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Accumulating Variation at Conserved Sites in Potyvirus Genomes Is Driven by Species Discovery and Affects Degenerate Primer Design  

PubMed Central

Unknown and foreign viruses can be detected using degenerate primers targeted at conserved sites in the known viral gene sequences. Conserved sites are found by comparing sequences and so the usefulness of a set of primers depends crucially on how well the known sequences represent the target group including unknown sequences. Methodology/Principal Findings We developed a method for assessing the apparent stability of consensus sequences at sites over time using deposition dates from Genbank. We tested the method using 17 conserved sites in potyvirus genomes. The accumulation of knowledge of sequence variants over 20 years caused ‘consensus decay’ of the sites. Rates of decay were rapid at all sites but varied widely and as a result, the ranking of the most conserved sites changed. The discovery and reporting of sequences from previously unknown and distinct species, rather than from strains of known species, dominated the decay, indicating it was largely a sampling effect related to the progressive discovery of species, and recent virus mutation was probably only a minor contributing factor. Conclusion/Significance We showed that in the past, the sampling bias has misled the choice of the most conserved target sites for genus specific degenerate primers. The history of sequence discoveries indicates primer designs should be updated regularly and provides an additional dimension for improving the design of degenerate primers.

Wayper, Paul J.; Gibbs, Adrian J.; Fourment, Mathieu; Rodoni, Brendan C.



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



Divisors on elliptic Calabi-Yau 4-folds and the superpotential in F-theory — I  

Microsoft Academic Search

Each smooth elliptic Calabi-Yau 4-fold determines both a three-dimensional physical theory (a compactification of “M-theory”) and a four-dimensional physical theory (using the “F-theory” construction). A key issue in both theories is the calculation of the “superpotential” of the theory, which by a result of Witten is determined by the divisors D on the 4-fold satisfying X(OD = 1. We propose

A. Grassi



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



Cerebellar Degeneration  


... 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 ...


Is the subcallosal medial prefrontal cortex a common site of atrophy in Alzheimer's disease and frontotemporal lobar degeneration?  

PubMed Central

Regions affected late in neurodegenerative disease are thought to be anatomically connected to regions affected earlier. The subcallosal medial prefrontal cortex (SMPC) has connections with the dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex (OFC), and hippocampus (HC), which are regions that may become atrophic in frontotemporal lobar degeneration (FTLD) and Alzheimer's disease (AD). We hypothesized that the SMPC is a common site of frontal atrophy in the FTLD subtypes and in AD. The volume of the SMPC, DLPFC, OFC, HC, and entorhinal cortex (EC) were manually delineated for 12 subjects with frontotemporal dementia (FTD), 13 with semantic dementia (SD), 9 with progressive nonfluent aphasia (PNFA), 10 AD cases, and 13 controls. Results revealed significant volume loss in the left SMPC in FTD, SD, and PNFA, while the right SMPC was also atrophied in SD and FTD. In AD a non significant tendency of volume loss in the left SMPC was found (p = 0.08), with no volume loss on the right side. Results indicated that volume loss reflected the degree of brain connectivity. In SD and AD temporal regions displayed most atrophy. Among the frontal regions, the SMPC (which receives the strongest temporal projections) demonstrated most volume loss, the OFC (which receives less temporal projections) less volume loss, while the DLPFC (which is at multisynaptic distance from the temporal regions) demonstrated no volume loss. In PNFA, the left SMPC was atrophic, possibly reflecting progression from the left anterior insula, while FTD patients may have had SMPC atrophy at the initial stages of the disease. Atrophy of the SMPC may thus be affected by either initial temporal or initial frontal atrophy, making it a common site of frontal atrophy in the dementia subtypes investigated.

Lindberg, Olof; Westman, Eric; Karlsson, Sari; Ostberg, Per; Svensson, Leif A.; Simmons, Andrew; Wahlund, Lars-Olof



ELAV-Mediated 3?-End Processing of ewg Transcripts Is Evolutionarily Conserved Despite Sequence Degeneration of the ELAV-Binding Site  

PubMed Central

Regulation of alternative mRNA processing by ELAV (embryonic lethal abnormal visual system)/Hu proteins is mediated by binding to AU-rich elements of low complexity. Since such sequences diverge very rapidly during evolution, it has not been clear if ELAV regulation is maintained over extended phylogenetic distances. The transcription factor Erect wing (Ewg) is a major target of ELAV in Drosophila melanogaster and coordinates metabolic gene expression with regulation of synaptic plasticity. Here, we demonstrate evolutionary conservation of ELAV regulation of ewg despite massive degeneration of its binding site and of associated elements in the regulated intronic 3?-end processing site in distantly related Drosophila virilis. In this species, the RNA-binding part of ELAV protein is identical to D. melanogaster. ELAV expression as well as expression and regulation of ewg are also conserved. Using in vitro binding assays and in vivo transgene analysis, we demonstrate, however, that the ELAV-binding site of D. virilis is fully functional in regulating alternative splicing of ewg intron 6 in D. melanogaster. Known features of the ELAV-binding site, such as the requirement of multiple poly(U) motifs spread over an extended binding site of ?150 nt and a higher affinity to the 3? part of the binding site, are conserved. We further show that the 135-bp ELAV-binding site from D. melanogaster is sufficient for ELAV recruitment in vivo. Hence, our data suggest that ELAV/Hu protein-regulated alternative RNA processing is more conserved than anticipated from the alignment of degenerate low-complexity sequences.

Haussmann, Irmgard U.; Li, Min; Soller, Matthias



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)



Effects of modifications near the 2-, 3- and 4-fold symmetry axes on human ferritin renaturation.  

PubMed Central

Ferritin is a protein of 24 subunits which assemble into a shell with 432 point symmetry. It can be denatured reversibly in acidic guanidine hydrochloride, with the formation of poorly populated renaturation intermediates. In order to increase the accumulation of intermediates and to study the mechanism of ferritin renaturation, we analysed variants of the human ferritin H-chain altered at the N-terminus (delta(1-13)), near the 4-fold axis (Leu-169 --> Arg), the 3-fold axis (Asp-131 --> Ile + Glu-134 --> Phe) or the 2-fold axis (Ile-85 --> Cys). We also carried out specific chemical modifications of Cys-130 (near the 3-fold axis) and Cys-85 (near the 2-fold axis). Renaturation of the modified ferritins yielded assembly intermediates that differed in size and physical properties. Alterations of residues around the 2-, 4- and 3-fold axes produced subunit monomers, dimers and higher oligomers respectively. All these intermediates could be induced to assemble into ferritin 24-mers by concentrating them or by co-renaturing them with wild-type H-ferritin. The results support the hypothesis that the symmetric subunit dimers are the building blocks of ferritin assembly, and are consistent with a reassembly pathway involving the coalescence of dimers, probably around the 4-fold axis, followed by stepwise addition of dimers until the 24-mer cage is completed. In addition they show that assembly interactions are responsible for the large hysteresis of folding and unfolding plots. The implications of the studies for in vivo heteropolymer formation in vertebrates, which have two types of ferritin chain (H and L), are discussed.

Santambrogio, P; Pinto, P; Levi, S; Cozzi, A; Rovida, E; Albertini, A; Artymiuk, P; Harrison, P M; Arosio, P



Unique Residues at the 3-Fold and 4-Fold Axis of Mycobacterial Ferritin Are Involved in Oligomer Switching.  


To identify the crucial residues involved in the self-assembly and function of BfrB, one of the important iron storage proteins of Mycobacterium tuberculosis, we constructed various mutants by employing site-directed mutagenesis. The analysis of mutants led to the identification of "interface hot-spot residues" (R69, L129, and F159) that act as "switch points" for BfrB oligomerization, and our observations show the importance of 4-fold axis residues in assembly formation. Moreover, we demonstrate that single-point mutations Q51A, Q126A, and E135A can enhance the thermal stability of the protein without affecting its assembly. Importantly, a comparative analysis of various mutations revealed that the function of various homologous positions in different ferritins could be at variance; hence, predicting the function of a residue just based on sequence-structure comparisons may not be appropriate. Thus, we report the identification of novel residues in the assembly formation and function of BfrB and show that single-point mutations have a remarkable potential for alteration of multiple properties of ferritins. Besides, "switch residues" or "interface hot spots" identified in this study could also prove to be helpful for the rational design of interfacial inhibitors. PMID:23409758

Khare, Garima; Nangpal, Prachi; Tyagi, Anil K



Macular Degeneration  

Microsoft Academic Search

Owing to the lack of an effective prevention and appropriate treatment, age-related macular degeneration (AMD) continues being\\u000a the leading cause of central vision loss in patients older than 65 yr of age in the first world, and the third cause in developing\\u000a countries. Despite a relatively low prevalence of choroideal neovascularization (CNV) in AMD, approximately a quarter of these\\u000a patients

Peter E. Liggett; Alejandro J. Lavaque


CpG site degeneration triggered by the loss of functional constraint created a highly polymorphic macaque drug-metabolizing gene, CYP1A2  

PubMed Central

Background Elucidating the pattern of evolutionary changes in drug-metabolizing genes is an important subject not only for evolutionary but for biomedical research. We investigated the pattern of divergence and polymorphisms of macaque CYP1A1 and CYP1A2 genes, which are major drug-metabolizing genes in humans. In humans, CYP1A2 is specifically expressed in livers while CYP1A1 has a wider gene expression pattern in extrahepatic tissues. In contrast, macaque CYP1A2 is expressed at a much lower level than CYP1A1 in livers. Interestingly, a previous study has shown that Macaca fascicularis CYP1A2 harbored unusually high genetic diversity within species. Genomic regions showing high genetic diversity within species is occasionally interpreted as a result of balancing selection, where natural selection maintains highly diverged alleles with different functions. Nevertheless many other forces could create such signatures. Results We found that the CYP1A1/2 gene copy number and orientation has been highly conserved among mammalian genomes. The signature of gene conversion between CYP1A1 and CYP1A2 was detected, but the last gene conversion event in the simian primate lineage occurred before the Catarrhini-Platyrrhini divergence. The high genetic diversity of macaque CYP1A2 therefore cannot be explained by gene conversion between CYP1A1 and CYP1A2. By surveying CYP1A2 polymorphisms in total 91 M. fascicularis and M. mulatta, we found several null alleles segregating in these species, indicating functional constraint on CYP1A2 in macaques may have weakened after the divergence between humans and macaques. We propose that the high genetic diversity in macaque CYP1A2 is partly due to the degeneration of CpG sites, which had been maintained at a high level by purifying selection, and the rapid degeneration process was initiated by the loss of functional constraint on macaque CYP1A2. Conclusions Our findings show that the highly polymorphic CYP1A2 gene in macaques has not been created by balancing selection but by the burst of CpG site degeneration after loss of functional constraint. Because the functional importance of CYP1A1/2 genes is different between humans and macaques, we have to be cautious in extrapolating a drug-testing data using substrates metabolized by CYP1A genes from macaques to humans, despite of their somewhat overlapping substrate specificity.



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

PubMed Central

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

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



Compactly supported orthogonal and biorthogonal square root 5-refinement wavelets with 4-fold symmetry.  


Recently, square root 5 -refinement hierarchical sampling has been studied and square root 5-refinement has been used for surface subdivision. Compared with other refinements, such as the dyadic or quincunx refinement, square root 5-refinement has a special property that the nodes in a refined lattice form groups of five nodes with these five nodes having different x and y coordinates. This special property has been shown to be very useful to represent adaptively and render complex and procedural geometry. When square root 5-refinement is used for multiresolution data processing, square root 5-refinement filter banks and wavelets are required. While the construction of 2-D nonseparable (bi)orthogonal wavelets with the dyadic or quincunx refinement has been studied by many researchers, the construction of (bi)orthogonal wavelets with square root 5-refinement has not been investigated. The main goal of this paper is to construct compactly supported orthogonal and biorthogonal wavelets with square root 5 -refinement. In this paper, we obtain block structures of orthogonal and biorthogonal square root 5-refinement FIR filter banks with 4-fold rotational symmetry. We construct compactly supported orthogonal and biorthogonal wavelets based on these block structures. PMID:18854246

Jiang, Qingtang



Molten globule monomer to condensed dimer: role of disulfide bonds in platelet factor-4 folding and subunit association.  


Platelet factor 4 (PF4) exhibits high affinity for heparin and exists as a tetramer in solution under physiologic conditions. Reduction of the two disulfide bridges in PF4 increases the protein's dissociation constant for heparin approximately 20-fold and shifts the highest apparent aggregation state from tetramer to dimer as evidenced by gel filtration, chemical cross-linking, and 1H-NMR studies. 1H-NMR spectra of reduced PF4 monomers generally show narrower, less dispersed, upfield-shifted NH and alpha H resonances, suggesting the presence of an unfolded monomer state. Reduced PF4 monomer folding, however, is evidenced by the presence of about 12 relatively long-lived backbone NHs and by CD spectra that indicate conservation of overall secondary structure. These data suggest the presence of a molten globule-type state. Urea denaturation shifts this apparent molten globule to a fully unfolded state characterized by more random coil-like resonance shifts. The reduced PF4 dimer state yields NMR and CD data consistent with preservation of tertiary structural folds found for the native species. In this regard, the reduced PF4 folding transition is thermodynamically linked with dimer formation which stabilizes tertiary structure. Monomer-dimer association equilibria for reduced PF4 essentially follow the same pH and salt titration trends as reported previously for native PF4 dimers [Mayo, K. H., & Chen, M. J. (1989) Biochemistry 28, 9469-9478], indicating that that dimer interface is generally conserved in the absence of disulfide constraints. Reduced PF4 tetramers are not apparent under any conditions investigated, suggesting that disulfides are necessary for efficient antiparallel beta-sheet alignment between dimer pairs. PMID:1457422

Mayo, K H; Barker, S; Kuranda, M J; Hunt, A J; Myers, J A; Maione, T E



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.

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



A 2-dimensional cadmium(II) coordination polymer with the unique 4-fold interpenetrated (4, 4) layered structure from a long bridging ligand  

NASA Astrophysics Data System (ADS)

A new 2D Cd(II) coordination polymer was hydrothermally synthesized, which possesses a unique 4-fold interpenetrated (4, 4) layered structure constructed by a long bridging ligand, and has the fluorescent emission with the maximum emission wavelength at 543 nm.

Niu, Cao-Yuan; Zheng, Xian-Fu; Feng, Cao-Ling; Kou, Chun-Hong



Indexing Degenerate Strings  

NASA Astrophysics Data System (ADS)

In this paper, we give the first, to our knowledge, structure and corresponding algorithm for indexing of factors of DNA and RNA sequences, where the text is degenerate i.e. contain sets of characters. The presented structure indexes so called k-factors, the factors of the degenerate text whose length does not exceed a given constant k. Our solution is based on the application of finite automata, the index is represented by Truncated Generalized Factor Automaton (TGFA). The size of TGFA is bounded from up by linear function of the length of text and it enables to find list occ(u) of all occurrences of for a given pattern u in degenerate text x~ in time |u|+|occ(u)|

Vorá?ek, Michal; Vagner, Ladislav; Flouri, Tomáš



Apraxia in Corticobasal Degeneration  

Microsoft Academic Search

Corticobasal degeneration (CBD) is a degenerative disease that often presents with an asymmetric progressive ideomotor limb apraxia. Some apraxic subjects may fail to perform skilled purposive movements on command because they have lost the memories or representations that specify how these movements should be performed (representational deficit). In contrast, other apraxic subjects may have the movement representations but are unable

Daniel H. Jacobs; John C. Adair; Beth Macauley; Michael Gold; Leslie J. Gonzalez Rothi; Kenneth M. Heilman



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)



Quantum degenerate systems  

NASA Astrophysics Data System (ADS)

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.

de Micheli, Fiorenza; Zanelli, Jorge



Anorexia and hypothalamic degeneration.  


Anorexia, meaning poor appetite, occurs in many human conditions, for example, anorexia nervosa, cachexia, and failure to thrive in infants. A key player in the regulation of appetite/food intake in general, as well as conditions of anorexia, is the hypothalamus, in particular, the AGRP/NPY and POMC/CART neurons in the arcuate nucleus. In this chapter, we review the hypothalamic aberrances seen in the anorectic anx/anx mouse. This mouse displays deviations in neuropeptidergic/-transmitter systems, including selective hypothalamic degeneration and inflammation that have been associated with mitochondrial dysfunction. In addition, we discuss data from other animal models, as well as clinical data relating hypothalamic inflammation/degeneration, neurogenesis, and mitochondrial dysfunction to conditions of disturbed regulation of food intake. PMID:23601420

Nilsson, Ida A K; Lindfors, Charlotte; Schalling, Martin; Hökfelt, Tomas; Johansen, Jeanette E




Microsoft Academic Search

Fungi are notorious for losing virulence and changing their morphology when successively subcultured on artificial media.\\u000a Various terms have been used to describe this phenomenon including phenotypic degeneration, phenotypic instability, phenotypic\\u000a deterioration, dual phenomenon, saltation and attenuation (Butt, 2002; Kawakami, 1960; Nagaich, 1973; Ibrahim et al., 2002; Ryan et al., 2001). Morphological changes include a change in colour, and growth

Tariq M. Butt; Chengshu Wang; Farooq A. Shah; Richard Hall


Degenerate perturbation theory  

SciTech Connect

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

Brandow, B.



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.

Rabinovici, Gil D.; Miller, Bruce L.




PubMed Central

It will be seen from the above that we have studied the conditions associated with the deposit of calcareous salts: (I) in connection with normal and pathological ossification, and (2) in pathological calcification as exhibited in (a) atheroma of the vessels; (b) calcification of caseating tubercular lesions; (c) calcification of inflammatory new growth, and (d) degenerating tumors; and we have induced experimentally deposits of calcareous salts in the lower animals: (a) within celloidin capsules containing fats and soaps; (b) in the kidney, and (c) in connection with fat necrosis. I. We have found that bone formation and pathological calcareous infiltration are wholly distinct processes. In the former there is no evidence of associated fatty change, and the cells associated with the process of deposition of calcium are functionally active. In the latter there is an antecedent fatty change in the affected areas, and the cells involved present constant evidences of degeneration. The view that would seem to account best for the changes observed in the latter case is that with lowered vitality the cells are unable to utilize the products brought to them by the blood, or which they continue to absorb, so that the normal series of decompositions associated with their metabolism fails to take place and hence they interact among themselves in the cytoplasm with the result that insoluble compounds replace soluble ones. II. Besides the fact that calcification is always preceded by fatty change within the cells, another fact should be emphasized. namely: that combination of the fats present with calcium salts to form calcium soaps tends to occur. The stages immediately preceding these are difficult to follow with anything approaching certainty, perhaps because the earlier stages vary under different conditions. In fat necrosis, for instance, the cells affected are normally storehouses for neutral fats, and as long as they remain healthy neutral fats alone are present in them. When they are subjected to the action of the pancreatic juice with its fat-splitting ferment the cells are killed and coincidently the neutral fats are decomposed, fatty acids being deposited. The fatty acids now slowly combine with the calcium salts. In degenerating lipomata the process would seem to be similar. But in other cases the cells are not obviously fat-containing in the normal state; nevertheless prior to calcification they undergo so-called fatty degeneration, which is really a form of cell degeneration accompanied by fat infiltration. As regards the source of the cell fats in general we may safely accept: 1. That fats are transported in the blood as diffusible soaps. 2. That taken up by the cells these soaps may either— (a) Be reconverted into neutral fats and become stored in the cytoplasm as such, or (b) undergo assimilation proper, becoming part and parcel of the cell substance, in which case they are not recognizable by the ordinary microchemical tests. 3. If these two possibilities be accepted it follows that the appearance of fats and soaps in the degenerating cell may be due to either— (a) Absorption or infiltration of soaps from the surrounding medium, the degenerating cell retaining the power of splitting off the fat but being unable to utilize this in metabolism. (b) Cytoplasmic disintegration with dissociation of the soap-albumen combination or, more broadly, liberation of the fats from their combination with the cytoplasm. The appearances seen in the cells of atheromatous areas indicate that the first of these does occur. III. In areas undergoing calcareous infiltration we have demonstrated. the presence of soaps, and this often in such quantities that they can be isolated and estimated by gross chemical methods. By microchemical methods also we have been able to show that after removing all the neutral fats and fatty acids by petroleum ether there remains behind a substance giving with Sudan III the reaction we associate with the presence of soap. And experimentally we have produced these soaps within the organism, more

Klotz, Oskar



Frontotemporal Disorders (Frontotemporal Lobar Degeneration)  


... rare diseases that involve shrinkage of specific areas of the brain that regulate behavior, personality, and language, a process termed frontotemporal lobar degeneration (FTLD). Frontotemporal ...


Systemic administration of MPTP induces thalamic neuronal degeneration in mice  

Microsoft Academic Search

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a known neurotoxicant primarily selective for catecholaminergic neurons, including those of the nigrostriatal dopaminergic system, thereby mimicking the pathology of Parkinson's disease (PD). In this study, serial transbrain sectioning, followed by staining with a newly developed fluorochrome (Fluoro-Jade) specific for degenerating neurons, was used to detect additional sites of MPTP-induced neuronal degeneration in mice. Male CD-1 mice

Tim E Freyaldenhoven; Syed F Ali; Larry C Schmued



GENERAL: Double Degenerate Stars  

NASA Astrophysics Data System (ADS)

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

Luo, Xin-Lian; Bai, Hua; Zhao, Lei



Photobiomodulation in inherited retinal degeneration  

Microsoft Academic Search

The retinal degenerative disease, retinitis pigmentosa (RP), is the most common cause of inherited blindness in the developed world and is caused by the progressive degeneration of rod photoreceptor cells preceding cone degeneration. Mitochondrial dysfunction and oxidative stress have been shown to play a significant role in the pathogenesis of RP and other retinal degenerative diseases. A growing body of

Sandeep Gopalakrishnan



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

SciTech Connect

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

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



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

PubMed Central

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

Baraibar, Martin A.; Muhoberac, Barry B.; Garringer, Holly J.; Hurley, Thomas D.; Vidal, Ruben



Unraveling of the E-helices and disruption of 4-fold pores are associated with iron mishandling in a mutant ferritin causing neurodegeneration.  


Mutations in the coding sequence of the ferritin light chain (FTL) gene cause a neurodegenerative disease known as neuroferritinopathy or hereditary ferritinopathy, which is characterized by the presence of intracellular inclusion bodies containing the mutant FTL polypeptide and by abnormal accumulation of iron in the brain. Here, we describe the x-ray crystallographic structure and report functional studies of ferritin homopolymers formed from the mutant FTL polypeptide p.Phe167SerfsX26, which has a C terminus that is altered in amino acid sequence and length. The structure was determined and refined to 2.85 A resolution and was very similar to the wild type between residues Ile-5 and Arg-154. However, instead of the E-helices normally present in wild type ferritin, the C-terminal sequences of all 24 mutant subunits showed substantial amounts of disorder, leading to multiple C-terminal polypeptide conformations and a large disruption of the normally tiny 4-fold axis pores. Functional studies underscored the importance of the mutant C-terminal sequence in iron-induced precipitation and revealed iron mishandling by soluble mutant FTL homopolymers in that only wild type incorporated iron when in direct competition in solution with mutant ferritin. Even without competition, the amount of iron incorporation over the first few minutes differed severalfold. Our data suggest that disruption at the 4-fold pores may lead to direct iron mishandling through attenuated iron incorporation by the soluble form of mutant ferritin and that the disordered C-terminal polypeptides may play a major role in iron-induced precipitation and formation of ferritin inclusion bodies in hereditary ferritinopathy. PMID:19923220

Baraibar, Martin A; Muhoberac, Barry B; Garringer, Holly J; Hurley, Thomas D; Vidal, Ruben



Mitochondrial dysfunction and spinocerebellar degenerations  

Microsoft Academic Search

A simplified classification of the spinocerebellar degenerations is proposed. Axonal ataxias include Friedreich’s ataxia and\\u000a other conditions involving, primarily, neurons with very long axons. Multiple system degenerations include the various olivopontocerebellar\\u000a atrophies and related disorders. Ataxic encephalopathies are diffuse diseases of the nervous system in which ataxia is a prominent\\u000a clinical feature. Several lines of data suggest that mitochondrial damage

Jesse M. Cedarbaum; John P. Blass



Axon degeneration in Parkinson's disease.  


Parkinson's disease (PD) is the most common neurodegenerative disease of the basal ganglia. Like other adult-onset neurodegenerative disorders, it is without a treatment that forestalls its chronic progression. Efforts to develop disease-modifying therapies to date have largely focused on the prevention of degeneration of the neuron soma, with the tacit assumption that such approaches will forestall axon degeneration as well. We herein propose that future efforts to develop neuroprotection for PD may benefit from a shift in focus to the distinct mechanisms that underlie axon degeneration. We review evidence from human post-mortem studies, functional neuroimaging, genetic causes of the disease and neurotoxin models that axon degeneration may be the earliest feature of the disease, and it may therefore be the most appropriate target for early intervention. In addition, we present evidence that the molecular mechanisms of degeneration of axons are separate and distinct from those of neuron soma. Progress is being made in understanding these mechanisms, and they provide possible new targets for therapeutic intervention. We also suggest that the potential for axon re-growth in the adult central nervous system has perhaps been underestimated, and it offers new avenues for neurorestoration. In conclusion, we propose that a new focus on the neurobiology of axons, their molecular pathways of degeneration and growth, will offer novel opportunities for neuroprotection and restoration in the treatment of PD and other neurodegenerative diseases. PMID:22285449

Burke, Robert E; O'Malley, Karen



X-linked recessive atrophic macular degeneration from RPGR mutation.  


