore, Dan H.; Ruska, Helmut; Copenhaver, Wilfred M.

1956-01-01

128

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

129

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

130

[Climate, brain, and degeneration in Cabanis].  

PubMed

This analysis of the arguments defended by Cabanis in "Rapports du physique et du moral de l'homme" takes as its point of departure his eighth and ninth Memoirs, which focus on analyzing the influences of regime and climate. These writings afford a new reading of the arguments Cabanis used to explain the relation between the physical traits and moral habits of individuals and races. The article analyzes his debts to natural history, especially Buffon's theory of degeneration; to the Hippocratic tradition, above all the humor theory; and to studies of brain anatomy and pathology. Lastly, it examines the role that the human and moral sciences of medicine and hygiene play in the regeneration of the human species. PMID:21461515

Caponi, Sandra

2009-01-01

131

Dispersion in a relativistic degenerate electron gas  

E-print Network

Relativistic effects on dispersion in a degenerate electron gas are discussed by comparing known response functions derived relativistically (by Jancovici) and nonrelativistically (by Lindhard). The main distinguishing feature is one-photon pair creation, which leads to logarithmic singularities in the response functions. Dispersion curves for longitudinal waves have a similar tongue-like appearance in the relativistic and nonrelativistic case, with the main relativistic effects being on the Fermi speed and the cutoff frequency. For transverse waves the nonrelativistic treatment has a nonphysical feature near the cutoff frequency for large Fermi momenta, and this is attributed to an incorrect treatment of the electron spin. We find (with two important provisos) that one-photon pair creation is allowed in superdense plasmas, implying relatively strong coupling between transverse waves and pair creation.

McOrist, J; Weise, J I

2006-01-01

132

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

133

DPPrimer – A Degenerate PCR Primer Design Tool  

PubMed Central

Designed degenerate primers unlike conventional primers are superior in matching and amplification of large number of genes, from related gene families. DPPrimer tool was designed to predict primers for PCR amplification of homologous gene from related or diverse plant species. The key features of this tool include platform independence and user friendliness in primer design. Embedded features such as search for functional domains, similarity score selection and phylogebetic tree further enhance the user friendliness of DPPrimer tool. Performance of DPPrimer tool was evaluated by successful PCR amplification of ADP-glucose phosphorylase genes from wheat, barley and rice. Availability DPPrimer is freely accessible at http://202.141.12.147/DGEN_tool/index.html PMID:24307773

Gahoi, Shachi; Arya, L; Anil, Rai; Marla, ss

2013-01-01

134

Preservation of retinotopic map in retinal degeneration  

PubMed Central

Retinal degenerations trigger the loss of photoreceptors and cause the remaining de-afferented neural retina to undergo remodeling. Concerns over this potential retinal synaptic reorganization following visual loss have raised questions regarding the usefulness of visual restoration via retinal electrical stimulation. We have used quantitative positron emission tomography (PET) and 2-deoxy-2-[18F]fluoro-d-glucose (FDG) to objectively evaluate the connection between the retina and the primary visual cortex under both light and transcorneal electrical stimulation (TcES) in five subjects with retinal degeneration (RD) who have had more than ten years of light-perception-only best visual acuity and five age-matched normal-sighted controls. All subjects underwent quantitative PET with FDG as the metabolic tracer during stimulation of the right eye under both light stimulation condition and transcorneal electrical stimulation (TcES) using ERG-Jet contact lens electrode. Cortical activation maps from each stimulation condition were obtained using statistical parametric mapping. TcES phosphene threshold current and qualitative visual cortex activation from both stimulation conditions were compared between the two subject groups. Average phosphene threshold current was 0.72 ± 0.18 mA for the five normal-sighted controls and 3.08 ± 2.01 mA for the retinal degenerative subjects. Phosphene threshold current was significantly higher in retinal degenerative subjects compared to normal-sighted controls (p < 0.05). We found both light stimulation and TcES resulted in retinotopically mapped primary visual cortex activation in both groups. In addition, the patterns of early visual area activation between the two subject groups are more similar during TcES than light stimulation. Our findings suggest primary visual cortex continues to maintain its retinotopy in RD subjects despite prolonged visual loss. PMID:22685713

Xie, John; Wang, Gene-Jack; Yow, Lindy; Humayun, Mark S.; Weiland, James D.; Cela, Carlos J.; Jadvar, Hossein; Lazzi, Gianluca; Dhrami-Gavazi, Elona; Tsang, Stephen H.

2015-01-01

135

Preservation of retinotopic map in retinal degeneration.  

PubMed

Retinal degenerations trigger the loss of photoreceptors and cause the remaining de-afferented neural retina to undergo remodeling. Concerns over this potential retinal synaptic reorganization following visual loss have raised questions regarding the usefulness of visual restoration via retinal electrical stimulation. We have used quantitative positron emission tomography (PET) and 2-deoxy-2-[18F]fluoro-d-glucose (FDG) to objectively evaluate the connection between the retina and the primary visual cortex under both light and transcorneal electrical stimulation (TcES) in five subjects with retinal degeneration (RD) who have had more than ten years of light-perception-only best visual acuity and five age-matched normal-sighted controls. All subjects underwent quantitative PET with FDG as the metabolic tracer during stimulation of the right eye under both light stimulation condition and transcorneal electrical stimulation (TcES) using ERG-Jet contact lens electrode. Cortical activation maps from each stimulation condition were obtained using statistical parametric mapping. TcES phosphene threshold current and qualitative visual cortex activation from both stimulation conditions were compared between the two subject groups. Average phosphene threshold current was 0.72 ± 0.18 mA for the five normal-sighted controls and 3.08 ± 2.01 mA for the retinal degenerative subjects. Phosphene threshold current was significantly higher in retinal degenerative subjects compared to normal-sighted controls (p < 0.05). We found both light stimulation and TcES resulted in retinotopically mapped primary visual cortex activation in both groups. In addition, the patterns of early visual area activation between the two subject groups are more similar during TcES than light stimulation. Our findings suggest primary visual cortex continues to maintain its retinotopy in RD subjects despite prolonged visual loss. PMID:22685713

Xie, John; Wang, Gene-Jack; Yow, Lindy; Humayun, Mark S; Weiland, James D; Cela, Carlos J; Jadvar, Hossein; Lazzi, Gianluca; Dhrami-Gavazi, Elona; Tsang, Stephen H

2012-05-01

136

Ouabain-induced cochlear degeneration in rat  

PubMed Central

Ouabain, an potent inhibitor of the Na+/K+-ATPase pump, selectively destroys spiral ganglion neurons (SGNs) in gerbils and mice whereas in guinea pigs it preferentially damages cochlear hair cells. To elucidate the effects of ouabain on the rat inner ear, a species widely used in research, 5 µl of 1 mM or 10 mM ouabain was applied to the round window membrane. Distortion product otoacoustic emissions (DPOAE) and auditory brainstem responses (ABR) were used identify functional deficits in hair cells and neurons respectively and histological techniques were used to characterize cochlear pathologies. High-frequency ABR thresholds were elevated after treatment with 1 mM ouabain whereas DPOAEs remained normal. In contrast, 10 mM ouabain increased ABR thresholds and reduced DPOAE amplitudes. Consistent with the physiological changes, 1 mM ouabain only damaged the SGNs and auditory nerve fibers in the basal turn of the cochlea whereas 10 mM ouabain destroyed both SGNs and cochlear hair cells; damage was greatest near the base and decreased toward the apex. The nuclei of degenerating SGNs and hair cells were condensed and fragmented and many cells were TUNEL-positive, morphological features of apoptotic cell death. Thus, ouabain-induced cochlear degeneration in rats is apoptotic and concentration dependent; low concentrations preferentially damage SGNs in the base of the cochlea, producing an animal model of partial auditory neuropathy, whereas high concentrations damage both hair cells and SGNs with damage decreasing from the base towards the apex. PMID:22476946

Fu, Yong; Ding, Dalian; Jiang, Haiyan; Salvi, Richard

2012-01-01

137

Crystallization and collapse in relativistically degenerate matter  

SciTech Connect

In this paper, it is shown that a mass density limit exists beyond which the relativistically degenerate matter would crystallize. The mass density limit, found here, is quite analogous to the mass limit predicted by Chandrasekhar for a type of compact stars called white dwarfs (M{sub Ch} Asymptotically-Equal-To 1.43 Solar Mass). In this study, the old problem of white dwarf core collapse, which has been previously investigated by Chandrasekhar using hydrostatic stability criteria, is revisited in the framework of the quantum hydrodynamics model by inspection of the charge screening at atomic scales in the relativistic degeneracy plasma regime taking into account the relativistic Fermi-Dirac statistics and electron interaction features such as the quantum statistical pressure, Coulomb attraction, electron exchange-correlation, and quantum recoil effects. It is revealed that the existence of ion correlation and crystallization of matter in the relativistically degenerate plasma puts a critical mass density limit on white dwarf core region. It is shown that a white dwarf star with a core mass density beyond this critical limit can undergo the spontaneous core collapse (SCC). The SCC phenomenon, which is dominantly caused by the electron quantum recoil effect (interference and localization of the electron wave function), leads to a new exotic state of matter. In such exotic state, the relativistic electron degeneracy can lead the white dwarf crystallized core to undergo the nuclear fusion and an ultimate supernova by means of the volume reduction (due to the enhanced compressibility) and huge energy release (due to the increase in cohesive energy), under the stars huge inward gravitational pressure. Moreover, it is found that the SCC phenomenon is significantly affected by the core composition (it is more probable for heavier plasmas). The critical mass density found here is consistent with the values calculated for core density of typical white dwarf stars.

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

2013-04-15

138

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

139

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

140

Single-Degenerate Type Ia Supernovae Are Preferentially Overluminous  

E-print Network

Recent observational and theoretical progress has favored merging and helium-accreting sub-Chandrasekhar mass white dwarfs in the double-degenerate and the double-detonation channels, respectively, as the most promising progenitors of normal Type Ia supernovae (SNe Ia). Thus the fate of rapidly-accreting Chandrasekhar mass white dwarfs in the single-degenerate channel remains more mysterious then ever. In this paper, we clarify the nature of ignition in Chandrasekhar-mass single-degenerate SNe Ia by analytically deriving the existence of a characteristic length scale which establishes a transition from central ignitions to buoyancy-driven ignitions. Using this criterion, combined with data from three-dimensional simulations of convection and ignition, we demonstrate that the overwhelming majority of ignition events within Chandrasekhar-mass white dwarfs in the single-degenerate channel are buoyancy-driven, and consequently lack a vigorous deflagration phase. We thus infer that single-degenerate SNe Ia are gen...

Fisher, Robert

2015-01-01

141

The fraction of double degenerates among DA white dwarfs  

E-print Network

We present the results of a radial velocity survey designed to measure the fraction of double degenerates among DA white dwarfs. The narrow core of the H-alpha line was observed twice or more for 46 white dwarfs yielding radial velocities accurate to a few km/s. This makes our survey the most sensitive to the detection of double degenerates undertaken to date. We found no new double degenerates in our sample, though H-alpha emission from distant companions is seen in two systems. Two stars known to be double degenerates prior to our observations are included in the analysis. We find a 95% probability that the fraction of double degenerates among DA white dwarfs lies in the range [0.017,0.19].

P. F. L. Maxted; T. R. Marsh

2000-05-23

142

Progranulin knockout accelerates intervertebral disc degeneration in aging mice.  

PubMed

Intervertebral disc (IVD) degeneration is a common degenerative disease, yet much is unknown about the mechanisms during its pathogenesis. Herein we investigated whether progranulin (PGRN), a chondroprotective growth factor, is associated with IVD degeneration. PGRN was detectable in both human and murine IVD. The levels of PGRN were upregulated in murine IVD tissue during aging process. Loss of PGRN resulted in an early onset of degenerative changes in the IVD tissue and altered expressions of the degeneration-associated molecules in the mouse IVD tissue. Moreover, PGRN knockout mice exhibited accelerated IVD matrix degeneration, abnormal bone formation and exaggerated bone resorption in vertebra with aging. The acceleration of IVD degeneration observed in PGRN null mice was probably due to the enhanced activation of NF-?B signaling and ?-catenin signaling. Taken together, PGRN may play a critical role in homeostasis of IVD, and may serve as a potential molecular target for prevention and treatment of disc degenerative diseases. PMID:25777988

Zhao, Yun-Peng; Tian, Qing-Yun; Liu, Ben; Cuellar, Jason; Richbourgh, Brendon; Jia, Tang-Hong; Liu, Chuan-Ju

2015-01-01

143

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

144

Potential regenerative treatment strategies for intervertebral disc degeneration in dogs.  

PubMed

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

Bach, Frances C; Willems, Nicole; Penning, Louis C; Ito, Keita; Meij, Björn P; Tryfonidou, Marianna A

2014-01-01

145

Statins for age-related macular degeneration  

PubMed Central

Background Age-related macular degeneration (AMD) is a progressive late onset disorder of the macula affecting central vision. Age-related macular degeneration is the leading cause of blindness in people over 65 years in industrialized countries (Congdon 2003). Recent epidemiologic, genetic and pathological evidence has shown AMD shares a number of risk factors with atherosclerosis, leading to the hypothesis that statins may exert protective effects in AMD. Objectives To examine the effectiveness of statins compared with other treatments, no treatment, or placebo in delaying the onset and/or progression of AMD. Search strategy We searched CENTRAL in The Cochrane Library, MEDLINE, EMBASE and LILACS on 30 April 2009 and the WHO International Clinical Trials Registry Platform on 11 May 2009. We searched reference lists and the Science Citation Index. There were no language or date restrictions in the search for trials. Selection criteria We included randomized controlled trials (RCTs) that compared statins with other treatments, no treatment, or placebo in participants who were either susceptible to or diagnosed as having early stages of AMD. Data collection and analysis Two authors independently evaluated the search results against the selection criteria. Two Italian speaking colleagues extracted data. One author entered data. We did not perform a meta-analysis because only one completed RCT was identified. Main results Two studies met the selection criteria. One trial reported insufficient details to assess the risk of bias; the other trial is ongoing. Of the completed trial, the analyses of 30 participants did not show a statistically significant difference between the simvastatin and the placebo arm in visual acuity at three months of treatment (decimal visual acuity 0.21± 0.56 in simvastatin and 0.19± 0.40 in placebo arm) or 45 days after the completion of treatment (decimal visual acuity 0.20± 0.50 in simvastatin and 0.19± 0.48 in placebo arm). The lens and retina status were unchanged during and after the treatment period for both groups. Of the ongoing trial, the preliminary analyses of 42 participants who completed 12 months follow-up did not show a statistically significant difference between the simvastatin and the placebo arm in visual acuity, drusen score or visual function (effect estimates and confidence intervals were not available). We contacted the investigators and will update the review as data become available. Authors' conclusions Evidence from currently available RCTs was insufficient to conclude that statins have any role in preventing or delaying the onset or progression of AMD. PMID:19588411

Gehlbach, Peter; Li, Tianjing; Hatef, Elham

2014-01-01

146

Establishment of monocular-limited photoreceptor degeneration models in rabbits  

PubMed Central

Background Numerous rodent models of photoreceptor degeneration have been developed for the study of visual function. However, no viable model has been established in a species that is more closely related to Homo sapiens. Here, we present a rabbit model of monocular photoreceptor degeneration. Methods We tested 2 chemicals, verteporfin and sodium nitroprusside (SNP), for developing a 1-eye limited photoreceptor degeneration model in pigmented rabbits. After the intravenous injection of verteporfin, the retina was exposed to light from a halogen lamp for 0, 10, 30, or 60 min. Alternately, 100 ?L of various concentrations of sodium nitroprusside (0.1 mM, 0.5 mM, and 1 mM) were intravitreously injected into the rabbit eye. Retinal degeneration was evaluated by fundus photography, electroretinogram (ERG), and histological examinations. Results Fundus photographs of animals in the verteporfin- or SNP-treated groups showed evidence of retinal degeneration. The severity of this degradation depended on the duration of light exposure and the concentration of SNP administered. The degeneration was clearly limited to the light-exposed areas in the verteporfin-treated groups. Extensive retinal atrophy was observed in the SNP-treated groups. The a- and b-wave amplitudes were dramatically decreased on the ERGs from SNP-treated groups. Histological examination revealed that either verteporfin or SNP induced severe photoreceptor degeneration. High-dose SNP treatment (1 mM) was also associated with inner retinal layer degeneration. Conclusions Both SNP and verteporfin clearly caused photoreceptor degeneration without any effect on the contralateral eye. These compounds therefore represent valuable tools for the empirical investigation of visual function recovery. The findings will inform guidelines for clinical applications such as retinal prostheses, cell-based therapy, and gene therapy. PMID:23683117

2013-01-01

147

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

148

Making the Diagnosis of Frontotemporal Lobar Degeneration  

PubMed Central

Context Autopsy evaluation of the brain of a patient with frontotemporal dementia (FTD) can be daunting to the general pathologist. At some point in their training, most pathologists learn about Pick disease, and can recognize Pick bodies, the morphologic hallmark of Pick disease. Pick disease is a type of frontotemporal lobar degeneration (FTLD), the general category of pathologic process underlying most cases of FTD. The 2 major categories of pathologic FTLD are tauopathies (FTLD-tau) and ubiquitinopathies (FTLD-U). Pick disease is one of the FTLD-tau subtypes and is termed FTLD-tau (PiD). Objective To “demystify” FTLDs, and to demonstrate that subtypes of FTLD-tau and FTLD-U can be easily determined by following a logical, stepwise, histochemical, and immunohistochemical investigation of the FTD autopsy brain. Data Sources Previously published peer-reviewed articles. Conclusions The hope is that this article will be a useful reference for the general pathologist faced with performing a brain autopsy on a decedent with frontotemporal dementia. PMID:23451743

Bigio, Eileen H.

2013-01-01

149

CERKL Knockdown Causes Retinal Degeneration in Zebrafish  

PubMed Central

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

150

Alzheimer's disease neurofibrillary degeneration: pivotal and multifactorial  

PubMed Central

Independent of the aetiology, AD (Alzheimer's disease) neurofibrillary degeneration of abnormally hyperphosphorylated tau, a hallmark of AD and related tauopathies, is apparently required for the clinical expression of the disease and hence is a major therapeutic target for drug development. However, AD is multifactorial and heterogeneous and probably involves several different aetiopathogenic mechanisms. On the basis of CSF (cerebrospinal fluid) levels of A?1-42 (where A? is amyloid ?-peptide), tau and ubiquitin, five different subgroups, each with its own clinical profile, have been identified. A successful development of rational therapeutic disease-modifying drugs for AD will require understanding of the different aetiopathogenic mechanisms involved and stratification of AD patients by different disease subgroups in clinical trials. We have identified a novel aetiopathogenic mechanism of AD which is initiated by the cleavage of SET, also known as inhibitor-2 (I2PP2A) of PP2A (protein phosphatase 2A) at Asn175 into N-terminal (I2NTF) and C-terminal (I2CTF) halves and their translocation from neuronal nucleus to the cytoplasm. AAV1 (adeno-associated virus 1)-induced expression of I2CTF in rat brain induces inhibition of PP2A activity, abnormal hyperphosphorylation of tau, neurodegeneration and cognitive impairment in rats. Restoration of PP2A activity by inhibition of the cleavage and of I2PP2A/SET activity offers a promising therapeutic opportunity in AD with this aetiopathogenic mechanism. PMID:20658985

Iqbal, Khalid; Wang, Xiaochuan; Blanchard, Julie; Liu, Fei; Gong, Cheng-Xin; Grundke-Iqbal, Inge

2011-01-01

151

[Criteria for the diagnosis of corticobasal degeneration].  

PubMed

Corticobasal degeneration (CBD) is a distinct neurodegenerative disorder characterized by widespread neuronal and glial accumulation of abnormally phosphorylated tau protein. Patients with CBD often present with corticobasal syndrome (CBS) showing impairment of the motor system, cognition, or both. Several studies demonstrate that they may also present with progressive supranuclear palsy syndrome (PSPS), aphasia, Alzheimer disease-like dementia, or behavioral changes, suggesting that CBS is merely one of the presenting phenotypes of CBD. Accurate diagnosis is important for future clinical trials using drugs aimed at modifying the underlying tau pathology. Although previous CBD diagnostic criteria reflected only CBS, Armstrong et al. proposed new diagnostic criteria for CBD in 2013 (Armstrong's criteria). The new criteria include 4 CBD phenotypes, including CBS, frontal behavioral-spatial syndrome (FBS), nonfluent/agrammatic variant of primary progressive aphasia (naPPA), and PSPS. These phenotypes were combined to create 2 sets of criteria: specific clinical research criteria for probable CBD (cr-CBD) and broader criteria for possible CBD that are more inclusive but have a higher probability of detecting other tau-based pathologies (p-CBD). However, two recent studies revealed that the sensitivity and specificity of these criteria were insufficient. Further refinement of the criteria is needed via biomarker research with prospective study designs. (Received August 19, 2014; Accepted December 26, 2014: Published April 1, 2015). PMID:25846600

Shimohata, Takayoshi; Aiba, Ikuko; Nishizawa, Masatoyo

2015-04-01

152

Animal models of age related macular degeneration  

PubMed Central

Age related macular degeneration (AMD) is the leading cause of vision loss of those over the age of 65 in the industrialized world. The prevalence and need to develop effective treatments for AMD has lead to the development of multiple animal models. AMD is a complex and heterogeneous disease that involves the interaction of both genetic and environmental factors with the unique anatomy of the human macula. Models in mice, rats, rabbits, pigs and non-human primates have recreated many of the histological features of AMD and provided much insight into the underlying pathological mechanisms of this disease. In spite of the large number of models developed, no one model yet recapitulates all of the features of human AMD. However, these models have helped reveal the roles of chronic oxidative damage, inflammation and immune dysregulation, and lipid metabolism in the development of AMD. Models for induced choroidal neovascularization have served as the backbone for testing new therapies. This article will review the diversity of animal models that exist for AMD as well as their strengths and limitations. PMID:22705444

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

2013-01-01

153

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

154

Determination of source terms in a degenerate parabolic equation  

NASA Astrophysics Data System (ADS)

In this paper, we prove Lipschitz stability results for inverse source problems relative to parabolic equations. We use the method introduced by Imanuvilov and Yamamoto in 1998 based on Carleman estimates. What is new here is that we study a class of one-dimensional degenerate parabolic equations. In our model, the diffusion coefficient vanishes at one extreme point of the domain. Instead of the classical Carleman estimates obtained by Fursikov and Imanuvilov for non degenerate equations, we use and extend some recent Carleman estimates for degenerate equations obtained by Cannarsa, Martinez and Vancostenoble. Finally, we obtain Lipschitz stability results in inverse source problems for our class of degenerate parabolic equations both in the case of a boundary observation and in the case of a locally distributed observation.

Cannarsa, P.; Tort, J.; Yamamoto, M.

2010-10-01

155

A uniqueness theorem for degenerate Kerr-Newman black holes  

E-print Network

We show that the domains of dependence of stationary, $I^+$-regular, analytic, electrovacuum space-times with a connected, non-empty, rotating, degenerate event horizon arise from Kerr-Newman space-times.

Piotr T. Chru?ciel; Luc Nguyen

2010-02-08

156

[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

157

Delivery systems for the treatment of degenerated intervertebral discs.  

PubMed

The intervertebral disc (IVD) is the most avascular and acellular tissue in the body and therefore prone to degeneration. During IVD degeneration, the balance between anabolic and catabolic processes in the disc is deregulated, amongst others leading to alteration of extracellular matrix production, abnormal enzyme activities and production of pro-inflammatory substances like cytokines. The established treatment strategy for IVD degeneration consists of physiotherapy, pain medication by drug therapy and if necessary surgery. This approach, however, has shown limited success. Alternative strategies to increase and prolong the effects of bioactive agents and to reverse the process of IVD degeneration include the use of delivery systems for drugs, proteins, cells and genes. In view of the specific anatomy and physiology of the IVD and depending on the strategy of the therapy, different delivery systems have been developed which are reviewed in this article. PMID:25451138

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

2014-10-25

158

Individual variations in hippocampal dentate degeneration following adrenalectomy.  