We mapped a new X-linked recessive atrophic macular degeneration locus to Xp21.1-p11.4 and show allelic involvement of the gene RPGR, which normally causes severe peripheral retinal degeneration leading to global blindness. Ten affected males whom we examined had primarily macular atrophy causing progressive loss of visual acuity with minimal peripheral visual impairment. One additional male showed extensive macular degeneration plus peripheral loss of retinal pigment epithelium and choriocapillaries. Full-field electroretinograms (ERGs) showed normal cone and rod responses in some affected males despite advanced macular degeneration, emphasizing the dissociation of atrophic macular degeneration from generalized cone degenerations, including X-linked cone dystrophy (COD1). The RPGR gene nonsense mutation G-->T at open reading frame (ORF)15+1164 cosegregated with the disease and may create a donor splice site. Identification of an RPGR mutation in atrophic maculardegeneration expands the phenotypic range associated with this gene and provides a new tool for the dissection of the relationship between clinically different retinal pathologies. PMID:12160730

Ayyagari, Radha; Demirci, F Yesim; Liu, Jiafan; Bingham, Eve L; Stringham, Heather; Kakuk, Laura E; Boehnke, Michael; Gorin, Michael B; Richards, Julia E; Sieving, Paul A



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


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



Age-related macular degeneration.  


Age-related macular degeneration is a major cause of blindness worldwide. With ageing populations in many countries, more than 20% might have the disorder. Advanced age-related macular degeneration, including neovascular age-related macular degeneration (wet) and geographic atrophy (late dry), is associated with substantial, progressive visual impairment. Major risk factors include cigarette smoking, nutritional factors, cardiovascular diseases, and genetic markers, including genes regulating complement, lipid, angiogenic, and extracellular matrix pathways. Some studies have suggested a declining prevalence of age-related macular degeneration, perhaps due to reduced exposure to modifiable risk factors. Accurate diagnosis combines clinical examination and investigations, including retinal photography, angiography, and optical coherence tomography. Dietary anti-oxidant supplementation slows progression of the disease. Treatment for neovascular age-related macular degeneration incorporates intraocular injections of anti-VEGF agents, occasionally combined with other modalities. Evidence suggests that two commonly used anti-VEGF therapies, ranibizumab and bevacizumab, have similar efficacy, but possible differences in systemic safety are difficult to assess. Future treatments include inhibition of other angiogenic factors, and regenerative and topical therapies. PMID:22559899

Lim, Laurence S; Mitchell, Paul; Seddon, Johanna M; Holz, Frank G; Wong, Tien Y



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.

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



Quantum degenerate dipolar Fermi gas.  


We report the first quantum degenerate dipolar Fermi gas, the realization of which opens a new frontier for exploring strongly correlated physics and, in particular, quantum liquid crystalline phases. A quantum degenerate Fermi gas of the most magnetic atom 161Dy is produced by laser cooling to 10 ?K before sympathetically cooling with ultracold, bosonic 162Dy. The temperature of the spin-polarized 161Dy is a factor T/T(F)=0.2 below the Fermi temperature T(F)=300 nK. The cotrapped 162Dy concomitantly cools to approximately T(c) for Bose-Einstein condensation, thus realizing a novel, nearly quantum degenerate dipolar Bose-Fermi gas mixture. Additionally, we achieve the forced evaporative cooling of spin-polarized 161Dy without 162Dy to T/T(F)=0.7. That such a low temperature ratio is achieved may be a first signature of universal dipolar scattering. PMID:23003275

Lu, Mingwu; Burdick, Nathaniel Q; Lev, Benjamin L



Quantum Degenerate Dipolar Fermi Gas  

NASA Astrophysics Data System (ADS)

We report the first quantum degenerate dipolar Fermi gas, the realization of which opens a new frontier for exploring strongly correlated physics and, in particular, quantum liquid crystalline phases. A quantum degenerate Fermi gas of the most magnetic atom Dy161 is produced by laser cooling to 10?K before sympathetically cooling with ultracold, bosonic Dy162. The temperature of the spin-polarized Dy161 is a factor T/TF=0.2 below the Fermi temperature TF=300nK. The cotrapped Dy162 concomitantly cools to approximately Tc for Bose-Einstein condensation, thus realizing a novel, nearly quantum degenerate dipolar Bose-Fermi gas mixture. Additionally, we achieve the forced evaporative cooling of spin-polarized Dy161 without Dy162 to T/TF=0.7. That such a low temperature ratio is achieved may be a first signature of universal dipolar scattering.

Lu, Mingwu; Burdick, Nathaniel Q.; Lev, Benjamin L.



Fluoroquinolone-induced retinal degeneration in cats.  


Although the exact mechanism of fluoroquinolone-induced retinal degeneration in cats remains to be elucidated, it appears from the literature that a similar retinal degeneration can be reproduced from either direct intravitreal injection of high concentrations of drug or exposure to UVA light and drug in laboratory animals. (19,25) The fluoroquinolone molecular structure is also similar structurally to other drugs that are known to directly induce retinal degeneration, including the cinchona alkaloids and halogenated hydroquinolones. Experimental evidence suggests that both the parent compound and its breakdown products via metabolism and photodegradation are active inducers of retinal degeneration. (18,25) Development of toxicoses also appears to be dependent on the maximum concentration of active drug, metabolite, or both reaching the retina over time. (18) Evaluation of the literature suggests that risk factors predisposing cats to fluoroquinolone-induced retinal degeneration may include the following: 1) large doses or plasma concentrations of drug, 2) rapid IV infusion of the antibiotic, 3) prolonged courses of treatment, and 4) age. Theoretically, other risk factors may also be involved including the following: 1) prolonged exposure to UVA light while the antibiotic is being administered, 2) drug interactions, and 3) drug or metabolite accumulation from altered metabolism or reduced elimination. To date, there are no published reports suggesting that the dose of fluoroquinolones should be reduced in geriatric cats or those with renal or hepatic failure. However, accumulation of fluoroquinolone metabolites in dogs and of the parent compound in humans with decreased renal function has been reported. (8-10) In humans with decreased renal function has been reported. (8-10) humans, fluoroquinolone doses are typically decreased in response to the degree of renal impairment. (28) In general, all fluoroquinolone antibiotics should be reserved for severe or recurrent infections, and whenever possible their use should be based on results whenever possible their use should be based on results of culture and susceptibility tests. When indicated, the fluoroquinolones, including enrofloxacin, can be used with limited risk of developing retinal degeneration in cats, provided the manufacturer's guidelines are adhered to and dose reduction is considered in geriatric cats or those with renal impairment. Dosing on renal impairment. Dosing on exact body weight using split dosing (2.5 mg/kg, PO, q 12 h) and avoidance of rapid IV infusions, and drug interactions may help to reduce the risk of retinal degeneration in some cases. Furthermore, monitoring cats for mydriasis and avoidance of UVA light while undergoing treatment may also be of benefit. Further evaluation of the pharmacokinetics of enrofloxacin and the other fluoroquinolones is required in geriatric cats or those with mild to moderate renal or liver impairment to determine whether drug accumulation, elevated peak concentrations of drug, or both may be occurring in this subset of cats. Therapeutic monitoring of drug concentrations may not always be feasible because of time and cost, but renal panels with dose or frequency reduction in response to the degree of renal impairment and the site and severity of infection may help to reduce retinal toxicosis. PMID:12479325

Wiebe, Valerie; Hamilton, Patti



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



The Degeneration of Tropical Geography  

Microsoft Academic Search

How did colonial and tropical geography as practiced in the aftermath of World War II become development geography by the 1970s? We excavate the genealogy of development geography, relating it to geopolitical, economic, and social traumas of decolonization. We examine how revolutionary pressures and insurgencies, coupled with the eclipse of formal colonialism, led to the degeneration and displacement of a

Marcus Power; James D. Sidaway



Cognitive Impairment in Spinocerebellar Degeneration  

Microsoft Academic Search

It has been reported that patients with spinocerebellar degenerations (SCDs) have cognitive dysfunction as well as limb and truncal ataxia, dysarthria and dysphagia. We review cognitive dysfunction in common types of SCD, including spinocerebellar ataxia types 1, 2, 3, 6, and 17, dentatorubral-pallidoluysian atrophy, Friedreich’s ataxia, and multiple system atrophy. There are few studies that address cognitive function in SCD.

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



Striatal glutamate degenerates thalamic neurons.  


Glutamate (GLU)-induced excitotoxicity is considered to be a frequent cause of cell degeneration in basal ganglia disorders; it is normally prevented by uptake of GLU by astrocytes. We recently found that transient perfusion of GLU in the striatum induces persistent accumulation of GLU in striatal astrocytes that could be from the initial administration or caused by the slow release from neurons or astrocytes in response to it. Endogenous production of GLU, that is, "self-induced GLU accumulation" (SIGA), may occur under physiological and pathological conditions. Here we studied the possible induction of SIGA after injury induced by perfusion of GLU receptor agonists into the striatum of rats. The agonists induced local degeneration in neurons and myelinated axons and microgliosis and astrocytosis; there was also gliosis and remote degeneration of neurons in the ventral-posterior complex of the thalamus that project to the cerebral cortex across the striatum. Reactive astrocytes showed persistent GLU accumulation in the striatum (local SIGA) and thalamus (remote SIGA) that persisted for at least 6 weeks after the injury. Thus, SIGA can be induced by neuronal degeneration retrogradely triggered from a remote brain region after excessive release of endogenous GLU from astrocytes. This may be an additional factor to be considered in basal ganglia disorders with glutamatergic excitotoxicity. PMID:23481706

Morales, Ingrid; Yanos, Catalina; Rodriguez-Sabate, Clara; Sanchez, Alberto; Rodriguez, Manuel



Testicular degeneration in Huntington disease  

Microsoft Academic Search

Huntington disease (HD) is an adult onset, neurodegenerative disorder that results from CAG expansion in the HD gene. Recent work has demonstrated testicular degeneration in mouse models of HD and alterations in the hypothalamic–pituitary–gonadal (HPG) axis in HD patients. Here, we show that HD patients have specific testicular pathology with reduced numbers of germ cells and abnormal seminiferous tubule morphology.

Jeremy M. Van Raamsdonk; Zoe Murphy; David M. Selva; Reza Hamidizadeh; Jacqueline Pearson; ?sa Petersén; Maria Björkqvist; Cameron Muir; Ian R. Mackenzie; Geoffrey L. Hammond; A. Wayne Vogl; Michael R. Hayden; Blair R. Leavitt



DNA sequencing by synthesis with degenerate primers  

Microsoft Academic Search

The degenerate primer-based sequencing was developed by a synthesis method (DP-SBS) for high-throughput DNA sequencing, in which a set of degenerate primers are hybridized on the arrayed DNA templates and extended by DNA polymerase on microarrays. In this method, a different set of degenerate primers containing a given number (n) of degenerate nucleotides at the 3?-ends were annealed to the

Chao Tang; Xiaolong Shi; Xiujie Li; Zuhong Lu



Electron tomography of degenerating neurons in mice with abnormal regulation of iron metabolism  

PubMed Central

Previous studies have shown that IRP1+/? IRP2?/? knockout mice develop progressive neurodegenerative symptoms similar to those observed in human movement disorders such as Parkinson's disease. Histological investigations using optical microscopy show that these IRP knockout mice display accumulation of ferritin in axonal tracts in the brain, suggesting a possible role for excess ferritin in mediating axonal degeneration. Direct observation of the 3D distribution of ferritin by electron tomography indicates that ferritin amounts are increased by 3- to 4-fold in selected regions of the brain, and structural damage is observed within the axon as evidenced by the loss of the internal network of filaments, and the invaginations of neighboring oligodendrocyte membranes into the axonal medium. While optical microscopic investigations suggest that there is a large increase in ferritin in the presumptive axonal regions of the IRP knockout mice, electron tomographic studies reveal that most of the excess ferritin is localized to double-walled vesicular compartments which are present in the interior of the axon and appear to represent invaginations of the oligodendrocyte cells into the axon. The amount of ferritin observed in the axonal space of the knockout mice is at least 10-fold less than the amount of ferritin observed in wild-type mouse axons. The surprising conclusion from our analysis, therefore, is that despite the overall increase in ferritin levels in the knockout mouse brain, ferritin is absent from axons of degenerating neurons, suggesting that trafficking is compromised in early stages of this type of neuronal degeneration.

Zhang, Peijun; Land, William; Lee, Stanton; Juliani, Jemma; Lefman, Jonathan; Smith, Sophia R.; Germain, David; Kessel, Martin; Leapman, Richard; Rouault, Tracey A.; Subramaniam, Sriram



Electron tomography of degenerating neurons in mice with abnormal regulation of iron metabolism.  


Previous studies have shown that IRP1(+/-) IRP2(-/-) knockout mice develop progressive neurodegenerative symptoms similar to those observed in human movement disorders such as Parkinson's disease. Histological investigations using optical microscopy show that these IRP knockout mice display accumulation of ferritin in axonal tracts in the brain, suggesting a possible role for excess ferritin in mediating axonal degeneration. Direct observation of the 3D distribution of ferritin by electron tomography indicates that ferritin amounts are increased by 3- to 4-fold in selected regions of the brain, and structural damage is observed within the axon as evidenced by the loss of the internal network of filaments, and the invaginations of neighboring oligodendrocyte membranes into the axonal medium. While optical microscopic investigations suggest that there is a large increase in ferritin in the presumptive axonal regions of the IRP knockout mice, electron tomographic studies reveal that most of the excess ferritin is localized to double-walled vesicular compartments which are present in the interior of the axon and appear to represent invaginations of the oligodendrocyte cells into the axon. The amount of ferritin observed in the axonal space of the knockout mice is at least 10-fold less than the amount of ferritin observed in wild-type mouse axons. The surprising conclusion from our analysis, therefore, is that despite the overall increase in ferritin levels in the knockout mouse brain, ferritin is absent from axons of degenerating neurons, suggesting that trafficking is compromised in early stages of this type of neuronal degeneration. PMID:15866737

Zhang, Peijun; Land, William; Lee, Stanton; Juliani, Jemma; Lefman, Jonathan; Smith, Sophia R; Germain, David; Kessel, Martin; Leapman, Richard; Rouault, Tracey A; Subramaniam, Sriram



Neurosyphilis masquerading as corticobasal degeneration.  


We report on a patient with a syndrome resembling corticobasal ganglionic degeneration (CBD), including slight cognitive impairment, asymmetric akinesia, rigidity with myoclonus, and arm levitation, which can be one of the features of alien limb phenomenon; however, further diagnostic testing was consistent with neurosyphilis. Syphilis, "the great imitator," may also masquerade as CBD. Because neurosyphilis is treatable, it should be considered in the workup of patients with cognitive impairment and motor signs of CBD. PMID:15389980

Benito-León, J; Alvarez-Linera, J; Louis, E D



Neuropsychiatric features of corticobasal degeneration  

Microsoft Academic Search

OBJECTIVETo characterise the neuropsychiatric symptoms of patients with corticobasal degeneration (CBD).METHODSThe neuropsychiatric inventory (NPI), a tool with established validity and reliability, was administered to 15 patients with CBD (mean (SEM), age 67.9 (2) years); 34 patients with progressive supranuclear palsy (PSP) (66.6 (1.2) years); and 25 controls (70 (0.8) years), matched for age and education. Both patient groups had similar

Irene Litvan; Jeffrey L Cummings; Michael Mega



Degenerate Fermi Gases of Ytterbium  

SciTech Connect

Evaporative cooling was performed to cool fermionic {sup 173}Yb atoms in a crossed optical dipole trap. The large elastic collision rate leads to efficient evaporation and we have successfully cooled the atoms to 0.37{+-}0.06 of the Fermi temperature, that is to say, to a quantum degenerate regime. In this regime, a plunge of evaporation efficiency was observed as a result of Fermi degeneracy.

Fukuhara, Takeshi [Department of Physics, Graduate School of Science, Kyoto University, Kyoto 606-8502 (Japan); Takasu, Yosuke [Department of Electronic Science and Engineering, Graduate School of Engineering, Kyoto University, Kyoto 615-8510 (Japan); Kumakura, Mitsutaka [Department of Physics, Graduate School of Science, Kyoto University, Kyoto 606-8502 (Japan); CREST, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012 (Japan); PRESTO, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012 (Japan); Takahashi, Yoshiro [Department of Physics, Graduate School of Science, Kyoto University, Kyoto 606-8502 (Japan); CREST, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012 (Japan)



Glial Vascular Degeneration in CADASIL  

PubMed Central

Background CADASIL is a genetic vascular dementia caused by mutations in the Notch 3 gene on Chromosome 19. However, little is known about the mechanisms of vascular degeneration. Methods We characterized upstream components of Notch signaling pathways that may be disrupted in CADASIL, by measuring expression of insulin, IGF-1, and IGF-2 receptors, Notch 1, Notch 3, and aspartyl-(asparaginyl)-?-hydroxylase (AAH) in cortex and white matter from 3 CADASIL and 6 control brains. We assessed CADASIL-associated cell loss by measuring mRNA corresponding to neurons, oligodendroglia, and astrocytes, and indices of vascular degeneration by measuring smooth muscle actin (SMA) and endothelin-1 (ET-1) expression in isolated vessels. Immunohistochemical staining was used to assess SMA degeneration. Results Significant abnormalities including reduced cerebral white matter mRNA levels of Notch 1, Notch 3, AAH, SMA, IGF receptors, myelin-associated glycoproteins, and glial fibrillary acidic protein, and reduced vascular expression of SMA, IGF receptors, Notch 1 and Notch 3 were detected in CADASIL-lesioned brains. In addition, we found CADASIL-associated reductions in SMA, and increases in ubiquitin immunoreactivity in the media of white matter and meningeal vessels. No abnormalities in gene expression or immunoreactivity were observed in CADASIL cerebral cortex. Conclusions Molecular abnormalities in CADASIL are largely restricted to white matter and white matter vessels, corresponding to the distribution of neuropathological lesions. These preliminary findings suggest that CADASIL is mediated by both glial and vascular degeneration with reduced expression of IGF receptors and AAH, which regulate Notch expression and function.

Brennan-Krohn, Thea; Salloway, Stephen; Correia, Stephen; Dong, Matthew; de la Monte, Suzanne M.



Striatonigral degeneration with neurofibrillary tangles  

Microsoft Academic Search

An autopsy was performed on a 48-year-old woman with clinical features of parkinsonism-plus syndrome with dominating akinesia. Neuropathological examination revealed striato-nigral degeneration (SND) and neurofibrillary tangles (NFT) characterizing progressive supranuclear palsy. Such an unusual combination of pathological findings may constitute a distinct clinico-pathological entity, with akinesia as the main clinical symptom, and with a pathological substrate of SND and NFT.

K. Renkawek; M. W. I. M. Horstink



The degeneration of Y chromosomes.  

PubMed Central

Y chromosomes are genetically degenerate, having lost most of the active genes that were present in their ancestors. The causes of this degeneration have attracted much attention from evolutionary theorists. Four major theories are reviewed here: Muller's ratchet, background selection, the Hill Robertson effect with weak selection, and the 'hitchhiking' of deleterious alleles by favourable mutations. All of these involve a reduction in effective population size as a result of selective events occurring in a non-recombining genome, and the consequent weakening of the efficacy of selection. We review the consequences of these processes for patterns of molecular evolution and variation at loci on Y chromosomes, and discuss the results of empirical studies of these patterns for some evolving Y-chromosome and neo-Y-chromosome systems. These results suggest that the effective population sizes of evolving Y or neo-Y chromosomes are severely reduced, as expected if some or all of the hypothesized processes leading to degeneration are operative. It is, however, currently unclear which of the various processes is most important; some directions for future work to help to resolve this question are discussed.

Charlesworth, B; Charlesworth, D



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.

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



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.



Ubiquitin-positive achromatic neurons in corticobasal degeneration  

Microsoft Academic Search

A 66-year-old woman presented with an alien limb syndrome without dementia. The course of her illness was unremitting and at autopsy 6 years later her diagnosis was confirmed as corticobasal degeneration without Alzheimer-type pathology. Although the presence of ballooned achromatic cortical neurons and cell loss from the substantia nigra distinguishes such patients, the site and density of achromatic neurons has

G. M. Halliday; L. Davies; D. A. McRitchie; H. Cartwright; R. Pamphlett; J. G. L. Morris



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

PubMed Central

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

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



Programmed cell death in intervertebral disc degeneration  

Microsoft Academic Search

Intervertebral disc (IVD) degeneration is largely a process of destruction and failure of the extracellular matrix (ECM),\\u000a and symptomatic IVD degeneration is thought to be one of the leading causes of morbidity or life quality deterioration in\\u000a the elderly. To date, however, the mechanism of IVD degeneration is still not fully understood. Cellular loss from cell death\\u000a in the process

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



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.

Guenther, Peter; Hoffmann, Karl-Titus



Diagnostics and the therapeutics for macular degeneration  

US Patent & Trademark Office Database

The invention relates to diagnostics and therapeutics and animal models for macular degeneration, specifically as they relate to the association described herein between macular degeneration and arterial wall disruptive disorders. In one embodiment, the invention provides kits and methods for diagnosing macular degeneration comprising identifying a marker for an arterial wall disruptive disorder, including an aneurysm. In one embodiment, the invention provides therapeutics for treating macular degeneration comprising delivering to a subject an agent useful for treating an arterial wall disruptive disorder, including an aneurysm.

Hageman; Gregory S. (Coralville, IA)



Inherited retinal degenerations: therapeutic prospects.  


Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal degenerative diseases, characterized by the progressive death of rod and cone photoreceptors. A tremendous genetic heterogeneity is associated with the RP phenotype. Most mutations affect rods selectively and, through an unknown pathway, cause the rod cells to die by apoptosis. Cones, on the other hand, are seldom directly affected by the identified mutations, and yet, in many cases, they degenerate secondarily to rods, which accounts for loss of central vision and complete blindness. Many animal models of RP are available and have led to a better understanding of the disease and to the development of therapeutic strategies aimed at curing the specific genetic disorder (gene therapy), slowing down or even stopping the process of photoreceptor degeneration (growth factors or calcium blockers applications, vitamin supplementation), preserving the cones implicated in the central visual function (identification of endogenous cone viability factors) or even replacing the lost cells (transplantation, use of stem or precursor cells). Still, many obstacles will need to be overcome before most of these strategies can be applied to humans. In this review, we describe the different therapeutic strategies being studied worldwide and report the latest results in this field. PMID:15145530

Delyfer, Marie-Noëlle; Léveillard, Thierry; Mohand-Saïd, Saddek; Hicks, David; Picaud, Serge; Sahel, José-Alain



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



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.

Galimberti, Daniela; Scarpini, Elio



Ischemic degeneration of the avian muscle spindle  

Microsoft Academic Search

The neurovascular supply to the pigeon's extensor digitorum communis muscle was disrupted. The muscle spindles were studied by light and electron microscopy to determine whether their degeneration was compatible with regeneration by activation of satellite cells within an intact spindle capsule. The denervation and ischemia induced intrafusal muscle fiber necrosis and degeneration of the sarcolemma and basal lamina. The muscle

R. S. Hikida; J. M. Walro; T. W. Miller



Drusen in Age-Related Macular Degeneration  

Microsoft Academic Search

Drusen are subretinal pigment epithelial deposits that are characteristic of but not uniquely associated with age-related macular degeneration (AMD). Age-related macular degeneration is associated with two types of drusen that have different clinical appearances and different prognoses. Hard drusen appear as small, punctate, yellow nodules and can precede the development of atrophic AMD. Areolar atrophy of the retinal pigment epithelium

Ahmed Abdelsalam; Lucian Del Priore; Marco A Zarbin



Inflammatory leukocytic recruitment and diffuse neuronal degeneration are separate pathological processes resulting from traumatic brain injury.  


The present study characterized whether inflammatory leukocytic infiltration is temporally and regionally correlated with neuronal degeneration and/or blood brain barrier (BBB) breakdown resulting from traumatic brain injury. Adult rats were sacrificed at 5 min, 2, 4, 12, 24, and 72 hr after lateral fluid percussion brain injury. BBB breakdown, neuronal degeneration and leukocyte infiltration were assessed using immunocytochemistry, silver impregnation and toluidine blue and eosin staining. BBB breakdown and neuronal degeneration occurred concomitantly in injured cortex, hippocampus, and along the dorsolateral quadrant of the diencephalon. However, neuronal degeneration within deep diencephalic structures transpired in the absence of IgG extravasation. Neutrophils were observed only in regions exhibiting BBB damage and were first apparent in injured cortex and hippocampus between 2-12 hr posttrauma lining the vasculature and filling subarachnoid/subdural spaces. Neutrophils then migrated from damaged vasculature into traumatized cortical and hippocampal parenchyma by 24 hr after lateral fluid percussion injury. Macrophages were also observed within cortical parenchyma at 24 hr and completely filled the cortical lesion site by 72 hr after injury. Macrophages were not as abundant throughout hippocampal parenchyma and were found only in hippocampal regions exhibiting focal hemorrhage at 72 hr. Finally, neutrophils did not migrate to deep diencephalic structures that showed no BBB damage despite extensive neuronal degeneration. Indeed, lateral fluid percussion elicits inflammatory leukocytic recruitment only in regions experiencing concomitant BBB damage and neuronal degeneration. In summary, inflammatory leukocytic recruitment and diffuse neuronal degeneration are separate pathological processes resulting from traumatic brain injury. PMID:8613756

Soares, H D; Hicks, R R; Smith, D; McIntosh, T K



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

Microsoft Academic Search

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

Matt S Ramer; Gavin D French; Mark A Bisby



Abnormal pseudospin-degenerate states in a graphene quantum dot with double vacancy defects  

NASA Astrophysics Data System (ADS)

We study valley-polarized states in an armchair graphene quantum dot with double vacancy defects. Half-filled doubly degenerate states are found in the middle of the gap only when two vacancies occupy certain specific sites in each of the sublattices of the quantum dot. The doubly degenerate states forming around the vacancies are shown to be entirely localized in their respective sublattice, which results in that the two parallel-spin electrons in the degenerate Fermi level carry purely opposite valley pseudospins. Surprisingly, the pseudospin-degenerate states are found to be symmetric even when the reflection symmetry of the structure has been broken by the vacancies. It is further shown that the pseudospin degeneracy, similar to the Kramer's degeneracy lifted by a magnetic field, can be removed by an applied electric field. Like the Zeeman effect, the split states would retain their original valley pseudospins and exhibit linear splitting energy with respect to the applied field.

Zhou, Aiping; Sheng, Weidong



Degeneration of Biogenic Superparamagnetic Magnetite  

SciTech Connect

ABSTRACT. Magnetite crystals precipitated as a consequence of Fe(III) reduction by Shewanella algae BrY after 265 hours incubation and 5-year storage were investigated with transmission electron microscopy, M ssbauer spectroscopy and X-ray diffraction. The magnetite crystals were typically superparamagnetic with an approximate size of 13 nm. The lattice constants of the 265 hour and 5-year crystals are 8.4164 and 8.3774 , respectively. The M ssbauer spectra indicated that the 265 hour magnetite had excess Fe(II) in its crystal-chemistry (Fe3+1.9901Fe2+ 1.0149O4) but the 5-year magnetite was Fe(II)-deficient in stoichiometry (Fe3+2.3875Fe2+0.4188O4). Such crystal-hemical changes may be indicative of the degeneration of superparamagnetic magnetite through the aqueous oxidization of Fe(II) anaerobically, and the concomitant oxidation of the organic phases(fatty acid methyl esters) that were present during the initial formation of the magnetite. The observation of a corona structure on the aged magnetite corroborates the oxidation of Fe(II) on the outer layers of magnetite crystals. These results suggest that there may be a possible link between the enzymatic activity of the bacteria and the stability of Fe(II)-excess magnetite, which may help explain why stable nano-magnetite grains are seldom preserved in natural environments.

Li, Dr. Yi-Liang [University of Tennessee, Knoxville (UTK); Pfiffner, Susan M. [University of Tennessee, Knoxville (UTK); Dyar, Dr. M Darby [Mount Holyoke College; Vali, Dr. Hojatolah [McGill University, Montreal, Quebec; Konhauser, Dr, Kurt [University of Alberta; Cole, David R [ORNL; Rondinone, Adam Justin [ORNL; Phelps, Tommy Joe [ORNL



Genetics of frontotemporal lobar degeneration  

PubMed Central

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

Aswathy, P. M.; Jairani, P. S.; Mathuranath, P. S.



Biomarkers in frontotemporal lobar degeneration  

PubMed Central

Purpose of review Recent findings assessing the utility of neuroimaging and biofluid biomarkers are reviewed that help identify patients with frontotemporal lobar degeneration (FTLD) spectrum abnormality. Recent findings Neuroimaging studies using T1 structural MRI and diffusion tensor imaging (DTI) distinguish between patients with FTLD and Alzheimer’s disease, although the reliability of these group-level findings in individual patients has been assessed only rarely. However, innovative analyses such as support vector machine approaches are able to integrate T1 and DTI imaging results and to identify specific MRI profiles that distinguish between individual patients with FTLD and Alzheimer’s disease. Novel radioligand positron emission tomography assessments also can recognize Alzheimer’s disease patients with a clinical phenotype resembling that seen in FTLD. Biofluid studies identify about 15% of patients with FTLD due to a genetic mutation that is associated with the specific histopathologic features of TDP-43 or a tauopathy. Other genetically-based risk factors and targeted proteomic searches of plasma and cerebrospinal fluid have suggested additional markers in sporadic cases of FTLD that will lead to the identification of patients with TDP-43 or tau histopathology. Summary Great progress has been made in developing biomarkers for FTLD, but additional work is needed to extend these advances so that the histopathologic abnormality causing FTLD can be specified in an individual patient.

Grossman, Murray



Degenerate coding in neural systems.  


When the dimensionality of a neural circuit is substantially larger than the dimensionality of the variable it encodes, many different degenerate network states can produce the same output. In this review I will discuss three different neural systems that are linked by this theme. The pyloric network of the lobster, the song control system of the zebra finch, and the odor encoding system of the locust, while different in design, all contain degeneracies between their internal parameters and the outputs they encode. Indeed, although the dynamics of song generation and odor identification are quite different, computationally, odor recognition can be thought of as running the song generation circuitry backwards. In both of these systems, degeneracy plays a vital role in mapping a sparse neural representation devoid of correlations onto external stimuli (odors or song structure) that are strongly correlated. I argue that degeneracy between input and output states is an inherent feature of many neural systems, which can be exploited as a fault-tolerant method of reliably learning, generating, and discriminating closely related patterns. PMID:16252121

Leonardo, Anthony



On the degeneration of rat neuromuscular junctions after nerve section  

PubMed Central

1. A study was made of functional and structural changes during degeneration of end-plates in the rat diaphragm after phrenic nerve section at two levels. 2. For 8-10 hr after cutting the nerve in the neck, all end-plates retain the ability to transmit impulses. During the following 8-10 hr, an increasing number of end-plates lose this ability so that after a total of about 20 hr, no end-plates can transmit. 3. Transmission failure occurs abruptly at most end-plates. This failure is usually accompanied by cessation of spontaneous miniature end-plate potentials (min.e.p.p.s), though in a few cases min.e.p.p.s persist after junctional transmission has failed. Several degenerating junctions were observed where the frequency of min.e.p.p.s was very low, suggesting an intermediate stage in min.e.p.p. failure. 4. The time of junctional failure depends on the length of the degenerating nerve stump. For each additional centimetre of nerve, failure is delayed about 45 min. 5. Changes in ultrastructure of nerve endings closely parallel those of function. For about 8-12 hr after cutting the nerve, nearly all end-plates appear normal. During the period when transmission is failing, some end-plates are clearly undergoing structural break-down. By the time functional failure is complete, all end-plates appear grossly abnormal. 6. During degeneration, the contents of the axoplasm undergo disruption and the nerve terminal breaks up into small fragments. In contrast, the Schwann cell appears to become very active and its processes extend into the synaptic cleft to surround fragments of the nerve terminal. Ultimately, the Schwann cell completely replaces the axon at the end-plate. 7. Increasing the length of the peripheral nerve stump delays the onset of structural break-down. Disruption of end-plates near the site of nerve entry into the muscle occurs before those farther away. 8. It is suggested that end-plate degeneration is triggered by a signal which passes from the site of injury to the nerve terminal. The duration of the period after transection when end-plates appear to be normal would then reflect the time required for this signal to travel the length of the isolated nerve stump. ImagesPlate 4Plate 5Plate 6Plate 7Plate 1Plate 2Plate 3

Miledi, R.; Slater, C. R.



On the degeneration of rat neuromuscular junctions after nerve section.  


1. A study was made of functional and structural changes during degeneration of end-plates in the rat diaphragm after phrenic nerve section at two levels.2. For 8-10 hr after cutting the nerve in the neck, all end-plates retain the ability to transmit impulses. During the following 8-10 hr, an increasing number of end-plates lose this ability so that after a total of about 20 hr, no end-plates can transmit.3. Transmission failure occurs abruptly at most end-plates. This failure is usually accompanied by cessation of spontaneous miniature end-plate potentials (min.e.p.p.s), though in a few cases min.e.p.p.s persist after junctional transmission has failed. Several degenerating junctions were observed where the frequency of min.e.p.p.s was very low, suggesting an intermediate stage in min.e.p.p. failure.4. The time of junctional failure depends on the length of the degenerating nerve stump. For each additional centimetre of nerve, failure is delayed about 45 min.5. Changes in ultrastructure of nerve endings closely parallel those of function. For about 8-12 hr after cutting the nerve, nearly all end-plates appear normal. During the period when transmission is failing, some end-plates are clearly undergoing structural break-down. By the time functional failure is complete, all end-plates appear grossly abnormal.6. During degeneration, the contents of the axoplasm undergo disruption and the nerve terminal breaks up into small fragments. In contrast, the Schwann cell appears to become very active and its processes extend into the synaptic cleft to surround fragments of the nerve terminal. Ultimately, the Schwann cell completely replaces the axon at the end-plate.7. Increasing the length of the peripheral nerve stump delays the onset of structural break-down. Disruption of end-plates near the site of nerve entry into the muscle occurs before those farther away.8. It is suggested that end-plate degeneration is triggered by a signal which passes from the site of injury to the nerve terminal. The duration of the period after transection when end-plates appear to be normal would then reflect the time required for this signal to travel the length of the isolated nerve stump. PMID:5499034

Miledi, R; Slater, C R



Optic-nerve degeneration in Alzheimer's disease.  


Alzheimer's disease is a dementing disorder of unknown cause in which there is degeneration of neuronal subpopulations in the central nervous system. In postmortem studies, we found widespread axonal degeneration in the optic nerves of 8 of 10 patients with Alzheimer's disease. The retinas of four of the patients were also examined histologically, and three had a reduction in the number of ganglion cells and in the thickness of the nerve-fiber layer. There was no retinal neurofibrillary degeneration or amyloid angiopathy, which are typically seen in the brains of patients with Alzheimer's disease. The changes we observed in the patients with Alzheimer's disease were clearly distinguishable from the findings in 10 age-matched controls and represent a sensory-system degeneration that occurs in Alzheimer's disease. Study of the retina in patients with this disease may be helpful diagnostically, and isolation of the affected ganglion cells may facilitate molecular analysis of the disorder. PMID:3736630

Hinton, D R; Sadun, A A; Blanks, J C; Miller, C A



Primary Lipoidal Degeneration of the Cornea.  

National Technical Information Service (NTIS)

A corneal button from an eye with presumed primary lipoidal degeneration of the cornea was examined by light and electron microscopy. The findings were compared with an uncomplicated arcus senilis as well as to reported cases with hereditary dystrophy of ...

B. S. Fine W. M. Townsend L. E. Zimmerman M. H. Lashkari



The mode of mitochondrial degeneration in gliomas  

Microsoft Academic Search

Summary Morphologically abnormal mitochondria from human glial tumours are described. For each tumour both the appearances of the mitochondria, and the subsequent mode of degeneration and formation of osmiophilic pigment is characteristic.

C. S. Foster; P. E. Spoerri; P. Glees; O. Spoerri



An early description of striatonigral degeneration.  


Our aim was to revisit the papers published by Scherer 1933 describing four cases of sporadic olivopontocerebellar atrophy (OPCA) thought to represent the earliest description of striatonigral degeneration. One should note that extrapyramidal rigidity associated with OPCA was then considered a type of cerebellar parkinsonism. Two of Scherer's four patients had severe parkinsonism masking cerebellar signs. Pathologically both cases displayed marked degeneration of the striatum and nigra and partially developed pontocerebellar atrophy. Cerebellar ataxia was the outstanding feature in the other two, their pathological study showing severe pontocerebellar lesions and incipient striatonigral atrophy. Scherer stated that the severity of parkinsonism in OPCA is not correlated with the degree of cerebellar degeneration but with that of striatum and nigra. We conclude that Scherer gave the first accurate description of striatonigral degeneration. Moreover, his contribution was essential in ruling out the prevalent notion of cerebellar parkinsonism in OPCA. PMID:10431772

Berciano, J; Combarros, O; Polo, J M; Pascual, J; Oterino, A



Photos, Images, and Videos (Macular Degeneration)  


Home » Photos, Images, and Videos » Search Results Photos, Images, and Videos Search Results Instructions for Downloading Photographs and Images Description: A fundus photo showing intermediate age-related macular degeneration. Credit: National ...


Malignant Degeneration of Gastric Ulcer  

PubMed Central

Malignant degeneration is the most serious complication of gastric ulcer. Its recognition is difficult both in the early stage and in advanced cases in which only the evidence of a previous ulcer-cavity, and the radiating folds of the mucous membrane indicate progressive development of carcinoma from an original ulcer. It is impossible to say how often gastric ulcer becomes malignant; one can only state the frequency of ulcer-carcinoma, found in gastric resections. One hundred and forty-one personal cases of ulcer-carcinoma are recorded, and are divided into three groups. Group I: 41 which were diagnosed clinically and at operation as cases of ulcer, but in which histological examination showed incipient cancer. Group II: 55 diagnosed clinically as cases of ulcer, but in which a diagnosis of ulcer-carcinoma was made during operation and afterwards histologically confirmed. Group III: 45 diagnosed both clinically and macroscopically (from the typical folding of the mucous membrane) as cases of ulcer-cancer, in which the cancer had entirely overgrown the ulcer. Therefore in the series of 532 resections for gastric ulcer the frequency of ulcer-carcinoma was 20.9%, or 15.2% if the third group is omitted. In a series of 718 resections for gastric cancer, the frequency of ulcer-carcinoma was 19.6% (or 14.2% if the third group is omitted). The mortality in simple two-third resection of the stomach is low (four deaths in 99 cases = 4%). When the pancreas, liver, colon, or œsophagus, is involved, the resection mortality is high (14 deaths in 42 cases = 33.3%), but even in these cases the operation is justifiable because permanent cures were achieved in a number of cases. The prognosis in cases of ulcer-cancer is very grave. In many cases, judging from the author's own experience, patients suffering from incipient ulcer-cancer—only histologically diagnosed as cancer—die from liver metastases, in spite of radical resection. It will thus be seen that the end-results of resection for ulcer-carcinoma are actually worse than those of resection for primary carcinoma. A. Ulcer-cancer: In Group I, 35 cases were operated on before 1933, and in 18 of these (51.4%) the patients have been free from symptoms for more than five years; in Group II, 27 cases were operated on before 1933, and in four of these (14.8%) the patients are still symptom-free. In Group III, out of 37 cases operated on, only two patients (5.4%) have been symptom-free for the same period. B. Primary cancer: Out of 260 cases of resection for primary cancer before 1933, 77 patients (29.6%) are permanently cured. If the ulcer-cancer is so far advanced that the diagnosis can be made clinically, or during operation, the prognosis is extremely bad (permanent cures having been only 9.3% in the series). In cases of gastric ulcer the best plan is to carry out resection before malignant degeneration begins. The result would then be that not merely 51% but at least 90% of the patients would be alive and well after five years. ImagesFig. 1Fig. 2

Finsterer, H.



Hydrop degeneration. A histopathological investigation of 260 early abortions.  


Placental tissue from 160 abortions provoked during the 6th--12th weeks, and 109 spontaneous abortions between weeks 5 and 16, were studied histopathologically on respect of a comparison and quantitation of hydrop degeneration. Significantly more cases of severe hydrop degeneration were observed among the spontaneous abortions (p < 0.001). Of these abortions, 87 per cent were hydrop degenerated to varying degrees; 41 per cent were severely hydrop degenerated. Among the provoked abortions, approximately 81 per cent were hydrop degenerated to varying degrees but only 6.9 per cent were severely hydrop degenerated. The relationship between severe hydrop degeneration and chromosome abnormality is discussed. PMID:7457094

Ladefoged, C



Prospectives for Gene Therapy of Retinal Degenerations  

PubMed Central

Retinal degenerations encompass a large number of diseases in which the retina and associated retinal pigment epithelial (RPE) cells progressively degenerate leading to severe visual disorders or blindness. Retinal degenerations can be divided into two groups, a group in which the defect has been linked to a specific gene and a second group that has a complex etiology that includes environmental and genetic influences. The first group encompasses a number of relatively rare diseases with the most prevalent being Retinitis pigmentosa that affects approximately 1 million individuals worldwide. Attempts have been made to correct the defective gene by transfecting the appropriate cells with the wild-type gene and while these attempts have been successful in animal models, human gene therapy for these inherited retinal degenerations has only begun recently and the results are promising. To the second group belong glaucoma, age-related macular degeneration (AMD) and diabetic retinopathy (DR). These retinal degenerations have a genetic component since they occur more often in families with affected probands but they are also linked to environmental factors, specifically elevated intraocular pressure, age and high blood sugar levels respectively. The economic and medical impact of these three diseases can be assessed by the number of individuals affected; AMD affects over 30 million, DR over 40 million and glaucoma over 65 million individuals worldwide. The basic defect in these diseases appears to be the relative lack of a neurogenic environment; the neovascularization that often accompanies these diseases has suggested that a decrease in pigment epithelium-derived factor (PEDF), at least in part, may be responsible for the neurodegeneration since PEDF is not only an effective neurogenic and neuroprotective agent but also a potent inhibitor of neovascularization. In the last few years inhibitors of vascularization, especially antibodies against vascular endothelial cell growth factors (VEGF), have been used to prevent the neovascularization that accompanies AMD and DR resulting in the amelioration of vision in a significant number of patients. In animal models it has been shown that transfection of RPE cells with the gene for PEDF and other growth factors can prevent or slow degeneration. A limited number of studies in humans have also shown that transfection of RPE cells in vivo with the gene for PEDF is effective in preventing degeneration and restore vision. Most of these studies have used virally mediated gene delivery with all its accompanying side effects and have not been widely used. New techniques using non-viral protocols that allow efficient delivery and permanent integration of the transgene into the host cell genome offer novel opportunities for effective treatment of retinal degenerations.

Thumann, Gabriele



A caspase cascade regulating developmental axon degeneration.  


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 prosurvival 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



XIAP Regulates Caspase Activity in Degenerating Axons.  


Our knowledge of the destructive events that regulate axonal degeneration is rudimentary. Here, we examine the role of caspases and their endogenous inhibitor, the X-linked inhibitor of apoptosis protein (XIAP), in axonal degeneration of dorsal root ganglion (DRG) axons. We show that caspase-3, caspase-6, and caspase-9 are present in axons and are cleaved upon nerve growth factor (NGF) withdrawal. We observed that caspase-3 activity is high in NGF-withdrawn axons and that CASP3(-/-) axons are protected from degeneration. XIAP(-/-) DRG sensory neurons degenerate more rapidly and contain more active caspase-3 than their wild-type counterparts, indicating that axonal caspases are normally regulated by XIAP. Importantly, axonal XIAP levels drop sharply after NGF withdrawal; if XIAP levels are maintained by overexpression, axonal caspase-3 activation and axonal degeneration are suppressed. Finally, we show that XIAP(-/-) embryos have stunted dermal innervation. We propose that XIAP-mediated caspase inhibition plays an important role in regulating morphogenic events that shape the nervous system during development. PMID:23954782

Unsain, Nicolas; Higgins, Julia M; Parker, Kristen N; Johnstone, Aaron D; Barker, Philip A




Technology Transfer Automated Retrieval System (TEKTRAN)

The use of degenerate primers designed to amplify resistance gene analogs has been successful in many crops. The primers are usually based on published resistance gene sequences and, in particular, conserved regions such as the nucleotide binding site (NBS). In some cases, the amplified fragments ha...


Potential Outcome Factors in Subacute Combined Degeneration  

PubMed Central

BACKGROUND Subacute combined degeneration is an acquired myelopathy caused by vitamin B12 deficiency. Therapy with B12 leads to improvement in most but to complete recovery in only a few patients. Prognostic indicators in subacute combined degeneration are unknown; therefore, predicting complete recovery of neurologic deficits is challenging. PURPOSE To identify potential correlates of outcome and to generate hypotheses concerning predictors of complete resolution of neurologic deficits in subacute combined degeneration. DATA SOURCE We searched EMBASE (1974 to October 2005), MEDLINE (1968 to October 2005), and references from identified reports. REPORTS SELECTION Reports of patients with subacute combined degeneration containing results of magnetic resonance imaging (MRI) and description of outcome and 1 patient treated by the authors. DATA EXTRACTION, SYNTHESIS We extracted data from 45 reports and 57 patients (36 males, 21 females; age range: 10 to 81) with a diagnosis of subacute combined degeneration, and estimated the strength of association between clinical, laboratory, and radiological factors and complete resolution of signs and symptoms. RESULTS Eight patients (14%) achieved clinical resolution and 49 (86%) improved with B12 therapy. The absence of sensory dermatomal deficit, Romberg, and Babinski signs were associated with a higher complete resolution rate. Patients with MRI lesions in ?7 segments and age less than 50 also appear to have higher rates of complete resolution. CONCLUSIONS B12 therapy is reported to stop progression and improve neurologic deficits in most patients with subacute combined degeneration. However, complete resolution only occurs in a small percentage of patients and appears to be associated with factors suggestive of less severe disease at the time of diagnosis.

Vasconcelos, Olavo M; Poehm, Erika H; McCarter, Robert J; Campbell, William W; Quezado, Zenaide M N



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.

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



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)



Degeneration under the microscope at the fin de siècle.  


Theories of familial, racial, and national degeneration in the late nineteenth and early twentieth centuries have been explored by historians in the context of social and moral pathology. At the same time nerve degeneration was studied in the post mortem room and in the laboratory but links to the broader ideology of degeneration have not been investigated by scholars. This paper joins these domains by examining the concept of Wallerian degeneration. It argues that various discourses--including those of the laboratory scientist, the clinician, and the social theorist--employed the term degeneration, and these discourses frequently overlapped demonstrating that degeneration was a ubiquitous fact of Victorian and Edwardian nature. PMID:20506746

Lawrence, Christopher



Role of rhodopsin and arrestin phosphorylation in retinal degeneration of Drosophila.  


Arrestins belong to a family of multifunctional adaptor proteins that regulate internalization of diverse receptors including G-protein-coupled receptors (GPCRs). Defects associated with endocytosis of GPCRs have been linked to human diseases. We used enhanced green fluorescent protein-tagged arrestin 2 (Arr2) to monitor the turnover of the major rhodopsin (Rh1) in live Drosophila. We demonstrate that during degeneration of norpA(P24) photoreceptors the loss of Rh1 is parallel to the disappearance of rhabdomeres, the specialized visual organelle that houses Rh1. The cause of degeneration in norpA(P24) is the failure to activate CaMKII (Ca(2+)/calmodulin-dependent protein kinase II) and retinal degeneration C (RDGC) because of a loss of light-dependent Ca(2+) entry. A lack of activation in CaMKII, which phosphorylates Arr2, leads to hypophosphorylated Arr2, while a lack of activation of RDGC, which dephosphorylates Rh1, results in hyperphosphorylated Rh1. We investigated how reversible phosphorylation of Rh1 and Arr2 contributes to photoreceptor degeneration. To uncover the consequence underlying a lack of CaMKII activation, we characterized ala(1) flies in which CaMKII was suppressed by an inhibitory peptide, and showed that morphology of rhabdomeres was not affected. In contrast, we found that expression of phosphorylation-deficient Rh1s, which either lack the C terminus or contain Ala substitution in the phosphorylation sites, was able to prevent degeneration of norpA(P24) photoreceptors. This suppression is not due to a loss of Arr2 interaction. Importantly, co-expression of these modified Rh1s offered protective effects, which greatly delayed photoreceptor degeneration. Together, we conclude that phosphorylation of Rh1 is the major determinant that orchestrates its internalization leading to retinal degeneration. PMID:22855823

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



Single Degenerate Progenitors of Type Ia Supernovae  

NASA Astrophysics Data System (ADS)

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

Bours, Madelon; Toonen, Silvia; Nelemans, Gijs



Double Degenerate Progenitors of Supernovae Type IA  

Microsoft Academic Search

While supernovae Ia (SNe Ia) play a prominent role in extragalactic astronomy the nature of their progenitors is still unknown. In one of the two viable progenitor scenarios SN Ia result from the merging of a binary consisting of two white dwarfs (double degenerates - DDs) exceeding the Chandrasekhar mass limit. I'll review the results of recent radial velocity surveys

Ralf Napiwotzki



Driving and Age-Related Macular Degeneration  

ERIC Educational Resources Information Center

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

Owsley, Cynthia; McGwin, Gerald, Jr.



Glutamate dehydrogenase deficiency in spinocerebellar degenerations  

Microsoft Academic Search

Glutamate dehydrogenase (GDH) activity in leukocytes and platelets in spinocerebellar degenerations (SCD) was determined. In the same subject, GDH activity was higher and more reproducible in platelets than in leukocytes. GDH was decreased significantly in olivopontocerebellar atrophy (OPCA) (Ca. 30% decrease). Pyruvate dehydrogenase (PDH) in platelets showed non specific decreased activity in SCD and amyotropic lateral sclerosis. Energy metabolism in

Tomoko Yamaguchi; Keirei Hayashi; Hirohiko Murakami; Kohei Ota; Shoichi Maruyama



Neuropsychological and neuroimaging correlates in corticobasal degeneration  

Microsoft Academic Search

The aim of this study was to correlate neuropsychological and neuroimaging findings in corticobasal degeneration (CBD). Three patients with clinical criteria for CBD were examined by means of neuropsychological tests, brain magnetic resonance imaging (MRI), and flow and metabolism neuroimaging techniques. Neuropsychological assessment revealed impairment in executive functions, manual dexterity and motor programming with significant asymmetry between upper limbs. Ideomotor

E. Frasson; G. Moretto; A. Beltramello; N. Smania; M. Pampanin; C. Stegagno; R. Tanel; N. Rizzuto



The Wnt signaling pathway in retinal degenerations.  


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

Hackam, Abigail S



Kinks in systems with degenerate critical points  

NASA Astrophysics Data System (ADS)

An analytical expression for the effective interaction force of a bound kink-antikink state in a general potential possessing two minima is obtained. For degenerate minima the interaction has a long range character. It is shown how the interaction force depends on the anharmonicity near the minima. Permanent address: ICIMAF (Academy of Sciences of Cuba), Calle 0 No. 8, Vedado, Havana, Cuba.