PubMed

Corticosterone appears to have two markedly different effects on cells of the hippocampus in rats. On one hand, elevated levels of corticosterone contribute to the degeneration of pyramidal cells. On the other hand, elimination of corticosterone by adrenalectomy may cause degeneration of dentate granule cells (Sloviter, Valiquette, Abrams, Ronk, Sollas, Paul, & Neubort, 1989). However, the latter response is variable. Low levels of corticoids from accessory adrenal tissue not consistently detectable by radioimmunoassay may provide sufficient hormone to maintain granule cell viability. We describe simple measures that predict which individual adrenalectomized rats have degeneration of the granule cell layer. Body weight gain after adrenalectomy is positively correlated with granule cell layer area at sacrifice 3 months after surgery. Also, short-term loss of body weight when saline drinking water is replaced with tap water predicts the degree of degeneration of the granule cell layer. These observations may aid further study of this striking effect of adrenal hormones on brain anatomy. PMID:2078164

Roy, E J; Lynn, D M; Bemm, C W

1990-11-01

159

Toric degenerations of Bezier patches Luis David Garcia-Puente  

E-print Network

Toric degenerations of B´ezier patches Luis David Garc´ia-Puente Sam Houston State University Format: Garc´ia-Puente, L. D., Sottile, F., and Zhu, C. G. 2010 Toric degeneration of B´ezier patches://doi.acm.org/10.1145/abcdefg.abcdefg Garc´ia-Puente and Sottile acknowledge a NHARP grant (010366-0054- 2007

Sottile, Frank

160

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

161

Linearization Technique for Source-Degenerated CMOS Differential Transconductors  

Microsoft Academic Search

A supplementary linearization technique for CMOS differential pairs with resistive source degeneration is proposed. The approach exploits an auxiliary (degenerated) differential pair to drive the bulk terminals of the main pair. Transistor-level simulations on a design using a 0.25-mum process and powered with 2.5 V and 1 mA, show that total harmonic distortion (THD) in the voltage-to-current conversion is decreased

Pietro Monsurro; Salvatore Pennisi; Giuseppe Scotti; Alessandro Trifiletti

2007-01-01

162

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

163

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

PubMed

Axonal degeneration is a prominent feature of amyotrophic lateral sclerosis (ALS) both in lower motor nerves as well as descending white matter axons in the spinal cord of human patients. Although the pathology of lower motor axonal degeneration has been described in both human ALS and related transgenic animal models, few studies have examined the pathological features of descending axon degeneration, particularly in mouse models of ALS. We have examined the degeneration of white matter tracts in the G93A mutant superoxide dismutase-1 (mSOD1+) mouse spinal cord white matter from 12 weeks of age to end-stage disease. In a G93A mSOD1 mouse model where green fluorescent protein was expressed in neurons (mSOD1+/GFP+), degeneration of white matter tracts was present from the ventral to dorsolateral funiculi. This pattern of axonal pathology occurred from 16 weeks of age. However, the dorsal funiculus, the site of the major corticospinal tract in mice, showed relatively less degeneration. Immunohistochemical analysis demonstrated that the neurofilament light chain (NFL) and neuronal intermediate filament protein alpha-internexin accumulated in axon swellings in the spinal white matter. Increased levels of alpha-internexin protein, in mSOD1+ mouse spinal cord tissue, were demonstrated by Western blotting. In contrast, degenerating axons did not show obvious accumulations of neurofilament medium and heavy chain proteins (NFM and NFH). These data suggest that white matter degeneration in this mouse model of ALS is widespread and involves a specific molecular signature, particularly the accumulation of NFL and alpha-internexin proteins. PMID:22609817

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

2012-07-17

164

Statins for age-related macular degeneration  

PubMed Central

Background Age-related macular degeneration (AMD) is a progressive late onset disorder of the macula affecting central vision. Age-related macular degeneration is the leading cause of blindness in people over 65 years in industrialized countries (Congdon 2003). Recent epidemiologic, genetic and pathological evidence has shown AMD shares a number of risk factors with atherosclerosis, leading to the hypothesis that statins may exert protective effects in AMD. Objectives To examine the effectiveness of statins compared with other treatments, no treatment, or placebo in delaying the onset and/or progression of AMD. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2011, Issue 9), MEDLINE (January 1950 to September 2011), EMBASE (January 1980 to September 2011), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to September 2011), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). There were no date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 16 September 2011. Selection criteria We included randomized controlled trials (RCTs) that compared statins with other treatments, no treatment, or placebo in participants who were either susceptible to or diagnosed as having early stages of AMD. Data collection and analysis Two authors independently evaluated the search results against the selection criteria. Two Italian speaking colleagues extracted data. One author entered data. We did not perform a meta-analysis because only one completed RCT was identified. Main results Two studies met the selection criteria. One trial reported insufficient details to assess the risk of bias; the other trial is ongoing. Of the completed trial, the analyses of 30 participants did not show a statistically significant difference between the simvastatin and the placebo arm in visual acuity at three months of treatment (decimal visual acuity 0.21± 0.56 in simvastatin and 0.19± 0.40 in placebo arm) or 45 days after the completion of treatment (decimal visual acuity 0.20± 0.50 in simvastatin and 0.19± 0.48 in placebo arm). The lens and retina status were unchanged during and after the treatment period for both groups. Of the ongoing trial, the preliminary analyses of 42 participants who completed 12 months follow-up did not show a statistically significant difference between the simvastatin and the placebo arm in visual acuity, drusen score or visual function (effect estimates and confidence intervals were not available). We contacted the investigators and will update the review as data become available. Authors' conclusions Evidence from currently available RCTs was insufficient to conclude that statins have any role in preventing or delaying the onset or progression of AMD. PMID:22419318

Gehlbach, Peter; Li, Tianjing; Hatef, Elham

2013-01-01

165

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

166

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

167

Treatment of macular degeneration, according to Bangerter.  

PubMed

Age-related macular degeneration (AMD) is a common cause of visual loss among elderly patients. Although some risk factors have been determined, the ultimate cause of the disease is not known. For a long time, therapeutic nihilism has been the rule among ophthalmologists confronted with such patients. Bangerter has not shared this attitude, especially since the time that he incidentally discovered, more than 40 years ago, the beneficial effects of radiotherapy, in discouraging the growth of new vessels at the posterior pole of the eye. A variety of approaches are combined and used by Bangerter in the treatment of the different types of AMD, including retrobulbar injections of either vasodilating medications (in the dry - or atrophic - type) or corticosteroids (in the wet - or exudative - type), general medical measures aimed at improving metabolic and vascular functions such as supplementation with trace elements, antioxidants, and vitamins; ozone therapy; advice to increase physical fitness, improve nutrition, and abstain from smoking; and protection from excessive light exposure. Being convinced of the usefulness of his type of combination treatment, he has always rejected undertaking controlled clinical trials, of only single aspects of the therapy, as unethical and invalid. For this reason, scientific journals have not proven cooperative in several attempts at publishing his results, as collected in retrospective surveys. Recently, however, some of the several approaches combined by Bangerter in treating AMD have been pronounced effective by other investigators. We present here an overview of his treatment approaches, as few people are aware of them, to clear up misconceptions and to set records straight. PMID:9348273

Teichmann, K D

1997-10-30

168

Criteria for the diagnosis of corticobasal degeneration  

PubMed Central

Current criteria for the clinical diagnosis of pathologically confirmed corticobasal degeneration (CBD) no longer reflect the expanding understanding of this disease and its clinicopathologic correlations. An international consortium of behavioral neurology, neuropsychology, and movement disorders specialists developed new criteria based on consensus and a systematic literature review. Clinical diagnoses (early or late) were identified for 267 nonoverlapping pathologically confirmed CBD cases from published reports and brain banks. Combined with consensus, 4 CBD phenotypes emerged: corticobasal syndrome (CBS), frontal behavioral-spatial syndrome (FBS), nonfluent/agrammatic variant of primary progressive aphasia (naPPA), and progressive supranuclear palsy syndrome (PSPS). Clinical features of CBD cases were extracted from descriptions of 209 brain bank and published patients, providing a comprehensive description of CBD and correcting common misconceptions. Clinical CBD phenotypes and features were combined to create 2 sets of criteria: more specific clinical research criteria for probable CBD and broader criteria for possible CBD that are more inclusive but have a higher chance to detect other tau-based pathologies. Probable CBD criteria require insidious onset and gradual progression for at least 1 year, age at onset ?50 years, no similar family history or known tau mutations, and a clinical phenotype of probable CBS or either FBS or naPPA with at least 1 CBS feature. The possible CBD category uses similar criteria but has no restrictions on age or family history, allows tau mutations, permits less rigorous phenotype fulfillment, and includes a PSPS phenotype. Future validation and refinement of the proposed criteria are needed. PMID:23359374

Armstrong, Melissa J.; Lang, Anthony E.; Bak, Thomas H.; Bhatia, Kailash P.; Borroni, Barbara; Boxer, Adam L.; Dickson, Dennis W.; Grossman, Murray; Hallett, Mark; Josephs, Keith A.; Kertesz, Andrew; Lee, Suzee E.; Miller, Bruce L.; Reich, Stephen G.; Riley, David E.; Tolosa, Eduardo; Tröster, Alexander I.; Vidailhet, Marie; Weiner, William J.

2013-01-01

169

Endothelin-2-Mediated Protection of Mutant Photoreceptors in Inherited Photoreceptor Degeneration  

PubMed Central

Expression of the Endothelin-2 (Edn2) mRNA is greatly increased in the photoreceptors (PRs) of mouse models of inherited PR degeneration (IPD). To examine the role of Edn2 in mutant PR survival, we generated Edn2?/? mice carrying homozygous Pde6brd1 alleles or the Tg(RHO P347S) transgene. In the Edn2?/? background, PR survival increased 110% in Pde6brd1/rd1 mice at post-natal (PN) day 15, and 60% in Tg(RHO P347S) mice at PN40. In contrast, PR survival was not increased in retinal explants of Pde6brd1/rd1; Edn2?/? mice. This finding, together with systemic abnormalities in Edn2?/? mice, suggested that the increased survival of mutant PRs in the Edn2?/? background resulted at least partly from the systemic EDN2 loss of function. To examine directly the role of EDN2 in mutant PRs, we used a scAAV5-Edn2 cDNA vector to restore Edn2 expression in Pde6brd1/rd1; Edn2?/? PRs and observed an 18% increase in PR survival at PN14. Importantly, PR survival was also increased after injection of scAAV5-Edn2 into Pde6brd1/rd1 retinas, by 31% at PN15. Together, these findings suggest that increased Edn2 expression is protective to mutant PRs. To begin to elucidate Edn2-mediated mechanisms that contribute to PR survival, we used microarray analysis and identified a cohort of 20 genes with >4-fold increased expression in Tg(RHO P347S) retinas, including Fgf2. Notably, increased expression of the FGF2 protein in Tg(RHO P347S) PRs was ablated in Tg(RHO P347S); Edn2?/? retinas. Our findings indicate that the increased expression of PR Edn2 increases PR survival, and suggest that the Edn2-dependent increase in PR expression of FGF2 may contribute to the augmented survival. PMID:23469133

Bramall, Alexa N.; Szego, Michael J.; Pacione, Laura R.; Chang, Inik; Diez, Eduardo; D'Orleans-Juste, Pedro; Stewart, Duncan J.; Hauswirth, William W.; Yanagisawa, Masashi; McInnes, Roderick R.

2013-01-01

170

A Novel Form of Transducin-Dependent Retinal Degeneration: Accelerated Retinal Degeneration in the Absence of Rod Transducin  

PubMed Central

PURPOSE Rhodopsin mutations account for approximately 25% of human autosomal dominant retinal degenerations. However, the molecular mechanisms by which rhodopsin mutations cause photoreceptor cell death are unclear. Mutations in genes involved in the termination of rhodopsin signaling activity have been shown to cause degeneration by persistent activation of the phototransduction cascade. This study examined whether three disease-associated rhodopsin substitutions Pro347Ser, Lys296Glu, and the triple mutant Val20Gly, Pro23His, Pro27Leu (VPP) caused degeneration by persistent transducin-mediated signaling activity. METHODS Transgenic mice expressing each of the rhodopsin mutants were crossed onto a transducin ?-subunit null (Tr??/?) background, and the rates of photoreceptor degeneration were compared with those of transgenic mice on a wild-type background. RESULTS Mice expressing VPP-substituted rhodopsin had the same severity of degeneration in the presence or absence of Tr?. Unexpectedly, mice expressing Pro347Ser- or Lys296Glu-substituted rhodopsins exhibited faster degeneration on a Tr??/? background. To test whether the absence of ?-transducin contributed to degeneration by favoring the formation of stable rhodopsin/arrestin complexes, mutant Pro347Ser+, Tr??/? mice lacking arrestin (Arr?/?) were analyzed. Rhodopsin/arrestin complexes were found not to contribute to degeneration. CONCLUSIONS The authors hypothesized that the decay of metarhodopsin to apo-opsin and free all-trans-retinaldehyde is faster with Pro347Ser-substituted rhodopsin than it is with wild-type rhodopsin. Consistent with this, the lipofuscin fluorophores A2PE, A2E, and A2PE-H2, which form from retinaldehyde, were elevated in Pro347Ser transgenic mice. PMID:18055791

Brill, Elliott; Malanson, Katherine M.; Radu, Roxana A.; Boukharov, Natalia V.; Wang, Zhongyan; Chung, Hae-Yun; Lloyd, Marcia B.; Bok, Dean; Travis, Gabriel H.; Obin, Martin; Lem, Janis

2008-01-01

171

Retinal degeneration modulates intracellular localization of CDC42 in photoreceptors  

PubMed Central

Purpose Rho GTPases such as RAS-related C3 botulinum substrate 1 (RAC1) and cell division cycle 42 homolog (S. cerevisiae; CDC42) have been linked to cellular processes including movement, development, and apoptosis. Recently, RAC1 has been shown to be a pro-apoptotic factor in the retina during light-induced photoreceptor degeneration. Here, we analyzed the role of CDC42 in the degenerating retina. Methods Photoreceptor degeneration was studied in a mouse model for autosomal dominant retinitis pigmentosa (VPP) with or without a rod-specific knockdown of Cdc42, as well as in wild-type and Cdc42 knockdown mice after light exposure. Gene and protein expression were analyzed by real-time PCR, western blotting, and immunofluorescence. Retinal morphology and function were assessed by light microscopy and electroretinography, respectively. Results CDC42 accumulated in the perinuclear region of terminal deoxynucleotidyl transferase dUTP nick end labeling–negative photoreceptors during retinal degeneration induced by excessive light exposure and in the rd1, rd10, and VPP mouse models of retinitis pigmentosa. The knockdown of Cdc42 did not affect retinal morphology or function in the adult mice and did not influence photoreceptor apoptosis or molecular signaling during induced and inherited retinal degeneration. Conclusions Retinal degeneration induces the accumulation of CDC42 in the perinuclear region of photoreceptors. In contrast to RAC1, however, lack of CDC42 does not affect the progression of degeneration. CDC42 is also dispensable for normal morphology and function of adult rod photoreceptor cells. Received: May 25, 2011 Accepted: November 10, 2011 PMID:22128240

Tanimoto, N.; Joly, S.; Seeliger, M.W.; Samardzija, M.; Grimm, C.

2011-01-01

172

Effects of bone cement on intervertebral disc degeneration  

PubMed Central

Percutaneous vertebroplasty (PVP) is popular for the treatment of intractable pain due to vertebral collapse from various lesions, intervertebral disk leakage of cement is a frequent complication. The aim of this study was to determine whether bone cement causes disc degeneration, and to evaluate the degree of intervertebral disc degeneration (IDD) according to the time period following cement injection, and the type and volume of cement injected. Sixteen dogs were randomly divided into two groups that were sacrificed at 12 or 24 weeks following cement injection. Five intervertebral discs in each dog were studied, including one control untreated disc and four discs randomly injected with polymethylmethacrylate (PMMA) or calcium phosphate cement (CPC) in two quantities. Radiographic and magnetic resonance imaging (MRI) studies were performed prior to animal sacrifice. T2-weighted mid-sagittal images of the discs were qualitatively analyzed for evidence of degeneration by calculating the MRI index, and all harvested discs were studied histopathologically. IDD was not evident in control discs. Univariate analysis revealed significant differences in the MRI index and the histological grade of disc degeneration in terms of the time period following cement injection, as well as the type and volume of cement injected. Result indicate that direct contact with PMMA and CPC can lead to IDD. However, IDD induced by PMMA was more severe than that induced by CPC. The extent of IDD was found to correlate with the time period post-cement injection and the volume of cement injected into the disc. PMMA and CPC may lead to intervertebral disc degeneration. Intervertebral disc degeneration induced by PMMA is more serious than that of CPC. The degree of intervertebral disc degeneration is correlative to the time after operation and the doses of bone cement. PMID:24669259

ZHAO, HUI; NI, CAI-FANG; HUANG, JIAN; ZHAO, SU-MING; GU, WEI-WEI; JIANG, HAO; CHEN, LONG; TAN, TIAN-SI

2014-01-01

173

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

174

ZFN-Site searches genomes for zinc finger nuclease target sites and off-target sites  

PubMed Central

Background Zinc Finger Nucleases (ZFNs) are man-made restriction enzymes useful for manipulating genomes by cleaving target DNA sequences. ZFNs allow therapeutic gene correction or creation of genetically modified model organisms. ZFN specificity is not absolute; therefore, it is essential to select ZFN target sites without similar genomic off-target sites. It is important to assay for off-target cleavage events at sites similar to the target sequence. Results ZFN-Site is a web interface that searches multiple genomes for ZFN off-target sites. Queries can be based on the target sequence or can be expanded using degenerate specificity to account for known ZFN binding preferences. ZFN off-target sites are outputted with links to genome browsers, facilitating off-target cleavage site screening. We verified ZFN-Site using previously published ZFN half-sites and located their target sites and their previously described off-target sites. While we have tailored this tool to ZFNs, ZFN-Site can also be used to find potential off-target sites for other nucleases, such as TALE nucleases. Conclusions ZFN-Site facilitates genome searches for possible ZFN cleavage sites based on user-defined stringency limits. ZFN-Site is an improvement over other methods because the FetchGWI search engine uses an indexed search of genome sequences for all ZFN target sites and possible off-target sites matching the half-sites and stringency limits. Therefore, ZFN-Site does not miss potential off-target sites. PMID:21569489

2011-01-01

175

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

176

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

177

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

178

Degenerate ground state and quantum tunneling in rotating condensates  

E-print Network

Quantum tunneling introduces a fundamental difference between classical and quantum mechanics. Whenever the classical ground state is non-unique (degenerate), quantum mechanics restore uniqueness thanks to tunneling. A condensate in a rotating trap with a vortex can have such a degenerate classical ground state, a degeneracy that is excluded in the absence of rotation at least when the Gross-Pitaevskii equation applies. If the rotating trap has a center of symmetry, like a figure eight (a peanut), the vortex may be on either side with the same energy yielding a degenerate ground state, a degeneracy lifted by quantum tunneling. We explain how to compute the rate of tunneling in the WKB limit by estimating the action of the trajectory in the Euclidean version of the dynamics.

Qiang Du; Martine Le Berre; Yves Pomeau

2012-09-07

179

Reprogramming of adult rod photoreceptors prevents retinal degeneration  

PubMed Central

A prime goal of regenerative medicine is to direct cell fates in a therapeutically useful manner. Retinitis pigmentosa is one of the most common degenerative diseases of the eye and is associated with early rod photoreceptor death followed by secondary cone degeneration. We hypothesized that converting adult rods into cones, via knockdown of the rod photoreceptor determinant Nrl, could make the cells resistant to the effects of mutations in rod-specific genes, thereby preventing secondary cone loss. To test this idea, we engineered a tamoxifen-inducible allele of Nrl to acutely inactivate the gene in adult rods. This manipulation resulted in reprogramming of rods into cells with a variety of cone-like molecular, histologic, and functional properties. Moreover, reprogramming of adult rods achieved cellular and functional rescue of retinal degeneration in a mouse model of retinitis pigmentosa. These findings suggest that elimination of Nrl in adult rods may represent a unique therapy for retinal degeneration. PMID:23319618

Montana, Cynthia L.; Kolesnikov, Alexander V.; Shen, Susan Q.; Myers, Connie A.; Kefalov, Vladimir J.; Corbo, Joseph C.

2013-01-01

180

Spectra of Type Ia Supernovae from Double Degenerate Mergers  

E-print Network

The merger of two white dwarfs (a.k.a. double degenerate merger) has often been cited as a potential progenitor of type Ia supernovae. Here we combine population synthesis, merger and explosion models with radiation-hydrodynamics light-curve models to study the implications of such a progenitor scenario on the observed type Ia supernova population. Our standard model, assuming double degenerate mergers do produce thermonuclear explosions, produces supernova light-curves that are broader than the observed type Ia sample. In addition, we discuss how the shock breakout and spectral features of these double degenerate progenitors will differ from the canonical bare Chandrasekhar-massed explosion models. We conclude with a discussion of how one might reconcile these differences with current observations.

Fryer, Chris L; Belczynski, Krzysztof; Brown, Peter J; Bufano, Filomena; Diehl, Steven; Fontes, Christopher J; Frey, Lucille H; Holland, Stephen T; Hungerford, Aimee L; Immler, Stefan; Mazzali, Paolo; Meakin, Casey; Milne, Peter A; Raskin, Cody; Timmes, Francis X

2010-01-01

181

Oxidative damage to mitochondria at the nodes of Ranvier precedes axon degeneration in ex vivo transected axons.  

PubMed

Oxidative stress and mitochondrial dysfunction appear to contribute to axon degeneration in numerous neurological disorders. However, how these two processes interact to cause axonal damage-and how this damage is initiated-remains unclear. In this study we used transected motor axons from murine peripheral roots to investigate whether oxidative stress alters mitochondrial dynamics in myelinated axons. We show that the nodes of Ranvier are the initial sites of mitochondrial damage induced by oxidative stress. There, mitochondria became depolarized, followed by alterations of the external morphology and disruption of the cristae, along with reduced mitochondrial transport. These mitochondrial changes expanded from the nodes of Ranvier bidirectionally towards both internodes and eventually affected the entire mitochondrial population in the axon. Supplementing axonal bioenergetics by applying nicotinamide adenine dinucleotide and methyl pyruvate, rendered the mitochondria at the nodes of Ranvier resistant to these oxidative stress-induced changes. Importantly, this inhibition of mitochondrial damage protected the axons from degeneration. In conclusion, we present a novel ex vivo approach for monitoring mitochondrial dynamics within axons, which proved suitable for detecting mitochondrial changes upon exogenous application of oxidative stress. Our results indicate that the nodes of Ranvier are the site of initial mitochondrial damage in peripheral axons, and suggest that dysregulation of axonal bioenergetics plays a critical role in oxidative stress-triggered mitochondrial alterations and subsequent axonal injury. These novel insights into the mechanisms underlying axon degeneration may have implications for neurological disorders with a degenerative component. PMID:24973623

Bros, Helena; Millward, Jason M; Paul, Friedemann; Niesner, Raluca; Infante-Duarte, Carmen

2014-11-01

182

Nerve fiber layer (NFL) degeneration associated with acute q-switched laser exposure in the nonhuman primate  

NASA Astrophysics Data System (ADS)

We have evaluated acute laser retinal exposure in non-human primates using a Rodenstock scanning laser ophthalmoscope (SLO) equipped with spectral imaging laser sources at 488, 514, 633, and 780 nm. Confocal spectral imaging at each laser wavelength allowed evaluation of the image plane from deep within the retinal vascular layer to the more superficial nerve fiber layer in the presence and absence of the short wavelength absorption of the macular pigment. SLO angiography included both fluorescein and indocyanine green procedures to assess the extent of damage to the sensory retina, the retinal pigment epithelium (RPE), and the choroidal vasculature. All laser exposures in this experiment were from a Q-switched Neodymium laser source at an exposure level sufficient to produce vitreous hemorrhage. Confocal imaging of the nerve fiber layer revealed discrete optic nerve sector defects between the lesion site and the macula (retrograde degeneration) as well as between the lesion site and the optic disk (Wallerian degeneration). In multiple hemorrhagic exposures, lesions placed progressively distant from the macula or overlapping the macula formed bridging scars visible at deep retinal levels. Angiography revealed blood flow disturbance at the retina as well as at the choroidal vascular level. These data suggest that acute parafoveal laser retinal injury can involve both direct full thickness damage to the sensory and non-sensory retina and remote nerve fiber degeneration. Such injury has serious functional implications for both central and peripheral visual function.

Zwick, Harry; Zuclich, Joseph A.; Stuck, Bruce E.; Gagliano, Donald A.; Lund, David J.; Glickman, Randolph D.

1995-01-01

183

Myelin sheath survival after guanethidine-induced axonal degeneration  

PubMed Central

Membrane-membrane interactions between axons and Schwann cells are required for initial myelin formation in the peripheral nervous system. However, recent studies of double myelination in sympathetic nerve have indicated that myelin sheaths continue to exist after complete loss of axonal contact (Kidd, G. J., and J. W. Heath. 1988. J. Neurocytol. 17:245-261). This suggests that myelin maintenance may be regulated either by diffusible axonal factors or by nonaxonal mechanisms. To test these hypotheses, axons involved in double myelination in the rat superior cervical ganglion were destroyed by chronic guanethidine treatment. Guanethidine-induced sympathectomy resulted in a Wallerian- like pattern of myelin degeneration within 10 d. In doubly myelinated configurations the axon, inner myelin sheath (which lies in contact with the axon), and approximately 75% of outer myelin sheaths broke down by this time. Degenerating outer sheaths were not found at later periods. It is probably that outer sheaths that degenerated were only partially displaced from the axon at the commencement of guanethidine treatment. In contrast, analysis of serial sections showed that completely displaced outer internodes remained ultrastructurally intact. These internodes survived degeneration of the axon and inner sheath, and during the later time points (2-6 wk) they enclosed only connective tissue elements and reorganized Schwann cells/processes. Axonal regeneration was not observed within surviving outer internodes. We therefore conclude that myelin maintenance in the superior cervical ganglion is not dependent on direct axonal contact or diffusible axonal factors. In addition, physical association of Schwann cells with the degenerating axon may be an important factor in precipitating myelin breakdown during Wallerian degeneration. PMID:1730762

1992-01-01

184

Thalamo-olivary degeneration in a patient with laryngopharyngeal dystonia.  

PubMed

A 67 year old woman with a two year history of laryngopharyngeal dystonia, spasmodic dysphonia, and parkinsonism succumbed to Wernicke's encephalopathy and died six months later. Necropsy showed, besides Wernicke's encephalopathy, degenerative changes in selected thalamic nuclei (dorsomedial, pulvinar, and the medial geniculate bodies) and the inferior olives and numerous cerebellar torpedoes. The substantia nigra and basal ganglia were spared. Immunostaining for prion protein was negative. This patient indicated a new type of presentation of so-called pure thalamic degeneration, or more precisely thalamo-olivary degeneration. PMID:7561927

Yamamoto, T; Yamashita, M

1995-10-01

185

Thalamic degeneration in X-chromosome--linked copper malabsorption.  

PubMed

Thalamic degeneration was present in 5 autopsied cases of X-chromosome-linked copper malabsorption (X-cLCM), Menkes' kinky hair disease. Among the thalamic nuclei, those in the formatio paraventricularis, intralamellaris, and extralamellaris were spared. The nuclei projecting to the granular cortices had severe neuronal depopulation. The thalamic nuclei that send axons to the agranular cortices were less often and less severely involved. The thalamic afferent system was intact except for degeneration of the red nucleus. Cerebral cortical lesions varied from case to case and usually were less marked than thalamic neuronal changes. PMID:443770

Iwata, M; Hirano, A; French, J H

1979-04-01

186

Local convergence of interior-point algorithms for degenerate LCP  

SciTech Connect

Most asymptotic convergence analysis of interior-point algorithms for monotone linear complementarily problems assumes that the problem is nondegenerate, that is, the solution set contains a strictly complementary solution. We investigate the behavior of these algorithms when this assumption is removed. We show that a large class of infeasible-interior point algorithms can not achieve superlinear convergence when the LCP is degenerate. We also give a feasible interior-point algorithm for degenerate monotone LCP with a reasonable linear rate, depending on the {open_quotes}size{close_quotes} of the degeneracy.

Monteiro, R.D.C.; Wright, S.

1994-12-31

187

Mouse models for studies of retinal degeneration and diseases  

PubMed Central

Summary Mouse models, with their well-developed genetics and similarity to human physiology and anatomy, serve as powerful tools with which to investigate the etiology of human retinal degeneration. Mutant mice also provide reproducible, experimental systems for elucidating pathways of normal development and function. Here, I describe the tools used in the discoveries of many retinal degeneration models, including indirect ophthalmoscopy (to look at the fundus appearance), fundus photography and fluorescein angiography (to document the fundus appearance), electroretinography (to check retinal function) as well as the heritability test (for genetic characterization). PMID:23150358

Chang, Bo

2013-01-01

188

Polarization degenerate micropillars fabricated by designing elliptical oxide apertures  

E-print Network

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

Morten P. Bakker; Ajit V. Barve; Alan Zhan; Larry A. Coldren; Martin P. van Exter; Dirk Bouwmeester

2014-04-17

189

Polarization degenerate micropillars fabricated by designing elliptical oxide apertures  

E-print Network

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

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

2014-01-01

190

Polarization degenerate micropillars fabricated by designing elliptical oxide apertures  

NASA Astrophysics Data System (ADS)

A method for fabrication of polarization degenerate oxide apertured micropillar cavities is demonstrated. Micropillars are etched such that the size and shape of the oxide front is controlled. The polarization splitting in the circular micropillar cavities due to the native and strain induced birefringence can be compensated by elongating the oxide front in the [110] direction, thereby reducing stress in this direction. By using this technique, we fabricate a polarization degenerate cavity with a quality factor of 1.7 × 104 and a mode volume of 2.7 ?m3, enabling a calculated maximum Purcell factor of 11.