González, Jorge A.; Estrada-Sarlabous, Jorge



Exploring Nonconvex, Crossed and Degenerate Polygons  

ERIC Educational Resources Information Center

An exploration of nonconvex, crossed, and degenerate polygons (NCCDPs) are described with the help of examples with pedagogical tips and recommendations that are found useful when teaching the mathematical process of extending geometric patterns to NCCDPs. The study concludes that investigating such extensions with interactive geometry software…

Contreras, Jose N.



Driving and Age-Related Macular Degeneration  

PubMed Central

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

Owsley, Cynthia; McGwin, Gerald



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

PubMed Central

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

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



Anesthetic management of a patient with spinocerebellar degeneration  

PubMed Central

Spinocerebellar degeneration or olivopontocerebellar degeneration denotes a group of disorders of various etiologies manifesting as degenerative changes of various part of the central nervous system. We describe the anesthetic management of a patient with severe olivopontocerebellar degeneration posted for vaginal hysterectomy. A combined spinal epidural technique was performed at the level of L2-L3. The anesthetic implications of the various aspects of spinocerebellar degeneration are discussed.

Vadhanan, Prasanna; Kumar, Pramod



Anesthetic management of a patient with spinocerebellar degeneration.  


Spinocerebellar degeneration or olivopontocerebellar degeneration denotes a group of disorders of various etiologies manifesting as degenerative changes of various part of the central nervous system. We describe the anesthetic management of a patient with severe olivopontocerebellar degeneration posted for vaginal hysterectomy. A combined spinal epidural technique was performed at the level of L2-L3. The anesthetic implications of the various aspects of spinocerebellar degeneration are discussed. PMID:21772692

Vadhanan, Prasanna; Kumar, Pramod



Risk of Retinal Detachment in Patients with Lattice Degeneration  

Microsoft Academic Search

To determine the risk of retinal detachment in patients with lattice degeneration of the retina, we statistically analyzed the incidence of retinal detachment in these patients. The data of hospital patients with retinal detachment associated with lattice degeneration in Kumamoto Prefecture, Japan, in 1990 were collected. The prevalence of lattice degeneration in Kumamoto was reported to be 9.5% in 1980.

Kiwamu Sasaki; Hidenao Ideta; Junichi Yonemoto; Sumiyoshi Tanaka; Akira Hirose; Chitoshi Oka



Normal cerebellar glutamate dehydrogenase protein in spinocerebellar degeneration  

Microsoft Academic Search

Immunochemical analyses (Western blots) of cerebellar homogenates for glutamate dehydrogenase (GDH) from patients with spinocerebellar degeneration and control subjects were conducted. Four patients with autosomal dominant Joseph disease type of spinocerebellar degeneration, one patient with autosomal dominant olivopontocerebellar degeneration and four control subjects were studied. GDH was of the same molecular weight and amount in all patients and control subjects.

R N Rosenberg; C Banner



Degeneration of the corticopontine tract in olivopontocerebellar atrophy  

Microsoft Academic Search

Summary Nine cases of sporadic olivopontocerebellar atrophy [Déjérine-Thomas type, multisystemic atrophy (MSA)] were examined histologically and electron microscopically with special reference to the corticopontine tract. Five of nine cases showed degeneration of the myelinated nerve fibres in this tract. More severe degeneration of the fibres at the level of the pons than the crus cerebri indicates that degeneration of the

S. Yagishita; S. Yokoi; K. Iwabuchi; N. Amano; Y. Mashuda; K. Hasegawa; H. Kohwa



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.



Iron homeostasis and toxicity in retinal degeneration.  


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 buildup 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 10 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



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.

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



Equivalent multipole operators for degenerate Rydberg states  

NASA Astrophysics Data System (ADS)

As shown by Pauli, [Z. Phys. 36, 336 (1926)], the electric dipole operator r can be replaced by the Runge-Lenz vector A when operating within the n2 degenerate manifold of hydrogenic states of principal quantum number n . We seek to develop similar rules for higher multipole operators by expressing equivalent operators in terms only of the two vector constants of motion—the orbital angular momentum L and the Runge-Lenz vector A —appropriate to the degenerate hydrogenic shell. Equivalence of two operators means here that they yield identical matrix elements within a subspace of Hilbert space that corresponds to fixed n . Such equivalent-operator techniques permit direct algebraic calculation of perturbations of Rydberg atoms by external fields and often exact analytical results for transition probabilities. Explicit expressions for equivalent quadrupole and octupole operators are derived, examples are provided, and general aspects of the problem are discussed.

Ostrovsky, V. N.; Vrinceanu, D.; Flannery, M. R.



Equivalent multipole operators for degenerate Rydberg states  

SciTech Connect

As shown by Pauli, [Z. Phys. 36, 336 (1926)], the electric dipole operator r can be replaced by the Runge-Lenz vector A when operating within the n{sup 2} degenerate manifold of hydrogenic states of principal quantum number n. We seek to develop similar rules for higher multipole operators by expressing equivalent operators in terms only of the two vector constants of motion - the orbital angular momentum L and the Runge-Lenz vector A - appropriate to the degenerate hydrogenic shell. Equivalence of two operators means here that they yield identical matrix elements within a subspace of Hilbert space that corresponds to fixed n. Such equivalent-operator techniques permit direct algebraic calculation of perturbations of Rydberg atoms by external fields and often exact analytical results for transition probabilities. Explicit expressions for equivalent quadrupole and octupole operators are derived, examples are provided, and general aspects of the problem are discussed.

Ostrovsky, V. N.; Vrinceanu, D.; Flannery, M. R. [V. Fock Institute of Physics, St. Petersburg State University, 198904 St. Petersburg (Russian Federation); Theoretical Division, Los Alamos National Laboratory, Los Alamos, New Mexico 87545 (United States); School of Physics, Georgia Institute of Technology, Atlanta, Georgia 30332 (United States)



SIRT3 Reverses Aging-associated Degeneration  

PubMed Central

SUMMARY Sirtuins extend lifespan across species, although the role in nematodes and fruitflies is controversial. Whether sirtuins can reverse aging-associated degeneration is unknown. Tissue-specific stem cells persist throughout the entire lifespan to repair and maintain tissues, but their self-renewal and differentiation potential become dysregulated with aging. We show that SIRT3, a mammalian sirtuin that regulates the global acetylation landscape of mitochondrial proteins and reduces oxidative stress, is highly enriched in hematopoietic stem cells (HSCs) where it regulates a stress response. SIRT3 is dispensable for HSC maintenance and tissue homeostasis at a young age under homeostatic conditions, but is essential under stress or at an old age. Importantly, SIRT3 is suppressed with aging, and SIRT3 upregulation in aged HSCs improves their regenerative capacity. Our study illuminates the plasticity of mitochondrial homeostasis controlling stem cell and tissue maintenance during the aging process, and shows that aging-associated degeneration can be reversed by a sirtuin.

Brown, Katharine; Xie, Stephanie; Qiu, Xiaolei; Mohrin, Mary; Shin, Jiyung; Liu, Yufei; Zhang, Dan; Scadden, David T.; Chen, Danica



Asymmetrical alien hands in corticobasal degeneration.  


There are several forms of alien limb, but alien limb in corticobasal degeneration (CBD) is not well understood. We studied a patient with CBD who demonstrated two different types of alien limb. With his right hand he demonstrated a tactile avoidance response with levitation. With his left hand, he demonstrated continuous tactile pursuit of the examiner's hand ("tactile mitgehen"). Mitgehen is often associated with frontal dysfunction, but avoidance response and levitation are often associated with parietal dysfunction. PMID:17230447

Fitzgerald, David B; Drago, Valeria; Jeong, Yong; Chang, Yu-Ling; White, Keith D; Heilman, Kenneth M



Chlorhexidine-induced degeneration of adrenergic nerves  

Microsoft Academic Search

Possible toxic effects of chlorhexidine (CHX) on the sympathetic adrenergic ground plexus were studied in whole mounts of albino rat irides using Falck-Hillarp fluorescence histochemistry. CHX dissolved in an isotone, buffered sodium-acetate solution or in 70% alcohol was injected into the anterior chamber of eye. CHX caused a marked and dose-dependent degeneration of adrenergic nerves. Two days after the lowest

A. Henschen; L. Olson



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



Sporadic SCA8 mutation resembling corticobasal degeneration  

Microsoft Academic Search

Spinocerebellar ataxia type 8 (SCA8) is caused by the expansion of CTA\\/CTG triplet repeats on 13q21. Cases can be familial or sporadic. The clinical findings include cerebellar ataxia with upper motor neuron dysfunction, dysphagia, peripheral sensory disturbances, or cognitive and psychiatric impairments, indicating phenotypic variability in SCA8. We report on a patient with rapidly progressive parkinsonism-plus syndrome resembling corticobasal degeneration

Yasuhiko Baba; Ryan J. Uitti; Matthew J. Farrer; Zbigniew K. Wszolek



An early description of striatonigral degeneration  

Microsoft Academic Search

Our aim was to revisit the papers published by Scherer 1933 describing four cases of sporadic olivopontocerebellar atrophy\\u000a (OPCA) thought to represent the earliest description of striatonigral degeneration. One should note that extrapyramidal rigidity\\u000a associated with OPCA was then considered a type of cerebellar parkinsonism. Two of Scherer’s four patients had severe parkinsonism\\u000a masking cerebellar signs. Pathologically both cases displayed

J. Berciano; O. Combarros; J. M. Polo; J. Pascual; A. Oterino



Frontotemporal lobar degeneration: clinical and pathological relationships  

Microsoft Academic Search

Frontotemporal lobar degeneration (FTLD) encompasses a heterogeneous group of clinical syndromes that include frontotemporal\\u000a dementia (FTD), frontotemporal dementia with motor neurone disease (FTD\\/MND), progressive non-fluent aphasia (PNFA), semantic\\u000a dementia (SD) and progressive apraxia (PAX). Clinical phenotype is often assumed to be a poor predictor of underlying histopathology.\\u000a Advances in immunohistochemistry provide the opportunity to re-examine this assumption. We classified pathological

Julie Snowden; David Neary; David Mann



Cerebellar hypermetabolism in paraneoplastic cerebellar degeneration  

Microsoft Academic Search

A 51 year old man with paraneoplastic cerebellar degeneration from gastric adenocarcinoma showed cerebellar hypermetabolism and increased perfusion on brain FDG-PET scan and SPECT during the acute stage of his illness. The patient underwent subtotal gastrectomy. The intensity of the hypermetabolism had decreased markedly on follow-up FDG-PET 3 months later following two cycles of chemotherapy. We suggest that the cerebellar

K-D Choi; J S Kim; S-H Park; Y K Kim; S E Kim; P S Smitt



Degenerate Fermion gas heating by hole creation  

Microsoft Academic Search

The usual loss-processes that remove particles from an ultra-cold atom trap leave behind holes in the single particle distribution if the atom gas is a degenerate fermion system. The appearance of Fermi holes increases the temperature and we show that the heating (i) is significant if the initial temperature is well-below the Fermi temperature T_F, and (ii) increases the temperature

Eddy Timmermans



Paranode Abnormalities and Oxidative Stress in Optic Nerve Vulnerable to Secondary Degeneration: Modulation by 670 nm Light Treatment  

PubMed Central

Secondary degeneration of nerve tissue adjacent to a traumatic injury results in further loss of neurons, glia and function, via mechanisms that may involve oxidative stress. However, changes in indicators of oxidative stress have not yet been demonstrated in oligodendrocytes vulnerable to secondary degeneration in vivo. We show increases in the oxidative stress indicator carboxymethyl lysine at days 1 and 3 after injury in oligodendrocytes vulnerable to secondary degeneration. Dihydroethidium staining for superoxide is reduced, indicating endogenous control of this particular reactive species after injury. Concurrently, node of Ranvier/paranode complexes are altered, with significant lengthening of the paranodal gap and paranode as well as paranode disorganisation. Therapeutic administration of 670 nm light is thought to improve oxidative metabolism via mechanisms that may include increased activity of cytochrome c oxidase. Here, we show that light at 670 nm, delivered for 30 minutes per day, results in in vivo increases in cytochrome c oxidase activity co-localised with oligodendrocytes. Short term (1 day) 670 nm light treatment is associated with reductions in reactive species at the injury site. In optic nerve vulnerable to secondary degeneration superoxide in oligodendrocytes is reduced relative to handling controls, and is associated with reduced paranode abnormalities. Long term (3 month) administration of 670 nm light preserves retinal ganglion cells vulnerable to secondary degeneration and maintains visual function, as assessed by the optokinetic nystagmus visual reflex. Light at a wavelength of 670 nm may serve as a therapeutic intervention for treatment of secondary degeneration following neurotrauma.

Cummins, Nadia; Bartlett, Carole A.; O'Hare Doig, Ryan L.; Savigni, Donna L.; Payne, Sophie C.; Harvey, Alan R.; Dunlop, Sarah A.; Fitzgerald, Melinda



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.



Degenerate Fermi Gas of {sup 87}Sr  

SciTech Connect

We report quantum degeneracy in a gas of ultracold fermionic {sup 87}Sr atoms. By evaporatively cooling a mixture of spin states in an optical dipole trap for 10.5 s, we obtain samples well into the degenerate regime with T/T{sub F}=0.26{sub -0.06}{sup +0.05}. The main signature of degeneracy is a change in the momentum distribution as measured by time-of-flight imaging, and we also observe a decrease in evaporation efficiency below T/T{sub F{approx}}0.5.

DeSalvo, B. J.; Yan, M.; Mickelson, P. G.; Martinez de Escobar, Y. N.; Killian, T. C. [Department of Physics and Astronomy, Rice University, Houston, Texas, 77251 (United States)



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



Quantum degenerate Fermi gas entanglement in optomechanics  

NASA Astrophysics Data System (ADS)

We explain the steady-state entanglement of a quantum degenerate Fermi gas with a light field inside a Fabry-Perot cavity. The logarithmic negativity, from the covariance matrix formalism in a unified framework, shows that the bi-stability parameter and the effective detuning depend explicitly on the behavior of the entanglement. Numerical experiments reveal the sensitivity of the entanglement to experimentally controlled parameters such as, the mass of the atoms, the pump rate of the cavity, the effective detuning, and the bi-stability parameters.

Asjad, Muhammad; Adnan Shahzad, Muhammad; Saif, Farhan



Development of detonations in degenerate stars  

SciTech Connect

It is now widely believed that thermal instability at the center of a carbon-oxygen white dwarf will produce a deflagration wave. In this paper, numerical analysis of the preoutburst conditions near the center of a C-O white dwarf as well as of the three stages of the thermonuclear explosion of the star (i.e., the stages of spontaneous burning front, shock formation, and postshock burning and shock amplification) is presented. It is demonstrated that when a degenerate C-O star explodes as a supernova, thermal instability may cause the thermonuclear burning front to develop into a detonation (rather than a deflagration) regime. 16 references.

Blinnikov, S.I.; Khoklov, A.M.



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)



Fundus autofluorescence in exudative age-related macular degeneration  

PubMed Central

Aim To evaluate the distribution of fundus autofluorescence in patients with age?related macular degeneration and choroidal neovascularisation (CNV). Methods Colour fundus photographs, fundus fluorescein angiograms (FFA) and fundus autofluorescence images were obtained from a group of 40 patients (43 eyes) with age?related macular degeneration and purely classic or occult CNV. Only patients with newly diagnosed CNV and in whom autofluorescence images were obtained within 2?weeks from FFA were included. The distribution of autofluorescence was qualitatively evaluated, and the findings compared with those from colour fundus photographs and FFA. Results 29 (67%) eyes had classic CNV and 14 (33%) had occult CNV. In 26 (90%) eyes with classic CNV, a low autofluorescence signal was detected at the site of the CNV; in 7 (50%) eyes with occult CNV, multiple foci of low autofluorescence signal were detected. Outside the area affected by the lesion, homogeneous autofluorescence was observed in most of the cases (n?=?33, 77%). Similarly, homogeneous autofluorescence was commonly observed in fellow eyes (62%). A pattern of focal increased autofluorescence was rarely seen in eyes with CNV (n?=?4, 9%) or in fellow eyes (n?=?4, 15%). In 11 of 43 (25%) eyes, areas of increased autofluorescence, other than a pattern of focal increased autofluorescence, were detected. In four patients, autofluorescence images had been obtained before the development of CNV; in none was any increased autofluorescence detected before the formation of CNV. Conclusions Distinct patterns of autofluorescence were observed in eyes with pure classic and occult CNV. Increased autofluorescence was rarely seen in eyes with CNV and in fellow eyes, suggesting that increased autofluorescence, and thus, retinal pigment epithelium lipofuscin, may not play an essential part in the formation of CNV.

McBain, Vikki A; Townend, John; Lois, Noemi



Multiple system atrophy with retinal degeneration in a young child.  


A 4-year-old girl with multiple system degeneration and retinal degeneration was presented. There was onset of an ataxic gait at two years and rapid progression of retinal degeneration, myoclonus and cranial nerve palsy. Neuropathological examination revealed severe degeneration of the cerebellar cortex and the pathways of auditory and deep sensation, as well as degeneration of the cerebellar efferent fibers, the striatonigral system, the cerebellar afferent fiber system and lower motor neurons. Cases of young children with spinocerebellar degeneration have been reported in several families of olivopontocerebellar atrophy (OPCA), but degenerative changes in our case were more widespread than those in OPCA cases. The multiple system lesions in the central nervous system and retina of this child are different from those of any other previously reported cases. PMID:3474543

Nishimura, M; Mito, T; Takashima, S; Kawahara, H; Tanaka, J; Nakamura, H; Kisa, T



Stanniocalcin-1 rescued photoreceptor degeneration in two rat models of inherited retinal degeneration.  


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, Robert H; Oh, Joo Youn; 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



Domoic acid-induced neuronal degeneration in the primate forebrain revealed by degeneration specific histochemistry  

Microsoft Academic Search

Domoic acid is a potent excitotoxin produced by diatoms which is subsequently passed along the marine food chain. Its chemical structure and toxicological properties are similar to kainic acid. Like kainic acid, exposure results in extensive hippocampal degeneration. The effect of domoic acid on other primate brain structures, however, is less resolved. In an attempt to clarify this issue, the

Larry C. Schmued; Andrew C. Scallet; William Slikker



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.

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



Genetics and molecular pathology of Stargardt-like macular degeneration  

Microsoft Academic Search

Stargardt-like macular degeneration (STGD3) is an early onset, autosomal dominant macular degeneration. STGD3 is characterized by a progressive pathology, the loss of central vision, atrophy of the retinal pigment epithelium, and accumulation of lipofuscin, clinical features that are also characteristic of age-related macular degeneration. The onset of clinical symptoms in STGD3, however, is typically observed within the second or third

Vidyullatha Vasireddy; Paul Wong; Radha Ayyagari



Melange a Six Ondes Degenere dans les Absorbants Saturables  

Microsoft Academic Search

Issus d'une generalisation du melange a quatre ondes degenere, les melanges a n ondes degeneres sont utiles pour la mesure des divers ordres de la susceptibilite nonlineaire. Nous avons procede a l'etude theorique et experimentale du melange a six ondes degenere dans des absorbants isotropes et anisotropes. Pour l'analyse theorique, nous avons developpe une methode de calcul basee sur une

Alain Blouin



Senile disciform macular degeneration in the second eye.  

PubMed Central

Development of senile disciform degeneration in the second eye was studied in a group of 104 patients over a period of up to five years. 12 to 15% of these patients develop disciform degeneration in the other eye each year. Patients with large and confluent drusen, especially if combined with accumulation of dye on fluorescein angiogram, were at greatest risk of developing disciform degeneration in the second eye. Images

Gregor, Z; Bird, A C; Chisholm, I H



Mechanism of Calcium Entry during Axon Injury and Degeneration  

Microsoft Academic Search

Axon degeneration is a hallmark consequence of chemical neurotoxicant exposure (e.g., acrylamide), mechanical trauma (e.g., nerve transection, spinal cord contusion), deficient perfusion (e.g., ischemia, hypoxia), and inherited neuropathies (e.g., infantile neuroaxonal dystrophy). Regardless of the initiating event, degeneration in the PNS and CNS progresses according to a characteristic sequence of morphological changes. These shared neuropathologic features suggest that subsequent degeneration,

Richard M. LoPachin; Ellen J. Lehning



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.

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



Progranulin in frontotemporal lobar degeneration and neuroinflammation  

PubMed Central

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

Ahmed, Zeshan; Mackenzie, Ian RA; Hutton, Michael L; Dickson, Dennis W



Retinoid receptors trigger neuritogenesis in retinal degenerations.  


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

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



Quantum Degenerate Gases of Atomic Strontium  

NASA Astrophysics Data System (ADS)

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

Killian, T. C.



Efficacy of suprachoroidal-transretinal stimulation in a rabbit model of retinal degeneration.  


Purpose. To develop a middle-sized animal model of outer retinal degeneration and to evaluate the effectiveness of suprachoroidal-transretinal stimulation (STS) in eliciting cortical potentials from this model. Methods. Twelve rabbits were intravenously injected with 0.47 mg/kg verteporfin and the retinas were irradiated with a red light for 90 minutes. Fluorescein angiography and full-field and focal electroretinography (ERG) were performed at 7 and 28 days after the irradiation. Electrically evoked potentials (EEPs) were elicited by electrical stimulation, with the STS electrode implanted over the irradiated region, 1 month and 1 year after the irradiation. EEPs were also recorded from three rabbits before and after retinotomy of the normal retina surrounding the degenerated area, to eliminate the influence of stray currents. The retina beneath the site of the STS electrode was examined histologically at 1 month (group 1) and 1 year (group 2) after the irradiation. Results. An extensive area of degeneration was detected histologically, mainly in the outer retina after the irradiation. Focal ERGs were not recorded when the stimulus was confined to the irradiated area; however, EEPs were successfully elicited by STS of the same area 1 month and 1 year after the irradiation. The 360 degrees retinectomy did not significantly alter the amplitudes, the implicit times, or the thresholds of EEPs evoked by STS. Conclusions. Verteporfin with light irradiation induces degeneration predominantly in the outer retinal layers in rabbits. The elicitation of EEPs by STS from the degenerated area suggests that the STS system may be useful in patients with retinitis pigmentosa. PMID:19933186

Nishida, Kentaro; Kamei, Motohiro; Kondo, Mineo; Sakaguchi, Hirokazu; Suzuki, Mihoko; Fujikado, Takashi; Tano, Yasuo



Differential Modulation of Retinal Degeneration by Ccl2 and Cx3cr1 Chemokine Signalling  

PubMed Central

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

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



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

PubMed Central

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 Ca2+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.

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



Frequency metrology in quantum degenerate helium  

NASA Astrophysics Data System (ADS)

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

Vassen, Wim



Thermally induced degenerate four-wave mixing  

NASA Astrophysics Data System (ADS)

Time-dependent aspects of thermally stimulated degenerate four-wave mixing (DFWM) in absorbing liquid solutions have been theoretically investigated through a coupled electromagnetic-hydrodynamic theory originally formulated to study stimulated scattering processes. The various time scales involved in the interaction (including those characteristic of acoustic modes and thermalization effects) are identified and relevant laser and media parameterical relations are sorted out. Suitable approximation regimes are then outlined, corresponding to specific experimental situations of interest and allowing for relatively simple and tractable analytic relations to be derived. In particular, the effects of finite rise time of thermalization were studied and found to lead to a possibly strong angular dependence in the conjugate reflectivity. Acoustic modes and their influence on the process efficiency were also investigated. The calculations culminate in a set of guidelines for optimizing conjugation efficiencies, through judicious choice of dye-solvent combinations, 'read' pump time delays, experimental arrangements, and laser pulse parameters.

Hoffman, H. J.



Frontotemporal lobar degeneration: Diversity of FTLD lesions.  


Frontotemporal lobar degeneration (FTLD) is a heterogeneous group including both sporadic and familial diseases, characterized by a macroscopic alteration. It may correspond to various cognitive syndromes: behavioral variant of frontotemporal dementia (bvFTD), progressive nonfluent aphasia, and semantic dementia. The neuropathologic classification is now based on identification of the protein that accumulates in neurons and glia: Tau, TAR DNA Binding Protein 43 (TDP-43), and FUsed in Sarcoma (FUS). The disorders in which the corresponding proteins accumulate have been named FTLD-Tau, FTLD-TDP, and FTLD-FUS. FTLD-Tau includes sporadic cases (e.g. Pick's disease) and Tau mutations. FTLD-TDP are subdivided within four types (A, B, C, D) according to the shape and distribution of TDP-43 positive lesions within the associative frontal cortex. The FTLD-FUS group includes atypical FTLD with ubiquitinated lesions (FTLD-U), Neuronal Intermediate Filament Inclusion Disease (NIFID) and Basophilic Inclusion Body Disease (BIBD). PMID:24035575

Seilhean, D; Bielle, F; Plu, I; Duyckaerts, C



Degenerate four-wave mixing in plasmas.  


We report an analysis of degenerate four-wave mixing in uniform plasmas and show that the magnitude of the third-order susceptibility (varying as lambda(2)) can be comparable to (10(-11) esu for lambda = 10.6 microm) or orders of magnitude larger (10(-3) esu for lambda= 10 cm) than the corresponding susceptibility in typical nonlinear materials. The nonlinear contribution to the macroscopic current resulting from the ponderomotive force is generated from the two-component fluid model by means of a linearized perturbation scheme. Numerical estimates of the nonlinear susceptibility show that relatively large signals can be produced easily without significant problems from competing physical phenomena such as self-focusing or stimulated Brillouin and Raman scattering. PMID:19687905

Steel, D G; Lam, J F



Bmi-1 Absence Causes Premature Brain Degeneration  

PubMed Central

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

Cao, Guangliang; Gu, Minxia; Zhu, Min; Gao, Junying; Yin, Ying; Marshall, Charles; Xiao, Ming; Ding, Jiong; Miao, Dengshun



Anterior insula degeneration in frontotemporal dementia  

PubMed Central

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



Age-related macular degeneration: current treatments  

PubMed Central

Purpose: Although important progress has been made in understanding age-related macular degeneration (AMD), management of the disease continues to be a challenge. AMD research has led to a widening of available treatment options and improved prognostic perspectives. This essay reviews these treatment options. Design: Interpretative essay. Methods: Literature review and interpretation. Results: Current treatments to preserve vision in patients with non-exudative AMD include antioxidant vitamins and mineral supplementations. Exudative AMD is currently most often treated monthly with anti-VEGF intravitreal injections. However, investigators are beginning to experiment with combination therapy and surgical approaches in an attempt to limit the number of treatment and reduce the financial burden on the health care system. Conclusion: By better understanding the basis and pathogenesis of AMD, newer therapies will continue to be developed that target specific pathways in patients with AMD, with the hoped for outcome of better management of the disease and improved visual acuity.

Hubschman, Jean Pierre; Reddy, Shantan; Schwartz, Steven D



a First Order Non-Degenerate Adiabatic  

NASA Astrophysics Data System (ADS)

Some of the most important theories in electron molecule scattering are discussed. Special attention is given to near threshold energies where some of the mostly used techniques (e.g. Adiabatic Nuclei) are expected to break down. A first order non-degenerate adiabatic theory which is not as demanding as some techniques (laboratory -frame close-coupling) and gives more accurate cross sections near threshold is explained. This theory is applied to H_2 with model exchange as well as exact exchange. In model exchange the first set of calculations treat the target as being a rigid rotator molecule. In the second set of calculations the effect of the vibration of the target is taken into account.

Abdolsalami, Mehran


Simplified models of completely degenerate, differentially rotating stars  

Microsoft Academic Search

The properties of differentially rotating, completely degenerate sections of infinite cylinders are examined. Their construction is simple, with variables depending only on the radial cylindrical coordinate. They are found to possess important characteristics which qualitatively resemble much more complicated two-dimensional models of differentially rotating degenerate stars: (1) an analog of the Chandrasekhar limit; (2) a limit to uniform rotation imposed

Sheridan A. Simon; Donna Hurley



Nmnat delays axonal degeneration caused by mitochondrial and oxidative stress  

PubMed Central

Axonal degeneration is a prominent feature of many neurological disorders that are associated with mitochondrial dysfunction, including Parkinson’s disease (PD), motor neuron disease, and inherited peripheral neuropathies. It is now thought that axonal degeneration is an active process, due in large part to studies of the Wlds mutant mouse, which undergoes delayed Wallerian degeneration in response to axonal injury. Wlds mice also have slower axonal degeneration and disease progression in numerous models of neurodegenerative disease. The Wlds mutation results in the production of a chimeric protein that contains the full length coding sequence of nicotinamide mononucleotide adenylyltransferase 1 (Nmnat1), which alone is sufficient for axonal protection in vitro. To test the effects of increased Nmnat expression on axonal degeneration induced by mitochondrial dysfunction, we examined dorsal root ganglia (DRG) neurons treated with rotenone. Rotenone induced profound axonal degeneration in DRG neurons; however, this degeneration was delayed by expression of Nmnat. Nmnat-mediated protection resulted in decreased axonal accumulation and sensitivity to reactive oxygen species (ROS) but did not affect the change in the rate of rotenone-induced loss in neuronal ATP. Nmnat also prevented axonal degeneration caused by exposure to exogenous oxidants and reduced the level of axonal ROS after treatment with vincristine, further supporting the idea that Nmnat promotes axonal protection by mitigating the effects of ROS.

Press, Craig; Milbrandt, Jeffrey



Shoulder pathology associated with symptomatic acromioclavicular joint degeneration  

Microsoft Academic Search

We report the incidence and nature of shoulder disease found in association with symptomatic degenerative change in the acromioclavicular joint in 218 shoulders. Coexisting pathologic conditions were present in 213 shoulders: rotator cuff degeneration in 176 shoulders (79 with complete thickness tears), labral tears in 72, glenohumeral degeneration in 31, and biceps tendon disease in 49. In 59 shoulders findings

Jeremy N. Brown; Simon N. J. Roberts; Michael G. Hayes; Andrew D. Sales



Degenerate Bernoulli polynomials, generalized factorial sums, and their applications  

Microsoft Academic Search

We prove a general symmetric identity involving the degenerate Bernoulli polynomials and sums of generalized falling factorials, which unifies several known identities for Bernoulli and degenerate Bernoulli numbers and polynomials. We use this identity to describe some combinatorial relations between these polynomials and generalized factorial sums. As further applications we derive several identities, recurrences, and congruences involving the Bernoulli numbers,

Paul Thomas Young



Stress Induced Urinary Incontinence in Patients With Spinocerebellar Degeneration  

Microsoft Academic Search

OBJECTIVESTo examine the pathophysiology of “stress induced urinary incontinence” (urinary incontinence evoked by abdominal straining) in patients with spinocerebellar degeneration.METHODSMicturitional symptoms of 184 patients with spinocerebellar degeneration who were admitted to hospital were studied repeatedly. Urodynamic studies were made in symptomatic patients, and consisted of uroflowmetry, measurement of residual urine, urethral pressure profilometry, medium fill water cystometry, and external sphincter

Ryuji Sakakibara; Takamichi Hattori; K. Kica; K. Aria; T. Yamnanishi; Kosaku Yasuda



Weibel instabilities in a completely degenerate electron Fermi gas  

SciTech Connect

Weibel instability in a degenerate Fermi plasma is studied. A new type of quantum Weibel instabilities is disclosed. In particular, a novel oscillatory Weibel instability is found and its growth rate is obtained. A transverse zero sound in a quantum degenerate electron gas, which has no counterpart in the classical consideration, is revealed.

Tsintsadze, Levan N. [Graduate School of Science, Hiroshima University, Higashi-Hiroshima, Hiroshima 739-8526 (Japan)



Thermonuclear burning and the explosion of degenerate matter in supernovae  

SciTech Connect

While focusing on the Hydrodynamics of thermonuclear explosions of degenerate stars as supernovae, the author devotes this review to the properties of burning fronts and to the initiation and the propagation of burning in degenerate matter. Topics covered include: Energetics and light curves, thermonuclear explosions: the qualitative picture, the structure of steady burning waves in supernovae, initiation of detonation in supernovae, and Nucleosynthesis.

Khokhlov, A.M. (Astronomical Council, USSR Academy of Sciences, Moscow (SU))



Neurofilament phosphoforms: surrogate markers for axonal injury, degeneration & loss  

Microsoft Academic Search

This review on the role of neurofilaments as surrogate markers for axonal degeneration in neurological diseases provides a brief background to protein synthesis, assembly, function and degeneration. Methodological techniques for quantification are described and a protein nomenclature is proposed. The relevance for recognising anti-neurofilament autoantibodies is noted. Pathological implications are discussed in view of immunocytochemical, cell- culture and genetic findings.

Axel Petzold



Photoreceptor degeneration: genetic and mechanistic dissection of a complex trait  

Microsoft Academic Search

The retina provides exquisitely sensitive vision that relies on the integrity of a uniquely vulnerable cell, the photoreceptor (PR). The genetic and mechanistic causes of retinal degeneration due to PR cell death — which occurs in conditions such as retinitis pigmentosa and age-related macular degeneration — are being successfully dissected. Over one hundred loci, some containing common variants but most

Christina F. Chakarova; Mai M. Abd El-Aziz; Alan F. Wright; Shomi S. Bhattacharya



Myocyte degeneration and cell death in hibernating human myocardium  

Microsoft Academic Search

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

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



Neurofilament phosphoforms: Surrogate markers for axonal injury, degeneration and loss  

Microsoft Academic Search

This review on the role of neurofilaments as surrogate markers for axonal degeneration in neurological diseases provides a brief background to protein synthesis, assembly, function and degeneration. Methodological techniques for quantification are described and a protein nomenclature is proposed. The relevance for recognising antineurofilament autoantibodies is noted. Pathological implications are discussed in view of immunocytochemical, cell-culture and genetic findings. With

Axel Petzold



Automatic parsing of degenerate quadric-surface intersections  

Microsoft Academic Search

In general, two quadric surfaces intersect in a nonsingular quartic space curve. Under special circumstances, however, this intersection may “degenerate” into a quartic with a double point, or a composite of lines, conics, and twisted cubics whose degrees, counted over the complex projective domain, sum to four. Such degenerate forms are important since they occur with surprising frequency in practice

Rida T. Farouki; C. Andrew Neff; M. A. O'Conner



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


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 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



Mammalian Sir2-related protein (SIRT) 2–mediated modulation of resistance to axonal degeneration in slow Wallerian degeneration mice: A crucial role of tubulin deacetylation  

Microsoft Academic Search

It has been shown that Wallerian degeneration, an anterograde degeneration of transected axons, is markedly delayed in a mutant mouse called slow Wallerian degeneration (WldS). These mice also show resistance to axonal degeneration caused by microtubule depolymerizing drugs, suggesting that axonal microtubules are stabilized. Here, we have focused on tubulin acetylation, a post-translational modification associated with microtubule stability. We found

K. Suzuki; T. Koike



Computer assisted characterization of cervical intervertebral disc degeneration in MRI  

NASA Astrophysics Data System (ADS)

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

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



Alteration of Enzymatic Activities Implicating Neuronal Degeneration in the Spinal Cord of the Motor Neuron Degeneration Mouse During Postnatal Development  

Microsoft Academic Search

Oxidative stress is suggested as a significant causative factor forpathogenesis of neuronal degeneration on spinal cord of human ALS. Wemeasured some enzymic activities implicating neuronal degenerationprocess, such as cytochrome c oxidase (CO), superoxidedismutase (SOD), and transglutaminase (TG) in spinalcord of an animal model of ALS, motor neuron degeneration(Mnd) mouse, a mutant that exhibits progressivedegeneration of lower spinal neurons during developmental

K. Fujita; K. Shibayama; M. Yamauchi; T. Kato; M. Ando; H. Takahashi; K. Iritani; N. Yoshimoto; Y. Nagata



Disc degeneration after disc herniation: are we accelerating the process?  

PubMed Central

Study design:?Systematic review. Study rationale:?Disc degeneration is a common process starting early in life. Often disc herniation is an early step in disc degeneration, which may cause pain or stenosis. How quickly this subsequent disc degeneration occurs following a disc herniation and subsequent surgical treatment and whether certain spinal procedures increase the rate of degeneration remain unclear. Objectives:?To investigate the risk of subsequent radiographic disc degeneration following discectomy, discography, and conservative care in patients with a first-time diagnosed herniated nucleus pulpous (HNP) and to ascertain whether this risk in these defined groups changes over time. Methods:?A systematic review of pertinent articles published up to June 2012. Key articles were searched to identify studies evaluating the risk of subsequent radiographic disc degeneration following treatment for HNP. Studies that included patients undergoing secondary surgery for disc herniation or that did not use a validated classification system to measure the severity of disc degeneration were excluded. Two independent reviewers assessed the strength of evidence using the GRADE criteria and disagreements were resolved by consensus. Results:?From a total of 147 possible citations, three cohort studies (class of evidence III) met our inclusion criteria and form the basis for this report. The risk of subsequent lumbar disc degeneration following standard discectomy was significantly greater compared with both microdiscectomy (48.7% vs 9.1%) and asymptomatic controls (90% vs 68%) in two studies with mean follow-ups of 5.5 and 25.3 years, respectively. Following conservative care for first-time HNP in the third study, the risk of progression of lumbar disc degeneration was 47.6% over the first 2 years of follow-up and 95.2% over the next 6 years of follow-up. In the same study, the risk of lumbar disc degeneration was shown to increase incrementally over the course of the 8-year follow-up, with all patients showing signs of degeneration at final examination. Conclusion:?Standard discectomy in first-time lumbar HNP may increase the risk of subsequent same-level lumbar disc degeneration compared with microdiscectomy as seen in one low-quality study. However, disc degeneration is likely a natural, temporal consequence following HNP, as demonstrated in a second low-quality study. The overall strength of evidence for the conclusions is very low.

Schroeder, Josh E.; Dettori, Joseph R.; Brodt, Erika D.; Kaplan, Leon



The genetics and neuropathology of frontotemporal lobar degeneration.  


Frontotemporal lobar degeneration (FTLD) is a heterogeneous group of disorders characterized by disturbances of behavior and personality and different types of language impairment with or without concomitant features of motor neuron disease or parkinsonism. FTLD is characterized by atrophy of the frontal and anterior temporal brain lobes. Detailed neuropathological studies have elicited proteinopathies defined by inclusions of hyperphosphorylated microtubule-associated protein tau, TAR DNA-binding protein TDP-43, fused-in-sarcoma or yet unidentified proteins in affected brain regions. Rather than the type of proteinopathy, the site of neurodegeneration correlates relatively well with the clinical presentation of FTLD. Molecular genetic studies identified five disease genes, of which the gene encoding the tau protein (MAPT), the growth factor precursor gene granulin (GRN), and C9orf72 with unknown function are most frequently mutated. Rare mutations were also identified in the genes encoding valosin-containing protein (VCP) and charged multivesicular body protein 2B (CHMP2B). These genes are good markers to distinguish underlying neuropathological phenotypes. Due to the complex landscape of FTLD diseases, combined characterization of clinical, imaging, biological and genetic biomarkers is essential to establish a detailed diagnosis. Although major progress has been made in FTLD research in recent years, further studies are needed to completely map out and correlate the clinical, pathological and genetic entities, and to understand the underlying disease mechanisms. In this review, we summarize the current state of the rapidly progressing field of genetic, neuropathological and clinical research of this intriguing condition. PMID:22890575

Sieben, Anne; Van Langenhove, Tim; Engelborghs, Sebastiaan; Martin, Jean-Jacques; Boon, Paul; Cras, Patrick; De Deyn, Peter-Paul; Santens, Patrick; Van Broeckhoven, Christine; Cruts, Marc



Disk degeneration in lumbar spine precedes osteoarthritic changes in hip.  


It is not clear whether spinal degeneration leads to hip arthritis, or hip arthritis leads to spinal degeneration. We conducted a study to determine which degenerative process precedes the other. We examined 340 cadaveric human specimens from the Hamann-Todd Osteological Collection (Cleveland, Ohio). Lumbar endplate degeneration was graded on a scale of 0 to 4, and hip degeneration on a scale of 0 to 3. Linear regression was used to analyze the relationship between hip osteoarthritis (OA) and lumbar degenerative disk disease (DDD). Exact tests were used to identify differences in each age group. Hip OA was significantly associated with endplate degeneration at the L1, L3, and L5 levels (P<.02). Of the specimens younger than 29 years, 35% had evidence of DDD in at least 1 lumbar level, and 17% of hip OA changes. At 70 years, 100% of the specimens had evidence of DDD and 50% of hip OA changes. There was a significant association between lumbar DDD and hip OA changes (P<.05). Early lumbar DDD was twice as common as hip OA changes in the early 20s age range. These findings suggest that lumbar degeneration precedes hip degeneration and may be a causative factor for hip OA. PMID:24078941

Bajwa, Navkirat S; Toy, Jason O; Young, Ernest Y; Cooperman, Daniel R; Ahn, Nicholas U



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.



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.

Bigio, Eileen H.



Age-related macular degeneration: choroidal ischaemia?  

PubMed Central

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

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



Evidence for degenerate tetraploidy in bdelloid rotifers  

PubMed Central

Rotifers of class Bdelloidea have evolved for millions of years apparently without sexual reproduction. We have sequenced 45- to 70-kb regions surrounding the four copies of the hsp82 gene of the bdelloid rotifer Philodina roseola, each of which is on a separate chromosome. The four regions comprise two colinear gene-rich pairs with gene content, order, and orientation conserved within each pair. Only a minority of genes are common to both pairs, also in the same orientation and order, but separated by gene-rich segments present in only one or the other pair. The pattern is consistent with degenerate tetraploidy with numerous segmental deletions, some in one pair of colinear chromosomes and some in the other. Divergence in 1,000-bp windows varies along an alignment of a colinear pair, from zero to as much as 20% in a pattern consistent with gene conversion associated with recombinational repair of DNA double-strand breaks. Although pairs of colinear chromosomes are a characteristic of sexually reproducing diploids and polyploids, a quite different explanation for their presence in bdelloids is suggested by the recent finding that bdelloid rotifers can recover and resume reproduction after suffering hundreds of radiation-induced DNA double-strand breaks per oocyte nucleus. Because bdelloid primary oocytes are in G1 and therefore lack sister chromatids, we propose that bdelloid colinear chromosome pairs are maintained as templates for the repair of DNA double-strand breaks caused by the frequent desiccation and rehydration characteristic of bdelloid habitats.

Mark Welch, David B.; Mark Welch, Jessica L.; Meselson, Matthew



Flavour identification in frontotemporal lobar degeneration  

PubMed Central

Background Deficits of flavour processing may be clinically important in frontotemporal lobar degeneration (FTLD). Objective To examine  flavour processing in FTLD. Methods We studied flavour identification prospectively in 25 patients with FTLD (12 with behavioural variant frontotemporal dementia (bvFTD), eight with semantic variant primary progressive aphasia (svPPA), five with non-fluent variant primary progressive aphasia (nfvPPA)) and 17 healthy control subjects, using a new test based on cross-modal matching of flavours to words and pictures. All subjects completed a general neuropsychological assessment, and odour identification was also assessed using a modified University of Pennsylvania Smell Identification Test. Brain MRI volumes from the patient cohort were analysed using voxel-based morphometry to identify regional grey matter associations of flavour identification. Results Relative to the healthy control group, the bvFTD and svPPA subgroups showed significant (p<0.05) deficits of flavour identification and all three FTLD subgroups showed deficits of odour identification. Flavour identification performance did not differ significantly between the FTLD syndromic subgroups. Flavour identification performance in the combined FTLD cohort was significantly (p<0.05 after multiple comparisons correction) associated with grey matter volume in the left entorhinal cortex, hippocampus, parahippocampal gyrus and temporal pole. Conclusions Certain FTLD syndromes are associated with impaired flavour identification and this is underpinned by grey matter atrophy in an anteromedial temporal lobe network. These findings may have implications for our understanding of abnormal eating behaviour in these diseases.

Omar, Rohani; Mahoney, Colin J; Buckley, Aisling H; Warren, Jason D



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.

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



[Multiple system atrophy - synuclein and neuronal degeneration].  


Multiple system atrophy (MSA) is a sporadic neurodegenerative disorder that encompasses olivopontocerebellar atrophy (OPCA), striatonigral degeneration (SND) and Shy-Drager syndrome (SDS). The histopathological hallmarks are ?-synuclein (AS) positive glial cytoplasmic inclusions (GCIs) in oligodendroglias. AS aggregation is also found in glial nuclear inclusions (GNIs), neuronal cytoplasmic inclusions (NCIs), neuronal nuclear inclusions (NNIs) and dystrophic neurties. Reviewing the pathological features of 102 MSA cases, OPCA-type was relatively more frequent and SND-type was less frequent in Japanese MSA cases, which suggested different phenotypic pattern of MSA might exist between races, compared to the relatively high frequency of SND-type in western countries. In early stage of MSA, NNIs, NCIs and diffuse homogenous stain of AS in neuronal nuclei and cytoplasm were observed in various vulnerable lesions including the pontine nuclei, putamen, substantia nigra, locus ceruleus, inferior olivary nucleus, intermediolateral column of thoracic cord, lower motor neurons and cortical pyramidal neurons, in additions to GCIs. These findings indicated that the primary nonfibrillar and fibrillar AS aggregation also occurred in neurons. Therefore both the direct involvement of neurons themselves and the oligodendroglia-myelin-axon mechanism may synergistically accelerate the degenerative process of MSA. PMID:22277386

Yoshida, Mari



Degenerating Synaptic Boutons in Prion Disease  

PubMed Central

A growing body of evidence suggests that the loss of synapses is an early and major component of a number of neurodegenerative diseases. Murine prion disease offers a tractable preparation in which to study synaptic loss in a chronic neurodegenerative disease and to explore the underlying mechanisms. We have previously shown that synaptic loss in the hippocampus underpins the first behavioral changes and that there is a selective loss of presynaptic elements. The microglia have an activated morphology at this stage but they have an anti-inflammatory phenotype. We reasoned that the microglia might be involved in synaptic stripping, removing synapses undergoing a degenerative process, and that this gives rise to the anti-inflammatory phenotype. Analysis of synaptic density revealed a progressive loss from 12 weeks post disease initiation. The loss of synapses was not associated with microglia processes; instead, we found that the postsynaptic density of the dendritic spine was progressively wrapped around the degenerating presynaptic element with loss of subcellular components. Three-dimensional reconstructions of these structures from Dual Beam electron microscopy support the conclusion that the synaptic loss in prion disease is a neuron autonomous event facilitated without direct involvement of glial cells. Previous studies described synapse engulfment by developing and injured neurons, and we suggest that this mechanism may contribute to developmental and pathological changes in synapse numbers.

Siskova, Zuzana; Page, Anton; O'Connor, Vincent; Perry, Victor Hugh



Mechanisms of age-related macular degeneration  

PubMed Central

Age-related macular degeneration (AMD), a progressive condition that is untreatable in up to 90% of patients, is a leading cause of blindness in the elderly worldwide. The two forms of AMD, wet and dry, are classified based on the presence or absence of blood vessels that have disruptively invaded the retina, respectively. A detailed understanding of the molecular mechanisms underlying wet AMD has led to several robust FDA-approved therapies. In contrast, there are not any approved treatments for dry AMD. In this review, we provide insight into the critical effector pathways that mediate each form of disease. The interplay of immune and vascular systems for wet AMD, and the proliferating interest in hunting for gene variants to explain AMD pathogenesis, are placed in the context of the latest clinical and experimental data. Emerging models of dry AMD pathogenesis are presented, with a focus on DICER1 deficit and the toxic accumulation of retinal debris. A recurring theme that spans most aspects of AMD pathogenesis is defective immune modulation in the classically immune-privileged ocular haven. Interestingly, the latest advances in AMD research highlight common molecular disease pathways with other common neurodegenerations. Finally, the therapeutic potential of intervening at known mechanisms of AMD pathogenesis is discussed.

Ambati, Jayakrishna; Fowler, Benjamin J.



[German consortium for frontotemporal lobar degeneration].  


Frontotemporal lobar degeneration (FTLD) is an umbrella term for an aetiologically diverse group of neurodegenerative disorders with prominent lobar cortical atrophy. First this disease group was restricted to Pick's disease or Pick's complex. Several updates of the clinical classification systems were performed and discussed. Currently we summarize the following diseases under the FTLD spectrum: frontotemporal dementia (FTD) as a behavioural variant, primary non-fluent aphasia (PNFA) and semantic dementia as language variants, amyotrophic lateral sclerosis with FTD (ALS-FTD), corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP).From the pathophysiological aspect major progress was made. Neuropathologically FTLDs are now defined based on the molecular composition of these protein accumulations. A major distinction of tau-associated (FTLD-tau) and TDP43-associated (FTLD-TDP43) and to a lesser extend FUS-associated (FTLD-FUS) has been made. Additional risk genes were described. However from the therapeutic perspective even symptomatic therapy is under discussion. A major aim of our consortium is to develop parameters allowing an early diagnosis and follow-up, thus providing effective and objective parameters for therapeutic strategies. PMID:21805118

Otto, M; Ludolph, A C; Landwehrmeyer, B; Förstl, H; Diehl-Schmid, J; Neumann, M; Kretzschmar, H A; Schroeter, M; Kornhuber, J; Danek, A



Differentiation and apoptosis without DNA fragmentation in cultured Schwann cells derived from wallerian-degenerated nerve.  


The Schwann cell cables provide particularly favorable sites for the growth of regenerating axonal sprouts. However, if they remain denervated, endoneurial fibrosis takes place with the Schwann cells atrophying and total Schwann cell number gradually decrease with time. Even when regenerating axonal sprouts invade into the cables, Schwann cells do not survive for long periods if they fail to make axonal contact. These observations strongly suggest the involvement of apoptosis in peripheral nerve degeneration and regeneration. So, we investigated the behavior of Schwann cells prepared from wallerian-degenerated adult rat sciatic nerve in vitro. The secondary cultured Schwann cells showed serial changes in morphology, mitotic activity and migratory activity as they do during Schwann cell cable formation in vivo. At the final stage of differentiation, the Schwann cells became rounded and detached from the flask with extensive blebbing. Electron micrographs clearly demonstrated typical cytoplasmic changes of apoptosis, but, nuclei of most of the cells retained their size and morphology with residual nucleolar structures. An agarose gel electrophoresis of DNA clearly demonstrated that there was not any DNA fragmentation up to 120 h after detachment. Results by in situ apoptosis detection assay did not show any DNA degradation despite the substantial decrease in Schwann cell number. In conclusion, during peripheral nerve degeneration and regeneration, supernumerary Schwann cells are removed by apoptosis, however, it lacks most of the nuclear events of usual apoptosis. PMID:14646482

Hirata, H; Hibasami, H; Yoshida, T; Morita, A; Ohkaya, S; Matsumoto, M; Sasaki, H; Uchida, A



Relationship of Facet Tropism with Degeneration and Stability of Functional Spinal Unit  

PubMed Central

Purpose The authors investigated the effect of lumbar facet tropism (FT) on intervertebral disc degeneration (DD), facet joint degeneration (FJD), and segmental translational motion. Materials and Methods Using kinetic MRI (KMRI), lumbar FT, which was defined as a difference in symmetry of more than 7° between the orientations of the facet joints, was investigated in 900 functional spinal units (300 subjects) in flexion, neutral, and extension postures. Each segment at L3-L4, L4-L5, and L5-S1 was assessed based on the extent of DD (grade I-V) and FJD (grade 1-4). According to the presence of FT, they were classified into two groups; one with FT and one with facet symmetry. For each group, demographics, DD, FJD and translational segmental motion were compared. Results The incidence of FT was 34.5% at L3-L4, 35.1% at L4-L5, and 35.2% at L5-S1. Age and gender did not show any significant relationship with FT. Additionally, no correlation was observed between DD and FT. FT, however, wasfound to be associated with a higher incidence of highly degenerated facet joints at L4-L5 when compared to patients without FT (p < 0.01). Finally, FT was not observed to have any effects upon translational segmental motion. Conclusion No significant correlation was observed between lumbar FT and DD or translational segmental motion. However, FT was shown to be associated significantly with the presence of high grades of FJD at L4-L5. This suggests that at active sites of segmental motion, FT may predispose to the development of facet joint degeneration.