Bakker, Morten P.; Barve, Ajit V.; Zhan, Alan; Coldren, Larry A.; van Exter, Martin P.; Bouwmeester, Dirk

2014-04-01

191

N=2 gauge theories and degenerate fields of Toda theory  

SciTech Connect

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

Kanno, Shoichi; Matsuo, Yutaka; Shiba, Shotaro [Department of Physics, Faculty of Science, University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Tachikawa, Yuji [School of Natural Sciences, Institute for Advanced Study, Princeton, New Jersey 08540 (United States)

2010-02-15

192

Adiabatic Perturbation Theory and Geometric Phases for Degenerate Systems  

E-print Network

We introduce an adiabatic perturbation theory for quantum systems with degenerate energy spectra. This perturbative series enables one to rigorously establish conditions for the validity of the adiabatic theorem of quantum mechanics for degenerate systems. The same formalism can be used to find non-adiabatic corrections to the non-Abelian Wilczek-Zee geometric phase. These corrections are relevant to assess the validity of the practical implementation of the concept of fractional exchange statistics. We illustrate the formalism by exactly solving a time-dependent problem and comparing its solution to the perturbative one.

Gustavo Rigolin; Gerardo Ortiz

2010-05-04

193

Coherent bimolecular reactions with quantum-degenerate matter waves  

NASA Astrophysics Data System (ADS)

We demonstrate theoretically that the abstraction reaction A+B2?AB+B can be driven coherently and efficiently with quantum-degenerate bosonic or fermionic matter waves. We show that the initial stages of the reaction are dominated by quantum fluctuations, resulting in the appearance of macroscopic nonclassical correlations in the final atomic and molecular fields. The dynamics associated with the creation of bosonic and of fermionic dimer-atom pairs is also compared. This study opens up a promising regime of quantum-degenerate matter-wave chemistry.

Jing, H.; Cheng, J.; Meystre, P.

2009-02-01

194

Intramuscular iron therapy and tapetoretinal degeneration. A case report.  

PubMed

A 63-years-old male with pernicious anemia had been treated for 20 years with weekly injections of iron-dextran and cyanocobalamine. Ophthalmological examination revealed the ophthalmoscopic picture of a tapetoretinal degeneration, reduced visual acuity and narrow visual fields. ERG and dark-adaptation test were normal. Hematological examination including liver and bone marrow biopsies gave no support for the existence of systemic siderosis. It is proposed that the retinal degeneration is due to the extensive parenteral iron treatment with a total dose of approximately 100 grams of iron. This theory is supported by a previous experimental report. PMID:474082

Syversen, K

1979-06-01

195

Degenerate band edge resonances in coupled periodic silicon optical waveguides.  

PubMed

Using full three-dimensional analysis we show that coupled periodic optical waveguides can exhibit a giant slow light resonance associated with a degenerate photonic band edge. We consider the silicon-on-insulator material system for implementation in silicon photonics at optical telecommunications wavelengths. The coupling of the resonance mode with the input light can be controlled continuously by varying the input power ratio and the phase difference between the two input arms. Near unity transmission efficiency through the degenerate band edge structure can be achieved, enabling exploitation of the advantages of the giant slow wave resonance. PMID:23571962

Burr, Justin R; Gutman, Nadav; de Sterke, C Martijn; Vitebskiy, Ilya; Reano, Ronald M

2013-04-01

196

Selective Rod Degeneration and Partial Cone Inactivation Characterize an Iodoacetic Acid Model of Swine Retinal Degeneration  

PubMed Central

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; de Castro, Juan Fernandez; Vukmanic, Eric; Zhou, Liang; Emery, Douglas; DeMarco, Paul J.; Kaplan, Henry J.

2011-01-01

197

The minimal degeneration singularities in the affine Grassmannians  

Microsoft Academic Search

The minimal degeneration singularities in the affine Grassmannians\\u000aof simple simply laced algebraic groups are determined to be\\u000aeither Kleinian singularities of type A or closures of minimal\\u000anilpotent orbits. The singularities for non-simply laced types\\u000aare studied by intersection cohomology and equivariant Chow group\\u000amethods.

Anton Malkin; Viktor Ostrik; Maxim Vybornov

198

The minimal degeneration singularities in the affine Grassmannians  

Microsoft Academic Search

The minimal degeneration singularities in the affine Grassmannians of simple simply-laced algebraic groups are determined to be either Kleinian singularities of type A, or closures of minimal orbits in nilpotent cones. The singularities for non-simply-laced types are studied by intersection cohomology and equivariant Chow group methods.

Anton Malkin; Viktor Ostrik; Maxim Vybornov

2003-01-01

199

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

200

Tau epitope display in progressive supranuclear palsy and corticobasal degeneration  

Microsoft Academic Search

Filamentous aggregates of the protein tau are a prominent feature of Alzheimer's disease (AD), progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). However, the extent to which the molecular structure of the tau in these aggregates is similar or differs between these diseases is unclear. We approached this question by examining these disorders with a panel of antibodies that represent

R. W. Berry; A. P. Sweet; F. A. Clark; S. Lagalwar; B. R. Lapin; T. Wang; S. Topgi; A. L. Guillozet-Bongaarts; E. J. Cochran; E. H. Bigio; L. I. Binder

2004-01-01

201

NUTRITIONAL SUPPLEMENTATION, CATARACTS AND AGE-RELATED MACULAR DEGENERATION  

Technology Transfer Automated Retrieval System (TEKTRAN)

Age-related cataract and age-related macular degeneration (AMD) are the major causes of visual impairment and blindness in the aging population. Specific nutrients in the diet that are thought to be important in the prevention of these diseases are vitamins C and E, the carotenoids, lutein and zeaxa...

202

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...

203

Degenerate atom-molecule mixture in a cold Fermi gas  

SciTech Connect

We show that the atom-molecule mixture formed in a degenerate atomic Fermi gas with interspecies repulsion near a Feshbach resonance constitutes a peculiar system where the atomic component is almost nondegenerate but quantum degeneracy of molecules is important. We develop a thermodynamic approach for studying this mixture, explain experimental observations, and predict optimal conditions for achieving molecular Bose-Einstein condensation.

Kokkelmans, S.J.J.M.F.; Salomon, C. [Laboratoire Kastler Brossel, Ecole Normale Superieure, 24 rue Lhomond, 75231 Paris 05 (France); Shlyapnikov, G.V. [Laboratoire Kastler Brossel, Ecole Normale Superieure, 24 rue Lhomond, 75231 Paris 05 (France); FOM Institute AMOLF, Kruislaan 407, 1098 SJ Amsterdam (Netherlands); Russian Research Center Kurchatov Institute, Kurchatov Square, 123182 Moscow (Russian Federation)

2004-03-01

204

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

ERIC Educational Resources Information Center

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

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

2012-01-01

205

On the Cahn–Hilliard Equation with Degenerate Mobility  

Microsoft Academic Search

An existence result for the Cahn-Hilliard equation with a concentration dependent diffusional mobility is presented. In particular the mobility is allowed to vanish when the scaled concentration takes the values \\\\Sigma1 and it is shown that the solution is bounded by 1 in magnitude. Finally applications of our method to other degenerate fourth order parabolic equations are discussed.

Charles M. Elliott; Harald Garcke

1996-01-01

206

Calpains mediate axonal cytoskeleton disintegration during Wallerian degeneration  

PubMed Central

In both the central nervous system (CNS) and peripheral nervous system (PNS), transected axons undergo Wallerian degeneration. Even though Augustus Waller first described this process after transection of axons in 1850, the molecular mechanisms may be shared, at least in part, by many human diseases. Early pathology includes failure of synaptic transmission, target denervation, and granular disintegration of the axonal cytoskeleton (GDC). The Ca2+-dependent proteases calpains have been implicated in GDC but causality has not been established. To test the hypothesis that calpains play a causal role in axonal and synaptic degeneration in vivo, we studied transgenic mice that express human calpastatin (hCAST), the endogenous calpain inhibitor, in optic and sciatic nerve axons. Five days after optic nerve transection and 48 hours after sciatic nerve transection, robust neurofilament proteolysis observed in wild-type controls was reduced in hCAST transgenic mice. Protection of the axonal cytoskeleton in sciatic nerves of hCAST mice was nearly complete 48 hours post-transection. In addition, hCAST expression preserved the morphological integrity of neuromuscular junctions. However, compound muscle action potential amplitudes after nerve transection were similar in wild-type and hCAST mice. These results, in total, provide direct evidence that calpains are responsible for the morphological degeneration of the axon and synapse during Wallerian degeneration. PMID:23542511

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

2013-01-01

207

Efficient mode transformations of degenerate LaguerreGaussian beams  

E-print Network

Efficient mode transformations of degenerate Laguerre­Gaussian beams Galina Machavariani, Amiel A for efficient conversion of a single-high-order-mode distribution from a laser to a nearly Gaussian distribution with several conversion arrangements are presented. The results reveal that conversion efficiency is typically

Friesem, Asher A.

208

A New Merging Double Degenerate Binary in the Solar Neighborhood  

E-print Network

Characterizing the local space density of double degenerate binary systems is a complementary approach to broad sky surveys of double degenerates to determine the expected rates of white dwarf binary mergers, in particular those that may evolve into other observable phenomena such as extreme helium stars, Am CVn systems, and supernovae Ia. However, there have been few such systems detected in local space. We report here the discovery that WD 1242$-$105, a nearby bright WD, is a double-line spectroscopic binary consisting of two degenerate DA white dwarfs of similar mass and temperature, despite it previously having been spectroscopically characterized as a single degenerate. Follow-up photometry, spectroscopy, and trigonometric parallax have been obtained in an effort to determine the fundamental parameters of each component of this system. The binary has a mass ratio of 0.7 and a trigonometric parallax of 25.5 mas, placing it at a distance of 39 pc. The system's total mass is 0.95 M$_\\odot$ and has an orbita...

Debes, John H; Tremblay, Pier-Emmanuel; López-Morales, Mercedes; Anglada-Escudé, Guillem; Napiwotzki, Ralf; Osip, David; Weinberger, Alycia

2015-01-01

209

Mechanism of Alzheimer neurofibrillary degeneration and the formation of tangles  

Microsoft Academic Search

The microtubule-associated protein (MAP) tau, which is abnormally hyperphosphorylated in the brain of patients with Alzheimer disease, sequesters normal MAPs and disassembles microtubules. The association between the abnormal tau and normal tau, and not MAP1 or MAP2, produces tangles of filaments. The breakdown of microtubule network most likely results in compromised axonal transport and retrograde degeneration of the affected neurons.

K Iqbal; I Grundke-Iqbal

1997-01-01

210

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

211

Histopathological changes underlying frontotemporal lobar degeneration with clinicopathological correlation  

Microsoft Academic Search

We have investigated the pathological correlates of dementia in the brains from a consecutive series of 70 patients dying with a clinical diagnosis of frontotemporal lobar degeneration (FTLD). Clinical misdiagnosis rate was low with only 3 patients (4%) failing to show pathological changes consistent with this diagnosis; 1 patient had Alzheimer’s disease and 2 had cerebrovascular disease (CVD). In the

Jing Shi; Catherine L. Shaw; Daniel Du Plessis; Anna M. T. Richardson; Kathryn L. Bailey; Camille Julien; Cheryl Stopford; Jennifer Thompson; Anoop Varma; David Craufurd; Jinzhou Tian; Stuart Pickering-Brown; David Neary; Julie S. Snowden; David M. A. Mann

2005-01-01

212

Why study rod cell death in retinal degenerations and how?  

Microsoft Academic Search

Age-related macular degeneration (AMD) is a main causes of severe visual impairment in the elderly in industrialized countries. The pathogenesis of this complex diseases is largely unknown, even though clinical characteristics and histopathology are well described. Because several aging changes are identical to those observed in AMD, there appears to exist an unknown switch mechanism from normal ageing to disease.

C. E. Remé; C. Grimm; F. Hafezi; H.-P. Iseli; A. Wenzel

2003-01-01

213

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

214

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

215

White Dwarf Properties and the Degenerate Electron Gas  

E-print Network

White Dwarf Properties and the Degenerate Electron Gas Nicholas Rowell April 10, 2008 Contents 1 . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 3.2 Consequences for the Mass of White Dwarfs . . . . . . . . . . . . . . . . . . . . 7 3 1 Introduction White dwarfs are the second most common type of star in the Galaxy, and represent

Tittley, Eric

216

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.

217

Superlinearly Convergent Infeasible-Interior-Point Algorithm for Degenerate LCP  

Microsoft Academic Search

A large-step infeasible path-following method is proposed for solving general linear complementarity problems with sufficient matrices. If the problem has a solution, the algorithm is superlinearly convergent from any positive starting points, even for degenerate problems. The algorithm generates points in a large neighborhood of the central path. Each iteration requires only one matrix factorization and at most three (asymptotically

F. A. Potra; R. Sheng

1998-01-01

218

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

219

Progressive Neuronal Degeneration of Childhood (PNDC) with Liver Disease  

Microsoft Academic Search

Thirteen children with progressive neuronal degeneration and liver disease are reported. Clinical features included developmental delay after a normal initial period with later onset of intractable epilepsy. The EEG showed an unusual but characteristic pattern, and visual evoked responses (VER) were abnormal. Rapidly progressive cerebral atrophy was seen on computerized axial tomography (CAT). Inheritance was consistent with an autosomal recessive

J. Egger; B. N. Harding; S. G. Boyd; J. Wilson; M. Erdohazi

1987-01-01

220

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

221

PGC-1? Regulation of Mitochondrial Degeneration in Experimental Diabetic Neuropathy  

PubMed Central

Mitochondrial degeneration is considered to play an important role in the development of diabetic peripheral neuropathy in humans. Mitochondrial degeneration and the corresponding protein regulation associated with the degeneration were studied in an animal model of diabetic neuropathy. PGC-1? and its-regulated transcription factors including TFAM and NRF1, which are master regulators of mitochondrial biogenesis, are significantly downregulated in streptozotocin diabetic dorsal root ganglion (DRG) neurons. Diabetic mice develop peripheral neuropathy, loss of mitochondria, decreased mitochondrial DNA content and increased protein oxidation. Importantly, this phenotype is exacerbated in PGC-1? (?/?) diabetic mice, which develop a more severe neuropathy with reduced mitochondrial DNA and a further increase in protein oxidation. PGC-1? (?/?) diabetic mice develop an increase in total cholesterol and triglycerides, and a decrease in TFAM and NRF1 protein levels. Loss of PGC-1? causes severe mitochondrial degeneration with vacuolization in DRG neurons, coupled with reduced state 3 and 4 respiration, reduced expression of oxidative stress response genes and an increase in protein oxidation. In contrast, overexpression of PGC-1? in cultured adult mouse neurons prevents oxidative stress associated with increased glucose levels. The study provides new insights into the role of PGC-1? in mitochondrial regeneration in peripheral neurons and suggests that therapeutic modulation of PGC-1? function may be an attractive approach for treatment of diabetic neuropathy. PMID:24423644

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

2014-01-01

222

Cognitive and motor assessment in autopsy-proven corticobasal degeneration  

Microsoft Academic Search

Objective: To investigate the clinical features of autopsy-proven corticobasal degeneration (CBD). Methods: We evaluated symptoms, signs, and neuropsychological deficits longitudinally in 15 patients with autopsy-proven CBD and related these observations directly to the neuroanatomic distribution of disease. Results: At presentation, a specific pattern of cognitive impairment was evident, whereas an extrapyramidal motor abnormality was present in less than half of

R. Murray; M. Neumann; M. S. Forman; J. Farmer; L. Massimo; A. Rice; B. L. Miller; J. K. Johnson; C. M. Clark; H. I. Hurtig; M. L. Gorno-Tempini; V. M.-Y. Lee; J. Q. Trojanowski; M. Grossman

2007-01-01

223

1Continue on pg 2 What Is Macular Degeneration?  

E-print Network

't By Jonna Jefferis Prevent Blindness America has designated February National Age-Related Macular already occurred. There is no FDA-approved treatment for dry AMD. Taking steps to prevent AMD from Degeneration Awareness Month to increase public education about this potentially devastating disease. Age

224

Preventing Depression in Age-Related Macular Degeneration  

Microsoft Academic Search

Context: Age-related macular degeneration is a preva- lent disease of aging that may cause irreversible vision loss, disability, and depression. The latter is rarely rec- ognized or treated in ophthalmologic settings. Objective: To determine whether problem-solving treat- ment can prevent depressive disorders in patients with recent vision loss. Design: Randomized, controlled trial. Setting: Outpatient ophthalmology offices in Philadel- phia, Pennsylvania.

Barry W. Rovner; Robin J. Casten; Mark T. Hegel; Benjamin E. Leiby; William S. Tasman

2007-01-01

225

Biological treatment strategies for disc degeneration: potentials and shortcomings  

PubMed Central

Recent advances in molecular biology, cell biology and material sciences have opened a new emerging field of techniques for the treatment of musculoskeletal disorders. These new treatment modalities aim for biological repair of the affected tissues by introducing cell-based tissue replacements, genetic modifications of resident cells or a combination thereof. So far, these techniques have been successfully applied to various tissues such as bone and cartilage. However, application of these treatment modalities to cure intervertebral disc degeneration is in its very early stages and mostly limited to experimental studies in vitro or in animal studies. We will discuss the potential and possible shortcomings of current approaches to biologically cure disc degeneration by gene therapy or tissue engineering. Despite the increasing number of studies examining the therapeutic potential of biological treatment strategies, a practicable solution to routinely cure disc degeneration might not be available in the near future. However, knowledge gained from these attempts might be applied in a foreseeable future to cure the low back pain that often accompanies disc degeneration and therefore be beneficial for the patient. PMID:16983559

Nerlich, Andreas G.; Boos, Norbert

2006-01-01

226

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

227

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

228

On root systems in spaces with degenerate metric  

E-print Network

A root systems in Carroll spaces with degenerate metric are defined. It is shown that their Cartan matrices and reflection groups are affine. With the help of the geometric consideration the root system structure of affine algebras is determined by a sufficiently simple algorithm.

I. V. Kostyakov; N. A. Gromov; V. V. Kuratov

2001-02-09

229

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

230

Calpains mediate axonal cytoskeleton disintegration during Wallerian degeneration.  

PubMed

In both the central nervous system (CNS) and peripheral nervous system (PNS), transected axons undergo Wallerian degeneration. Even though Augustus Waller first described this process after transection of axons in 1850, the molecular mechanisms may be shared, at least in part, by many human diseases. Early pathology includes failure of synaptic transmission, target denervation, and granular disintegration of the axonal cytoskeleton (GDC). The Ca(2+)-dependent protease calpains have been implicated in GDC but causality has not been established. To test the hypothesis that calpains play a causal role in axonal and synaptic degeneration in vivo, we studied transgenic mice that express human calpastatin (hCAST), the endogenous calpain inhibitor, in optic and sciatic nerve axons. Five days after optic nerve transection and 48 h after sciatic nerve transection, robust neurofilament proteolysis observed in wild-type controls was reduced in hCAST transgenic mice. Protection of the axonal cytoskeleton in sciatic nerves of hCAST mice was nearly complete 48 h post-transection. In addition, hCAST expression preserved the morphological integrity of neuromuscular junctions. However, compound muscle action potential amplitudes after nerve transection were similar in wild-type and hCAST mice. These results, in total, provide direct evidence that calpains are responsible for the morphological degeneration of the axon and synapse during Wallerian degeneration. PMID:23542511

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

2013-08-01

231

A common allele in RPGRIP1L is a modifier of retinal degeneration in ciliopathies.  

PubMed

Despite rapid advances in the identification of genes involved in disease, the predictive power of the genotype remains limited, in part owing to poorly understood effects of second-site modifiers. Here we demonstrate that a polymorphic coding variant of RPGRIP1L (retinitis pigmentosa GTPase regulator-interacting protein-1 like), a ciliary gene mutated in Meckel-Gruber (MKS) and Joubert (JBTS) syndromes, is associated with the development of retinal degeneration in individuals with ciliopathies caused by mutations in other genes. As part of our resequencing efforts of the ciliary proteome, we identified several putative loss-of-function RPGRIP1L mutations, including one common variant, A229T. Multiple genetic lines of evidence showed this allele to be associated with photoreceptor loss in ciliopathies. Moreover, we show that RPGRIP1L interacts biochemically with RPGR, loss of which causes retinal degeneration, and that the Thr229-encoded protein significantly compromises this interaction. Our data represent an example of modification of a discrete phenotype of syndromic disease and highlight the importance of a multifaceted approach for the discovery of modifier alleles of intermediate frequency and effect. PMID:19430481

Khanna, Hemant; Davis, Erica E; Murga-Zamalloa, Carlos A; Estrada-Cuzcano, Alejandro; Lopez, Irma; den Hollander, Anneke I; Zonneveld, Marijke N; Othman, Mohammad I; Waseem, Naushin; Chakarova, Christina F; Maubaret, Cecilia; Diaz-Font, Anna; MacDonald, Ian; Muzny, Donna M; Wheeler, David A; Morgan, Margaret; Lewis, Lora R; Logan, Clare V; Tan, Perciliz L; Beer, Michael A; Inglehearn, Chris F; Lewis, Richard A; Jacobson, Samuel G; Bergmann, Carsten; Beales, Philip L; Attié-Bitach, Tania; Johnson, Colin A; Otto, Edgar A; Bhattacharya, Shomi S; Hildebrandt, Friedhelm; Gibbs, Richard A; Koenekoop, Robert K; Swaroop, Anand; Katsanis, Nicholas

2009-06-01

232

A common allele in RPGRIP1L is a modifier of retinal degeneration in ciliopathies  

PubMed Central

Despite rapid advances in disease gene identification, the predictive power of the genotype remains limited, in part due to poorly understood effects of second-site modifiers. Here we demonstrate that a polymorphic coding variant of RPGRIP1L (retinitis pigmentosa GTPase regulator-interacting protein-1 like), a ciliary gene mutated in Meckel-Gruber (MKS) and Joubert (JBTS) syndromes, is associated with the development of retinal degeneration in patients with ciliopathies caused by mutations in other genes. As part of our resequencing efforts of the ciliary proteome, we identified several putative loss of function RPGRIP1L mutations, including one common variant, A229T. Multiple genetic lines of evidence showed this allele to be associated with photoreceptor loss in ciliopathies. Moreover, we show that RPGRIP1L interacts biochemically with RPGR, loss of which causes retinal degeneration, and that the 229T-encoded protein significantly compromises this interaction. Our data represent an example of modification of a discrete phenotype of syndromic disease and highlight the importance of a multifaceted approach for the discovery of modifier alleles of intermediate frequency and effect. PMID:19430481

Khanna, Hemant; Davis, Erica E.; Murga-Zamalloa, Carlos A.; Estrada, Alejandro; Lopez, Irma; den Hollander, Anneke I.; Zonneveld, Marijke N.; Othman, Mohammad I.; Waseem, Naushin; Chakarova, Christina F.; Maubaret, Cecilia; Diaz-Font, Anna; MacDonald, Ian; Muzny, Donna M.; Wheeler, David A.; Morgan, Margaret; Lewis, Lora R.; Logan, Clare V.; Tan, Perciliz L.; Beer, Michael A.; Inglehearn, Chris F.; Lewis, Richard A.; Jacobson, Samuel G.; Bergmann, Carsten; Beales, Philip L.; Attié-Bitach, Tania; Johnson, Colin A.; Otto, Edgar A.; Bhattacharya, Shomi S.; Hildebrandt, Friedhelm; Gibbs, Richard A.; Koenekoop, Robert K.; Swaroop, Anand; Katsanis, Nicholas

2009-01-01

233

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

MedlinePLUS

... Training and Jobs Three studies point to same risk gene for age-related macular degeneration Listen NIH- ... the same gene as a rare, but powerful risk factor for age-related macular degeneration (AMD), a ...