He, Wubing; Tsai, Yu-Duan; Chen, Nan-Fu; Keorochana, Gun; Do, Duc H.; Wang, Jeffrey C.



Erythrocyte Degeneration in the Atlantic Herring, 'Clupea harengus harengus L.  

National Technical Information Service (NTIS)

Cytoplasmic inclusions, associated with erythrocytic degeneration, were found in the circulating blood of herring from Boothbay Harbor, Maine, and from Passamaquoddy Bay at Deer Island, N.B., Canada, in 1969. Except in one instance, when inclusions occurr...

S. W. Sherburne



Melange a Six Ondes Degenere dans les Absorbants Saturables  

NASA Astrophysics Data System (ADS)

Issus d'une generalisation du melange a quatre ondes degenere, les melanges a n ondes degeneres sont utiles pour la mesure des divers ordres de la susceptibilite nonlineaire. Nous avons procede a l'etude theorique et experimentale du melange a six ondes degenere dans des absorbants isotropes et anisotropes. Pour l'analyse theorique, nous avons developpe une methode de calcul basee sur une approche holographique. Cette methode fut utilisee pour l'etude du melange a six ondes en regimes stationnaire et transitoire sous des conditions de faibles et de fortes saturations. Des experiences realisees a l'aide d'impulsions excitatrices de courte duree, soit 33 picosecondes, dans des verres dopes aux semi-conducteurs et dans la Rhodamine 6G en solution ont permis de verifier la validite de notre modele theorique. Nous avons aussi etudie les oscillateurs auto-pompes par melange a six ondes degenere.

Blouin, Alain


Many-Body Green Function of Degenerate Systems  

SciTech Connect

A rigorous nonperturbative adiabatic approximation of the evolution operator in the many-body physics of degenerate systems is derived. This approximation is used to solve the long-standing problem of the choice of the initial states of H{sub 0} leading to eigenstates of H{sub 0}+V for degenerate systems. These initial states are eigenstates of P{sub 0}VP{sub 0}, where P{sub 0} is the projection onto a degenerate eigenspace of H{sub 0}. This result is used to give the proper definition of the Green function, the statistical Green function and the nonequilibrium Green function of degenerate systems. The convergence of these Green functions is established.

Brouder, Christian [Institut de Mineralogie et de Physique des Milieux Condenses, CNRS UMR 7590, Universites Paris 6 et 7, IPGP, 140 rue de Lourmel, 75015 Paris (France); Panati, Gianluca [Dipartimento di Matematica, Universita di Roma La Sapienza, Roma (Italy); Stoltz, Gabriel [Universite Paris Est, CERMICS, Projet MICMAC ENPC-INRIA, 6 and 8 Avenue Pascal, 77455 Marne-la-Vallee Cedex 2 (France)



Identification of homologous gene sequences by PCR with degenerate primers.  


Degenerate primers are mixtures of similar oligonucleotides that are used in a PCR, so-called degenerate PCR, to amplify unknown DNA sequences, typically coding sequences of genes. Degenerate primers are designed based on sequence data of related and already sequenced gene homologs. This method is useful for identifying new members of a gene family or orthologous genes from different organisms where genomic information is not available. We describe here how to design degenerate primers, set up the PCR (with genomic DNA or cDNA as a template), clone the resulting PCR fragments, and sequence them. Since this method only yields partial coding sequences, complete gene sequences must then be achieved by other approaches such as inverse PCR (see Chapter 16), 5' RACE, 3' RACE, or circular RACE (see Chapter 15). PMID:22065442

Lang, Michael; Orgogozo, Virginie



Intervertebral disc degeneration: evidence for two distinct phenotypes.  


We review the evidence that there are two types of disc degeneration. 'Endplate-driven' disc degeneration involves endplate defects and inwards collapse of the annulus, has a high heritability, mostly affects discs in the upper lumbar and thoracic spine, often starts to develop before age 30 years, usually leads to moderate back pain, and is associated with compressive injuries such as a fall on the buttocks. 'Annulus-driven' disc degeneration involves a radial fissure and/or a disc prolapse, has a low heritability, mostly affects discs in the lower lumbar spine, develops progressively after age 30 years, usually leads to severe back pain and sciatica, and is associated with repetitive bending and lifting. The structural defects which initiate the two processes both act to decompress the disc nucleus, making it less likely that the other defect could occur subsequently, and in this sense the two disc degeneration phenotypes can be viewed as distinct. PMID:22881295

Adams, Michael A; Dolan, Patricia



Identification of a suppressor of retinal degeneration in Drosophila photoreceptors.  


During sensory transduction, Drosophila photoreceptors experience substantial increases in intracellular Ca(2+) levels ([Ca(2+)](i)). Nevertheless in a number of mutants associated with excessive Ca(2+) influx through transient receptor potential (TRP) channels, Drosophila photoreceptors undergo loss of normal cellular structure manifest as a retinal degeneration. However, the molecular mechanisms that underpin this degeneration process remain unclear. The authors previously isolated a mutant, su(40), that is able to suppress the retinal degeneration seen in photoreceptors from loss-of-function alleles of rdgA that are known to have constitutively active TRP channels. Here the authors report the genetic mapping of su(40) as well the isolation of additional alleles of su(40). Studies of su(40) as well as these new alleles should facilitate the understanding of the mechanisms by which excessive Ca(2+) influx results in retinal degeneration. PMID:23043643

Georgiev, Plamen; Toscano, Sarah; Nair, Amit; Hardie, Roger; Raghu, Padinjat



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


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



Critical Mass Transfer in Double-Degenerate Type Ia Supernovae  

Microsoft Academic Search

Doubly-degenerate binary systems consisting of two white dwarfs both composed\\u000aof carbon and oxygen and close enough that mass is transferred from the less\\u000amassive to the more massive are possible progenitors of type Ia supernovae. If\\u000athe mass transfer rate is slow enough that the accreting white dwarf can reach\\u000a1.38 solar masses then it can ignite carbon degenerately

Rebecca G. Martin; Christopher A. Tout; Pierre Lesaffre



Ubiquitin expression in degenerating axons of equine cervical compressive myelopathy.  


Neuropathologic examination revealed axonal swelling and breakdown leading to Wallerian degeneration of affected myelinated nerve fibers in the spinal cord white matter of four young horses with equine cervical compressive myelopathy. Immunohistochemical reactions for the cell stress protein ubiquitin revealed an enhanced presence in the swollen axons, which may reflect a role for ubiquitin in the neuronal catabolic process of axonal compression and degeneration in this myelopathy. PMID:8740714

Jortner, B S; Scarratt, W K; Modransky, P D; Walton, A; Perkins, S K



Molecular Inflammatory Mediators in Peripheral Nerve Degeneration and Regeneration  

Microsoft Academic Search

Wallerian degeneration, the self-destructive set of cellular and molecular processes by which degenerating axons and myelin are cleared after injury, is initiated by macrophages and Schwann cells. Molecular inflammatory mediators such as cytokines (IL-1, IL-6, IL-10, and TNF-?, among others), transcription factors (NF-?B, c-Jun), the complement system and arachidonic acid metabolites have been shown to modulate these processes in various

Carlos Rodrigo Cámara-Lemarroy; Francisco Javier Guzmán-de la Garza; Nancy Esthela Fernández-Garza



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



Tissue factor with age-related macular degeneration  

PubMed Central

Wet age-related macular degeneration which incidence increases year by year is a blinding eye disease, but current clinical methods of treatment on this disease are limited and the outcome is not ideal. Recent studies have found abnormally high expression of tissue factors which are targets for the treatment of wet age-related macular degeneration to achieve a certain effect in the choroidal neovascularization. Related literatures are reviewed as following.

Wang, Guan-Feng; Zou, Xiu-Lan



Ultrasonographic evaluation of vitreous degeneration in normal dogs.  


Vitreous degeneration is common in dogs and may be associated with cataract formation. Vitreous degeneration may be identified using B-mode ultrasonography and appears as multiple, small, motile, point-like echoes within the vitreous cavity. In humans, vitreous degeneration has also been observed in normal aging eyes but the incidence of vitreous degeneration in dogs without cataract has not previously been documented. The purpose of this study was to describe the ultrasonographic appearance of vitreous degeneration and to investigate its incidence in a population of dogs without cataract or other apparent eye disease. The eyes of 62 dogs were evaluated as part of a prospective study. All dogs underwent ophthalmological and ultrasonographic examinations and vitreal changes were graded on ultrasonography using a predetermined grading scheme. Vitreous degeneration was found in 20% (23/114) of the eyes on ultrasonographic examination but in only 8% (9/114) of eyes on direct ophthalmoscopy. Sensitivity and specificity of ophthalmoscopy using ultrasonography as a gold standard were respectively, 39% and 100%. Vitreal syneresis and asteroid hyalosis could be distinguished according to their ultrasonographic characteristics. The probability of having vitreous degeneration increased with the age of the dog (odds ratio = 6.7 for dogs of 7 + years compared with 0-6 years) and also increased in females compared with males (odds ratio = 3.6). Vitreous degeneration, especially mild vitreal syneresis, is not uncommon in normal dogs; it was shown to be an age-related condition and its significance should not be overinterpreted on ocular ultrasonography. PMID:18418998

Labruyère, Julien J; Hartley, Claudia; Rogers, Katherine; Wetherill, Graham; McConnell, J Fraser; Dennis, Ruth


Solitary waves in an ultrarelativistic degenerate dense plasma  

SciTech Connect

Solitary waves in an ultrarelativistic degenerate dense plasma have been investigated by the reductive perturbation method. The modified Korteweg-de Vries equation has been derived and its numerical solutions have been analyzed to identify the basic features of spherical electrostatic solitary structures that may form in such a degenerate dense plasma. The implications of our results in compact astrophysical objects, particularly in white dwarfs, have been briefly discussed.

Mamun, A. A.; Shukla, P. K. [RUB International Chair, International Centre for Advanced Studies in Physical Sciences, Faculty of Physics and Astronomy, Ruhr-Universitaet Bochum, Bochum D-44780 (Germany)



Rosette-forming glioneuronal tumor of the fourth ventricle with bilateral olivary degeneration.  


Rosette-forming glioneuronal tumor (RGNT) of the fourth ventricle has been recognized as a new type of glioneuronal tumor. RGNTs are typically located in the infratentorial midline with involvement of the fourth ventricle. They occasionally involve the aqueduct and/or vermis. RGNTs of unusual anatomical sites or those with unusual findings have been reported. The present case reports describe RGNT of the fourth ventricle with bilateral olivary degeneration. It is important to accumulate imaging findings and biological behaviors of RGNTs given the limited number of cases. PMID:21786101

Fushimi, Yasutaka; Miyasaki, Akihiro; Taki, Hideaki; Aoyama, Kunihiro; Hirato, Junko; Kanagaki, Mitsunori; Togashi, Kaori



The advantages of frontotemporal degeneration drug development (part 2 of frontotemporal degeneration: the next therapeutic frontier).  


Frontotemporal degeneration (FTD) encompasses a spectrum of related neurodegenerative disorders with behavioral, language, and motor phenotypes for which there are currently no effective therapies. This is the second of two articles that summarize the presentations and discussions that occurred at two symposia in 2011 sponsored by the Frontotemporal Degeneration Treatment Study Group, a collaborative group of academic and industry researchers that is devoted to developing treatments for FTD. This article discusses the current status of FTD clinical research that is relevant to the conduct of clinical trials, and why FTD research may be an attractive pathway for developing therapies for neurodegenerative disorders. The clinical and molecular features of FTD, including rapid disease progression and relatively pure molecular pathology, suggest that there are advantages to developing drugs for FTD as compared with other dementias. FTD qualifies as orphan indication, providing additional advantages for drug development. Two recent sets of consensus diagnostic criteria will facilitate the identification of patients with FTD, and a variety of neuropsychological, functional, and behavioral scales have been shown to be sensitive to disease progression. Moreover, quantitative neuroimaging measurements demonstrate progressive brain atrophy in FTD at rates that may surpass Alzheimer's disease. Finally, the similarities between FTD and other neurodegenerative diseases with drug development efforts already underway suggest that FTD researchers will be able to draw on this experience to create a road map for FTD drug development. We conclude that FTD research has reached sufficient maturity to pursue clinical development of specific FTD therapies. PMID:23062850

Boxer, Adam L; Gold, Michael; Huey, Edward; Hu, William T; Rosen, Howard; Kramer, Joel; Gao, Fen-Biao; Burton, Edward A; Chow, Tiffany; Kao, Aimee; Leavitt, Blair R; Lamb, Bruce; Grether, Megan; Knopman, David; Cairns, Nigel J; Mackenzie, Ian R; Mitic, Laura; Roberson, Erik D; Van Kammen, Daniel; Cantillon, Marc; Zahs, Kathleen; Jackson, George; Salloway, Stephen; Morris, John; Tong, Gary; Feldman, Howard; Fillit, Howard; Dickinson, Susan; Khachaturian, Zaven S; Sutherland, Margaret; Abushakra, Susan; Lewcock, Joseph; Farese, Robert; Kenet, Robert O; Laferla, Frank; Perrin, Steve; Whitaker, Steve; Honig, Lawrence; Mesulam, Marsel M; Boeve, Brad; Grossman, Murray; Miller, Bruce L; Cummings, Jeffrey L



Frontotemporal degeneration, the next therapeutic frontier: molecules and animal models for frontotemporal degeneration drug development.  


Frontotemporal degeneration (FTD) is a common cause of dementia for which there are currently no approved therapies. Over the past decade, there has been an explosion of knowledge about the biology and clinical features of FTD that has identified a number of promising therapeutic targets as well as animal models in which to develop drugs. The close association of some forms of FTD with neuropathological accumulation of tau protein or increased neuroinflammation due to progranulin protein deficiency suggests that a drug's success in treating FTD may predict efficacy in more common diseases such as Alzheimer's disease. A variety of regulatory incentives, clinical features of FTD such as rapid disease progression, and relatively pure molecular pathology suggest that there are advantages to developing drugs for FTD as compared with other more common neurodegenerative diseases such as Alzheimer's disease. In March 2011, the Frontotemporal Degeneration Treatment Study Group sponsored a conference entitled "FTD, the Next Therapeutic Frontier," which focused on preclinical aspects of FTD drug development. The goal of the meeting was to promote collaborations between academic researchers and biotechnology and pharmaceutical researchers to accelerate the development of new treatments for FTD. Here we report the key findings from the conference, including the rationale for FTD drug development; epidemiological, genetic, and neuropathological features of FTD; FTD animal models and how best to use them; and examples of successful drug development collaborations in other neurodegenerative diseases. PMID:23043900

Boxer, Adam L; Gold, Michael; Huey, Edward; Gao, Fen-Biao; Burton, Edward A; Chow, Tiffany; Kao, Aimee; Leavitt, Blair R; Lamb, Bruce; Grether, Megan; Knopman, David; Cairns, Nigel J; Mackenzie, Ian R; Mitic, Laura; Roberson, Erik D; Van Kammen, Daniel; Cantillon, Marc; Zahs, Kathleen; Salloway, Stephen; Morris, John; Tong, Gary; Feldman, Howard; Fillit, Howard; Dickinson, Susan; Khachaturian, Zaven; Sutherland, Margaret; Farese, Robert; Miller, Bruce L; Cummings, Jeffrey



A novel retinal degeneration locus identified by linkage and comparative mapping of canine early retinal degeneration.  


Early retinal degeneration (erd) is an early onset progressive retinal atrophy, a hereditary canine retinal disease phenotypically similar to human retinitis pigmentosa (RP). In previous efforts to identify the erd locus, canine homologs of genes causally associated with RP in humans, such as opsin (RHO), the beta-subunit gene for cyclic GMP phosphodiesterase (PDE6B), and RDS/peripherin, were excluded. A genome-wide screen was undertaken on canine families segregating the erd disease. Analysis of over 150 canine-specific markers has localized erd to a single linkage group comprising two previously identified canine linkage groups, 20 and 26, corresponding to canine radiation hybrid groups RH.34-a and RH.40-a. Multipoint analysis places erd in the interval between marker FH2289 (distance 23.6 cM) and FH2407 (5.9 cM) with a lod score of 12.23. Although the erd linkage group has not been assigned to an identified canine chromosome, conserved synteny of this linkage group with human 12p13-q13 suggests several candidates for erd and identifies a novel retinal degeneration locus. The rapid progress now occurring in canine genetics will expedite identification of the genes and molecular mechanisms underlying the inherited traits and diseases that make the dog a unique asset for study of mammalian traits. PMID:10409424

Acland, G M; Ray, K; Mellersh, C S; Langston, A A; Rine, J; Ostrander, E A; Aguirre, G D



Are frontotemporal lobar degeneration, progressive supranuclear palsy and corticobasal degeneration distinct diseases?  


New findings relating to the clinical, genetic and molecular bases of neurodegenerative disorders have led to a shift away from traditional nomenclatures of clinical syndromes. Historically, frontotemporal lobar degeneration (FTLD), corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) were classified on the basis of distinct clinical and pathological features. In recent years, however, advances in molecular and genetic research have led clinicians to suggest that the similar etiologies of the three disorders warrant their amalgamation into a single disorder with three subtypes. In this Review, we consider the utility and validity of combining FTLD, CBD and PSP. The earliest reports of these disorders demonstrate their distinctiveness, whereas recent findings challenge traditional nomenclatures by showing etiological overlap. For example, tau inclusions have been confirmed in patients with CBD and those with PSP, and in some patients with FTLD, implying that all three disorders are 'tauopathies'. Furthermore, most patients with progressive nonfluent aphasia, a subtype of FTLD, show PSP or CBD post-mortem. Even tau-related cases of FTLD, CBD and PSP are distinguishable on the basis of other criteria, however, and many FTLD cases do not show tau pathology. We argue, therefore, that FTLD, CBD and PSP should be considered as pathologically similar but distinct syndromes. New research criteria for CBD and PSP should note that progressive nonfluent aphasia is often a precursor of these conditions. PMID:17117169

Sha, Sharon; Hou, Craig; Viskontas, Indre V; Miller, Bruce L



Gene expression profile analysis of human intervertebral disc degeneration  

PubMed Central

In this study, we used microarray analysis to investigate the biogenesis and progression of intervertebral disc degeneration. The gene expression profiles of 37 disc tissue samples obtained from patients with herniated discs and degenerative disc disease collected by the National Cancer Institute Cooperative Tissue Network were analyzed. Differentially expressed genes between more and less degenerated discs were identified by significant analysis of microarray. A total of 555 genes were significantly overexpressed in more degenerated discs with a false discovery rate of < 3%. Functional annotation showed that these genes were significantly associated with membrane-bound vesicles, calcium ion binding and extracellular matrix. Protein-protein interaction analysis showed that these genes, including previously reported genes such as fibronectin, COL2A1 and ?-catenin, may play key roles in disc degeneration. Unsupervised clustering indicated that the widely used morphology-based Thompson grading system was only marginally associated with the molecular classification of intervertebral disc degeneration. These findings indicate that detailed, systematic gene analysis may be a useful way of studying the biology of intervertebral disc degeneration.

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



Frontotemporal lobar degeneration with motor neuron disease-type inclusions predominates in 76 cases of frontotemporal degeneration  

Microsoft Academic Search

This report presents the largest series of consecutive, neuropathologically confirmed cases of frontotemporal degeneration (FTD). Prior studies have found dementia lacking distinctive histology (DLDH) to be the most common pathology underlying the clinical diagnosis of FTD. In this series of 76 cases, 29 (38%) were found to have frontotemporal lobar degeneration with motor neuron disease-type inclusions (FTLD-MND-type) or FTLD-MND (with

Anne M. Lipton; Charles L. White; Eileen H. Bigio



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


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



The birth rate of supernovae from double-degenerate and core-degenerate systems  

NASA Astrophysics Data System (ADS)

Context. Some recent observations of the delay-time distribution (DTD) of Type Ia supernovae (SNe Ia) seem to uphold the double-degenerate (DD) scenario as the progenitor model of SNe Ia, but the core-degenerate (CD) scenario remains a strong competitor to the DD one. Aims: We investigate the effects of metallicity and the different treatments of common envelope (CE) on the DTD of SNe Ia by considering the DD and CD scenarios, and check the suggestion that the total mass of DD system is the main dependent variable of Phillips relation. Methods: We perform a series of Monte Carlo simulations based on a rapid binary evolution code and consider two treatments of CE evolution, i.e. ?-formalism and ?-algorithm. Results: We find that only when the ?-formalism is considered with a high CE ejection efficiency, may the shape of the DTD for DD systems be consistent with that derived observationally, i.e. a power law of ~t-1, while the value of the birth rate of SNe Ia marginally matches observations. For the ?-formalism with a low CE ejection efficiency and the ?-algorithm, neither the shape of the DTD nor the value of the birth rate can be compared with those of the observations. Metallicity may not have a significant influence on the shape of DTD, but a lower metallicity may lead to a slightly higher birth rate of SNe Ia by a factor of 2, especially for SNe Ia with long delay times. If the results for the single-degenerate (SD) channel are incorporated into those for the DTD, both the shape of DTD and its value may be closely consistent with observations for SNe Ia younger than 2.5 Gyr, and SD and DD channels provide comparable contributions to the total SNe Ia, while for SNe Ia with delay times longer than 2.5 Gyr, DD is the dominant channel and the birth rate is lower than that derived from observations by a factor up to about four. In addition, we calculate the evolutions of various integral parameters of DD systems, and do not find any one suitable to explain the correlation between the brightness of SNe Ia and its delay time. Moreover, there are three channels producing CD systems that may contribute a few SNe Ia, but the contribution of CD systems to the total SNe Ia is no more than 1%. Conclusions: There may be other channels or mechanisms contributing to SNe Ia with long delay times.

Meng, X.; Yang, W.



Genetic Association Studies in Lumbar Disc Degeneration: A Systematic Review  

PubMed Central

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

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



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.



Resveratrol abolishes resistance to axonal degeneration in slow Wallerian degeneration ( Wld S ) mice: Activation of SIRT2, an NAD-dependent tubulin deacetylase  

Microsoft Academic Search

Resveratrol is a natural polyphenol having a wide range of biological and pharmacological activities. Here we have investigated the effect of resveratrol on neurodegeneration in cultured cerebellar granule cells from slow Wallerian degeneration (WldS) mice, characteristic of substantial delay of degeneration in the distal stump of transected axons. Resveratrol diminished resistance of WldS neurons to axonal degeneration induced by colchicine,

Kazuhiko Suzuki; Tatsuro Koike



Review: retinal degeneration: focus on the unfolded protein response.  


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, Marina; Gorbatyuk, Oleg



Radiologic Evaluation of Degeneration in Isthmic and Degenerative Spondylolisthesis  

PubMed Central

Study Design A cross-sectional imaging study. Purpose The objective was to assess the degree of degeneration and the associated factors through imaging studies of the lesion segment and the adjacent superior and inferior segments of isthmic and degenerative spondylolisthesis. Overview of Literature Few articles existed for degeneration and related factors in isthmic and degenerative spondylolisthesis. Methods The subjects were 95 patients diagnosed with spondylolisthesis. Simple plain radiographs including flexion and extension and magnetic resonance imaging were used to investigate the degree of translation, disc degeneration, high intensity zone (HIZ) lesion, Schmorl's node (SN) and Modic changes. Results Advanced disc degeneration, grade 5, was shown to be significant in the index segment of the isthmic type (p=0.034). Overall, type 2 Modic change was most common in both groups and also, it was observed more in the isthmus group, specifically, the index segment compared to the degenerative group (p=0.03). For the SN, compared to the degenerative type, the isthmus type had a significantly high occurrence in the index segment (p=0.04). For the HIZ lesions, the isthmus type had a higher occurrence than the degenerative type, especially in the upper segment (p=0.03). Conclusions Most advanced disc degeneration, fifth degree, SN and Modic change occurred more frequently in the lesions of the isthmus type. HIZ lesions were observed more in the isthmus type, especially in the segment superior to the lesion.

Jeong, Hyun-Yoon; Sohn, Hong-Moon; Park, Sang-Ha



Sequential Involvement of the Nervous System in Subacute Combined Degeneration  

PubMed Central

Purpose Subacute combined degeneration (SCD) involves progressive degeneration of the spinal cord, optic nerve, and peripheral nerves. Vitamin B12 (VB12) is a co-factor in myelin synthesis. Because each cell that constitutes the myelin component in the central nervous system and peripheral nervous system is different, it is improbable that these cells undergo simultaneous degeneration. However, the sequence of degeneration in SCD has not been established. Materials and Methods In this study, we analysed medical records and electrophysiological data of patients who showed neurological symptoms and whose serum VB12 levels were lower than 200 pg/mL. Results We enrolled 49 patients in this study. Their mean VB12 level was 68.3 pg/mL. Somatosensory evoked potential (SEP) study showed abnormal findings in 38 patients. Of the 40 patients who underwent visual evoked potential (VEP) study, 14 showed abnormal responses. Eighteen patients showed abnormal findings on a nerve conduction study (NCS). In this study, abnormal posterior tibial nerve SEPs only were seen in 16 patients, median nerve SEPs only were seen in 3 patients, abnormal VEPs only in two, and abnormal NCS responses in one patient. No patient complained of cognitive symptoms. Conclusion In SCD, degeneration appears to progress in the following order: lower spinal cord, cervical spinal cord, peripheral nerve/optic nerve, and finally, the brain.

Minn, Yang-Ki; Kim, Seung-Min; Kim, Se-Hoon; Kwon, Ki-Han



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.

Gorbatyuk, Oleg



Construction of "small-intelligent" focused mutagenesis libraries using well-designed combinatorial degenerate primers.  


Site-saturation mutagenesis is a powerful tool for protein optimization due to its efficiency and simplicity. A degenerate codon NNN or NNS (K) is often used to encode the 20 standard amino acids, but this will produce redundant codons and cause uneven distribution of amino acids in the constructed library. Here we present a novel "small-intelligent" strategy to construct mutagenesis libraries that have a minimal gene library size without inherent amino acid biases, stop codons, or rare codons of Escherichia coli by coupling well-designed combinatorial degenerate primers with suitable PCR-based mutagenesis methods. The designed primer mixture contains exactly one codon per amino acid and thus allows the construction of small-intelligent mutagenesis libraries with one gene per protein. In addition, the software tool DC-Analyzer was developed to assist in primer design according to the user-defined randomization scheme for library construction. This small-intelligent strategy was successfully applied to the randomization of halohydrin dehalogenases with one or two randomized sites. With the help of DC-Analyzer, the strategy was proven to be as simple as NNS randomization and could serve as a general tool to efficiently randomize target genes at positions of interest. PMID:22401547

Tang, Lixia; Gao, Hui; Zhu, Xuechen; Wang, Xiong; Zhou, Ming; Jiang, Rongxiang



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.

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.



An organotypic culture model to study nigro-striatal degeneration.  


Functional and reliable in vitro models of Parkinson's disease (PD) are valuable for studying mechanisms of dopaminergic degeneration before proceeding to animal testing. At present, all in vitro models involve substitute cell types and thus their direct relevance to PD is questionable. Here, we describe an organotypic culture model which conserves the 3D architecture of the nigro-striatal pathway, together with the subventricular zone and cerebral cortex, and recapitulates a specific pattern of dopaminergic degeneration which is the principal hallmark of PD. The organotypic culture is kept in vitro for up to 12 days and dopaminergic degeneration is induced by the simple cutting of dopaminergic fibers. This organotypic model represents a rapid and useful method (30 min/pup for preparation and up to 12 days of cultivation) to investigate in vitro the mechanisms underlying neuronal death and protection, as well as neurogenesis and repair after nigro-striatal neurodegeneration. PMID:20153372

Cavaliere, Fabio; Vicente, Edurne San; Matute, Carlos



Degenerate tetraploidy was established before bdelloid rotifer families diverged.  


Rotifers of Class Bdelloidea are abundant freshwater invertebrates known for their remarkable ability to survive desiccation and their lack of males and meiosis. Sequencing and annotation of approximately 50-kb regions containing the four hsp82 heat shock genes of the bdelloid Philodina roseola, each located on a separate chromosome, have suggested that its genome is that of a degenerate tetraploid. In order to determine whether a similar structure exists in a bdelloid distantly related to P. roseola and if degenerate tetraploidy was established before the two species separated, we sequenced regions containing the hsp82 genes of a bdelloid belonging to a different family, Adineta vaga, and the histone gene clusters of P. roseola and A. vaga. Our findings are entirely consistent with degenerate tetraploidy and show that it was established before the two bdelloid families diverged and therefore probably before the bdelloid radiation. PMID:18996928

Hur, Jae H; Van Doninck, Karine; Mandigo, Morgan L; Meselson, Matthew



Proteoglycan-mediated axon degeneration corrects pretarget topographic sorting errors.  


Proper arrangement of axonal projections into topographic maps is crucial for brain function, especially in sensory systems. An important mechanism for map formation is pretarget axon sorting, in which topographic ordering of axons appears in tracts before axons reach their target, but this process remains poorly understood. Here, we show that selective axon degeneration is used as a correction mechanism to eliminate missorted axons in the optic tract during retinotectal development in zebrafish. Retinal axons are not precisely ordered during initial pathfinding but become corrected later, with missorted axons selectively fragmenting and degenerating. We further show that heparan sulfate is required non-cell-autonomously to correct missorted axons and that restoring its synthesis at late stages in a deficient mutant is sufficient to restore topographic sorting. These findings uncover a function for developmental axon degeneration in ordering axonal projections and identify heparan sulfate as a key regulator of that process. PMID:23583107

Poulain, Fabienne E; Chien, Chi-Bin



The Case for a Neutrino-Degenerate Universe  

NASA Astrophysics Data System (ADS)

We reanalyze the cosmological constraints on the existence of a net universal lepton asymmetry and neutrino degeneracy based upon the latest high resolution CMB sky maps from BOOMERANG, DASI, and MAXIMA-1. We compute likelihood functions for flat cosmological models with and without degenerate neutrinos. We adopt priors on the degeneracy parameters and baryon content based upon light-element constraints on primordial nucleosynthesis. We also adopt the prior of h = 0.72 +/- 0.08 from the Hubble Key Project results. Our neutrino-degenerate CMB models include a correction for that change in neutrino decoupling temperature with degeneracy. The marginalized likelihood functions show a slight preference for a neutrino-degenerate universe.

Mathews, G. J.; Orito, M.; Kajino, T.; Wang, Y.



Stem cell regeneration of degenerated intervertebral discs: current status.  


Low back pain (LBP) is one of the most common musculoskeletal conditions, and intervertebral disc (IVD) degeneration is associated with most cases. Although many treatment options are available, they focus on the removal of symptoms rather than repair of the degenerate tissue. However, there is a growing interest in the potential of cell-based tissue engineering strategies for regeneration of the damaged IVD. To achieve this, investigators are now focusing on the use of mesenchymal stem cells (MSCs), which offer several advantages over more mature cell types. A number of problems must be overcome for MSC-based IVD regeneration to be successful, including determining a method for the differentiation of stem cells into nucleus pulposus-like cells. Although this is still a relatively new field, it offers huge potential for the clinical treatment of IVD degeneration and LBP in the future. PMID:18474185

Richardson, Stephen M; Hoyland, Judith A



Sagittal alignment as a risk factor for adjacent level degeneration: a case-control study.  


This study examined whether sagittal alignment, preexisting adjacent level degeneration, and smoking predispose patients to adjacent segment degeneration following lumbar fusion. Fifty-one patients with adjacent segment degeneration were identified and matched with control patients based on age, sex, level, and date of index surgery. Preexisting adjacent level degeneration and sagittal alignment through the fusion and from L1-S1 were determined before and after initial surgery. Patients with adjacent segment degeneration had significantly less lordosis through the fusion and lumbar spine following their initial surgery. There was no significant difference in the amount of preexisting adjacent level degeneration and smoking between the adjacent segment degeneration and control groups. Fusion of the lumbar spine in abnormal sagittal alignment, with loss of lumbar lordosis, predisposes patients to the development of adjacent segment degeneration. Adjacent segment degeneration does not appear to be just a progression of preexisting degenerative changes at the adjacent level. PMID:19292354

Djurasovic, Mladen O; Carreon, Leah Y; Glassman, Steven D; Dimar, John R; Puno, Rolando M; Johnson, John R



Rapid glutamate receptor 2 trafficking during retinal degeneration  

PubMed Central

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



Degenerate band edge resonances in coupled periodic silicon optical waveguides.  


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



Diagnostic tools and imaging methods in intervertebral disk degeneration.  


Low back pain has a negative impact on the economy and society. Intervertebral disk degeneration is linked to the occurrence of low back pain. MRI provides three-dimensional morphologic and biochemical information regarding the status of the disk. This article reviews new and evolving MRI disk-imaging techniques, including grading, relaxation-time measurements, diffusion, and contrast perfusion. In addition, high-resolution magic-angle spinning methods to correlate in vitro disk degeneration (with pain, etc) and in vivo spectroscopic results are discussed. With the potential for morphologic and biochemical characterization of the intervertebral disk, MRI shows promise as a tool to quantitatively assess disk health. PMID:21944587

Majumdar, Sharmila; Link, Thomas M; Steinbach, Lynne S; Hu, Serena; Kurhanewicz, John



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)



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.



Axonal degeneration within the tympanal nerve of Schistocerca gregaria  

Microsoft Academic Search

This study describes time course and ultrastructural changes during axonal degeneration of different neurones within the tympanal nerve of the locust Schistocerca gregaria. The tympanal nerve innervates the tergit and pleurit of the first abdominal segment and contains the axons of both sensory and motor neurones. The majority of axons (approx. 97%) belong to several types of sensory neurones: mechano-

Kirsten Jacobs; Reinhard Lakes-Harlan



On a Degenerate Heat Equation with a Singular Potential  

Microsoft Academic Search

Using a new method, we generalize the blow up and existence result from P. Baras and J. A. Goldstein (1984, Trans. Amer. Math. Soc.284, 121–139) to heat equations on the Heisenberg group. In doing so we need to overcome the difficulty that the equation in this case is both degenerate and of variable coefficients. Comparing with the Euclidean case, an

Jerome A. Goldstein; Qi S. Zhang



An organotypic culture model to study nigro-striatal degeneration  

Microsoft Academic Search

Functional and reliable in vitro models of Parkinson's disease (PD) are valuable for studying mechanisms of dopaminergic degeneration before proceeding to animal testing. At present, all in vitro models involve substitute cell types and thus their direct relevance to PD is questionable. Here, we describe an organotypic culture model which conserves the 3D architecture of the nigro-striatal pathway, together with

Fabio Cavaliere; Edurne San Vicente; Carlos Matute



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



Emerging Pharmacologic Therapies for Wet Age-Related Macular Degeneration  

Microsoft Academic Search

As researchers and clinicians are beginning to understand that wet age-related macular degeneration (AMD) is more than simply a vascular disease that includes angiogenic, vascular and inflammatory components, they are exploring new agents with different mechanisms of action addressing multiple targets in this complex pathophysiology. Some of them are already available in human trials or even approved vascular epithelial growth

Zhang Ni; Peng Hui



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



Quantitative multiplex degenerate PCR for human endogenous retrovirus expression profiling  

Microsoft Academic Search

Expression of human endogenous retroviruses (HERV) has been recurrently observed during cellular differentiation or transformation processes in both cell culture and in vivo. Quantitative approaches that analyze variations in HERV transcription could therefore be valuable for cancer diagnosis. We have developed a quantitative assay combining multiplex degenerate PCR (MD-PCR) and a colorimetric Oligo Sorbent Array (OLISA). Quantification of the expression

Jean-Philippe Pichon; Bertrand Bonnaud; François Mallet



Lithium niobate laser with frequency-degenerate pumping  

SciTech Connect

For the first time, lasing has been achieved in a frequency-degenerate four-wave interaction of beams from a helium-cadmium laser in lithium niobate crystals with nonlocal nonlinearities. The nonlinearities result from a redistribution of space charge during diffusion of the photoexcited carriers or from photovoltaic currents that oscillate over space.

Odulov, S.G.; Soskin, M.S.



Retinal Remodeling: Circuitry Revisions Triggered by Photoreceptor Degeneration  

Microsoft Academic Search

Structural, molecular and physiological responses of the neural retina to ablation of the sensory retina triggered by inherited or induced photoreceptor degeneration reveal a surprising degree of dynamic capacity in mature neurons. All classes of mature retinal neurons (bipolar, horizontal, amacrine and ganglion cells) show the capacity for five dynamic processes characteristic of developing neurons and stressed neurons displaying negative

Robert E. Marc; Bryan W. Jones; Carl B. Watt


Early bioprosthetic mitral valve degeneration due to subchordal apparatus impingement.  


We present a case of early degeneration of a bioprosthesis in the mitral position three years after implantation. Valve explantation revealed complete neo-intima formation and complete fusion of one commissure due to papillary muscle and chordae tendineae embedding in the bioprosthetic leaflets. PMID:23311618

Bianchi, Giacomo; Solinas, Marco; Gilmanov, Daniyar; Glauber, Mattia



Light exotic particle flux from degenerate strange quark matter  

SciTech Connect

We calculate the axion and photino energy flux from relativistic degenerate strange quark matter which is predicted to exist in the core of some dense neutron and collapsed stars. The energy flux is compared to the corresponding flux from nucleon matter.

Anand, J.D.; Goyal, A.; Jha, R.N. (Department of Physics and Astrophysics, University of Delhi, Delhi (India))



Photoreceptor Loss in Age-Related Macular Degeneration  

Microsoft Academic Search

Purpose. The authors showed previously that parafoveal rods, but not cones, decrease during the course of adulthood in donor eyes that were screened to exclude the grossly visible macular drusen and pigmentary disturbances typical of age-related macular degeneration (AMD). Because AMD begins in the parafovea, this selective loss of rods actually may be subclinical AMD not yet visible in the

Christine A. Curcio; Nancy E. Medeiros; C. Leigh Millican



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



Mitochondrial degeneration after organic phosphate poisoning in prosimian primates  

Microsoft Academic Search

The degenerative reaction of mitochondria to tricresylphosphate (TCP) poisoning in spinal ganglion cells of Slow Loris (Nycticebus coucang coucang) were studied with the electron microscope. In neurones of animals treated with TCP, mitochondria display various stages of alterations which confirm mitochondrial involvement in TCP poisoning. The role of degenerated mitochondria in the formation of neuronal lipofuscin is discussed. It is

M. Mumtazuddin Ahmed; Paul Glees



Rhein: A potential biological therapeutic drug for intervertebral disc degeneration  

Microsoft Academic Search

Intervertebral disc degeneration (IDD) is regarded as an important cause of low back pain, which continues to be a common disability. IDD is thought to involve sequential changes of intervertebral disc that lead to the reduction of disc cells and the extracellular matrix. In addition, inflammation is crucially involved in IDD. Currently, there is urgent need to develop biological therapies

Hao Li; Chengzhen Liang; Qixin Chen; Zhengming Yang



Degeneration of myelinated sympathetic nerve fibres following treatment with guanethidine  

Microsoft Academic Search

Summary The specificity and characteristics of the degeneration of myelinated axons after chronic guanethidine treatment have been investigated in sympathetic and non-sympathetic nerves. Adult male Sprague-Dawley rats aged approximately 43 weeks were treated with guanethidine sulphate (50 mg per kg body weight per day) for between ten days and six weeks. Tissues were examined by qualitative and quantitative light and

G. J. Kidd; J. W. Heath; P. R. Dunkley



Hereditary ectodermal dysplasia, olivopontocerebellar degeneration, short stature, and hypogonadism  

Microsoft Academic Search

Two teenaged children born of normal parents in a consanguineous family had evidence of abnormal neurological, endocrine, and ectodermal development. They had mental retardation, hearing loss, ocular dysmetria, hyperreflexia, and ataxia consistent with olivopontocerebellar degeneration. They had hypogonadotrophic hypogonadism and extremely short stature despite normal serum growth hormone and somatomedin-C. There was also hypodontia with peg shaped teeth and mid-face

A R Rushton; M Genel



Striatonigral degeneration, olivopontocerebellar atrophy and „atypical” Pick disease  

Microsoft Academic Search

A 75-year-old woman with parkinsonism plus was found at autopsy to have striatonigral degeneration (SND), olivopontocerebellar atrophy (OPCA) and intracytoplasmic neuronal inclusions, mostly confined to the hippocampus and pontine nuclei. These inclusions were intensely argyrophilic, ubiquitinated and expressed variable immunoreactivity for neurofilament but not for tau-1 and Alz 50 proteins. Ultrastructurally, they were formed of skeins of intermediate filaments averaging

D. S. Horoupian; D. W. Dickson



Multiple system degeneration with glutamate dehydrogenase deficiency: pathology and biochemistry  

Microsoft Academic Search

The neuropathological findings in a patient with antemortem diagnosis of olivopontocerebellar atrophy (OPCA) and reduced leucocytic glutamate dehydrogenase (GDH) activity included cerebellar cortical degeneration, most marked in the superior vermis, mild atrophy of the pons and the inferior olivary nucleus, marked reduction of anterior horn cells at all levels and gliosis in both lateral columns. GDH activities and their thermolability

S Chokroverty; W Nicklas; D C Miller; J Goldberg; J Choe; C Banner; J Thomas; R Duvoisin



Biomarkers for Age-Related Macular Degeneration (AMD).  

National Technical Information Service (NTIS)

Provided are methods of using levels of markers of systemic inflammation, e.g., CRP, to predict a subject's risk of development or progression of Age-Related Macular Degeneration (AMD), and methods of treating, delaying or preventing the development or pr...

J. M. Seddon



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



Degenerate 1 GHz repetition rate femtosecond optical parametric oscillator.  


We report a degenerate femtosecond optical parametric oscillator (OPO) that is synchronously pumped by a mode-locked Ti:sapphire laser at 1 GHz repetition rate. The OPO produces an 85 nm (10 THz) wide frequency comb centered at 1.6 ?m. Stable long-term operation with >100 mW of average output power has been achieved. PMID:23114363

Vainio, Markku; Merimaa, Mikko; Halonen, Lauri; Vodopyanov, Konstantin



Wallerian Degeneration of Pyramidal Tract after Paramedian Pons Infarct  

Microsoft Academic Search

Background: The intention of this study was the prospective analysis of Wallerian degeneration of the pyramidal tract after paramedian pons infarction. Methods: Patients with paramedian pons infarct underwent MR imaging including diffusion tensor imaging at admission and got 1–3 MR scans up to 6 months of follow-up. Clinical scores and transcranial magnetic stimulation were acquired in the acute phase and

David Grä?el; Thomas M. Ringer; Clemens Fitzek; Sabine Fitzek; Matthias Kohl; Werner A. Kaiser; Otto W. Witte; Hubertus Axer



Progressive neuronal degeneration of childhood (Alpers syndrome) with hepatic cirrhosis  

Microsoft Academic Search

Four children, from two families, suffered from fatal degeneration of the cerebral grey matter. Their disease was characterised by intractable epilepsy, epilepsia partialis continua, progressive deterioration, and terminal hepatic dysfunction. EEG showed marked and distinctive slow wave abnormality, visual evoked responses were diminished, and cerebral atrophy was seen on CT scan. Pathological findings were of neuronal loss and hepatic cirrhosis.

D. C. Wilson; D. McGibben; E. M. Hicks; I. V. Allen



Progressive Right Frontotemporal Degeneration: Clinical, Neuropsychological and SPECT Characteristics  

Microsoft Academic Search

The behavioral, neuropsychological and single photon emission computerized tomography characteristics of 5 patients with progressive degeneration of the right hemisphere are described. In all, the brain regions with greatest involvement were right-frontal and temporal. Psychosis, compulsions and behavioral disinhibition were the dominant, and often first, symptoms. Affect was flattened and the patients seemed distant and remote. Neuropsychological testing did not

Bruce L. Miller; Linda Chang; Ismael Mena; Kyle Boone; Ira M. Lesser



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



Genetic Factors Associated with Age-Related Macular Degeneration  

Microsoft Academic Search

Age-related macular degeneration (AMD) is a complex, multifactorial disease associated with environmental and genetic factors. This review emphasizes the clinical impact of the major genetic factors mainly located in the complement factor H gene and on the 10q26 locus, and their current and future implications for the management of AMD.

Nicolas Leveziel; Julien Tilleul; Nathalie Puche; Jennyfer Zerbib; Franck Laloum; Giuseppe Querques; Eric H. Souied



Gonadal hormones affect neuronal vulnerability to excitotoxin-induced degeneration  

Microsoft Academic Search

The role of endogenous gonadal secretions in neuroprotection has been assessed in a model of hippocampal degeneration induced by the systemic administration of kainic acid to adult male and female rats. A low dose of kainic acid (7 mg\\/Kg b.w.) induced a significant loss of hilar dentate neurons in castrated males and did not affect hilar neurons in intact males.

Iñigo Azcoitia; Carmen Fernandez-Galaz; Amanda Sierra; Luis M. Garcia-Segura



T1? MRI Quantification of Arthroscopically-Confirmed Cartilage Degeneration  

PubMed Central

9 asymptomatic subjects and 6 patients underwent T1? MRI to determine whether Outerbridge grade 1 or 2 cartilage degeneration observed during arthroscopy could be detected noninvasively. MRI was performed 2–3 months post-arthroscopy using sagittal T1-weighted and axial and coronal T1? MRI from which spatial T1? relaxation maps were calculated from segmented T1-weighted images. Median T1? relaxation times of patients with arthroscopically documented cartilage degeneration and asymptomatic subjects were significantly different (p < 0.001) and median T1? exceeded asymptomatic articular cartilage median T1? by 2.5 to 9.2 ms. In 8 observations of mild cartilage degeneration at arthroscopy (Outerbridge grades 1 and 2), mean compartment T1? was elevated in 5, but in all observations, large foci of increased T1? were observed. It was determined that T1? could detect some, but not all, Outerbridge grade 1 and 2 cartilage degeneration but that a larger patient population is needed to determine the sensitivity to these changes.

Witschey, Walter RT; Borthakur, Arijitt; Fenty, Matt; Kneeland, J Bruce; Lonner, Jess H; McArdle, Erin L.; Sochor, Matt; Reddy, Ravinder



Cerebellar degeneration in the Niemann-Pick type C mouse  

Microsoft Academic Search

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

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



Diffuse thalamic degeneration in fatal familial insomnia. A morphometric study  

Microsoft Academic Search

A morphometric investigation disclosed most thalamic nuclei severely degenerated in two patients with fatal familial insomnia. Associative and motor nuclei lost 90% neurons, and limbic–paralimbic, intralaminar and reticular nuclei lost 60%. These findings point to the disorganization of most thalamic circuits as a condition necessary for the sleep–wake rhythm being affected.

Giorgio Macchi; Giacomina Rossi; Anna Laura Abbamondi; Giorgio Giaccone; Domenico Mancia; Fabrizio Tagliavini; Orso Bugiani



Submacular scar excision in age-related macular degeneration.  


Disciform scars secondary to age-related macular degeneration were surgically removed in three patients. Postoperative visual acuity improved minimally in one case and decreased in the other two cases. The results suggest further investigation is needed with possible modifications of our technique for future studies. PMID:1917314

Blinder, K J; Peyman, G A; Paris, C L; Gremillion, C M



Genetic Background Predicts Poor Prognosis in Frontotemporal Lobar Degeneration  

Microsoft Academic Search

Background: Ruling out predictors of survival in frontotemporal lobar degeneration (FTLD) is a clinical challenge for defining disease outcomes and monitoring therapeutic interventions. Little is known about determinants of survival in FTLD. Objective: The aim of the present study was to identify whether genetic determinants are key, not only as risk factors but as predictors of survival in FTLD. Methods:

B. Borroni; M. Grassi; S. Archetti; A. Papetti; R. Del Bo; C. Bonvicini; G. P. Comi; M. Gennarelli; G. Bellelli; M. Di Luca; A. Padovani



Unraveling A Complex Genetic Disease: Age-related Macular Degeneration  

Microsoft Academic Search

In most of the Western world, age-related macular degeneration (AMD) remains the largest single cause of severe visual impairment, and its prevalence continues to increase. It is considered to be a complex disease, in which multiple genes and environment play a role in pathogenesis. Several environmental insults are implicated with smoking, serum cholesterol, hypertension, sunlight exposure, and many other factors

Matt Chamberlain; Paul Baird; Mohamed Dirani; Robyn Guymer



Progressive language disorder associated with frontal lobe degeneration  

Microsoft Academic Search

We report a patient KC who presented with a profound disorder of propositional language in association with progressive frontal lobe degeneration. The salient clinical feature was her marked difficulty in responding to open-ended questions, contrasting with the relative preservation of performance on more closed, structured language tasks. Experimental investigations of her language skills revealed significant temporal organizational difficulties. She could

Julie S. Snowden; Helen L. Griffiths; David Neary



The Cerebellum and Language: Evidence from Patients with Cerebellar Degeneration  

ERIC Educational Resources Information Center

Clinical and imaging studies suggest that the cerebellum is involved in language tasks, but the extent to which slowed language production in cerebellar patients contributes to their poor performance on these tasks is not clear. We explored this relationship in 18 patients with cerebellar degeneration and 16 healthy controls who completed measures…

Stoodley, Catherine J.; Schmahmann, Jeremy D.