234

Extracellular matrix remodeling in experimental intervertebral disc degeneration  

PubMed Central

OBJECTIVE: To evaluate the remodeling of the extracellular matrix in intervertebral disc degeneration through the experimental model of intervertebral disc degeneration. METHODS: The model of disc degeneration induction, using needle 20G and 360° rotation, was applied for 30 seconds between the 6th/7th, and 8th/9th coccygeal vertebrae of Wistar rats. The intermediary level, between the 7th and 8th vertebrae, was taken as control, not being subjected puncture. The distribution of the extracellular matrix components involved in the remodeling and inflammation process, such as proteoglycans (aggrecan, decorin, biglycan), growth factors (TGF?), heparanase isoforms (HPSE1, HPSE2), metaloprotesasis-9 (MMP9) and interleukins (IL-6, IL-10) was analyzed during the post-injury period (15 to 30 days) and in the control group (discs collected immediately after the puncture, day zero). On the 15th day, acute phase of the disease, a reduced expression of extracellular matrix components had been observed, whilst there were no differences in the interleukins expression. At 30 days, the molecules followed a very similar pattern of expression in the control group (not affected by disc degeneration). RESULTS: The results show that during the acute phase significant alterations in the extracellular matrix components occur and in the late phase intervertebral disc returns to a profile similar to noninvolved tissue, probably due to extensive remodeling process of the extracellular matrix that is capable of regenerating the damaged tissue. CONCLUSION : The experimental model used demonstrated the occurrence of significant changes in the extracellular matrix during the period analyzed after induction of intervertebral disc degeneration. Laboratory investigation. PMID:24453658

de Oliveira, Cintia Pereira; Rodrigues, Luciano Miller Reis; Fregni, Maria Vitória Ventura Dias; Gotfryd, Alberto; Made, Ana Maria; Pinhal, Maria Aparecida da Silva

2013-01-01

235

Cotton embryogenesis: The identification, as nuclei, of the X-bodies in the degenerated synergid  

Microsoft Academic Search

The “x-bodies” present in the degenerated synergid of cotton were shown to contain DNA by specific staining with Azure B, the Feulgen procedure, and by labelling with 3H-actinomycin D. They are identified on a morphological basis as the degenerated vegetative nucleus of the pollen tube which is always found in the degenerated synergid tip, and as the degenerated synergid nucleus,

Donald B. Fisher; William A. Jensen

1968-01-01

236

Protective role of Wallerian degeneration slow (Wlds) gene against retinal ganglion cell body damage in a Wallerian degeneration model  

PubMed Central

Nerve distal axon injury-induced Wallerian degeneration is significantly delayed in Wallerian degeneration slow (Wlds) mutant mice, although the associated mechanisms are not completely clear and the role of Wlds in retinal ganglion cell (RGC) body damage is not fully understood. In the present study, a Wallerian degeneration model was established in wild-type (WT) and Wlds mutant mice by creating mechanical injury in the optic nerves. Wallerian degeneration and RGC body collapse were observed to be significantly delayed in the Wlds mice. Electroretinograms (ERG) and visual evoked potentials (VEPs) in Wlds mice were also significantly improved at the earlier stages (one week) following injury. The retina immunohistochemistry results showed that Wlds mice had more ordered cells and improved inner granular cell layer arrangement compared with the WT mice. Optic nerve Luxol Fast Blue (LFB) staining showed greater axon demyelination in WT mice than in Wlds mice. A large number of apoptotic cells were also observed in the WT mice. The present results suggest that the Wlds gene may also protect the RGC body following nerve injury. PMID:23403739

WANG, CHENG-HU; WANG, BO; WENDU, RI-LE; BI, HUI-E; CAO, GUO-FAN; JI, CHAO; JIANG, QIN; YAO, JIN

2013-01-01

237

Regenerative effects of transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated intervertebral disc  

Microsoft Academic Search

Intervertebral disc (IVD) degeneration, a common cause of low back pain in humans, is a relentlessly progressive phenomenon with no currently available effective treatment. In an attempt to solve this dilemma, we transplanted autologous mesenchymal stem cells (MSCs) from bone marrow into a rabbit model of disc degeneration to determine if stem cells could repair degenerated IVDs. LacZ expressing MSCs

Daisuke Sakai; Joji Mochida; Toru Iwashina; Akihiko Hiyama; Hiroko Omi; Masaaki Imai; Tomoko Nakai; Kiyoshi Ando; Tomomitsu Hotta

2006-01-01

238

Cortical Interneurons Upregulate Neurotrophins in Vivo in Response to Targeted Apoptotic Degeneration of Neighboring Pyramidal Neurons  

E-print Network

Degeneration of Neighboring Pyramidal Neurons Youzhen Wang,1 Volney L. Sheen,1 and Jeffrey D. Macklis Division molecules, produced by degenerating pyramidal neurons and/or by neighbor- ing neurons or nonneuronal cells neuronal degeneration and specifically during the period of ongoing pyramidal neuron apopto- sis

239

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

240

Bilateral hypertrophic olivary degeneration following surgical resection of a posterior fossa epidermoid cyst  

PubMed Central

Hypertrophic olivary degeneration is a result of a primary lesion damaging the dento-rubro-olivary pathway. It is a transynaptic form of degeneration and is unique, causing hypertrophy rather than atrophy of the inferior olivary nucleus. We report a case of bilateral hypertrophic olivary degeneration following surgical excision of a posterior fossa epidermoid cyst and review the relevant literature. PMID:20846979

Vaidhyanath, R; Thomas, A; Messios, N

2010-01-01

241

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 based on membrane protein aromatic surface amino acids, whose disturbance or overload leads to excessive membrane protein oxidation and neuronal death. Membrane proteins have rarely been investigated as potential victims of oxidative stress in the context of neurodegeneration. This study provides evidence that excessive one-electron oxidation of membrane proteins from within the lipid bilayer, depicted in the graphic, is a functionally decisive step toward neuronal cell death in response to different toxins. PMID:25393523

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

2015-05-01

242

Ataxia and Purkinje cell degeneration in mice lacking the CAMTA1 transcription factor  

PubMed Central

Members of the calmodulin-binding transcription activator (CAMTA) family of proteins function as calcium-sensitive regulators of gene expression in multicellular organisms ranging from plants to humans. Here, we show that global or nervous system deletion of CAMTA1 in mice causes severe ataxia with Purkinje cell degeneration and cerebellar atrophy, partially resembling the consequences of haploinsufficiency of the human CAMTA1 locus. Gene-expression analysis identified a large collection of neuronal genes that were dysregulated in the brains of CAMTA1-mutant mice, and elucidation of a consensus sequence for binding of CAMTA proteins to DNA revealed the association of CAMTA-binding sites with many of these genes. We conclude that CAMTA1 plays an essential role in the control of Purkinje cell function and survival. CAMTA1-mutant mice provide a model to study the molecular mechanisms of neurodegenerative diseases and for screening potential therapeutic interventions for such disorders. PMID:25049392

Long, Chengzu; Grueter, Chad E.; Song, Kunhua; Qin, Song; Qi, Xiaoxia; Kong, Y. Megan; Shelton, John M.; Richardson, James A.; Zhang, Chun-Li; Bassel-Duby, Rhonda; Olson, Eric N.

2014-01-01

243

Degeneration and gluing of Kuranishi structures in Gromov-Witten theory and the degeneration/gluing axioms for open Gromov-Witten invariants under a symplectic cut  

E-print Network

We study the degeneration and the gluing of Kuranishi structures in Gromov-Witten theory under a symplectic cut. This leads us to a degeneration axiom and a gluing axiom for open Gromov-Witten invariants. They provide then a route to the construction of virtual fundamental chains via specialization. Comments on the equivalence of the degeneration formula of closed Gromov-Witten invariants by Li-Ruan/Li versus Ionel-Parker are given in the Appendix.

Chien-Hao Liu; Shing-Tung Yau

2006-09-18

244

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

PubMed

Mechanisms underlying motor neuron degeneration in spinal muscular atrophy (SMA), the leading inherited cause of infant mortality, remain largely unknown. Many studies have established the importance of hyperphosphorylation of the microtubule-associated protein tau in various neurodegenerative disorders, including Alzheimer's and Parkinson's diseases. However, tau phosphorylation in SMA pathogenesis has yet to be investigated. Here we show that tau phosphorylation on serine 202 (S202) and threonine 205 (T205) is increased significantly in SMA motor neurons using two SMA mouse models and human SMA patient spinal cord samples. Interestingly, phosphorylated tau does not form aggregates in motor neurons or neuromuscular junctions (NMJs), even at late stages of SMA disease, distinguishing it from other tauopathies. Hyperphosphorylation of tau on S202 and T205 is mediated by cyclin-dependent kinase 5 (Cdk5) in SMA disease condition, because tau phosphorylation at these sites is significantly reduced in Cdk5 knock-out mice; genetic knock-out of Cdk5 activating subunit p35 in an SMA mouse model also leads to reduced tau phosphorylation on S202 and T205 in the SMA;p35(-/-) compound mutant mice. In addition, expression of the phosphorylation-deficient tauS202A,T205A mutant alleviates motor neuron defects in a zebrafish SMA model in vivo and mouse motor neuron degeneration in culture, whereas expression of phosphorylation-mimetic tauS202E,T205E promotes motor neuron defects. More importantly, genetic knock-out of tau in SMA mice rescues synapse stripping on motor neurons, NMJ denervation, and motor neuron degeneration in vivo. Altogether, our findings suggest a novel mechanism for SMA pathogenesis in which hyperphosphorylation of non-aggregating tau by Cdk5 contributes to motor neuron degeneration. PMID:25878277

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

2015-04-15

245

Radiative generation of neutrino mixing: Degenerate masses and threshold corrections  

NASA Astrophysics Data System (ADS)

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 quasidegenerate mass spectrum. For the lightest neutrino mass larger than roughly 0.1 eV, we analyze 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 flavor violating. Flavor-diagonal, nonuniversal 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 nonminimal flavor 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

2015-02-01

246

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

247

Iron in hereditary retinal degeneration: PIXE microanalysis. Preliminary results  

NASA Astrophysics Data System (ADS)

Several types of hereditary retinal degeneration with progressive alteration of photoreceptors exist in men and animals. Recent immunohistochemical results have shown strong degradation of transferrin, the protein responsible for iron transport, in retinas of rats with hereditary retinal degeneration. Freeze-dried thin sections of rat retinas from different stages of the disease, and respective coeval control sections, have been analyzed using nuclear microprobe. In this first part of the study, the rat retinas at post-natal stages of 35 and 45 days have been analyzed. The sample preparation and the post-irradiation staining to determine precisely the retinal layers involved are described. Preliminary results of element distributions (K, Ca, Fe) in the rat retina layers are discussed. A very high content of calcium in the choriocapillaris of dystrophic rat retinas was observed. Preliminary results on iron distribution in the rat retina layers are presented.

Sergeant, C.; Gouget, B.; Llabador, Y.; Simonoff, M.; Yefimova, M.; Courtois, Y.; Jeanny, J. C.

1999-10-01

248

Paraneoplastic cerebellar degeneration associated with serous adenocarcinoma of the ovary.  

PubMed

We report a case of a 68-year-old woman who presented with symptoms of cerebellar degeneration which initiated a suspicion of underlying malignancy. The patient presented with progressive ataxia and dysarthria and after excluding primary cerebellar pathology, paraneoplastic syndrome was suspected and she was investigated for a malignancy. CT scan of the pelvis showed a left-sided ovarian mass later diagnosed as serous adenocarcinoma of the ovary. She underwent surgery and histology of the mass showed poorly-differentiated serous adenocarcinoma. Paraneoplastic neurological syndrome encompasses several neurological disorders including paraneoplastic cerebellar degeneration (PCD) caused by an immune-mediated mechanism in patients with an underlying malignancy. PCD is a rare condition that occurs in less than 1% of patients with cancer and is associated with specific groups of cancer. It is important to identify PCD due to its association with certain cancers and also to limit the disabilities associated with the syndrome. PMID:25432905

Saeed, Duaa B; Gupta, Limci

2014-01-01

249

Multisystemic chromatolytic neuronal degeneration in a Cairn terrier pup.  

PubMed

In a four-month-old female Cairn terrier with mild episodic paraparesis, a multisystemic chromatolytic degeneration affected widespread neuronal populations in the brain and spinal cord as well as spinal, autonomic, and enteric ganglia. There was little axon degeneration or cell body loss, and the latter findings may explain the mild clinical signs. Among affected perikarya the extent and distribution of chromatolysis varied. While peripheral lysis of Nissl substance occurred often in spinal motoneurons, central chromatolysis was frequent in brain stem nuclei, and patchy Nissl loss appeared in some neurons including those in the cerebral cortex and spinal dorsal horns. Although prior studies of various chromatolytic neurodegenerations often have demonstrated characteristic massings of neurofilaments, the major, and invariable ultrastructural finding in this study was dispersion and loss of ribosomes. Neurofilamentous accumulations were observed less consistently. The clinical and pathologic findings in this pup were compared and constrasted with those made in prior studies of chromatolytic neurodegenerations. PMID:3402224

Cummings, J F; De Lahunta, A; Moore, J J

1988-07-01

250

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

251

Juvenile-Onset Macular Degeneration and Allied Disorders  

PubMed Central

While age-related macular degeneration (AMD) is a leading cause of central vision loss among the elderly, many inherited diseases that present earlier in life share features of AMD. These diseases of juvenile-onset macular degeneration include Stargardt disease, Best disease, retinitis pigmentosa, X-linked retinoschisis, and other allied disorders. In particular, they can be accompanied by the appearance of drusen, geographic atrophy, macular hyperpigmentation, choroidal neovascularization, and disciform scarring just as in AMD, and often may be confused for the adult form of the disease. Diagnosis based on funduscopic findings alone can be challenging. However, the use of diagnostic studies such as electroretinography, electrooculography, optical coherence tomography, and fundus autofluorescence in conjunction with genetic testing can lead to an accurate diagnosis. PMID:24732760

North, Victoria; Gelman, Rony; Tsang, Stephen H.

2015-01-01

252

Ignition Regime for Fusion in a Degenerate Plasma  

SciTech Connect

We identify relevant parameter regimes in which aneutronic fuels can undergo fusion ignition in hot-ion degenerate plasma. Because of relativistic effects and partial degeneracy, the self-sustained burning regime is considerably larger than previously calculated. Inverse bremsstrahlung plays a major role in containing the reactor energy. We solve the radiation transfer equation and obtain the contribution to the heat conductivity from inverse bremsstrahlung.

Son, S.; Fisch, N.J.

2005-12-01

253

Therapy of Nonexudative Age-Related Macular Degeneration  

Microsoft Academic Search

\\u000a Age related macular degeneration (AMD) is the leading cause of blindness among adults over the age of 65 in the Western world.\\u000a The prevalence of AMD is expected to increase dramatically, from 1.75 million in 2000 to 2.95 million in 2020, due to the\\u000a rapidly aging population. Given the large and now increasing burden of disease, the identification of modifiable

Annal D. Meleth; Veena R. Raiji; Nupura Krishnadev; Emily Y. Chew

254

Smoking and age-related macular degeneration: review and update.  

PubMed

Age-related macular degeneration (AMD) is one of the main socioeconomical health issues worldwide. AMD has a multifactorial etiology with a variety of risk factors. Smoking is the most important modifiable risk factor for AMD development and progression. The present review summarizes the epidemiological studies evaluating the association between smoking and AMD, the mechanisms through which smoking induces damage to the chorioretinal tissues, and the relevance of advising patients to quit smoking for their visual health. PMID:24368940

Velilla, Sara; García-Medina, José Javier; García-Layana, Alfredo; Dolz-Marco, Rosa; Pons-Vázquez, Sheila; Pinazo-Durán, M Dolores; Gómez-Ulla, Francisco; Arévalo, J Fernando; Díaz-Llopis, Manuel; Gallego-Pinazo, Roberto

2013-01-01

255

Smoking and Age-Related Macular Degeneration: Review and Update  

PubMed Central

Age-related macular degeneration (AMD) is one of the main socioeconomical health issues worldwide. AMD has a multifactorial etiology with a variety of risk factors. Smoking is the most important modifiable risk factor for AMD development and progression. The present review summarizes the epidemiological studies evaluating the association between smoking and AMD, the mechanisms through which smoking induces damage to the chorioretinal tissues, and the relevance of advising patients to quit smoking for their visual health. PMID:24368940

Velilla, Sara; García-Medina, José Javier; García-Layana, Alfredo; Pons-Vázquez, Sheila; Pinazo-Durán, M. Dolores; Gómez-Ulla, Francisco; Arévalo, J. Fernando; Díaz-Llopis, Manuel; Gallego-Pinazo, Roberto

2013-01-01

256

Methamphetamine exposure can produce neuronal degeneration in mouse hippocampal remnants  

Microsoft Academic Search

Neuronal cell death in hippocampal remnants was seen after methamphetamine (METH) exposure. Two techniques (Fluoro-Jade labeling and argyrophylia) showed that neuronal degeneration occurred in the indusium griseum, tenia tecta and fasciola cinerea within 5 days post-METH exposure in 70% of the mice. Neurodegeneration also occasionally occurred in the piriform cortex, hippocampus and frontal\\/parietal cortex. This cell death, unlike striatal neurotoxicity,

Larry C Schmued; John F Bowyer

1997-01-01

257

On modular transformations of non-degenerate toric conformal blocks  

E-print Network

We derive and solve the difference equations on the toric modular kernel following from the consistency relations in the fusion algebra. The result is explicit and simple series expansion for the toric modular kernel of non-degenerate Virasoro conformal blocks. We show that this expansion is equivalent to the celebrated integral representation due to B. Ponsot and J. Teschner. We also interpret obtained series representation as a non-perturbative expansion and note that this raises further questions.

Nemkov, Nikita

2015-01-01

258

Suppression of Density Fluctuations in a Quantum Degenerate Fermi Gas  

NASA Astrophysics Data System (ADS)

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

2010-07-01

259

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

260

Junctions of singularly degenerating domains with different limit dimensions 1  

Microsoft Academic Search

The asymptotic series for solutions of the mixed boundary-value problem for the Poisson equation in a domain, which is a junction\\u000a of singularly degenerating domains, are constructed. In this paper, which is the first part of the publication, the three-dimensional\\u000a problem (“wheel hub with spokes”) and the analogous two-dimensional problems are considered. The methods of matched and compound\\u000a asymptotic expansions

S. A. Nazarov

1996-01-01

261

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

262

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

263

Advances in repairing the degenerate retina by rod photoreceptor transplantation.  

PubMed

Despite very different aetiologies, age-related macular degeneration (AMD) and most inherited retinal disorders culminate in the same final common pathway, loss of the light-sensitive photoreceptors. There are few clinical treatments and none can reverse the loss of vision. Photoreceptor replacement by transplantation is proposed as a broad treatment strategy applicable to all degenerations. The past decade has seen a number of landmark achievements in this field, which together provide strong justification for continuing investigation into photoreceptor replacement strategies. These include proof of principle for restoring vision by rod-photoreceptor transplantation in mice with congenital stationary night blindness and advances in stem cell biology, which have led to the generation of complete optic structures in vitro from embryonic stem cells. The latter represents enormous potential for generating suitable and renewable donor cells with which to achieve the former. However, there are still challenges presented by the degenerating recipient retinal environment that must be addressed as we move to translating these technologies towards clinical application. PMID:24412415

Pearson, Rachael A

2014-01-01

264

Degeneration of the Y chromosome in evolutionary aging models  

NASA Astrophysics Data System (ADS)

The Y chromosomes are genetically degenerated and do not recombine with their matching partners X. Recombination of XX pairs is pointed out as the key factor for the Y chromosome degeneration. However, there is an additional evolutionary force driving sex-chromosomes evolution. Here we show this mechanism by means of two different evolutionary models, in which sex chromosomes with non-recombining XX and XY pairs of chromosomes is considered. Our results show three curious effects. First, we observed that even when both XX and XY pairs of chromosomes do not recombine, the Y chromosomes still degenerate. Second, the accumulation of mutations on Y chromosomes followed a completely different pattern then those accumulated on X chromosomes. And third, the models may differ with respect to sexual proportion. These findings suggest that a more primeval mechanism rules the evolution of Y chromosomes due exclusively to the sex-chromosomes asymmetry itself, i.e., the fact that Y chromosomes never experience female bodies. Over aeons, natural selection favored X chromosomes spontaneously, even if at the very beginning of evolution, both XX and XY pairs of chromosomes did not recombine.

Lobo, M. P.; Onody, R. N.

2005-06-01

265

Plant Y chromosome degeneration is retarded by haploid purifying selection.  

PubMed

Sex chromosomes evolved many times independently in many different organisms [1]. According to the currently accepted model, X and Y chromosomes evolve from a pair of autosomes via a series of inversions leading to stepwise expansion of a nonrecombining region on the Y chromosome (NRY) and the consequential degeneration of genes trapped in the NRY [2]. Our results suggest that plants represent an exception to this rule as a result of their unique life-cycle that includes alteration of diploid and haploid generations and widespread haploid expression of genes in plant gametophytes [3]. Using a new high-throughput approach, we identified over 400 new genes expressed from X and Y chromosomes in Silene latifolia, a plant that evolved sex chromosomes about 10 million years ago. Y-linked genes show faster accumulation of amino-acid replacements and loss of expression, compared to X-linked genes. These degenerative processes are significantly less pronounced in more constrained genes and genes that are likely exposed to haploid-phase selection. This may explain why plants retain hundreds of expressed Y-linked genes despite millions of years of Y chromosome degeneration, whereas animal Y chromosomes are almost completely degenerate. PMID:21889890

Chibalina, Margarita V; Filatov, Dmitry A

2011-09-13

266

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

267

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

THE AFTERCLAP OF DEGENERATE CARBON IGNITION REVISITED Abstract.- Whether the degenerate C-0 cores on the results of carbon ignition and on the nature of the propagation of the burning front. The velocity front is shown to propagate by convection. We conclude that if ignition occurs at sufficiently high

Boyer, Edmond

268

Enhanced NLRP3, Caspase-1, and IL- 1? Levels in Degenerate Human Intervertebral Disc and Their Association with the Grades of Disc Degeneration.  

PubMed

The NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome plays an important role in a variety of diseases. However, the role of NLRP3 in the human intervertebral disc (IVD) degeneration remains unknown. In the present study, we assessed the expression levels of the NLRP3 inflammasome and its downstream targets caspase-1 and IL-1? in 45 degenerate and seven nondegenerate IVD samples. The correlation between the degeneration scores and expression levels of NLRP3, caspase-1, and IL-1? were also analyzed. The mRNA expression levels of the three molecules (NLRP3, caspase-1, and IL-1?) were higher in the degenerate IVDs group than the controls (nondegenerate IVDs group). Immunohistochemistry showed that the expression levels of all three molecules were markedly increased in the nucleus pulposus of degenerate IVDs compared with nondegenerate IVDs. There was a positive correlation between the degeneration scores and the expression levels of the NLRP3 inflammasome as well as its downstream targets caspase-1 and IL-1?. The findings suggest that excessive activation of the NLRP3 inflammasome results in overproduction of downstream IL-1?, which participates in the pathogenesis of human IVD degeneration. Therefore, the NLRP3 inflammasome might serve as a potential therapeutic target for the prevention and treatment of IVD degeneration. Anat Rec, 298:720-726, 2015. © 2014 The Authors The Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology Published by Wiley Periodicals, Inc. PMID:25284686

Chen, Zhong-Hua; Jin, Shen-Hui; Wang, Min-Yan; Jin, Xiao-Liang; Lv, Chen; Deng, Ying-Feng; Wang, Jun-Lu

2015-04-01

269

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

270

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

271

Inhibition of Polyisoprenylated Methylated Protein Methyl Esterase by Synthetic Musks Induces Cell Degeneration  

PubMed Central

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 µM, respectively. Galaxolide and Tonalide also induced human cancer cell degeneration with EC50 values of 26 and 98 µM (neuroblastoma SH-SY5Y cells) and 58 and 14 µM (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.

2013-01-01

272

Catabolic cytokine expression in degenerate and herniated human intervertebral discs: IL-1? and TNF? expression profile  

PubMed Central

Low back pain is a common and debilitating disorder. Current evidence implicates intervertebral disc (IVD) degeneration and herniation as major causes, although the pathogenesis is poorly understood. While several cytokines have been implicated in the process of IVD degeneration and herniation, investigations have predominately focused on Interleukin 1 (IL-1) and tumor necrosis factor alpha (TNF?). However, to date no studies have investigated the expression of these cytokines simultaneously in IVD degeneration or herniation, or determined which may be the predominant cytokine associated with these disease states. Using quantitative real time PCR and immunohistochemistry we investigated gene and protein expression for IL-1?, TNF? and their receptors in non-degenerate, degenerate and herniated human IVDs. IL-1? gene expression was observed in a greater proportion of IVDs than TNF? (79% versus 59%). Degenerate and herniated IVDs displayed higher levels of both cytokines than non-degenerate IVDs, although in degenerate IVDs higher levels of IL-1? gene expression (1,300 copies/100 ng cDNA) were observed compared to those of TNF? (250 copies of TNF?/100 ng cDNA). Degenerate IVDs showed ten-fold higher IL-1 receptor gene expression compared to non-degenerate IVDs. In addition, 80% of degenerate IVD cells displayed IL-1 receptor immunopositivity compared to only 30% of cells in non-degenerate IVDs. However, no increase in TNF receptor I gene or protein expression was observed in degenerate or herniated IVDs compared to non-degenerate IVDs. We have demonstrated that although both cytokines are produced by human IVD cells, IL-1? is expressed at higher levels and in more IVDs, particularly in more degenerate IVDs (grades 4 to 12). Importantly, this study has highlighted an increase in gene and protein production for the IL-1 receptor type I but not the TNF receptor type I in degenerate IVDs. The data thus suggest that although both cytokines may be involved in the pathogenesis of IVD degeneration, IL-1 may have a more significant role than TNF?, and thus may be a better target for therapeutic intervention. PMID:17688691

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

2007-01-01

273

Taurine provides neuroprotection against retinal ganglion cell degeneration.  

PubMed

Retinal ganglion cell (RGC) degeneration occurs in numerous retinal diseases leading to blindness, either as a primary process like in glaucoma, or secondary to photoreceptor loss. However, no commercial drug is yet directly targeting RGCs for their neuroprotection. In the 70s, taurine, a small sulfonic acid provided by nutrition, was found to be essential for the survival of photoreceptors, but this dependence was not related to any retinal disease. More recently, taurine deprivation was incriminated in the retinal toxicity of an antiepileptic drug. We demonstrate here that taurine can improve RGC survival in culture or in different animal models of RGC degeneration. Taurine effect on RGC survival was assessed in vitro on primary pure RCG cultures under serum-deprivation conditions, and on NMDA-treated retinal explants from adult rats. In vivo, taurine was administered through the drinking water in two glaucomatous animal models (DBA/2J mice and rats with vein occlusion) and in a model of Retinitis pigmentosa with secondary RGC degeneration (P23H rats). After a 6-day incubation, 1 mM taurine significantly enhanced RGCs survival (+68%), whereas control RGCs were cultured in a taurine-free medium, containing all natural amino-acids. This effect was found to rely on taurine-uptake by RGCs. Furthermore taurine (1 mM) partly prevented NMDA-induced RGC excitotoxicity. Finally, taurine supplementation increased RGC densities both in DBA/2J mice, in rats with vein occlusion and in P23H rats by contrast to controls drinking taurine-free water. This study indicates that enriched taurine nutrition can directly promote RGC survival through RGC intracellular pathways. It provides evidence that taurine can positively interfere with retinal degenerative diseases. PMID:23115615

Froger, Nicolas; Cadetti, Lucia; Lorach, Henri; Martins, Joao; Bemelmans, Alexis-Pierre; Dubus, Elisabeth; Degardin, Julie; Pain, Dorothée; Forster, Valérie; Chicaud, Laurent; Ivkovic, Ivana; Simonutti, Manuel; Fouquet, Stéphane; Jammoul, Firas; Léveillard, Thierry; Benosman, Ryad; Sahel, José-Alain; Picaud, Serge

2012-01-01

274

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

275

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

276

Taurine Provides Neuroprotection against Retinal Ganglion Cell Degeneration  

PubMed Central

Retinal ganglion cell (RGC) degeneration occurs in numerous retinal diseases leading to blindness, either as a primary process like in glaucoma, or secondary to photoreceptor loss. However, no commercial drug is yet directly targeting RGCs for their neuroprotection. In the 70s, taurine, a small sulfonic acid provided by nutrition, was found to be essential for the survival of photoreceptors, but this dependence was not related to any retinal disease. More recently, taurine deprivation was incriminated in the retinal toxicity of an antiepileptic drug. We demonstrate here that taurine can improve RGC survival in culture or in different animal models of RGC degeneration. Taurine effect on RGC survival was assessed in vitro on primary pure RCG cultures under serum-deprivation conditions, and on NMDA-treated retinal explants from adult rats. In vivo, taurine was administered through the drinking water in two glaucomatous animal models (DBA/2J mice and rats with vein occlusion) and in a model of Retinitis pigmentosa with secondary RGC degeneration (P23H rats). After a 6-day incubation, 1 mM taurine significantly enhanced RGCs survival (+68%), whereas control RGCs were cultured in a taurine-free medium, containing all natural amino-acids. This effect was found to rely on taurine-uptake by RGCs. Furthermore taurine (1 mM) partly prevented NMDA-induced RGC excitotoxicity. Finally, taurine supplementation increased RGC densities both in DBA/2J mice, in rats with vein occlusion and in P23H rats by contrast to controls drinking taurine-free water. This study indicates that enriched taurine nutrition can directly promote RGC survival through RGC intracellular pathways. It provides evidence that taurine can positively interfere with retinal degenerative diseases. PMID:23115615

Froger, Nicolas; Cadetti, Lucia; Lorach, Henri; Martins, Joao; Bemelmans, Alexis-Pierre; Dubus, Elisabeth; Degardin, Julie; Pain, Dorothée; Forster, Valérie; Chicaud, Laurent; Ivkovic, Ivana; Simonutti, Manuel; Fouquet, Stéphane; Jammoul, Firas; Léveillard, Thierry; Benosman, Ryad; Sahel, José-Alain; Picaud, Serge

2012-01-01

277

Sequestration of tau by granulovacuolar degeneration in Alzheimer's disease.  

PubMed Central

Antibodies directed against three regions of tau have been used in a histologic study of granulovacuolar degeneration (GVD) in Alzheimer's disease (AD). Granulovascular degeneration complexes, consisting of a dense granule in a less-dense vacuole, were found in hippocampal pyramidal neurons in all patients studied. Anti-tau antibodies directed against the N-and C-termini, and the repeat region of tau, were found to immunolabel the granule of the GVD complex. Intracellular neurofibrillary tangles also were labeled by these antibodies. In particular, MAb6.423, which recognizes tau protein sequestered in paired helical filaments (PHF) in AD, but not the normal tau proteins so far described in human brain, labeled GVD granules. Contrarily, a generic tau marker (MAb7.51), which immunolabels all known isoforms of isolated and expressed tau protein, including PHF-tau, did not label the GVD granule. These findings demonstrate that the entire tau molecule is sequestered within the GVD granule, and that the tau protein found in GVD complexes is antigenically related to that found in PHFs. There is, however, a difference in the way in which the repeat region of tau is incorporated into the two structures, making the MAb7.51 epitope unavailable in the GVD complex. These findings suggest that the formation of GVD complexes in hippocampal pyramidal neurons vulnerable to neurofibrillary degeneration may represent an alternative pathway for dealing with an aberrant molecular complex, which contributes to the formation of GVD granules and neurofibrillary tangles in AD. Images Figure 1 PMID:1909492

Bondareff, W.; Wischik, C. M.; Novak, M.; Roth, M.

1991-01-01

278

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

279

Molecular genetics of retinal degeneration: A Drosophila perspective.  

PubMed

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 Ca ( 2+) influx directly or indirectly by promoting the turnover of the second messenger and regeneration of PIP 2, or mediate the Ca ( 2+) -dependent regulation of the visual response. These gene products are critical for the increase in cytosolic Ca ( 2+ ) 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

Shieh, Bih-Hwa

2011-01-01

280

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

281

Degenerate quantum codes and the quantum Hamming bound  

SciTech Connect

The parameters of a nondegenerate quantum code must obey the Hamming bound. An important open problem in quantum coding theory is whether the parameters of a degenerate quantum code can violate this bound for nondegenerate quantum codes. In this article we show that Calderbank-Shor-Steane (CSS) codes, over a prime power alphabet q{>=}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

Sarvepalli, Pradeep [Department of Physics and Astronomy, University of British Columbia, Vancouver V6T 1Z1 (Canada); Klappenecker, Andreas [Department of Computer Science, Texas A and M University, College Station, Texas 77843 (United States)

2010-03-15

282

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

283

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

284

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

285

Expansion of a quantum degenerate boson-fermion mixture  

SciTech Connect

We study the expansion of an ultracold boson-fermion mixture released from an elongated magnetic trap, by using a scaling approach. We discuss in detail the role of the boson-fermion interaction on the evolution of the radial-to-axial aspect ratio of the condensate, and show that the latter depends crucially on the relative dynamics of the condensate and degenerate Fermi gas in the radial direction, which is characterized by the ratio between the trapping frequencies for fermions and bosons. The numerical solution of the scaling equations provides a reasonable agreement with the recent experiment [G. Roati et al., Phys. Rev. Lett. 89, 150403 (2002)].

Hu, Hui [Abdus Salam International Center for Theoretical Physics, P.O. Box 586, Trieste 34100, (Italy); Liu, Xia-Ji [LENS, Universita di Firenze, Via Nello Carrara 1, 50019 Sesto Fiorentino, (Italy); Institute of Theoretical Physics, Academia Sinica, Beijing 100080, (China); Modugno, Michele [INFM, LENS, and Dipartimento di Fisica, Universita di Firenze, Via Nello Carrara 1, 50019 Sesto Fiorentino, (Italy)

2003-06-01

286

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

287

A Coherent Ising Machine Based On Degenerate Optical Parametric Oscillators  

E-print Network

A degenerate optical parametric oscillator network is proposed to solve the NP-hard problem of finding a ground state of the Ising model. The underlying operating mechanism originates from the bistable output phase of each oscillator and the inherent preference of the network in selecting oscillation modes with the minimum photon decay rate. Computational experiments are performed on all instances reducible to the NP-hard MAX-CUT problems on cubic graphs of order up to 20. The numerical results reasonably suggest the effectiveness of the proposed network.

Zhe Wang; Alireza Marandi; Kai Wen; Robert L. Byer; Yoshihisa Yamamoto

2013-11-12

288

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

289

Future Therapies of Wet Age-Related Macular Degeneration  

PubMed Central

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly population, and the prevalence of the disease increases exponentially with every decade after the age of 50 years. While VEGF inhibitors are promising drugs for treating patients with ocular neovascularization, there are limitations to their potential for improving vision in AMD patients. Thus, future therapies are required to have the potential to improve visual outcomes. This paper will summarize the future strategies and therapeutic targets that are aimed at enhancing the efficacy and duration of effect of antiangiogenic strategies. PMID:25802751

Jin, Daisuke; Sawada, Yu; Abe, Sanae; Yoshitomi, Takeshi

2015-01-01

290

Two-photon interferences with degenerate and nondegenerate paired photons  

NASA Astrophysics Data System (ADS)

We generate narrow-band frequency-tunable entangled photon pairs from spontaneous four-wave mixing in three-level cold atoms and study their two-photon quantum interference after a beam splitter. We find that the path-exchange symmetry plays a more important role in the Hong-Ou-Mandel interference than the temporal or frequency indistinguishability, and observe coalescence interference for both degenerate and nondegenerate photons. We also observe a quantum beat in the same experimental setup using either slow or fast detectors.

Liu, Chang; Chen, J. F.; Zhang, Shanchao; Zhou, Shuyu; Kim, Yoon-Ho; Loy, M. M. T.; Wong, G. K. L.; Du, Shengwang

2012-02-01

291

Construction of Gaiotto states with fundamental multiplets through Degenerate DAHA  

E-print Network

We construct Gaiotto states with fundamental multiplets in $SU(N)$ gauge theories, in terms of the orthonormal basis of spherical degenerate double affine Hecke algebra (SH in short), the representations of which are equivalent to those of $W_n$ algebra with additional $U(1)$ current. The generalized Whittaker conditions are demonstrated under the action of SH, and further rewritten in terms of $W_n$ algebra. Our approach not only consists with the existing literature but also holds for general $SU(N)$ case.

Yutaka Matsuo; Chaiho Rim; Hong Zhang

2014-05-26

292

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

293

Manipulation of photon statistics of highly degenerate chaotic radiation  

E-print Network

Highly degenerate chaotic radiation has a Gaussian density matrix and a large occupation number of modes $f $. If it is passed through a weakly transmitting barrier, its counting statistics is close to Poissonian. We show that a second identical barrier, in series with the first, drastically modifies the statistics. The variance of the photocount is increased above the mean by a factor $f$ times a numerical coefficient. The photocount distribution reaches a limiting form with a Gaussian body and highly asymmetric tails. These are general consequences of the combination of weak transmission and multiple scattering.

M. Kindermann; Yu. V. Nazarov; C. W. J. Beenakker

2001-07-05

294

Degenerate horizons, Einstein metrics, and Lens space bundles  

NASA Astrophysics Data System (ADS)

We present a new infinite class of near-horizon geometries of degenerate horizons, satisfying Einstein's equations for all odd dimensions greater than five. The symmetry and topology of these solutions is compatible with those of black holes. The simplest examples give horizons of spatial topology S3 ×S2 or the non-trivial S3-bundle over S2. More generally, the horizons are Lens space bundles associated to certain principal torus-bundles over Fano Kähler-Einstein manifolds. We also consider the classification problem for Einstein metrics on such Lens space bundles and derive a family which unifies all the known examples (Sasakian and non-Sasakian).

Kunduri, Hari K.; Lucietti, James

2014-12-01

295

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

PubMed

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. PMID:25657736

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

2014-12-15

296

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. PMID:25657736

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

2014-01-01

297

Cost-effectiveness of smoking cessation to prevent age-related macular degeneration  

Microsoft Academic Search

BACKGROUND: Tobacco smoking is a risk factor for age-related macular degeneration, but studies of ex-smokers suggest quitting can reduce the risk. METHODS: We fitted a function predicting the decline in risk of macular degeneration after quitting to data from 7 studies involving 1,488 patients. We assessed the cost-effectiveness of smoking cessation in terms of its impact on macular degeneration-related outcomes

Susan F Hurley; Jane P Matthews; Robyn H Guymer

2008-01-01

298

A widely tunable CMOS GmC filter with a negative source degeneration resistor transconductor  

Microsoft Academic Search

We propose a new negative source degeneration resistor (NSDR) transconductor to achieve a wide continuous-tuning range gm-C filter applicable for IEEE802.11a\\/b\\/g wireless-LANs and W-CDMA. The NSDR-transconductor using a source degeneration resistor and positive feedback differential amplifier that acts as a negative resistor. This configuration enables the equivalent source degeneration resistance to be drastically increased without degrading linearity, thus resulting in

Shinichi Hori; Tadashi Maeda; hitoshi Yano; Noriaki Matsuno; Keiichi Numata; Nobuhide Yoshida; Yuji Takahashi; Tomoyuki Yamase; Robert Walkington; Hikaru Hida

2003-01-01

299

Growth of injured rabbit optic axons within their degenerating optic nerve  

SciTech Connect

Spontaneous growth of axons after injury is extremely limited in the mammalian central nervous system (CNS). It is now clear, however, that injured CNS axons can be induced to elongate when provided with a suitable environment. Thus injured CNS axons can elongate, but they do not do so unless their environment is altered. We now show apparent regenerative growth of injured optic axons. This growth is achieved in the adult rabbit optic nerve by the use of a combined treatment consisting of: (1) supplying soluble substances originating from growing axons to be injured rabbit optic nerves, and (2) application of low energy He-Ne laser irradiation, which appears to delay degenerative changes in the injured axons. Two to 8 weeks after this treatment, unmyelinated and thinly myelinated axons are found at the lesion site and distal to it. Morphological and immunocytochemical evidence indicate that these thinly myelinated and unmyelinated axons are growing in close association with glial cells. Only these axons are identified as being growing axons. These newly growing axons transverse the site of injury and extend into the distal stump of the nerve, which contains degenerating axons. Axons of this type could be detected distal to the lesion only in nerves subjected to the combined treatment. No unmyelinated or thinly myelinated axons in association with glial cells were seen at 6 or 8 weeks postoperatively in nerves that were not treated, or in nerves in which the two stumps were completely disconnected. Two millimeters distal to the site of injury, the growing axons are confined to a compartment comprising 5%-30% of the cross section of the nerve. A temporal analysis indicates that axons have grown as far as 6 mm distal to the site of injury, by 8 weeks postoperatively.

Lavie, V.; Murray, M.; Solomon, A.; Ben-Bassat, S.; Belkin, M.; Rumelt, S.; Schwartz, M. (Weizmann Institute of Science, Rehovot (Israel))

1990-08-15

300

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

301

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

302

Resveratrol delays Wallerian degeneration in a NAD(+) and DBC1 dependent manner.  

PubMed

Axonal degeneration is a central process in the pathogenesis of several neurodegenerative diseases. Understanding the molecular mechanisms that are involved in axonal degeneration is crucial to developing new therapies against diseases involving neuronal damage. Resveratrol is a putative SIRT1 activator that has been shown to delay neurodegenerative diseases, including Amyotrophic Lateral Sclerosis, Alzheimer, and Huntington's disease. However, the effect of resveratrol on axonal degeneration is still controversial. Using an in vitro model of Wallerian degeneration based on cultures of explants of the dorsal root ganglia (DRG), we showed that resveratrol produces a delay in axonal degeneration. Furthermore, the effect of resveratrol on Wallerian degeneration was lost when SIRT1 was pharmacologically inhibited. Interestingly, we found that knocking out Deleted in Breast Cancer-1 (DBC1), an endogenous SIRT1 inhibitor, restores the neuroprotective effect of resveratrol. However, resveratrol did not have an additive protective effect in DBC1 knockout-derived DRGs, suggesting that resveratrol and DBC1 are working through the same signaling pathway. We found biochemical evidence suggesting that resveratrol protects against Wallerian degeneration by promoting the dissociation of SIRT1 and DBC1 in cultured ganglia. Finally, we demonstrated that resveratrol can delay degeneration of crushed nerves in vivo. We propose that resveratrol protects against Wallerian degeneration by activating SIRT1 through dissociation from its inhibitor DBC1. PMID:24252177

Calliari, Aldo; Bobba, Natalia; Escande, Carlos; Chini, Eduardo N

2014-01-01

303

Coupled modes in magnetized dense plasma with relativistic-degenerate electrons  

SciTech Connect

Low frequency electrostatic and electromagnetic waves are investigated in ultra-dense quantum magnetoplasma with relativistic-degenerate electron and non-degenerate ion fluids. The dispersion relation is derived for mobile as well as immobile ions by employing hydrodynamic equations for such plasma under the influence of electromagnetic forces and pressure gradient of relativistic-degenerate Fermi gas of electrons. The result shows the coexistence of shear Alfven and ion modes with relativistically modified dispersive properties. The relevance of results to the dense degenerate plasmas of astrophysical origin (for instance, white dwarf stars) is pointed out with brief discussion on ultra-relativistic and non-relativistic limits.

Khan, S. A. [National Centre for Physics, Quaid-i-Azam University Campus, Islamabad 45320 (Pakistan)

2012-01-15

304

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

305

Mutant HSPB8 causes motor neuron-specific neurite degeneration  

PubMed Central

Missense mutations (K141N and K141E) in the ?-crystallin domain of the small heat shock protein HSPB8 (HSP22) cause distal hereditary motor neuropathy (distal HMN) or Charcot-Marie-Tooth neuropathy type 2L (CMT2L). The mechanism through which mutant HSPB8 leads to a specific motor neuron disease phenotype is currently unknown. To address this question, we compared the effect of mutant HSPB8 in primary neuronal and glial cell cultures. In motor neurons, expression of both HSPB8 K141N and K141E mutations clearly resulted in neurite degeneration, as manifested by a reduction in number of neurites per cell, as well as in a reduction in average length of the neurites. Furthermore, expression of the K141E (and to a lesser extent, K141N) mutation also induced spheroids in the neurites. We did not detect any signs of apoptosis in motor neurons, showing that mutant HSPB8 resulted in neurite degeneration without inducing neuronal death. While overt in motor neurons, these phenotypes were only very mildly present in sensory neurons and completely absent in cortical neurons. Also glial cells did not show an altered phenotype upon expression of mutant HSPB8. These findings show that despite the ubiquitous presence of HSPB8, only motor neurons appear to be affected by the K141N and K141E mutations which explain the predominant motor neuron phenotype in distal HMN and CMT2L. PMID:20538880

Irobi, Joy; Almeida-Souza, Leonardo; Asselbergh, Bob; De Winter, Vicky; Goethals, Sofie; Dierick, Ines; Krishnan, Jyothsna; Timmermans, Jean-Pierre; Robberecht, Wim; De Jonghe, Peter; Van Den Bosch, Ludo; Janssens, Sophie; Timmerman, Vincent

2010-01-01

306

Perpendicular propagating modes for weakly magnetized relativistic degenerate plasma  

SciTech Connect

Using the Vlasov-Maxwell system of equations, the dispersion relations for the perpendicular propagating modes (i.e., X-mode, O-mode, and upper hybrid mode) are derived for a weakly magnetized relativistic degenerate electron plasma. By using the density (n{sub 0}=p{sub F}{sup 3}/3{pi}{sup 2} Planck-Constant-Over-Two-Pi {sup 3}) and the magnetic field values for different relativistic degenerate environments, the propagation characteristics (i.e., cutoff points, resonances, dispersions, and band widths in k-space) of these modes are examined. It is observed that the relativistic effects suppress the effect of ambient magnetic field and therefore the cutoff and resonance points shift towards the lower frequency regime resulting in enhancement of the propagation domain. The dispersion relations of these modes for the non-relativistic limit (p{sub F}{sup 2} Much-Less-Than m{sub 0}{sup 2}c{sup 2}) and the ultra-relativistic limit (p{sub F}{sup 2} Much-Greater-Than m{sub 0}{sup 2}c{sup 2}) are also presented.

Abbas, Gohar; Bashir, M. F. [Salam Chair in Physics, G. C. University Lahore, Punjab 54000 (Pakistan); Department of Physics, G. C. University Lahore, Punjab 54000 (Pakistan); Murtaza, G. [Salam Chair in Physics, G. C. University Lahore, Punjab 54000 (Pakistan)

2012-07-15

307

Diffusion tensor imaging in a child with hypertrophic olivary degeneration.  

PubMed

Hypertrophic olivary degeneration (HOD) is caused by disruptive lesions affecting components of the Guillain-Mollaret triangle (GMT). We present conventional magnetic resonance and diffusion tensor imaging (DTI) findings in a 6-year-old girl with HOD after surgery for a midbrain pilocytic astrocytoma. To our knowledge, this is the first dedicated DTI analysis of GMT in a child with HOD in the literature. In our patient, we found higher fractional anisotropy (FA) and axial diffusivity values of the inferior olivary nucleus (ION) and lower FA, but higher radial diffusivity (RD) values of all other GMT components compared to age-matched controls. Increased FA values of the ION may be explained by increased packing of white matter fibers. However, associated hyperintense T2 signal is contradictory and the association between increased FA values and hyperintense T2 signal remains unclear. Low FA and high RD values of the other GMT components likely reflect demyelination with axonal degeneration and correlate well with histopathological findings. PMID:23307661

Meoded, Avner; Poretti, Andrea; Ilica, A Turan; Perez, Randall; Jallo, George; Burger, Peter C; Huisman, Thierry A G M; Izbudak, Izlem

2013-08-01

308

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

309

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

310

Hydrogen peroxide induces neurite degeneration: Prevention by tocotrienols.  

PubMed

Reactive oxygen species (ROS) may attack several types of tissues and chronic exposure to ROS may attenuate various biological functions and increase the risk of several types of serious disorders. It is known that treatments with ROS attack neurons and induce cell death. However, the mechanisms of neuronal change by ROS prior to induction of cell death are not yet understood. Here, it was found that treatment of neurons with low concentrations of hydrogen peroxide induced neurite injury, but not cell death. Unusual bands located above the original collapsin response mediator protein (CRMP)-2 protein were detected by western blotting. Treatment with tocopherol or tocotrienols significantly inhibited these changes in neuro2a cells and cerebellar granule neurons (CGCs). Furthermore, prevention by tocotrienols of hydrogen peroxide-induced neurite degeneration was stronger than that by tocopherol. These findings indicate that neurite beading is one of the early events of neuronal degeneration prior to induction of death of hydrogen peroxide-treated neurons. Treatment with tocotrienols may protect neurite function through its neuroprotective function. PMID:21417547

Fukui, Koji; Takatsu, Hirokatsu; Koike, Tatsuro; Urano, Shiro

2011-06-01

311

Vitamin E deficiency induces axonal degeneration in mouse hippocampal neurons.  

PubMed

Several lines of evidence demonstrate the relationship between vitamin E deficiency and cognitive dysfunction in rodent models, but little is known about the underlying mechanisms. In this study, we found axonal injury in the hippocampal CA1 region of vitamin E-deficient and normal old mice using immunohistochemical assay. The number of cells in the hippocampal CA1 region of vitamin E-deficient mice and normal old mice was significantly lower than in normal young mice. It is well known that collapsin response mediator protein (CRMP)-2 plays a crucial role in the maintenance of axonal conditions. The expressions of CRMP-2 in the cerebral cortex and hippocampus of vitamin E-deficient mice were significantly lower than both the regions of normal ones. In normal old mice, the expression of CRMP-2 in the cerebral cortex was significantly lower than in the normal ones. In addition, the appearance of microtubule-associated protein (MAP)-light chain 3 (LC3), a major index of autophagy, was higher in the cerebral cortex and hippocampus of vitamin E-deficient mice than in normal young and old mice. These results indicate that axonal degeneration is induced in living tissues, but not cultured cells, and that changes in CRMP-2 and MAP-LC3 may underlie vitamin E-deficiency-related axonal degeneration. PMID:23419395

Fukui, Koji; Kawakami, Hiroaki; Honjo, Tatsuki; Ogasawara, Reiko; Takatsu, Hirokatsu; Shinkai, Tadashi; Koike, Tatsuro; Urano, Shiro

2012-01-01

312

Network oscillations in rod-degenerated mouse retinas.  

PubMed

In the mammalian retina, excitatory and inhibitory circuitries enable retinal ganglion cells (RGCs) to signal the occurrence of visual features to higher brain areas. This functionality disappears in certain diseases of retinal degeneration because of the progressive loss of photoreceptors. Recent work in a mouse model of retinal degeneration (rd1) found that, although some intraretinal circuitry is preserved and RGCs maintain characteristic physiological properties, they exhibit increased and aberrant rhythmic activity. Here, extracellular recordings were made to assess the degree of aberrant activity in adult rd1 retinas and to investigate the mechanism underlying such behavior. A multi-transistor array with thousands of densely packed sensors allowed for simultaneous recordings of spiking activity in populations of RGCs and of local field potentials (LFPs). The majority of identified RGCs displayed rhythmic (7-10 Hz) but asynchronous activity. The spiking activity correlated with the LFPs, which reflect an average synchronized excitatory input to the RGCs. LFPs initiated from random positions and propagated across the retina. They disappeared when ionotrophic glutamate receptors or electrical synapses were blocked. They persisted in the presence of other pharmacological blockers, including TTX and inhibitory receptor antagonists. Our results suggest that excitation-transmitted laterally through a network of electrically coupled interneurons-leads to large-scale retinal network oscillations, reflected in the rhythmic spiking of most rd1 RGCs. This result may explain forms of photopsias reported by blind patients, while the mechanism involved should be considered in future treatment strategies targeting the disease of retinitis pigmentosa. PMID:21307264

Menzler, Jacob; Zeck, Günther

2011-02-01

313

Strongly enhanced infrared vibrational transitions in electronically degenerate states  

NASA Astrophysics Data System (ADS)

Various types of strongly enhanced infrared vibrational transitions, with transition moments comparable to those characteristic of allowed electronic transitions in visible or UV spectra, may ensue in spatially degenerate electronic states of nonlinear molecules. The intimate correlation between the intensity of the enhanced infrared vibrational transitions and the anomalous pure rotational microwave spectra and the Stark effect is elucidated. The rules of Child and Longuet-Higgins with regard to infrared activity and infrared intensity enhancements in electronically degenerate states require revision and extension when properly considering the ramifications of the Jahn-Teller effect and invoking the action of mixed quadratic nuclear potential terms. Significantly, the enhancements of IR transition moments should allow the observation of symmetrical free radicals and molecular ions whose laboratory concentrations are often below the level of detectability for ``normal'' IR transition strengths. In addition, these effects could lead to multi-enhancement effects in nonlinear infrared and Raman vibrational spectra as well as enhanced radiative and nonradiative vibrational relaxations.

Scharf, Benjamin; Miller, Terry A.

1986-01-01

314

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

315

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

316

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

317

Ghost Sites  

NSDL National Science Digital Library

There is much on the Net that is living and vibrant, but there is also much that is dead, stuffed, or embalmed, as Steve Baldwin, former Pathfinder (discussed in the November 14, 1997 ScoutReport) writer likes to say. At this site Baldwin tracks notable embalmed, dead, or dying web sites. Each issue of Ghost Sites reviews five to ten such sites. Sites discussed include the latest Pathfinder out-of-date update on the Unibomber, the stillborn MecklerWeb, and Electric Minds (discussed in the November 22, 1996 Scout Report), abandoned by Howard Rheingold. Sites are rated from Dying in I.C.U. to Site is Stuffed, Embalmed and Ready for Internet Museum. Ironically, several of the sites discussed have been resurrected or metamorphosed since they were discussed, proving, if nothing else, that anything is possible in cyberspace. Note that clicking on discussed sites opens a new browser window.

318

Reduction of GABA/sub B/ receptor binding induced by climbing fiber degeneration in the rat cerebellum  

SciTech Connect

When the rat cerebellar climbing fibers degenerated, as induced by lesioning the inferior olive with 3-acetylpyridine (3-AP), GABA/sub B/ receptor binding determined with /sup 3/H-(+/-)baclofen was reduced in the cerebellum but not in the cerebral cortex of rats. Computer analysis of saturation data revealed two components of the binding sites, and indicated that decrease of the binding in the cerebellum was due to reduction in receptor density, mainly of the high-affinity sites, the B/sub max/ of which was reduced to one-third that in the control animals. In vitro treatment with 3-AP, of the membranes prepared from either the cerebellum or the cerebral cortex, induced no alteration in the binding sites, thereby indicating that the alteration of GABA/sub B/ sites induced by in vivo treatment with 3-AP is not due to a direct action of 3-AP on the receptor. GABA/sub A/ and benzodiazepine receptor binding labelled with /sup 3/H-muscimol and /sup 3/H-diazepam, respectively, in both of brain regions was not affected by destruction of the inferior olive. These results provide evidence that some of the GABA/sub B/ sites but neither GABA/sub A/ nor benzodiazepine receptors in the cerebellum are located at the climbing fiber terminals. 28 references, 4 figures, 2 tables.

Kato, K.; Fukuda, H.

1985-07-22

319

Behavioral/Systems/Cognitive Adding Insult to Injury: Cochlear Nerve Degeneration after  

E-print Network

Behavioral/Systems/Cognitive Adding Insult to Injury: Cochlear Nerve Degeneration after "Temporary or permanent hearing loss. Postexposure recovery of threshold sensitivity has been assumed to indicate reversal intact, but cause acute loss of afferent nerve terminals and delayed degeneration of the cochlear nerve

Allen, Jont

320

Histogenesis of Primary Localized Cutaneous Amyloidosis: Sequential Change of Epidermal Keratinocytes to Amyloid via Filamentous Degeneration  

Microsoft Academic Search

Two cases of lichen amyloidosus and 8 cases of macular amyloidosis were examined by electron microscopy. Epidermal keratinocytes showed variable degrees of focal degeneration in the basal or lower Malpighian layer. The primary change was seen in cells which contain fibrillar (30 nm in thickness) cytoplasmic inclusion. The following developments seemed to lead to filamentous degeneration (colloid bodies): (1) aggregation

Masanobu Kumakiri; Ken Hashimoto

1979-01-01

321

Mitochondrial dysfunction as a cause of axonal degeneration in multiple sclerosis patients  

Microsoft Academic Search

Objective: Degeneration of chronically demyelinated axons is a major cause of irreversible neurological disability in multiple sclerosis (MS) patients. Development of neuroprotective therapies will require elucidation of the molecular mechanisms by which neurons and axons degenerate. Methods: We report ultrastructural changes that support Ca2- mediated destruction of chronically demyelinated axons in MS patients. We compared expression levels of 33,000 char-

Ranjan Dutta; Jennifer McDonough; Xinghua Yin; John Peterson; Ansi Chang; Thalia Torres; Tatyana Gudz; Wendy B. Macklin; David A. Lewis; Robert J. Fox; Richard Rudick; Karoly Mirnics; Bruce D. Trapp

2006-01-01

322

Cataract Surgery and the Development or Progression of Age-related Macular Degeneration: A Systematic Review  

Microsoft Academic Search

Age-related macular degeneration and cataract are the most frequent eye disorders of elderly people worldwide. The aim of this systematic review was to evaluate the effect of cataract surgery on the development and progression of age-related macular degeneration. Data were collected by means of a systematic literature search in 28 databases and an additional update in Pubmed. Search results were

Angelina Bockelbrink; Stephanie Roll; Klaus Ruether; Andrej Rasch; Wolfgang Greiner; Stefan N. Willich

2008-01-01

323

Reducing the Number of Microlocations in Oligonucleotide Microchip Matrices by the Application of Degenerate Oligonucleotides  

Microsoft Academic Search

The application of degenerate oligonucleotides to DNA Sequencing by Hybridisation with Oligonucleotide Matrix (SHOM) is proposed. The use of degenerate oligonucleotides is regarded as an example of pooling methods that are suitable for various laboratory procedures requiring numerous samples to be assayed. As each DNA sequence coded by four letters (A, G, C, T) may be defined by two sequences:

Pawe? Sachadyn; Józef Kur

1999-01-01

324

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

325

Reproducible long-term disc degeneration in a large animal model  

Microsoft Academic Search

Study Design. Twelve goats were chemically degenerated and the development of the degenerative signs was followed for 26 weeks to evaluate the progression of the induced degeneration. The results were also compared with a previous study to determine the reproducibility. Objectives. The purpose of this study was determine whether this Chondroitinase ABC (CABC) induced goat model is reproducible and to

Roel J. W. Hoogendoorn; Marco N. Helder; Robert Jan Kroeze; Ruud A. Bank; Theo H. Smit; Paul I. J. M. Wuisman

2008-01-01

326

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

PubMed Central

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

2005-01-01

327

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

328

A Nonlinear Master Equation for a Degenerate Diffusion Model of Biofilm Growth  

E-print Network

A Nonlinear Master Equation for a Degenerate Diffusion Model of Biofilm Growth Hassan Khassehkhan1@math.ualberta.ca Abstract. We present a continuous time/discrete space model of biofilm growth, starting from the semi models of biofilms. Grid refinement leads formally to a degenerate parabolic equation. We show that a set

Hillen, Thomas

329

Correlation between sagittal plane changes and adjacent segment degeneration following lumbar spine fusion  

Microsoft Academic Search

Adjacent segment degeneration following lumbar spine fusion remains a widely acknowledged problem, but there is insufficient knowledge regarding the factors that contribute to its occurrence. The aim of this study is to analyse the relationship between abnormal sagittal plane configuration of the lumbar spine and the development of adjacent segment degeneration. Eighty-three consecutive patients who underwent lumbar fusion for degenerative

Malhar N. Kumar; Andrei Baklanov; Daniel Chopin

2001-01-01

330

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

331

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

332

Next generation therapeutic solutions for age-related macular degeneration  

PubMed Central

Age-related macular degeneration (AMD) is the primary cause of blindness among the elderly worldwide. To date, no cure is available, and the available palliative treatments only showed limited efficacy in improving visual acuity. The etiology of AMD remains elusive but research over the past decade has uncovered characteristic features of the disease. Known as the hallmarks of AMD, these features include (A) oxidative stress and RPE cytotoxicity; (B) loss of macromolecular permeability and hydraulic conductivity: (C) inflammation; (D) choroidal neovascularization and vascular leakage; and (E) loss of neuroprotection. Recent breakthrough in understanding the pathogenesis of AMD has spawned an array of novel therapeutic agents designed to address these hallmarks. Here we review the features of AMD and highlight the most promising therapeutic and diagnostic approaches based on the patents published from 2008 to 2011. Most likely, a next generation treatment for AMD will be developed from these emerging efforts. PMID:24040506

Cunnsamy, Khrishen; Ufret-Vincenty, Rafael; Wang, Shusheng

2013-01-01

333

Nutritional supplements in age-related macular degeneration.  

PubMed

Age-related macular degeneration (AMD) is the most frequent cause of blindness in the Western World. While with new therapies that are directed towards vascular endothelial growth factor (VEGF), a potentially efficient treatment option for the wet form of the disease has been introduced, a therapeutic regimen for dry AMD is still lacking. There is evidence from several studies that oral intake of supplements is beneficial in preventing progression of the disease. Several formulations of micronutrients are currently available. The present review focuses on the role of supplements in the treatment and prevention of AMD and sums up the current knowledge about the most frequently used micronutrients. In addition, regulatory issues are discussed, and future directions for the role of supplementation in AMD are highlighted. PMID:25586104

Schmidl, Doreen; Garhöfer, Gerhard; Schmetterer, Leopold

2015-03-01

334

Magnetohydrodynamic spin waves in degenerate electron-positron-ion plasmas  

SciTech Connect

Low frequency magnetosonic waves are studied in magnetized degenerate electron-positron-ion plasmas with spin effects. Using the fluid equations of magnetoplasma with quantum corrections due to the Bohm potential, temperature degeneracy, and spin magnetization energy, a generalized dispersion relation for oblique magnetosonic waves is derived. Spin effects are incorporated via spin force and macroscopic spin magnetization current. For three different values of angle {theta}, the generalized dispersion relation is reduced to three different relations under the low frequency magnetohydrodynamic assumptions. It is found that the effect of quantum corrections in the presence of positron concentration significantly modifies the dispersive properties of these modes. The importance of the work relevant to compact astrophysical bodies is pointed out.

Mushtaq, A. [TPPD, PINSTECH Nilore, 44000 Islamabad (Pakistan); National Center for Physics, Shahdrah Valley Road, 44000 Islamabad (Pakistan); Maroof, R.; Ahmad, Zulfiaqr [Institute of Physics and Electronics, University of Peshawar, 25000 Peshawar (Pakistan); Qamar, A. [National Center for Physics, Shahdrah Valley Road, 44000 Islamabad (Pakistan); Institute of Physics and Electronics, University of Peshawar, 25000 Peshawar (Pakistan)

2012-05-15

335

Structural neuroanatomy of face processing in frontotemporal lobar degeneration.  

PubMed

Impairments of face processing occur frequently in frontotemporal lobar degeneration (FTLD) but the neuroanatomical basis for these deficits has seldom been studied systematically. Here a prospective voxel based morphometry study is described addressing the neuroanatomy of two key dimensions of face processing--face identification and facial emotion recognition--in a single cohort of 32 patients with FTLD (19 with frontal variant and 13 with temporal variant FTLD). For the FTLD group as a whole, face identification was positively associated with grey matter in the right anterior fusiform gyrus while recognition of angry expressions was positively associated with grey matter in the bilateral insula cortex. FTLD provides a perspective on the neuroanatomy of face processing that is complementary to focal lesion and normal functional imaging work. PMID:21172863

Omar, Rohani; Rohrer, Jonathan D; Hailstone, Julia C; Warren, Jason D

2011-12-01

336

The physical properties of double degenerate common proper motion binaries  

NASA Technical Reports Server (NTRS)

Spectral types and spectrophotometry are presented for 21 double degenerate (DD) common proper motion binaries, along with estimates of their colors, absolute visual and bolometric magnitudes, and cooling ages. The oldest pairs in the sample are 9 x 10 to the 9th yr; the differential cooling ages range from 0.01 to 0.84. The median and mean separations of the DD pairs are 426 and 407 Au, respectively, both apparently smaller than the WD+MS values. The average UVW motions and velocity dispersions are significantly larger than the average velocities and dispersions associated with selected samples of single white dwarfs and MS+WD binaries when the latter are restricted to the same color/Mv range as the DD systems. This may be a result of the dynamical inflation of the velocity dispersion of DD systems due to their extremely ancient total stellar ages.

Sion, Edward M.; Oswalt, Terry D.; Liebert, James; Hintzen, Paul

1991-01-01

337

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

338

Ion-acoustic waves in a degenerate multicomponent magnetoplasma  

NASA Astrophysics Data System (ADS)

The hydrodynamic equations of positive and negative ions, degenerate electrons, and the Poisson equation are used along with the reductive perturbation method to derive the three-dimensional Zakharov-Kuznetsov (ZK) equation. The G'/G-expansion method is used to obtain a new class of solutions for the ZK equation. At certain condition, these solutions can describe the solitary waves that propagate in our plasma. The effects of negative ion concentrations, the positive/negative ion cyclotron frequency, as well as positive-to-negative ion mass ratio on solitary pulses are examined. Finally, the present study might be helpful to understand the propagation of nonlinear ion-acoustic solitary waves in a dense plasma, such as in astrophysical objects.

Abdelsalam, U. M.; Selim, M. M.; Selim

2013-04-01

339

Scalable arrays of RF Paul traps in degenerate Si  

E-print Network

We report techniques for the fabrication of multi-zone linear RF Paul traps that exploit the machinability and electrical conductivity of degenerate silicon. The approach was tested by trapping and laser cooling 24Mg+ ions in two trap geometries: a single-zone two-layer trap and a multi-zone surface-electrode trap. From the measured ion motional heating rate we determine an electric field spectral density at the ion's position of approximately 1E-10 (V/m)^2/Hz at a frequency of 1.125 MHz when the ion lies 40 micron above the trap surface. One application of these devices is controlled manipulation of atomic ion qubits, the basis of one form of quantum information processing.

J. Britton; D. Leibfried; J. Beall; R. B. Blakestad; J. H. Wesenberg; D. J. Wineland

2009-08-26

340

Age-Related Macular Degeneration: Insights into Inflammatory Genes  

PubMed Central

Age-related macular degeneration (AMD) is a progressive neurodegenerative disease that affects approximately 8.7% of elderly people worldwide (>55 years old). AMD is characterized by a multifactorial aetiology that involves several genetic and environmental risk factors (genes, ageing, smoking, family history, dietary habits, oxidative stress, and hypertension). In particular, ageing and cigarette smoking (including oxidative compounds and reactive oxygen species) have been shown to significantly increase susceptibility to the disease. Furthermore, different genes (CFH, CFI, C2, C3, IL-6, IL-8, and ARMS2) that play a crucial role in the inflammatory pathway have been associated with AMD risk. Several genetic and molecular studies have indicated the participation of inflammatory molecules (cytokines and chemokines), immune cells (macrophages), and complement proteins in the development and progression of the disease. Taking into consideration the genetic and molecular background, this review highlights the genetic role of inflammatory genes involved in AMD pathogenesis and progression. PMID:25478207

Ragazzo, Michele; Missiroli, Filippo; Borgiani, Paola; Angelucci, Francesco; Marsella, Luigi Tonino; Cusumano, Andrea; Novelli, Giuseppe; Ricci, Federico; Giardina, Emiliano

2014-01-01

341

Lifespan maturation and degeneration of human brain white matter  

PubMed Central

Properties of human brain tissue change across the lifespan. Here we model these changes in the living human brain by combining quantitative MRI measurements of R1 (1/T1) with diffusion MRI and tractography (N=102, ages 7–85). The amount of R1 change during development differs between white matter fascicles, but in each fascicle the rate of development and decline are mirror symmetric; the rate of R1 development as the brain approaches maturity predicts the rate of R1 degeneration in aging. Quantitative measurements of macromolecule tissue volume (MTV) confirm that R1 is an accurate index of the growth of new brain tissue. In contrast to R1, diffusion development follows an asymmetric time-course with rapid childhood changes but a slow rate of decline in old age. Together, the time-courses of R1 and diffusion changes demonstrate that multiple biological processes drive changes in white matter tissue properties over the lifespan. PMID:25230200

Yeatman, Jason D.; Wandell, Brian A.; Mezer, Aviv A.

2014-01-01

342

Observations of cataclysmic variable and double degenerate stars  

NASA Astrophysics Data System (ADS)

The author discusses cataclysmic variable stars and close pairs of white dwarfs or "double degenerates". These stars are connected through their evolution. The author begins by looking first at the method of "eclipse mapping" to address the problem of understanding light curves of systems with discs, next at "Doppler tomography", which deals with line emission. The emphasis of these sections is on the disk-accreting systems, and to redress the balance the author then considers the magnetic accretors, for which similar techniques have been applied in more recent years. Finally he discusses the evolution of close binaries by focusing upon near-relatives of CV's in evolutionary terms, close pairs of white dwarfs.

Marsh, Tom R.

343

[Visual fixation features after treatment of exudative age macular degeneration].  

PubMed

Changes of visual fixation in patients with choroidal neovascularitation (CNV) associated with age macular degeneration (AMD) after bevacizumab are studied. 45 patients (45 eyes) with active CNV treated with intravitreal bevacizumab were enrolled into the study. Visual fixation was studied before and 3-6 months after treatment using original method that included fundus foto and fluorescein angiography. Fixation relative to fovea and lesion was evaluated. Foveal fixation beyond lesion was found in 9%, foveal fixation within lesion--in 47%, extrafoveal fixation beyond lesion--in 18%, extrafoveal fixation within lesion--in 26% of patients. Changes of fixation localization after treatment was found in 24% patients. Examination of visual fixation may be useful for prognosis of anti-VEGF treatment efficacy in patients with CNV. PMID:21721271

Surguch, V K; Surnina, Z V; Sizova, M V

2011-01-01

344

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

345

Blood-Flow Magnetic Resonance Imaging of Retinal Degeneration  

PubMed Central

Purpose To investigate quantitative basal blood flow, hypercapnia- and hyperoxia-induced blood-flow changes in the retinas of the Royal-College-of-Surgeons (RCS) rats with spontaneous retinal degeneration and to compare with those of normal rat retinas. Methods Experiments were performed on male RCS rats at post-natal day P90 (n=4), P220 (n=5) and age-matched controls at P90 (n=7) and P220 (n=6). Hyperoxic (100% O2) and hypercapnic (5% CO2, 21% O2, balance N2) challenges were used to modulate blood flow. Quantitative baseline blood flow, hypercapnia- and hyperoxia-induced blood-flow changes in the retinas were imaged using continuous arterial-spin-labeling magnetic resonance imaging at 90×90×1500 ?m. Results In the normal rat retinas, basal blood flow was 5.5ml/gram/min, significantly higher than those reported in the brain (?1ml/gram/min). Hyperoxia decreased blood flow due to vasoconstriction and hypercapnia increased blood flow due to vasodilation in the normal retinas. In the RCS rat retinas, basal blood flow was diminished significantly (P<0.05). Interestingly, absolute hyperoxia- and hypercapnia-induced blood-flow changes in the RCS retinas were not statistically different from those in the normal retinas (P>0.05). However, percent changes in blood-flow were significantly larger than in normal retinas due to lower basal blood flow. Conclusion Retinal degeneration markedly reduces basal blood-flow but does not appear to impair vascular reactivity. These data also suggest caution when interpreting the relative stimulus-evoked functional MRI changes in diseased states where basal parameters are significantly perturbed. Quantitative blood-flow MRI may serve as a valuable tool to study the retina without depth limitation. PMID:18952917

Li, Yingxia; Cheng, Haiying; Shen, Qiang; Kim, Moon; Thule, Peter M; Olson, Darin E; Pardue, Machelle T; Duong, Timothy Q

2009-01-01

346

Transretinal degeneration in ageing human retina: a multiphoton microscopy analysis  

PubMed Central

Aim Retinal cell remodelling has been reported as a consistent feature of ageing. However, the degree to which this results in transretinal degeneration is unclear. To address this, the authors used multiphoton microscopy to quantify retinal degeneration in postmortem human eyes of two age groups. Methods Retinas from six young subjects (18–33 years old) and six older subjects (74–90 years old) were prepared as wholemount preparations. All retinas were stained with 4,6-diamidino-2-phenylindole and imaged by multiphoton confocal microscopy to quantify neuron densities in the retinal ganglion cell layer (RGCL), inner nuclear layer (INL) and outer nuclear layer (ONL). Neurons were counted using automated cell identification algorithms. All retinas were imaged hydrated to minimise tissue artefacts. Results In both groups, 56% of the area within the central 4 mm eccentricity and 27% of the area with eccentricity between 4 mm and 7 mm were imaged. Compared with young subjects, the peak RGCL neuron loss in the aged subjects (25.5%) was at 1 mm eccentricity. INL and ONL neuron densities significantly decreased at 1–2 mm eccentricity (8.7%) and 0.5–4 mm eccentricity (15.6%) respectively (P <0.05). The reduction in neuron density in the INL corresponded, spatially, to the region with the greatest neuron loss in the RGCL and ONL. Conclusions This is the first study to correlate neurodegeneration in different populations of cells in the ageing retinas. These data confirm that the greatest neuronal loss occurs in the RGCL and ONL in human ageing retinas, whereas the INL is relatively preserved. PMID:21183516

Lei, Y; Garrahan, N; Hermann, B; Fautsch, M P; Johnson, D H; Hernandez, M R; Boulton, M; Morgan, J E

2014-01-01

347

Degeneration of Brainstem Respiratory Neurons in Dementia with Lewy Bodies  

PubMed Central

Background: Respiratory dysfunction, including sleep disordered breathing, is characteristic of multiple system atrophy (MSA) and may reflect degeneration of brainstem respiratory nuclei involved in respiratory rhythmogenesis and chemosensitivity, including the pre-Bötzinger complex (preBötC), nucleus raphe pallidus (RPa), and nucleus raphe obscurus (ROb). However, impaired ventilatory responses to hypercapnia have also been reported in dementia with Lewy bodies (DLB), suggesting that these nuclei may also be affected in DLB. Objectives: To determine whether there is involvement of the preBötC, RPa, and ROb in DLB. Design: We applied stereological methods to analyze sections immunostained for neurokinin-1 receptor and tryptophan hydroxylase in neuropathologically confirmed cases of DLB, MSA, and controls. Results: Reduction of neuronal density occurred in all three nuclei in DLB, as well as in MSA. The magnitude of neuronal depletion in ROb was similar in DLB and MSA (49% versus 56% respectively, compared to controls, P < 0.05), but neuronal loss in the preBötC and RPa was less severe in DLB than in MSA (40% loss in preBötC of DLB, P < 0.05 and 68% loss in MSA, P < 0.0001, compared to controls; 46% loss in RPa of DLB, P < 0.05 and 73% loss in MSA P < 0.0001, compared to controls). Conclusions: Medullary respiratory nuclei are affected in dementia with Lewy bodies but less severely than in multiple system atrophy. This may help explain differences in the frequency of sleep disordered breathing in these two disorders. Citation: Presti MF; Schmeichel MA; Low PA; Parisi JE; Benarroch EE. Degeneration of brainstem respiratory neurons in dementia with Lewy bodies. SLEEP 2014;37(2):373-378. PMID:24501436

Presti, Michael F.; Schmeichel, Ann M.; Low, Phillip A.; Parisi, Joseph E.; Benarroch, Eduardo E.

2014-01-01

348

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

349

Contribution of disc degeneration to osteophyte formation in the cervical spine: a biomechanical investigation.  

PubMed

Cervical spine disorders such as spondylotic radiculopathy and myelopathy are often related to osteophyte formation. Bone remodeling experimental-analytical studies have correlated biomechanical responses such as stress and strain energy density to the formation of bony outgrowth. Using these responses of the spinal components, the present study was conducted to investigate the basis for the occurrence of disc-related pathological conditions. An anatomically accurate and validated intact finite element model of the C4-C5-C6 cervical spine was used to simulate progressive disc degeneration at the C5-C6 level. Slight degeneration included an alteration of material properties of the nucleus pulposus representing the dehydration process. Moderate degeneration included an alteration of fiber content and material properties of the anulus fibrosus representing the disintegrated nature of the anulus in addition to dehydrated nucleus. Severe degeneration included decrease in the intervertebral disc height with dehydrated nucleus and disintegrated anulus. The intact and three degenerated models were exercised under compression, and the overall force-displacement response, local segmental stiffness, anulus fiber strain, disc bulge, anulus stress, load shared by the disc and facet joints, pressure in the disc, facet and uncovertebral joints, and strain energy density and stress in the vertebral cortex were determined. The overall stiffness (C4-C6) increased with the severity of degeneration. The segmental stiffness at the degenerated level (C5-C6) increased with the severity of degeneration. Intervertebral disc bulge and anulus stress and strain decreased at the degenerated level. The strain energy density and stress in vertebral cortex increased adjacent to the degenerated disc. Specifically, the anterior region of the cortex responded with a higher increase in these responses. The increased strain energy density and stress in the vertebral cortex over time may induce the remodeling process according to Wolff's law, leading to the formation of osteophytes. PMID:11562150

Kumaresan, S; Yoganandan, N; Pintar, F A; Maiman, D J; Goel, V K

2001-09-01

350

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

351

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

352

Infrared Divergence and Non-Fermi Liquid in Multichannel Degenerate Anderson Model  

NASA Astrophysics Data System (ADS)

As a straightforward extention of the study on infrared divergences in pseudo-particle spectra in the single-channel degenerate impurity Anderson model, those of the multichannel model are examined with use of the expansion from the large limit of the spin-orbital degeneracy N. Analysis with the most divergent terms in the expansion shows that exponents of spectra of the slave boson and the pseudo-fermion in the M-channel model with 1 ?M ?N are given respectively by 1-nf2M/N and (2nf-nf2)M/N, where nf is the average number of localized electrons at the impurity site. When M=1, the results recover those obtained earlier in the single channel model. In the limits, nf ?1 and M-2 ?1, these results tend to those obtained by the non-crossing approximation (NCA) study. It also shows that the scattering rate of the conduction electrons in the M-channel model includes infrared divergent terms proportional to (1-nf)(1-M-2) in contrast to the absence of infrared divergent terms in the single-channel model.

Tsuruta, Atsushi; ?no, Yoshiaki; Matsuura, Tamifusa; Kuroda, Yoshihiro

1997-11-01

353

Global solutions to a degenerate solutal phase-field model for the solidification of a binary alloy  

Microsoft Academic Search

We consider a degenerate solutal phase-field model for the solidification of a binary alloy. This model is devoted to the evolution of the phase-field variable together with the relative concentration of the alloy for which the equation may degenerate. The existence of global weak solutions is proved for the degenerate case with a loss of regularity for the concentration in

J.-F. Scheid

2004-01-01

354

Safety and Tolerability Study of AAV2-sFLT01 in Patients With Neovascular Age-Related Macular Degeneration (AMD)  

ClinicalTrials.gov

Macular Degeneration; Age-Related Maculopathies; Age-Related Maculopathy; Maculopathies, Age-Related; Maculopathy, Age-Related; Retinal Degeneration; Retinal Neovascularization; Gene Therapy; Therapy, Gene; Eye Diseases

2015-02-18

355

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

356

Genetic and Clinical Features of Progranulin-Associated Frontotemporal Lobar Degeneration  

PubMed Central

Objective To assess the relative frequency of unique mutations and their associated characteristics in 97 individuals with mutations in progranulin (GRN), an important cause of frontotemporal lobar degeneration (FTLD). Participants and Design A 46-site International Frontotemporal Lobar Degeneration Collaboration was formed to collect cases of FTLD with TAR DNA-binding protein of 43-kDa (TDP-43)–positive inclusions (FTLD-TDP). We identified 97 individuals with FTLD-TDP with pathogenic GRN mutations (GRN+ FTLD-TDP), assessed their genetic and clinical characteristics, and compared them with 453 patients with FTLD-TDP in which GRN mutations were excluded (GRN? FTLD-TDP). No patients were known to be related. Neuropathologic characteristics were confirmed as FTLD-TDP in 79 of the 97 GRN+ FTLDTDP cases and all of the GRN? FTLD-TDP cases. Results Age at onset of FTLD was younger in patients with GRN+ FTLD-TDP vs GRN? FTLD-TDP (median, 58.0 vs 61.0 years; P<.001), as was age at death (median, 65.5 vs 69.0 years; P<.001). Concomitant motor neuron disease was much less common in GRN+ FTLDTDP vs GRN? FTLD-TDP (5.4% vs 26.3%; P<.001). Fifty different GRN mutations were observed, including 2 novel mutations: c.139delG (p.D47TfsX7) and c.378C>A (p.C126X). The 2 most common GRN mutations were c.1477C>T (p.R493X, found in 18 patients, representing 18.6% of GRN cases) and c.26C>A (p.A9D, found in 6 patients, representing 6.2% of cases). Patients with the c.1477C>T mutation shared a haplotype on chromosome 17; clinically, they resembled patients with other GRN mutations. Patients with the c.26C>A mutation appeared to have a younger age at onset of FTLD and at death and more parkinsonian features than those with other GRN mutations. Conclusion GRN+ FTLD-TDP differs in key features from GRN? FTLD-TDP. PMID:21482928

Chen-Plotkin, Alice S.; Martinez-Lage, Maria; Sleiman, Patrick M. A.; Hu, William; Greene, Robert; Wood, Elisabeth McCarty; Bing, Shaoxu; Grossman, Murray; Schellenberg, Gerard D.; Hatanpaa, Kimmo J.; Weiner, Myron F.; White, Charles L.; Brooks, William S.; Halliday, Glenda M.; Kril, Jillian J.; Gearing, Marla; Beach, Thomas G.; Graff-Radford, Neill R.; Dickson, Dennis W.; Rademakers, Rosa; Boeve, Bradley F.; Pickering-Brown, Stuart M.; Snowden, Julie; van Swieten, John C.; Heutink, Peter; Seelaar, Harro; Murrell, Jill R.; Ghetti, Bernardino; Spina, Salvatore; Grafman, Jordan; Kaye, Jeffrey A.; Woltjer, Randall L.; Mesulam, Marsel; Bigio, Eileen; Lladó, Albert; Miller, Bruce L.; Alzualde, Ainhoa; Moreno, Fermin; Rohrer, Jonathan D.; Mackenzie, Ian R. A.; Feldman, Howard H.; Hamilton, Ronald L.; Cruts, Marc; Engelborghs, Sebastiaan; De Deyn, Peter P.; Van Broeckhoven, Christine; Bird, Thomas D.; Cairns, Nigel J.; Goate, Allison; Frosch, Matthew P.; Riederer, Peter F.; Bogdanovic, Nenad; Lee, Virginia M. Y.; Trojanowski, John Q.; Van Deerlin, Vivianna M.

2011-01-01

357

Influence of IL-20 on lumbar disc degeneration:An experimental study  

PubMed Central

Objective: To determine the influence of IL-20 on the development of lumbar degeneration. Methods: The study design was prospective and carried out in Tianjin Fourth center Hospital, Tianjin, China between Jan 2012 and Jan 2014. Sixty-nine patients with degenerative disc disease treated surgically were included in experimental group, and fifteen patients with normal discs were included in control group. The evaluation of disc degeneration was performed using T2-weighted sagittal MRI according to the Modified Pfirrmann Grading System. After surgery, the intervertebral disc in both groups was collected and the content of proteoglycan and IL-20 were measured, the correlation between the content of IL-20, proteoglycan and the degeneration grade of lumbar disc was analyzed. Results: Compared to control group, the content of proteoglycan in experimental group is significantly lower (P=0.000), but IL-20 is significantly higher (P=0.001). In addition, with the advance of intervertebral disc degeneration, the content of IL-20 increase, while proteoglycan decrease gradually. There is significant correlation between the content of proteoglycan (p=0.001), IL-20 (p=0.002) and the degeneration grade of lumbar disc. Conclusion: In patients with degenerative disc disease, the content of IL-20 and proteoglycan has significant correlation with degeneration grade of lumbar disc, and IL-20 may promote the degeneration of lumbar disc by affecting the synthesis of proteoglycan.

Yang, Tianjing; Xu, Huaqing

2015-01-01

358

Degeneration of spermatocytes during meiotic divisions in the golden hamster testis.  

PubMed

The appearance and morphology of spontaneously degenerating meiotic spermatocytes was studied in late pubertal golden hamster testes by high resolution light and electron microscopy. While degeneration of primary spermatocytes during the long prophase of meiosis I is chiefly confined to midpachytene cells in stages VII-VIII of the seminiferous cycle, the subsequent meiotic phases (and their degenerative disorders) appear side by side in stage XIII of the cycle. Degeneration regularly concerns, in decreasing order of frequency, midpachytene primary spermatocytes (prophase I), metaphases I/II, telophases I/II, prophase II, and anaphases I/II. This closely corresponds to the apparent durations of these respective phases. In all meiotic phases studied, degeneration follows the same morphological pattern, including an initial vacuolar transformation of the cytoplasm and accumulation of densely staining material along membranes and microtubules, a progressive condensation of all nuclear and cytoplasmic structures, and the final cellular disintegration. In meta- and anaphase cells, meiotic spindle fibres are often perceivable even in advanced stages of degeneration. Both the morphological uniformity of spermatocyte degeneration and the constant susceptibility of meiotic phases to degeneration throughout meiotic divisions point to a generally similar mechanism underlying the physiological loss of meiotic spermatocytes. PMID:9066139

Miething, A

1997-01-01

359

Distinct Pathways Mediate Axon Degeneration during Apoptosis and Axon-Specific Pruning  

PubMed Central

Neurons can activate pathways that destroy the whole cell via apoptosis or selectively degenerate only the axon (pruning). Both apoptosis and axon degeneration require Bax and caspases. Here we demonstrate that despite this overlap, the pathways mediating axon degeneration during apoptosis versus axon pruning are distinct. While caspase-6 is activated in axons following nerve growth factor (NGF) deprivation, microfluidic chamber experiments reveal that caspase-6 deficiency only protects axons during axon-specific but not whole-cell (apoptotic) NGF deprivation. Strikingly, axon-selective degeneration requires the apoptotic proteins Caspase-9 and Caspase-3 but, in contrast to apoptosis, not Apaf-1. Additionally, cell bodies of degenerating axons are protected from caspase activation by protea some activity and XIAP. Also, mature neurons restrict apoptosis but remain permissive for axon degeneration, further demonstrating the independent regulation of these two pathways. These results reveal insight into how neurons allow for precise control over apoptosis and axon-selective degeneration pathways, thereby permitting long-term plasticity without risking neurodegeneration. PMID:23695670

Cusack, Corey L.; Swahari, Vijay; Henley, W. Hampton; Ramsey, J. Michael; Deshmukh, Mohanish

2014-01-01

360

Anterograde Degeneration along the Visual Pathway after Optic Nerve Injury  

PubMed Central

Purpose To investigate anterograde degenerative changes along the visual pathway in a rat model of optic nerve axotomy. Methods Optic nerve transection was performed in adult Sprague-Dawley rats. Animals were sacrificed at regular time intervals and tissues harvested. Immunoblotting followed by densitometric analysis was used to determine the phosphorylation profile of Akt in the dorsal lateral geniculate nucleus (dLGN) and the primary visual cortex (V1). The neuronal cell size and cell density were measured in the dLGN and the V1 using Nissl staining. The prevalence of apoptosis was characterized by terminal deoxynucleotidyl-transferase-mediated biotin-dUTP nick end labelling (TUNEL) histochemistry. Caspase-3 antibodies were also used to identify apoptotic cells. Neurons and astrocytes were detected using NeuN and glial fibrillary acidic protein (GFAP), respectively. Results An early and sustained loss of Akt phosphorylation was observed after optic nerve transection in both dLGN and V1. At week one, a decrease in the neuronal cell size (50.5±4.9 vs 60.3±5.0 µm2, P?=?0.042) and an increase of TUNEL positive cells (7.9±0.6 vs 1.4±0.5 ×102 cells/mm2, P<0.001) were evident in the dLGN but not in V1. A significant decline in neuronal cell number (14.5±0.1 vs 17.4±1.3 ×102 cells/mm2, P?=?0.048), cell size (42.5±4.3 vs 62.1±4.7 µm2, P?=?0.001) and an increase in apoptotic cells (5.6±0.5 vs 2.0±0.4 ×102 cells/mm2, P<0.001) appeared in V1 initially at one month post-transection. The changes in the visual pathway continued through two months. Both neuronal cells and GFAP-positive glial cells were affected in this anterograde degeneration along the visual pathway. Conclusions Anterograde degeneration along the visual pathway takes place in target relay (LGN) and visual cortex following the optic nerve injury. Apoptosis was observed in both neural and adjacent glial cells. Reduction of Akt phosphorylation preceded cellular and apoptotic changes. PMID:23300590

Graham, Stuart L.; Klistorner, Alexander

2012-01-01

361

Human retinal gene therapy for Leber congenital amaurosis shows advancing retinal degeneration despite enduring visual improvement  

PubMed Central

Leber congenital amaurosis (LCA) associated with retinal pigment epithelium-specific protein 65 kDa (RPE65) mutations is a severe hereditary blindness resulting from both dysfunction and degeneration of photoreceptors. Clinical trials with gene augmentation therapy have shown partial reversal of the dysfunction, but the effects on the degeneration are not known. We evaluated the consequences of gene therapy on retinal degeneration in patients with RPE65-LCA and its canine model. In untreated RPE65-LCA patients, there was dysfunction and degeneration of photoreceptors, even at the earliest ages. Examined serially over years, the outer photoreceptor nuclear layer showed progressive thinning. Treated RPE65-LCA showed substantial visual improvement in the short term and no detectable decline from this new level over the long term. However, retinal degeneration continued to progress unabated. In RPE65-mutant dogs, the first one-quarter of their lifespan showed only dysfunction, and there was normal outer photoreceptor nuclear layer thickness retina-wide. Dogs treated during the earlier dysfunction-only stage showed improved visual function and dramatic protection of treated photoreceptors from degeneration when measured 5–11 y later. Dogs treated later during the combined dysfunction and degeneration stage also showed visual function improvement, but photoreceptor loss continued unabated, the same as in human RPE65-LCA. The results suggest that, in RPE65 disease treatment, protection from visual function deterioration cannot be assumed to imply protection from degeneration. The effects of gene augmentation therapy are complex and suggest a need for a combinatorial strategy in RPE65-LCA to not only improve function in the short term but also slow retinal degeneration in the long term. PMID:23341635

Cideciyan, Artur V.; Jacobson, Samuel G.; Beltran, William A.; Sumaroka, Alexander; Swider, Malgorzata; Iwabe, Simone; Roman, Alejandro J.; Olivares, Melani B.; Schwartz, Sharon B.; Komáromy, András M.; Hauswirth, William W.; Aguirre, Gustavo D.

2013-01-01

362

Association between apparent diffusion coefficient and intervertebral disc degeneration in patients with ankylosing spondylitis  

PubMed Central

Purpose: To assess the relation between ankylosing spondylitis (AS) and degenerative disc disease emerging in association with various intrinsic and extrinsic factors and to evaluate the correlation between degree of degeneration in intervertebral discs and apparent diffusion coefficient (ADC) values. Methods: Thirty-five patients with AS and a control group of 35 patients were included in the study. Three hundred fifty intervertebral discs were assessed in terms of degeneration by analyzing signal intensities and morphologies on T2 weighted series of a 1.5 Tesla magnetic resonance scanner. ADC values were determined in diffusion weighted images (DWI) using a “b value of 500 s/mm2”. Patients in the AS and control groups were compared in terms of intervertebral disc degeneration, and association between degree of degeneration and ADC values was analyzed. Results: The mean of total degeneration degrees for five lumbar intervertebral discs was significantly higher in the patients with AS compared to the control group (16.77±4.67 vs 13.00±4.08, respectively; P=0.001). When intervertebral discs were analyzed separately, disc degeneration was again significantly higher in patients with AS compared to the control group, with the exception of L5-S1. Age, cholesterol level, triglyceride level, duration of disease and BASFI index were significantly associated with degree of degeneration in patients with AS. A negative correlation was determined between disc degeneration and ADC value. Conclusion: AS is a risk factor for degenerative disc disease due to its systemic effects, the fact it leads to posture impairment and its inflammatory effects on the vertebrae. A decrease in ADC values is observed as degeneration worsens in degenerative disc disease. PMID:25785119

Resorlu, Mustafa; Gokmen, Ferhat; Resorlu, Hatice; Adam, Gurhan; Akbal, Ayla; Cevizci, Sibel; Sariyildirim, Abdullah; Savas, Yilmaz; Guven, Mustafa; Aras, Adem Bozkurt

2015-01-01

363

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

364

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

365

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

366

Clinical characteristics and current therapies for inherited retinal degenerations.  

PubMed

Inherited retinal degenerations (IRDs) encompass a large group of clinically and genetically heterogeneous diseases that affect approximately 1 in 3000 people (>2 million people worldwide) (Bessant DA, Ali RR, Bhattacharya SS. 2001. Molecular genetics and prospects for therapy of the inherited retinal dystrophies. Curr Opin Genet Dev 11: 307-316.). IRDs may be inherited as Mendelian traits or through mitochondrial DNA, and may affect the entire retina (e.g., rod-cone dystrophy, also known as retinitis pigmentosa, cone dystrophy, cone-rod dystrophy, choroideremia, Usher syndrome, and Bardet-Bidel syndrome) or be restricted to the macula (e.g., Stargardt disease, Best disease, and Sorsby fundus dystrophy), ultimately leading to blindness. IRDs are a major cause of severe vision loss, with profound impact on patients and society. Although IRDs remain untreatable today, significant progress toward therapeutic strategies for IRDs has marked the past two decades. This progress has been based on better understanding of the pathophysiological pathways of these diseases and on technological advances. PMID:25324231

Sahel, José-Alain; Marazova, Katia; Audo, Isabelle

2015-02-01

367

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

368

Argentina's early contributions to the understanding of frontotemporal lobar degeneration.  

PubMed

Over a 100 years have passed since Pick's description of what is now termed frontotemporal lobar degeneration (FTLD). FTLD is a topic of intense current research interest yet some relevant contributions by non-English speaking authors have received little attention, which makes the history of FTLD research incomplete. In the hopes of filling some of the gaps in the history of FTLD research, the present article introduces fundamental work carried out in Argentina during the first half of the 20th century by Christfried Jakob and Braulio A. Moyano. Jakob's neurophilosophy, as well as his empirical descriptions on dementia and theoretic insights into the role of the frontal lobes are highlighted. Moyano's works on frontotemporal dementia (FTD), specifically concerning language deficits and the concept of focal pathology in Alzheimer disease presenting with progressive aphasia are introduced. These early contributions are examined in the light of the current knowledge on FTLD, highlighting some of the authors' early original contributions, as well as their misconceptions. These authors remain largely unknown despite the fact that their contributions were fundamental in kindling interest in behavioral neurology in Latin America, which continues to this day. PMID:20579637

Barutta, Joaquín; Hodges, John; Ibáñez, Agustín; Gleichgerrcht, Ezequiel; Manes, Facundo

2011-05-01

369

Degenerate gaugino mass region and mono-boson collider signatures  

NASA Astrophysics Data System (ADS)

In this paper we discuss search strategies at the LHC for light electroweak gauginos which are mostly wino-like, Higgsino-like or an admixture. These states are typically degenerate with decay products that are less energetic and hence difficult to detect. In addition, their production cross sections at a hadron collider are suppressed compared to colored states such as the gluinos. In order to detect these states one needs to trigger on initial-or final-state radiation. Many previous analyses have focussed on mono-jet and mono-photon triggers. In this paper we argue and show that these triggers are unlikely to succeed, due to the large background from QCD backgrounds for the mono-jet searches and the fact that the pT distribution of the mono-photons are rapidly decreasing functions of pT. We show this with both an analytic calculation of photons in the initial-state radiation and also a detailed numerical analysis. We then argue that mono-Z triggers, from Z decaying into charged leptons may well provide the best search strategy, in particular for Higgsino-like and mixed cases.

Anandakrishnan, Archana; Carpenter, Linda M.; Raby, Stuart

2014-09-01

370

Chapter 61: Photoreceptor Cell Degeneration in Abcr?/? Mice  

PubMed Central

Mice harboring a null mutation in Abca4/Abcr serve as a model of autosomal recessive Stargardt disease. Consistent with the human retinal disorder, deficiency in Abcr is associated with substantial accumulations of lipofuscin pigments in retinal pigment epithelial (RPE) cells. To observe for photoreceptor cell degeneration in these mutant mice, outer nuclear layer (ONL) thickness was measured at 200 ?m intervals superior and inferior to the optic nerve head. ONL width in Abcr?/? mouse was reduced at 8–9 month and 11 and 13 months relative to Abcr+/+ mice; thinning was more pronounced centrally and in superior retina. The numbers of photoreceptor nuclei spanning the width of the outer nuclear layer were also reduced. No evidence of age-related ONL thinning was observed in Abcr+/+ mice at these ages. We conclude that albino Abcr?/? mice exhibit progressive photoreceptor cell loss that is detectable at 8 months of age and that has worsened by 11 and 13 months of age. The measurement of ONL thickness is an established approach to assessing photoreceptor cell integrity and can be used in preclinical studies using Abcr?/? mice. PMID:20238056

Wu, Li; Nagasaki, Taka; Sparrow, Janet R.

2010-01-01

371

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

372

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

373

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

374

Age-Related Macular Degeneration: Genetics and Biology Coming Together  

PubMed Central

Genetic and genomic studies have enhanced our understanding of complex neurodegenerative diseases that exert a devastating impact on individuals and society. One such disease, age-related macular degeneration (AMD), is a major cause of progressive and debilitating visual impairment. Since the pioneering discovery in 2005 of complement factor H (CFH) as a major AMD susceptibility gene, extensive investigations have confirmed 19 additional genetic risk loci, and more are anticipated. In addition to common variants identified by now-conventional genome-wide association studies, targeted genomic sequencing and exome-chip analyses are uncovering rare variant alleles of high impact. Here, we provide a critical review of the ongoing genetic studies and of common and rare risk variants at a total of 20 susceptibility loci, which together explain 40–60% of the disease heritability but provide limited power for diagnostic testing of disease risk. Identification of these susceptibility loci has begun to untangle the complex biological pathways underlying AMD pathophysiology, pointing to new testable paradigms for treatment. PMID:24773320

Fritsche, Lars G.; Fariss, Robert N.; Stambolian, Dwight; Abecasis, Gonçalo R.; Curcio, Christine A.

2014-01-01

375

Global L p estimates for degenerate Ornstein–Uhlenbeck operators  

Microsoft Academic Search

We consider a class of degenerate Ornstein–Uhlenbeck operators in $${\\\\mathbb{R}^{N}}$$ , of the kind\\u000a \\u000a \\u000a \\u000a $$\\\\mathcal{A}\\\\equiv\\\\sum_{i, j=1}^{p_{0}}a_{ij}\\\\partial_{x_{i}x_{j}}^{2} + \\\\sum_{i, j=1}^{N}b_{ij}x_{i}\\\\partial_{x_{j}}$$\\u000a \\u000a \\u000a \\u000a where (a\\u000a \\u000a ij\\u000a ), (b\\u000a \\u000a ij\\u000a ) are constant matrices, (a\\u000a \\u000a ij\\u000a ) is symmetric positive definite on $${\\\\mathbb{R} ^{p_{0}}}$$ (p\\u000a 0 ? N), and (b\\u000a \\u000a ij\\u000a ) is such that $${\\\\mathcal{A}}$$ is hypoelliptic. For this class of operators we prove global

Marco Bramanti; Giovanni Cupini; Ermanno Lanconelli; Enrico Priola

2010-01-01

376

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

377

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

378

Superradiance of Degenerate Fermi Gases in a Cavity  

NASA Astrophysics Data System (ADS)

In this Letter we consider spinless Fermi gases placed inside a cavity and study the critical strength of a pumping field for driving a superradiance transition. We emphasize that the Fermi surface nesting effect can strongly enhance the superradiance tendency. Around certain fillings, when the Fermi surface is nearly nested with a relevant nesting momentum, the susceptibility of the system toward a checkboard density-wave ordered state is greatly enhanced in comparison with a Bose gas with the same density, because of which a much smaller (sometime even vanishingly small) critical pumping field strength can give rise to superradiance. This effect leads to interesting reentrance behavior and a topologically distinct structure in the phase diagram. Away from these fillings, the Pauli exclusion principle brings about the dominant effect for which the critical pumping strength is lowered in the low-density regime and increased in the high-density regime. These results open the prospect of studying the rich phenomena of degenerate Fermi gases in a cavity.

Chen, Yu; Yu, Zhenhua; Zhai, Hui

2014-04-01

379

Chronic acquired hepatocerebral degeneration: case reports and new insights.  

PubMed

Chronic acquired hepatocerebral degeneration (CAHD) is a heterogeneous disorder that can occur with a primary neurologic, hepatic, or combined presentation. Little has been added to the understanding of this disorder since the detailed, early clinical and pathological descriptions. The spectrum of clinical presentations can be neuropsychiatric (apathy, lethargy, excessive somnolence), a movement disorder (ataxia, tremor, chorea, parkinsonism, myoclonus, dystonia), or both. Cortical laminar necrosis and polymicrocavitation in the cortex and basal ganglia are combined with cerebral and cerebellar atrophy. Microscopically, Alzheimer type II astrocytes and cytoplasmic glycogen granules are characteristic. Recent neuroradiological observations in patients with liver failure have shown a specific magnetic resonance (MR) imaging appearance with a hyperintense T1 signal in the pallidum, putamen, and, rarely, mesencephalon. Using clues from a similar MR appearance in patients receiving total parenteral nutrition as well as animals given parenteral manganese, and the knowledge that manganese is cleared by the hepatobiliary system, deposition of manganese in the brain is postulated in patients with CAHD. In this review we describe three cases of CAHD with detailed clinical and radiological documentation and discuss the aforementioned pathogenetic mechanisms. PMID:8749990

Jog, M S; Lang, A E

1995-11-01

380

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

381

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

382

Analytical study of two-dimensional degenerate metamaterial antennas  

NASA Astrophysics Data System (ADS)

Dispersion curves of metamaterial steerable antennas composed of two-dimensional arrays of metallic unit structures with the C4v and C6v symmetries are calculated both qualitatively by the tight-binding approximation and quantitatively by the finite-difference time-domain method. Special attention is given to the case of eigenmodes of the E symmetry of the C4v point group and those of the E1 and E2 symmetries of the C6v point group, since they are doubly degenerate on the ? point of the Brillouin zone so that they naturally satisfy the steerability condition. We show that their dispersion curves have quadratic dependence on the wave vector in the vicinity of the ? point. To get a linear dispersion, which is advantageous for steerable antennas, we propose a method of controlled symmetry reduction. The present theory is an extension of our previous one [Opt. Express 18, 27371 (2010)] to two-dimensional systems, for which we can achieve the deterministic degeneracy due to symmetry and the controlled symmetry reduction becomes available. This design of metamaterial steerable antennas is advantageous in the optical frequency.

Sakoda, Kazuaki; Zhou, Haifeng

2011-07-01

383

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

384

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

385

Cadmium exposure and age-related macular degeneration.  

PubMed

Cadmium (Cd) has been proposed as a risk factor for age-related macular degeneration (AMD), but the association between Cd exposure and AMD risk in large population studies is unknown. This study evaluated the association of Cd exposure with AMD in a large representative sample of Korean men and women. This was a cross-sectional study of 3865 Korean adults ?40 years of age who participated in the Korean National Health and Nutrition Examination Survey (KNHANES) during 2008-2011. Cd concentrations in whole blood were measured by graphite-furnace atomic absorption spectrometry. The presence of AMD was determined in digital non-mydriatic fundus photographs. Cd levels were higher in participants with AMD compared with those without AMD (1.3 vs 1.1??g/l, respectively, P<0.001). In fully adjusted models, the odds ratio for AMD comparing the highest with the lowest Cd quartiles was 1.92 (95% CI=1.08-3.39; P for trend 0.029). In restricted cubic spline models, the association between Cd and AMD was approximately linear, with no evidence of threshold effects. Blood Cd concentrations were independently associated with the prevalence of AMD. If the association is proven causal, population-based preventive strategies to decrease Cd exposure could reduce the population burden of AMD.Journal of Exposure Science and Environmental Epidemiology advance online publication, 12 November 2014; doi:10.1038/jes.2014.75. PMID:25388812

Kim, Myung Hun; Zhao, Di; Cho, Juhee; Guallar, Eliseo

2014-11-12

386

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

387

Sustained Inflammation Induces Degeneration of the Temporomandibular Joint  

PubMed Central

The temporomandibular joint (TMJ) undergoes degenerative changes among patients who suffer from arthritis, and yet the pathogenesis of TMJ osteoarthritis and rheumatoid arthritis is poorly understood. We hypothesized that sustained inflammation in the TMJ induces structural abnormalities, and accordingly characterized the disc and synovium in a novel model with double injections of complete Freund’s adjuvant (CFA), using behavioral, morphological, cellular, and molecular assessments. Thirty-five days following double CFA injections in seven-week-old female Sprague-Dawley rats, the disc in the CFA-induced inflammation group demonstrated multiple degenerative changes, including marked thickening, opacity, and deformation. The discs in the CFA group further showed significantly greater wet and net weights, and elevated collagen, aggrecan, and total glycosaminoglycan contents. The synovium in the CFA-induced inflammation group showed marked infiltration of mononucleated cells and accumulated sub-synovial adipose tissue. Both the disc and synovium had significantly higher iNOS and IL-1? mRNA expression than controls (saline injections). These findings are consistent with our hypothesis that sustained TMJ inflammation, even within the presently observed 35 days, may be a predisposing factor for structural abnormalities. Insight into TMJ inflammation and degeneration is anticipated to improve our understanding of the pathogenesis of TMJ arthritis and help design clinically relevant strategies for tissue engineering. PMID:22427270

Wang, X.D.; Kou, X.X.; Mao, J.J.; Gan, Y.H.; Zhou, Y.H.

2012-01-01

388

Value siting  

SciTech Connect

Finding an appropriate site is becoming an increasing challenge in building new power projects. One of the first orders of business in project development is identifying a site that offers the maximum spread between the cost of fuel and net power price. The collection of sites that exhibit an adequate spread - presenting a first-order, acceptable economic expectation - must now be subjected to an ever increasing number of political, societal, technical, and economic exclusion screens. The barriers can include cooling water constraints, community resistance, visual incompatibility, archaeological concerns and endangered species preservation issues. Most power siting difficulties can be substantially mitigated by gaining access to developed, but under-used sites, whose current owners are bound by circumstances - political or financial - that prevent them from using such locations. There are two such categories of sites: Utilities that have sites on which depreciated power production assets rest; and, The federal government, with numerous sites throughout the country, particularly military bases subject to closure under the Base Realignment and Closure (BRAC) proceedings. It is in the interests of developers, as well as consumers, investors and taxpayers, ti undertake a thorough examination of these overlooked pearls of opportunities and develop their potential.

Ferrar, T.A. [PRA Management Consultants, Atlanta, GA (United States); Howes, J.A. [Redland Energy Group, Arlington, VA (United States)

1995-02-01

389

Loss of MEC-17 leads to microtubule instability and axonal degeneration.  

PubMed

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

2014-01-16

390

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

391

Liouville-Type Theorems for Steady Flows of Degenerate Power Law Fluids in the Plane  

NASA Astrophysics Data System (ADS)

We extend the Liouville-type theorems of Gilbarg and Weinberger and of Koch, Nadirashvili, Seregin and Sverák valid for the stationary variant of the classical Navier-Stokes equations in 2 D to the degenerate power law fluid model.

Bildhauer, Michael; Fuchs, Martin; Zhang, Guo

2013-09-01

392

A novel idiopathic superficial neocortical degeneration and atrophy in young adult dogs.  

PubMed

A diffuse, chronic, superficial neocortical degeneration that resulted in atrophy was detected in five 1 to 2-year-old-dogs. Presenting neurologic signs included ataxia, dysphagia, blindness, and mentation changes. Magnetic resonance imaging on brains from 2 dogs demonstrated severe bilateral cerebrocortical atrophy and enlarged lateral and third ventricles. Grossly, multifocal, bilaterally symmetrical, extensive areas of neocortical brownish discoloration associated with atrophy of gyri and sulcal widening were recorded in the dorsal and lateral cerebral hemispheres in 3 dogs. Microscopically, in all dogs there was subacute to chronic superficial neocortical degeneration affecting all cerebral lobes, ranging from loss of the molecular layer to less frequent larger and deeper cavitations of variable size. Clinical signs probably resulted from a combination of primary neocortical degeneration and secondary degeneration in the corticobulbar and corticospinal tracts. The distribution pattern of gross and histologic cerebrocortical lesions suggests that this is a novel degenerative canine cerebral disease. PMID:24782390

Cahalan, S D; Cappello, R; de Lahunta, A; Summers, B A

2015-03-01

393

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

394

Effect of trapping in a degenerate plasma in the presence of a quantizing magnetic field  

SciTech Connect

Effect of trapping as a microscopic phenomenon in a degenerate plasma is investigated in the presence of a quantizing magnetic field. The plasma comprises degenerate electrons and non-degenerate ions. The presence of the quantizing magnetic field is discussed briefly and the effect of trapping is investigated by using the Fermi-Dirac distribution function. The linear dispersion relation for ion acoustic wave is derived in the presence of the quantizing magnetic field and its influence on the propagation characteristics of the linear ion acoustic wave is discussed. Subsequently, fully nonlinear equations for ion acoustic waves are used to obtain the Sagdeev potential and the investigation of solitary structures. The formation of solitary structures is studied both for fully and partially degenerate plasmas in the presence of a quantizing magnetic field. Both compressive and rarefactive solitons are obtained for different conditions of temperature and magnetic field.

Shah, H. A.; Iqbal, M. J.; Qureshi, M. N. S. [Department of Physics, GC University, Lahore 54000 (Pakistan); Tsintsadze, N. [Department of Physics, GC University, Lahore 54000 (Pakistan); Institute of Physics, Tbilisi 0177 (Georgia); Masood, W. [Theoretical Physics Division, PINSTECH, P.O. Nilore, Islamabad (Pakistan)

2012-09-15

395

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

396

Electron distribution of the degenerate electron gas of a plasma in a strong electromagnetic field  

NASA Astrophysics Data System (ADS)

The paper determines the electron energy distribution function for the degenerate electron gas of a dense plasma in an intense electromagnetic field. The analysis is applicable to conditions in solid state plasmas.

Ablekov, V. K.; Babaev, Iu. N.; Frolov, A. M.

1980-01-01

397

Methamphetamine-Induced Degeneration of Dopaminergic Neurons Involves Autophagy and Upregulation of  

E-print Network

Methamphetamine-Induced Degeneration of Dopaminergic Neurons Involves Autophagy and Upregulation and Physiology, University of California, San Francisco, California 94143 Methamphetamine (METH) selectively cellular pathway that is activated when DA cannot be effectively sequestered in synaptic vesicles, thereby

Sulzer, David

398

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

PubMed

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

399

Hypertrophic olivary degeneration following pontine haemorrhage: hypertensive crisis or cavernous haemangioma bleeding?  

PubMed

The clinical and magnetic resonance (MR) features of hypertrophic olivary degeneration are described, along with a rare but treatable cause of this entity-pontine cavernous haemangioma. Hypertrophic olivary degeneration occurs after focal lesions to the dentato-rubro-olivary pathway, typically following a pontine haemorrhage involving the ipsilateral central tegmental tract, the contralateral superior cerebellar peduncle, or the dentate nucleus. Clinically, there is palatal myoclonus and an uncontrollable tremor, presumably caused by loss of inhibitory control. On MR imaging, hypertrophic olivary degeneration is characterised by a non-enhancing T1 isointense, T2 hyperintense enlargement confined to the olivary nucleus. Typically, haemorrhages following a hypertensive crisis are responsible for hypertrophic olivary degeneration. However, in the three reported cases, imaging findings within the former bleeding cavity suggested a cavernous haemangioma as the source of the haemorrhage. PMID:12754356

Krings, T; Foltys, H; Meister, I G; Reul, J

2003-06-01

400

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

401

Natural guardians of the race: heredity, hygiene, alcohol, and degeneration in Scottish Psychiatry, c. 1860 – 1920   

E-print Network

This thesis investigates the ways in which hereditary degeneration was discussed by Scottish psychiatrists in the late nineteenth and early twentieth centuries with particular reference to the anti-alcohol debate. I ...

Wood, James Anthony

2012-06-29

402

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.

403

Suspensory ligament degeneration associated with pituitary pars intermedia dysfunction in horses.  

PubMed

In older horses, pituitary pars intermedia dysfunction (PPID) and suspensory ligament (SL) degeneration are common. The aim of the present study was to identify histopathological changes in the SL in horses with PPID. SLs of four horses with clinical signs of PPID (17-26 years of age) were compared with SLs from four old horses (18-31 years of age) and three young horses (4-9 years of age). In horses with PPID, there was reduced longitudinal arrangement of collagen fibres in SLs, along with inclusions of cartilage, extracellular matrix and haemorrhage, as well as significant proteoglycan accumulations between SL fibres. These changes are similar to the degeneration of connective tissues in Peruvian Paso horses with SL degeneration and in humans with Cushing's disease or after long term high dose corticosteroid treatments. These findings indicate an association between degeneration of the SL and PPID. PMID:25641552

Hofberger, Sina; Gauff, Felicia; Licka, Theresia

2015-03-01

404

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

405

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

406

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

407

Inhibition of de novo ceramide biosynthesis by FTY720 protects rat retina from light-induced degeneration[S  

PubMed Central

Light-induced retinal degeneration (LIRD) in albino rats causes apoptotic photoreceptor cell death. Ceramide is a second messenger for apoptosis. We tested whether increases in ceramide mediate photoreceptor apoptosis in LIRD and if inhibition of ceramide synthesis protects the retina. Sprague-Dawley rats were exposed to 2,700 lux white light for 6 h, and the retinal levels of ceramide and its intermediary metabolites were measured by GC-MS or electrospray ionization tandem mass spectrometry. Enzymes of the de novo biosynthetic and sphingomyelinase pathways of ceramide generation were assayed, and gene expression was measured. The dosage and temporal effect of the ceramide synthase inhibitor FTY720 on the LIRD retina were measured by histological and functional analyses. Retinal ceramide levels increased coincident with the increase of dihydroceramide at various time points after light stress. Light stress in retina induces ceramide generation predominantly through the de novo pathway, which was prevented by systemic administration of FTY720 (10 mg/kg) leading to the protection of retinal structure and function. The neuroprotection of FTY720 was independent of its immunosuppressive action. We conclude that ceramide increase by de novo biosynthesis mediates photoreceptor apoptosis in the LIRD model and that inhibition of ceramide production protects the retina against light stress. PMID:23468130

Chen, Hui; Tran, Julie-Thu A.; Eckerd, Annette; Huynh, Tuan-Phat; Elliott, Michael H.; Brush, Richard S.; Mandal, Nawajes A.

2013-01-01

408

Sodium dodecyl sulfate-insoluble oligomers are involved in polyglutamine degeneration  

Microsoft Academic Search

In polyglutamine (polyQ) degeneration, disease protein that carries an expanded polyQ tract is neurotoxic. Expanded polyQ protein exists in different conformations that display distinct solubility proper- ties. In this study, an inducible transgenic Drosophila model is established to define the pathogenic form of polyQ protein at an early stage of degeneration in vivo. We show that microscopic polyQ aggregates are

S. L. Alan Wong; Wing Man Chan; H. Y. Edwin Chan

2008-01-01

409

Photoreceptor degeneration in mice: adeno-associated viral vector-mediated delivery of erythropoietin.  

PubMed

The exogenous delivery of erythropoietin (EPO) and EPO derivatives (EPO-Ds) represents a valuable strategy to protect the retina from degeneration. In this chapter we describe a method to deliver EPO and the EPO derivative S100E in the light-damage model of induced retinal degeneration using adeno--associated viral (AAV) vectors and to evaluate the functional and morphological protection of the retina from light damage. PMID:23456874

Colella, Pasqualina; Auricchio, Alberto

2013-01-01

410

Degeneration of Trigonometric Dynamical Difference Equations for Quantum Loop Algebras to Trigonometric Casimir Equations for Yangians  

NASA Astrophysics Data System (ADS)

We show that, under Drinfeld's degeneration (Proceedings of the International Congress of Mathematicians. American Mathematical Society, Providence, pp 798-820, 1987) of quantum loop algebras to Yangians, the trigonometric dynamical difference equations [Etingof and Varchenko (Adv Math 167:74-127, 2002)] for the quantum affine algebra degenerate to the trigonometric Casimir differential equations [Toledano Laredo (J Algebra 329:286-327, 2011)] for Yangians.

Balagovi?, Martina

2015-03-01

411

HORMONAL CONTROL OF REVERSIBLE DEGENERATION OF FLIGHT MUSCLE IN THE COLORADO POTATO BEETLE, LEPTINOTARSA DECEMLINEATA  

E-print Network

In the hibernating (diapausing) Colorado potato beetle, Leptinotarsa decemlineata Say, the flight muscles show pronounced degeneration. The muscle fibrils are greatly reduced in diameter and the sarcosomes are virtually absent. Similar signs of degeneration could be produced by extirpation of the postcerebral complex of endocrine glands, the corpora cardiaca and corpora allata. Reimplantation of active postcerebral complexes resulted in a very rapid regeneration of the muscle fibrils and new formation of sareosomes.

D. Stegwee; E. C. Kimmel; J. A. De Boer; S. Henstra

412

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

413

Effects of aging and spinal degeneration on mechanical properties of lumbar supraspinous and interspinous ligaments  

Microsoft Academic Search

Background context: The effects of aging and spinal degeneration on the mechanical properties of spinal ligaments are still unknown, although there have been several studies demonstrating those of normal spinal ligaments.Purpose: To investigate the mechanical properties of the human posterior spinal ligaments in human lumbar spine, and their relation to age and spinal degeneration parameters.Study design\\/setting: Destructive uniaxial tensile tests

Takahiro Iida; Kuniyoshi Abumi; Yoshihisa Kotani; Kiyoshi Kaneda

2002-01-01

414

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

415

Quantum Degenerate Two-Species Fermi-Fermi Mixture Coexisting with a Bose-Einstein Condensate  

Microsoft Academic Search

We report on the generation of a quantum degenerate Fermi-Fermi mixture of two different atomic species. The quantum degenerate mixture is realized employing sympathetic cooling of fermionic Li6 and K40 gases by an evaporatively cooled bosonic Rb87 gas. We describe the combination of trapping and cooling methods that proved crucial to successfully cool the mixture. In particular, we study the

M. Taglieber; A.-C. Voigt; T. Aoki; T. W. Hänsch; K. Dieckmann

2008-01-01

416

Autoradiography with [ 3 H]PK11195 of spinal tract degeneration in amyotrophic lateral sclerosis  

Microsoft Academic Search

The diagnostic hallmarks of amyotrophic lateral sclerosis (ALS) are degeneration of upper and lower motor neurons and of corticospinal tracts. Here, we demonstrate the suitability of the gliosis marker [3H]PK11195 for quantitative evaluation of tract degeneration in ALS in vitro. Binding of [3H]PK11195 was increased in lateral and ventral white matter of ALS spinal cords but not in the anterior

H. H. Sitte; J. Wanschitz; H. Budka; M. L. Berger

2001-01-01

417

Characterization of RPGR Variants and Their Role in Inherited Retinal Degeneration  

E-print Network

3. Mutations in the XLRP3 locus have been associated not only with RP as described (25,26,28-30), but also with cone-rod dystrophy (31), cone dystrophy (32) and recessive atrophic macular degeneration (33). In all RP cases, the outer... dystrophy and atrophic macular degeneration and ciliary dyskinesia. ORF15 mutations have also been associated with X-linked dominant forms of RP. These mutations result in phenotype manifestations in both hemizygous males and heterozygous females...

Wright, Rachel

2012-10-19

418

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

419

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

420

Cataract surgery and the development or progression of age-related macular degeneration: a systematic review.  

PubMed

Age-related macular degeneration and cataract are the most frequent eye disorders of elderly people worldwide. The aim of this systematic review was to evaluate the effect of cataract surgery on the development and progression of age-related macular degeneration. Data were collected by means of a systematic literature search in 28 databases and an additional update in Pubmed. Search results were evaluated using pre-defined inclusion and exclusion criteria. All relevant publications were rated in terms of scientific quality and analyzed regarding their results. The literature search generated a total of 2,827 hits. Seven publications on five observational studies and two non-randomized clinical trials were eligible for analysis. The observational studies provided some evidence for an increased incidence of late age-related macular degeneration, respectively, for a promoting influence of cataract surgery on the progression of early types of age-related macular degeneration. The clinical trials did yield inconsistent results. In conclusion, only a small number of published studies investigated the development or progression of age-related macular degeneration following cataract surgery. The scientific level of evidence of these articles was not high and results were inconsistent, nevertheless a promoting influence of cataract surgery on the progression of early age-related macular degeneration can be assumed. PMID:18572053

Bockelbrink, Angelina; Roll, Stephanie; Ruether, Klaus; Rasch, Andrej; Greiner, Wolfgang; Willich, Stefan N

2008-01-01

421

Identification of Degenerate Nuclei and Development of a SCAR Marker for Flammulina velutipes  

PubMed Central

Flammulina velutipes is one of the major edible mushrooms in the world. Recently, abnormalities that have a negative impact on crop production have been reported in this mushroom. These symptoms include slow vegetative growth, a compact mycelial mat, and few or even no fruiting bodies. The morphologies and fruiting capabilities of monokaryons of wild-type and degenerate strains that arose through arthrospore formation were investigated through test crossing. Only one monokaryotic group of the degenerate strains and its hybrid strains showed abnormal phenotypes. Because the monokaryotic arthrospore has the same nucleus as the parent strain, these results indicated that only one aberrant nucleus of the two nuclei in the degenerate strain was responsible for the degeneracy. A sequence-characterized amplified region marker that is linked to the degenerate monokaryon was identified based on a polymorphic sequence that was generated using random primers. Comparative analyses revealed the presence of a degenerate-specific genomic region in a telomere, which arose via the transfer of a genomic fragment harboring a putative helicase gene. Our findings have narrowed down the potential molecular targets responsible for this phenotype for future studies and have provided a marker for the detection of degenerate strains. PMID:25221949

Kim, Sun Young; Kim, Kyung-Hee; Im, Chak Han; Ali, Asjad; Lee, Chang Yun; Kong, Won-Sik; Ryu, Jae-San

2014-01-01

422

Linkage of Oxidative Stress and Mitochondrial Dysfunctions to Spontaneous Culture Degeneration in Aspergillus nidulans*  

PubMed Central

Filamentous fungi including mushrooms frequently and spontaneously degenerate during subsequent culture maintenance on artificial media, which shows the loss or reduction abilities of asexual sporulation, sexuality, fruiting, and production of secondary metabolites, thus leading to economic losses during mass production. To better understand the underlying mechanisms of fungal degeneration, the model fungus Aspergillus nidulans was employed in this study for comprehensive analyses. First, linkage of oxidative stress to culture degeneration was evident in A. nidulans. Taken together with the verifications of cell biology and biochemical data, a comparative mitochondrial proteome analysis revealed that, unlike the healthy wild type, a spontaneous fluffy sector culture of A. nidulans demonstrated the characteristics of mitochondrial dysfunctions. Relative to the wild type, the features of cytochrome c release, calcium overload and up-regulation of apoptosis inducing factors evident in sector mitochondria suggested a linkage of fungal degeneration to cell apoptosis. However, the sector culture could still be maintained for generations without the signs of growth arrest. Up-regulation of the heat shock protein chaperones, anti-apoptotic factors and DNA repair proteins in the sector could account for the compromise in cell death. The results of this study not only shed new lights on the mechanisms of spontaneous degeneration of fungal cultures but will also provide alternative biomarkers to monitor fungal culture degeneration. PMID:24345786

Li, Lin; Hu, Xiao; Xia, Yongliang; Xiao, Guohua; Zheng, Peng; Wang, Chengshu

2014-01-01

423

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

424

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

425

Gait speed in Parkinson disease correlates with cholinergic degeneration  

PubMed Central

Objective: We investigated dopaminergic and cholinergic correlates of gait speed in Parkinson disease (PD) and non-PD control subjects to test the hypothesis that gait dysfunction in PD may result from multisystem degeneration. Methods: This was a cross-sectional study. Subjects with PD but without dementia (n = 125, age 65.6 ± 7.3 years) and elderly subjects without PD (n = 32, age 66.0 ± 10.6 years) underwent [11C]dihydrotetrabenazine dopaminergic and [11C]methyl-4-piperidinyl propionate acetylcholinesterase PET imaging, and cognitive and clinical testing, including an 8.5-m walk in the dopaminergic “off” state. The fifth percentile of cortical cholinergic activity in the elderly without PD was used to define normal-range activity in the subjects with PD. Results: Normal-range cortical cholinergic activity was present in 87 subjects with PD (69.6%). Analysis of covariance using gait speed as the dependent variable demonstrated a significant model (F = 6.70, p < 0.0001) with a significant group effect (F = 3.36, p = 0.037) and significant slower gait speed in the low cholinergic PD subgroup (0.97 ± 0.22 m/s) with no significant difference between the normal-range cholinergic PD subgroup (1.12 ± 0.20 m/s) and control subjects (1.17 ± 0.18 m/s). Covariate effects were significant for cognition (F = 6.58, p = 0.011), but not for striatal dopaminergic innervation, sex, or age. Conclusion: Comorbid cortical cholinergic denervation is a more robust marker of slowing of gait in PD than nigrostriatal denervation alone. Gait speed is not significantly slower than normal in subjects with PD with relatively isolated nigrostriatal denervation. PMID:24078735

Frey, Kirk A.; Studenski, Stephanie; Kotagal, Vikas; Koeppe, Robert A.; Scott, Peter J.H.; Albin, Roger L.; Müller, Martijn L.T.M.

2013-01-01

426

Hsp90 inhibition protects against inherited retinal degeneration  

PubMed Central

The molecular chaperone Hsp90 is important for the functional maturation of many client proteins, and inhibitors are in clinical trials for multiple indications in cancer. Hsp90 inhibition activates the heat shock response and can improve viability in a cell model of the P23H misfolding mutation in rhodopsin that causes autosomal dominant retinitis pigmentosa (adRP). Here, we show that a single low dose of the Hsp90 inhibitor HSP990 enhanced visual function and delayed photoreceptor degeneration in a P23H transgenic rat model. This was associated with the induction of heat shock protein expression and reduced rhodopsin aggregation. We then investigated the effect of Hsp90 inhibition on a different type of rod opsin mutant, R135L, which is hyperphosphorylated, binds arrestin and disrupts vesicular traffic. Hsp90 inhibition with 17-AAG reduced the intracellular accumulation of R135L and abolished arrestin binding in cells. Hsf-1?/? cells revealed that the effect of 17-AAG on P23H aggregation was dependent on HSF-1, whereas the effect on R135L was HSF-1 independent. Instead, the effect on R135L was mediated by a requirement of Hsp90 for rhodopsin kinase (GRK1) maturation and function. Importantly, Hsp90 inhibition restored R135L rod opsin localization to wild-type (WT) phenotype in vivo in rat retina. Prolonged Hsp90 inhibition with HSP990 in vivo led to a posttranslational reduction in GRK1 and phosphodiesterase (PDE6) protein levels, identifying them as Hsp90 clients. These data suggest that Hsp90 represents a potential therapeutic target for different types of rhodopsin adRP through distinct mechanisms, but also indicate that sustained Hsp90 inhibition might adversely affect visual function. PMID:24301679

Aguilà, Mònica; Bevilacqua, Dalila; McCulley, Caroline; Schwarz, Nele; Athanasiou, Dimitra; Kanuga, Naheed; Novoselov, Sergey S.; Lange, Clemens A.K.; Ali, Robin R.; Bainbridge, James W.; Gias, Carlos; Coffey, Peter J.; Garriga, Pere; Cheetham, Michael E.

2014-01-01

427

Hsp90 inhibition protects against inherited retinal degeneration.  

PubMed

The molecular chaperone Hsp90 is important for the functional maturation of many client proteins, and inhibitors are in clinical trials for multiple indications in cancer. Hsp90 inhibition activates the heat shock response and can improve viability in a cell model of the P23H misfolding mutation in rhodopsin that causes autosomal dominant retinitis pigmentosa (adRP). Here, we show that a single low dose of the Hsp90 inhibitor HSP990 enhanced visual function and delayed photoreceptor degeneration in a P23H transgenic rat model. This was associated with the induction of heat shock protein expression and reduced rhodopsin aggregation. We then investigated the effect of Hsp90 inhibition on a different type of rod opsin mutant, R135L, which is hyperphosphorylated, binds arrestin and disrupts vesicular traffic. Hsp90 inhibition with 17-AAG reduced the intracellular accumulation of R135L and abolished arrestin binding in cells. Hsf-1(-/-) cells revealed that the effect of 17-AAG on P23H aggregation was dependent on HSF-1, whereas the effect on R135L was HSF-1 independent. Instead, the effect on R135L was mediated by a requirement of Hsp90 for rhodopsin kinase (GRK1) maturation and function. Importantly, Hsp90 inhibition restored R135L rod opsin localization to wild-type (WT) phenotype in vivo in rat retina. Prolonged Hsp90 inhibition with HSP990 in vivo led to a posttranslational reduction in GRK1 and phosphodiesterase (PDE6) protein levels, identifying them as Hsp90 clients. These data suggest that Hsp90 represents a potential therapeutic target for different types of rhodopsin adRP through distinct mechanisms, but also indicate that sustained Hsp90 inhibition might adversely affect visual function. PMID:24301679

Aguilà, Mònica; Bevilacqua, Dalila; McCulley, Caroline; Schwarz, Nele; Athanasiou, Dimitra; Kanuga, Naheed; Novoselov, Sergey S; Lange, Clemens A K; Ali, Robin R; Bainbridge, James W; Gias, Carlos; Coffey, Peter J; Garriga, Pere; Cheetham, Michael E

2014-04-15

428

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

429

Echelle Studies of the DB Degenerate GD358  

NASA Astrophysics Data System (ADS)

Our Tenth Episode high resolution SWP image of the first DB white dwarf (GD358) ever to be observed with the IUE echelle unexpectedly revealed the apparent presence of an Einstein-redshifted C II absorption line at the 200 mA level. If real, this detection is the first of carbon in a hot DB star and should lead to a major breakthrough in our understanding of DB evolution by providing a critical test of the role of convective dredge-up versus interstellar cloud accretion (or radiative levitation) in explaining the presence of carbon in hot DB stars and therefore in their cooler helium-rich, presumed descendants, the class of carbon band DQ degenerates. The resulting carbon abundance would be a direct test of the theoretical prediction of convective dredge-up of core carbon from its equilibrium diffusion tail by Fontaine et al (1984) and by Pelletier et al (1986). It would also provide a clear cut test of convective efficiency/mixing length theory in DB envelopes. Our scientific objective here is two-fold: (1) We must have a confirmatory second SWP image of this hottest (and pulsating prototype) DB in order to confirm this critically important feature and several other somewhat weaker possible photospheric candidates in SWP31432; (2) In order to search further for the presence of trace metals as a test of accretion versus dredge-up and to derive stringent upper limit metal abundances (or abundances from the mix of detected ions) we propose to obtain the first and only LWP high resolution image of a DB. In selecting GD358, we will therefore have complete high resolution IUE coverage of this object in our search for trace metals undetectable at low IUE resolution.

Sion, Edward M.

430

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

431

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

432

Frontotemporal lobar degeneration: defining phenotypic diversity through personalized medicine.  

PubMed

Frontotemporal lobar degeneration (FTLD) comprises two main classes of neurodegenerative diseases characterized by neuronal/glial proteinaceous inclusions (i.e., proteinopathies) including tauopathies (i.e., FTLD-Tau) and TDP-43 proteinopathies (i.e., FTLD-TDP) while other very rare forms of FTLD are known such as FTLD with FUS pathology (FTLD-FUS). This review focuses mainly on FTLD-Tau and FLTD-TDP, which may present as several clinical syndromes: a behavioral/dysexecutive syndrome (behavioral variant frontotemporal dementia); language disorders (primary progressive aphasia variants); and motor disorders (amyotrophic lateral sclerosis, corticobasal syndrome, progressive supranuclear palsy syndrome). There is considerable heterogeneity in clinical presentations of underlying neuropathology and current clinical criteria do not reliably predict underlying proteinopathies ante-mortem. In contrast, molecular etiologies of hereditary FTLD are consistently associated with specific proteinopathies. These include MAPT mutations with FTLD-Tau and GRN, C9orf72, VCP and TARDBP with FTLD-TDP. The last decade has seen a rapid expansion in our knowledge of the molecular pathologies associated with this clinically and neuropathologically heterogeneous group of FTLD diseases. Moreover, in view of current limitations to reliably diagnose specific FTLD neuropathologies prior to autopsy, we summarize the current state of the science in FTLD biomarker research including neuroimaging, biofluid and genetic analyses. We propose that combining several of these biomarker modalities will improve diagnostic specificity in FTLD through a personalized medicine approach. The goals of these efforts are to enhance power for clinical trials focused on slowing or preventing progression of spread of tau, TDP-43 and other FTLD-associated pathologies and work toward the goal of defining clinical endophenotypes of FTD. PMID:25549971

Irwin, David J; Cairns, Nigel J; Grossman, Murray; McMillan, Corey T; Lee, Edward B; Van Deerlin, Vivianna M; Lee, Virginia M-Y; Trojanowski, John Q

2015-04-01

433

Self-appraisal in behavioural variant frontotemporal degeneration  

PubMed Central

Objective Previous work investigating deficits in self-appraisal in behavioural-variant frontotemporal degeneration (bvFTD) has focused on a single domain: social/behavioural processes. We examined whether a domain-specific versus multi-domain model best explains degraded self-appraisal in bvFTD. Methods 49 patients with bvFTD and 73 patients with Alzheimer’s disease (AD) were administered quantitative assessments of episodic memory, naming and grammatical comprehension. Self-appraisal of cognitive test performance was assessed by asking patients to rate their performance immediately after completing each neuropsychological test. A discrepancy score was created to reflect the difference between patient performance on neuropsychological tests and self-appraisal of their test performance. Self-appraisal for each neuropsychological measure was related to grey matter (GM) density in each group using voxel-based morphometry. Results bvFTD patients were poor at evaluating their own performance on all cognitive tests, with no significant correlations between self-appraisal and actual performance. By contrast, poor self-appraisal in AD was restricted to episodic memory performance. Poor self-appraisal on each task in bvFTD and AD was related to reduced GM density in several ventral and rostral medial prefrontal regions. Crucially, poor self-appraisal for all domains in bvFTD was related to a specific area of reduced GM density in the subgenual cingulate (BA 25). Conclusion Poor self-appraisal in bvFTD affects multiple domains, and this multi-domain impairment pattern is associated with frontal disease in the subgenual cingulate. PMID:22952324

Massimo, Lauren; Libon, David J; Chandrasekaran, Keerthi; Dreyfuss, Michael; McMillan, Corey T; Rascovsky, Katya; Boller, Ashley; Grossman, Murray

2013-01-01

434

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