A method for detecting degenerate structures in planetary gear trains  

Microsoft Academic Search

A method for detecting degenerate structures in planetary gear trains (PGTs) is presented. In the context of the graph representation of the kinematic structure of PGTs, the method uses the concept of fundamental circuits and their grouping to generate the detection algorithm. The main advantage is the reduction in the required combinatorial analysis relative to other methods. A computer implementation

D. R. Salgado; J. M. Del Castillo



VBM signatures of abnormal eating behaviours in frontotemporal lobar degeneration  

Microsoft Academic Search

The brain bases of specific human behaviours in health and disease are not well established. In this voxel-based morphometric (VBM) study we demonstrate neuroanatomical signatures of different abnormalities of eating behaviour (pathological sweet tooth and increased food consumption, or hyperphagia) in individuals with frontotemporal lobar degeneration (FTLD). Sixteen male patients with FTLD were assessed using the Manchester and Oxford Universities

Jennifer L. Whitwell; Elizabeth L. Sampson; Clement T. Loy; Jane E. Warren; Martin N. Rossor; Nick C. Fox; Jason D. Warren



Anatomic correlates of stereotypies in frontotemporal lobar degeneration  

Microsoft Academic Search

Stereotypies are common in frontotemporal lobar degeneration (FTLD) however the anatomical correlates of stereotypies are unknown. We therefore set out to compare patterns of grey matter volume loss in FTLD subjects with and without stereotypies. Subjects with a diagnosis of FTLD that met international consensus criteria were prospectively recruited and separated into those with and without stereotypies. MRI and cognitive

Keith A. Josephs; Jennifer L. Whitwell; Clifford R. Jack



Morphometric analyses of the visual pathways in macular degeneration.  


INTRODUCTION: Macular degeneration (MD) causes central visual field loss. When field defects occur in both eyes and overlap, parts of the visual pathways are no longer stimulated. Previous reports have shown that this affects the grey matter of the primary visual cortex, but possible effects on the preceding visual pathway structures have not been fully established. METHODS: In this multicentre study, we used high-resolution anatomical magnetic resonance imaging and voxel-based morphometry to investigate the visual pathway structures up to the primary visual cortex of patients with age-related macular degeneration (AMD) and juvenile macular degeneration (JMD). RESULTS: Compared to age-matched healthy controls, in patients with JMD we found volumetric reductions in the optic nerves, the chiasm, the lateral geniculate bodies, the optic radiations and the visual cortex. In patients with AMD we found volumetric reductions in the lateral geniculate bodies, the optic radiations and the visual cortex. An unexpected finding was that AMD, but not JMD, was associated with a reduction in frontal white matter volume. CONCLUSION: MD is associated with degeneration of structures along the visual pathways. A reduction in frontal white matter volume only present in the AMD patients may constitute a neural correlate of previously reported association between AMD and mild cognitive impairment. PMID:23453791

Hernowo, Aditya T; Prins, Doety; Baseler, Heidi A; Plank, Tina; Gouws, Andre D; Hooymans, Johanna M M; Morland, Antony B; Greenlee, Mark W; Cornelissen, Frans W



Correlation of Slipped Capital Femoral Epiphysis With Disk Degeneration.  


SUMMARY OF BACKGROUND DATA:: Spinal osteoarthritis is greater in patients with known hip pathology secondary to alterations in spinopelvic geometry. To our knowledge, no study has investigated the long-term impact of slipped capital femoral epiphysis (SCFE) on the spine. OBJECTIVE:: To evaluate the relationship between SCFE and the presence of degenerative disk disease and facet arthrosis. STUDY DESIGN:: An anatomic study of disk degeneration in cadaveric lumbar spines with SCFE. METHODS:: An observational study was performed on 25 cadaveric specimens with SCFE and 647 controls that were identified out of 3100 total cadaveric specimens in an osteological collection. The specimens were evaluated for disk degeneration and facet arthrosis at L1/2 to L5/S1 using the classification of Eubanks and colleagues. Linear regression analyses were then used to determine the relationship between SCFE and lumbar disk and facet degeneration at each level, correcting for confounding factors such as age, sex, and race. RESULTS:: Linear regression demonstrated a significant association (P<0.01) that was found between SCFE and degenerative disk disease at all levels from L1/2 to L5/S1. In addition, a significant association (P<0.01) was found between SCFE and facet arthrosis at all levels from L1/2 to L5/S1. CONCLUSIONS:: The findings of this study show a relationship between SCFE and lumbar disk degeneration and facet arthrosis. This relationship may prove useful in predicting the course of spinal osteoarthritis in patients with SCFE. PMID:22362110

Toy, Jason O; Gordon, Zachary L; Eubanks, Jason D; Cooperman, Daniel R; Ahn, Nicholas U




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...


Inflammation in Dry Age-Related Macular Degeneration  

Microsoft Academic Search

Purpose: To summarize the current information regarding the role of immune and inflammatory response in the pathogenesis of dry age-related macular degeneration (ARMD). Methods: A Pubmed search was conducted of the period January 1999 to 2005. Relevant information in the literature on the role of inflammation in early dry ARMD was reviewed. Results: Some important evidence for inflammation in early

Eduardo B. Rodrigues



Diffusion Tensor MR Study of Optic Nerve Degeneration in Glaucoma  

Microsoft Academic Search

Axonal degeneration has been known to occur in the optic nerve (ON) of rat glaucoma model. Recently, quantitative diffusion tensor imaging (DTI) has been developed to investigate various white matter diseases in vivo. In this study, longitudinal DTI was thus employed to study such animal model in the present study. The results showed that radial diffusivity (lambdaperp) and fractional anisotropy

Edward S. Hui; Qing-ling Fu; Kwok-fai So; Ed X. Wu



Realization and research of optically-trapped quantum degenerate gases  

NASA Astrophysics Data System (ADS)

With experimental realization of atomic Bose Einstein condensation (BEC) and rapid development of laser cooling and trapping techniques, all optical routes to quantum degenerate gases and related experimental studies have generated considerable interests and activities in the field of atomic, molecular and optical physics. Here, we discuss special features of two kinds of far-off-resonance optical dipole traps (FORT) and present a review of recent experimental realization and research of optically-trapped quantum degenerate gases. Topics covered include optical confinement and manipulation of atomic BECs, Feshbach resonance and photoassociation methods, all-optical realization of atomic BEC and atom laser, all-optical generation of ultracold molecules, and fermionization of Bose atomic gases. This review also includes all optical or hybrid optical magnetic preparation of quantum degenerate Fermi gases and molecular BECs, realization of condensations of fermionic atom pairs, and studies of BEC BCS (Bardeen Cooper Schrieffev) crossovers. Finally, applications of all-optical quantum degenerate gases and future prospects are briefly discussed.

Yin, Jianping



Quantum Degenerate Exciton-Polaritons in Thermal Equilibrium  

NASA Astrophysics Data System (ADS)

We study the momentum distribution and relaxation dynamics of semiconductor microcavity polaritons by angle-resolved and time-resolved spectroscopy. Above a critical pump level, the thermalization time of polaritons at positive detunings becomes shorter than their lifetime, and the polaritons form a quantum degenerate Bose-Einstein distribution in thermal equilibrium with the lattice.

Deng, Hui; Press, David; Götzinger, Stephan; Solomon, Glenn S.; Hey, Rudolf; Ploog, Klaus H.; Yamamoto, Yoshihisa



Quantum degenerate exciton-polaritons in thermal equilibrium.  


We study the momentum distribution and relaxation dynamics of semiconductor microcavity polaritons by angle-resolved and time-resolved spectroscopy. Above a critical pump level, the thermalization time of polaritons at positive detunings becomes shorter than their lifetime, and the polaritons form a quantum degenerate Bose-Einstein distribution in thermal equilibrium with the lattice. PMID:17155273

Deng, Hui; Press, David; Götzinger, Stephan; Solomon, Glenn S; Hey, Rudolf; Ploog, Klaus H; Yamamoto, Yoshihisa



Near infrared light reduces oxidative stress and preserves function in CNS tissue vulnerable to secondary degeneration following partial transection of the optic nerve.  


Traumatic injury to the central nervous system (CNS) is accompanied by the spreading damage of secondary degeneration, resulting in further loss of neurons and function. Partial transection of the optic nerve (ON) has been used as a model of secondary degeneration, in which axons of retinal ganglion cells in the ventral ON are spared from initial dorsal injury, but are vulnerable to secondary degeneration. We have recently demonstrated that early after partial ON injury, oxidative stress spreads through the ventral ON vulnerable to secondary degeneration via astrocytes, and persists in the nerve in aggregates of cellular debris. In this study, we show that diffuse transcranial irradiation of the injury site with far red to near infrared (NIR) light (WARP 10 LED array, center wavelength 670?nm, irradiance 252?W/m(-2), 30?min exposure), as opposed to perception of light at this wavelength, reduced oxidative stress in areas of the ON vulnerable to secondary degeneration following partial injury. The WARP 10 NIR light treatment also prevented increases in NG-2-immunopositive oligodendrocyte precursor cells (OPCs) that occurred in ventral ON as a result of partial ON transection. Importantly, normal visual function was restored by NIR light treatment with the WARP 10 LED array, as assessed using optokinetic nystagmus and the Y-maze pattern discrimination task. To our knowledge, this is the first demonstration that 670-nm NIR light can reduce oxidative stress and improve function in the CNS following traumatic injury in vivo. PMID:20822460

Fitzgerald, Melinda; Bartlett, Carole A; Payne, Sophie C; Hart, Nathan S; Rodger, Jenny; Harvey, Alan R; Dunlop, Sarah A



Features of intervertebral disc degeneration in rat's aging process*  

PubMed Central

Objective: The age-related change is important part of degenerative disc disease. However, no appropriate animal model or objective evaluation index is available. This study aimed to investigate the features of intervertebral disc degeneration in aging process of rats. Methods: 22-month-old Sprague-Dawley (SD) rats were used as spontaneously occurring intervertebral disc degeneration models and 6-month-old rats as young controls. Expression of collagen types II and X was measured by immunohistochemistry. Degenerations of intervertebral discs were scored according to Miyamoto’s method. Numbers and areas of afferent vascular buds were measured. The thicknesses of non-calcified and calcified layers were measured and statistically analyzed. Results: There were less collagen type II expression and more collagen type X expression in the calcified layer of the cartilage endplates and nucleus pulposus in the rats of the aged group than in the young control. There were fewer and smaller afferent vascular buds in the rats of the aged group than in the young control group. The ratio of the non-calcified to the calcified layers in the rats of the aged group significantly decreased, compared with that of the young control group (P<0.01). Conclusion: Rats can spontaneously establish intervertebral disc age-related degeneration. The expression of collagen types II and X, numbers and areas of afferent vascular buds, the ratio of the non-calcified to the calcified layers, and water and glycosaminoglycan contents in the nucleus pulposus are sensitive indexes of intervertebral disc degeneration.

Zhang, Yin-gang; Sun, Zheng-ming; Liu, Jiang-tao; Wang, Shi-jie; Ren, Feng-ling; Guo, Xiong



Viruses Associated with Ovarian Degeneration in Apis mellifera L. Queens  

PubMed Central

Queen fecundity is a critical issue for the health of honeybee (Apis mellifera L.) colonies, as she is the only reproductive female in the colony and responsible for the constant renewal of the worker bee population. Any factor affecting the queen's fecundity will stagnate colony development, increasing its susceptibility to opportunistic pathogens. We discovered a pathology affecting the ovaries, characterized by a yellow discoloration concentrated in the apex of the ovaries resulting from degenerative lesions in the follicles. In extreme cases, marked by intense discoloration, the majority of the ovarioles were affected and these cases were universally associated with egg-laying deficiencies in the queens. Microscopic examination of the degenerated follicles showed extensive paracrystal lattices of 30 nm icosahedral viral particles. A cDNA library from degenerated ovaries contained a high frequency of deformed wing virus (DWV) and Varroa destructor virus 1 (VDV-1) sequences, two common and closely related honeybee Iflaviruses. These could also be identified by in situ hybridization in various parts of the ovary. A large-scale survey for 10 distinct honeybee viruses showed that DWV and VDV-1 were by far the most prevalent honeybee viruses in queen populations, with distinctly higher prevalence in mated queens (100% and 67%, respectively for DWV and VDV-1) than in virgin queens (37% and 0%, respectively). Since very high viral titres could be recorded in the ovaries and abdomens of both functional and deficient queens, no significant correlation could be made between viral titre and ovarian degeneration or egg-laying deficiency among the wider population of queens. Although our data suggest that DWV and VDV-1 have a role in extreme cases of ovarian degeneration, infection of the ovaries by these viruses does not necessarily result in ovarian degeneration, even at high titres, and additional factors are likely to be involved in this pathology.

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



Yeti--a degenerate gypsy-like LTR retrotransposon in the filamentous ascomycete Podospora anserina.  


In the filamentous ascomycete Podospora anserina a 6,935-bp retrotransposon, Yeti, has been identified and characterized. It is flanked by a 5-bp target site duplication and contains long terminal repeats (LTRs) 354 bp in length. The LTRs show a high degree of identity to the previously reported repetitive element repa, a sequence suggested to represent a solo-LTR element of an unknown transposon. In the investigated Podospora strains, the number of complete Yeti copies is significantly lower than the number of repa elements, with up to 25 copies. Yeti appears to be inactive: it is highly degenerate and no transcripts of the element have been detected even in Podospora cultures grown under elevated stress conditions. The amino acid sequences deduced from Yeti display significant homology, particularly in the reverse transcriptase region, to those of other fungal retrotransposons, indicating that it is a member of the gypsy family. As suggested by the unusual dinucleotide content, degeneration of Yeti appears to be the result of a molecular mechanism resembling repeat-induced point mutation in Neurospora crassa. PMID:11057446

Hamann, A; Feller, F; Osiewacz, H D



Structural mechanisms of the degenerate sequence recognition by Bse634I restriction endonuclease  

PubMed Central

Restriction endonuclease Bse634I recognizes and cleaves the degenerate DNA sequence 5?-R/CCGGY-3? (R stands for A or G; Y for T or C, ‘/’ indicates a cleavage position). Here, we report the crystal structures of the Bse634I R226A mutant complexed with cognate oligoduplexes containing ACCGGT and GCCGGC sites, respectively. In the crystal, all potential H-bond donor and acceptor atoms on the base edges of the conserved CCGG core are engaged in the interactions with Bse634I amino acid residues located on the ?6 helix. In contrast, direct contacts between the protein and outer base pairs are limited to van der Waals contact between the purine nucleobase and Pro203 residue in the major groove and a single H-bond between the O2 atom of the outer pyrimidine and the side chain of the Asn73 residue in the minor groove. Structural data coupled with biochemical experiments suggest that both van der Waals interactions and indirect readout contribute to the discrimination of the degenerate base pair by Bse634I. Structure comparison between related enzymes Bse634I (R/CCGGY), NgoMIV (G/CCGGC) and SgrAI (CR/CCGGYG) reveals how different specificities are achieved within a conserved structural core.

Manakova, Elena; Grazulis, Saulius; Zaremba, Mindaugas; Tamulaitiene, Giedre; Golovenko, Dmitrij; Siksnys, Virginijus



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.




Adult onset thalamocerebellar degeneration in dogs associated to neuronal storage of ceroid lipopigment  

Microsoft Academic Search

Late onset of hereditary cerebellar cortical abiotrophy has been described in a large variety of canine breeds. In some reported conditions, the cerebellar lesion is combined with degeneration of other systems. Here we describe a new hereditary cerebellar cortical degeneration in eight adult American Staffordshire and Pit Bull Terriers. The neuronal degeneration in these animals not only affects Purkinje cells

S. Sisó; C. Navarro; D. Hanzlí?ek; M. Vandevelde



135. AAV-Mediated Gene Delivery To Evaluate the Biology of an Inherited Macular Degeneration  

Microsoft Academic Search

Malattia Leventinese (ML) is an autosomal dominant inherited macular degeneration with a middle-age onset. Phenotypically, the disease closely resembles Age-related Macular Degeneration (AMD), a condition affecting 20% of the population over age 65 and the leading cause of blindness in the elderly in the Western world. There is no cure for macular degeneration, and the supportive treatments are limited. Patients

Nicholas W. Keiser; Daniel C. Chung; Waixing Tang; Zhanyong Wei; Albert Maguire; Jean Bennett; Jeannette L. Bennicelli



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



Degenerate stars and gravitational collapse in AdS/CFT  

NASA Astrophysics Data System (ADS)

We construct composite CFT operators from a large number of fermionic primary fields corresponding to states that are holographically dual to a zero temperature Fermi gas in AdS space. We identify a large N regime in which the fermions behave as free particles. In the hydrodynamic limit the Fermi gas forms a degenerate star with a radius determined by the Fermi level, and a mass and angular momentum that exactly matches the boundary calculations. Next we consider an interacting regime, and calculate the effect of the gravitational back-reaction on the radius and the mass of the star using the Tolman-Oppenheimer-Volkoff equations. Ignoring other interactions, we determine the "Chandrasekhar limit" beyond which the degenerate star (presumably) undergoes gravitational collapse towards a black hole. This is interpreted on the boundary as a high density phase transition from a cold baryonic phase to a hot deconfined phase.

Arsiwalla, Xerxes; de Boer, Jan; Papadodimas, Kyriakos; Verlinde, Erik



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



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


We report a case of mucoid degeneration of the posterior cruciate ligament (PCL) who complained of knee joint pain on flexion. Magnetic resonance imaging (MRI) showed a diffusely thickened PCL with increased signal intensity on the T2-weighted sequence. A few intact fibers were observed with continuous margin from origin to insertion. Arthroscopy revealed yellow crumbly tissues among the PCL fibers. There was no tear of PCL fibers, thus their tension was preserved. Curettage of degenerative tissue and decompression of the PCL resulted in symptom relief without instability of the knee joint. Notably, the MRI features of mucoid degeneration of the cruciate ligament can be mistaken for those of partial tear of the ligament. PMID:20549189

Okazaki, Ken; Deguchi, Shinji; Katai, Kenso; Iwamoto, Yukihide



Protein Gq modulates termination of phototransduction and prevents retinal degeneration.  


Appropriate termination of the phototransduction cascade is critical for photoreceptors to achieve high temporal resolution and to prevent excessive Ca(2+)-induced cell toxicity. Using a genetic screen to identify defective photoresponse mutants in Drosophila, we isolated and identified a novel G?(q) mutant allele, which has defects in both activation and deactivation. We revealed that G(q) modulates the termination of the light response and that metarhodopsin/G(q) interaction affects subsequent arrestin-rhodopsin (Arr2-Rh1) binding, which mediates the deactivation of metarhodopsin. We further showed that the G?(q) mutant undergoes light-dependent retinal degeneration, which is due to the slow accumulation of stable Arr2-Rh1 complexes. Our study revealed the roles of G(q) in mediating photoresponse termination and in preventing retinal degeneration. This pathway may represent a general rapid feedback regulation of G protein-coupled receptor signaling. PMID:22389492

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



Nonplanar Electrostatic Solitary Waves in a Relativistic Degenerate Dense Plasma  

NASA Astrophysics Data System (ADS)

By employing the reductive perturbation technique, the propagation of cylindrical and spherical ion acoustic solitary waves is studied in an unmagnetized dense relativistic plasma, consisting of relativistically degenerate electrons and cold fluid ions. A modified Korteweg-de-Vries equation is derived and its numerical solutions have been analyzed to identify the basic features of electrostatic solitary structures that may form in such a degenerate Fermi plasma. Different degrees of relativistic electron degeneracy are discussed and compared. It is found that increasing number density leads to decrease the amplitude the width of the ion acoustic solitary wave in both the cylindrical and spherical geometries. The relevance of the work to the compact astrophysical objects, particularly white dwarfs is pointed out.

Ata-ur-Rahman; Mushtaq, A.; S., Ali; Qamar, A.



Photothrombosis-induced ischemic neuronal degeneration in the rat retina.  


Here we describe a new model for inducing ischemic neuronal degeneration in the adult rat retina. Rose bengal dye was injected intravenously; then the retina was exposed to intense light which caused vascular photothrombosis resulting in acute degeneration of retinal neurons. By either light or electron microscopical criteria, the acute neurodegernative reaction was judged identical in pattern, cytopathological appearance, and time course to the excitotoxic type of reaction typically seen in the retina following exposure to exogenous glutamate. These results reinforce other accumulating evidence suggesting that ischemic CNS damage is mediated by glutamate or related excitotoxins. The advantages of this model of CNS ischemia include its noninvasiveness, ease of application, authentic simulation of vascular thrombosis, and accessibility for application of neuroprotective drugs. PMID:2744125

Mosinger, J L; Olney, J W



Critical mass transfer in double-degenerate Type Ia supernovae  

Microsoft Academic Search

Doubly-degenerate binary systems consisting of two white dwarfs (WDs) both composed of carbon and oxygen and close enough that mass is transferred from the less massive to the more massive are possible progenitors of Type Ia supernovae. If the mass-transfer rate is slow enough that the accreting WD can reach a mass of 1.38 Msolar, then it can ignite carbon

Rebecca G. Martin; Christopher A. Tout; Pierre Lesaffre



Memory Deficits in a Demented Patient with Probable Corticobasal Degeneration  

Microsoft Academic Search

Anterograde and retrograde amnesia in a patient with probable corticobasal degeneration (pCBD) and dementia were studied in a university medical center setting. The patient with pCBD and four comparison patients of comparable global mental status (Mini-Mental State Exam) who met NINCDS-ADRDA criteria for Alzheimer's disease (AD) were included. Standard neuropsychological tests of naming, intelligence, achievement, verbal fluency, anterograde and remote

William W. Beatty; James G. Scott; Don A. Wilson; John R. Prince; David J. Williamson



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.



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


Sarcomatous degeneration in fibrous dysplasia of the rib cage.  


Malignant degeneration in fibrous dysplasia is a rare occurrence. Most cases are reported in polyostotic fibrous dysplasia with predisposition of the femur, tibia, maxilla, and mandible. The most commonly observed malignant tumors are osteosarcoma, fibrosarcoma, and chondrosarcoma. We describe a case of a low-grade osteosarcoma occurring in polyostotic fibrous dysplasia of the rib cage in a 50-year-old man. PMID:24088499

Van Rossem, Carolin; Pauwels, Patrick; Somville, Johan; Camerlinck, Michael; Bogaerts, Peter; Van Schil, Paul E



The complement system and age-related macular degeneration  

Microsoft Academic Search

PurposeAge-related macular degeneration (AMD) is the leading cause of blindness in the developed world. There are increasing evidences to suggest the complement system may play a significant role on the pathogenesis of AMD. In this review, we summarise the current research in this area.MethodsReview of literature.ResultsThe complement system is a complex system with several activation pathways. Complement factor H (CFH)

S Sivaprasad; N V Chong



Oral and silent reading performance with macular degeneration  

Microsoft Academic Search

Summary Previous studies have shown that reading rate for very large print (68, 1.86 logMAR character size) is a strong predictor of oral reading rate with low vision devices (LVDs). We investigated whether this would apply using large print sizes more readily available in clinical situations (e.g. 28, 1.4 logMAR), for subjects with macular degeneration. We assessed rauding rates—reading for

Jan E. Lovie-Kitchin; Alex R. Bowers; Russell L. Woods



On the Convergence to Equilibrium for Degenerate Transport Problems  

NASA Astrophysics Data System (ADS)

We give a counterexample which shows that the asymptotic rate of convergence to the equilibrium state for the transport equation, with a degenerate cross section and in the periodic setting, cannot be better than t -1/2 in the general case. We suggest, moreover, that the geometrical properties of the cross section are the key feature of the problem and impose, through the distribution of the forward exit time, the speed of convergence to the stationary state.

Bernard, Étienne; Salvarani, Francesco



The degeneration of internal waves in lakes with sloping topography  

Microsoft Academic Search

In a laboratory study, we quantified the temporal energy flux associated with the degeneration of basin-scale internal waves in closed basins. The system is two-layer stratified and subjected to a single forcing event creating available potential energy at time zero. A downscale energy transfer was observed from the wind-forced basin-scale motions to the turbulent motions, where energy was lost due

L. Boegman; G. N. Ivey; J. Imberger



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



Resistance to axonal degeneration after nerve compression in experimental diabetes.  

PubMed Central

To determine the effect of diabetes on the development of axonal degeneration after acute nerve compression, the mobilized peroneal nerves of rats with streptozotocin-induced diabetes and of control rats were compressed at 150 mmHg (1 mmHg = 133 Pa) for 30 min by using specially devised cuffs. At three intervals after compression--3 days, rats diabetic for 31 wk; 14 days, diabetic for 6 wk; and 24 days, diabetic for 31 wk--groups of nerves were studied to assess numbers and sizes of fibers above, at, and below the cuff and to assess frequency of fiber degeneration in teased fibers from nerve distal to the cuff. Teased fibers with pathologic abnormalities were more frequent in nerves from controls than in nerves from diabetic rats in all three groups but the difference was statistically significant only at 3 and 14 days after compression. The lack of significant difference at 24 days may be explained by higher rates of disappearance of degenerating products and of fiber regeneration at 24 than at 3 and 14 days. This study provides evidence that in addition to delaying the reported functional deficit of vibratory detection threshold and conduction block during nerve compression, diabetes also may partially prevent axonal injury. Low nerve myo-inositol concentration did not predispose diabetic nerve to acute compression injury. If these results also apply to human diabetes and if repeated acute compression is involved in the genesis of fiber degeneration in entrapment, then a higher frequency of entrapment neuropathy among diabetics might be due to mechanisms other than increased susceptibility of fibers to acute compression--e.g., possibly to greater constriction of nerve due to pathologic alterations of the carpal ligament. Images

Dyck, P J; Engelstad, J K; Giannini, C; Lais, A C; Minnerath, S R; Karnes, J L



Neural arch load-bearing in old and degenerated spines  

Microsoft Academic Search

We validate a technique for measuring neural arch load-bearing in cadaveric spines, and use it to test the hypothesis that such load-bearing rises to high levels in old and degenerated spines. Fifty-nine cadaveric lumbar motion segments, aged 19–92yr, were subjected to compressive creep loading to reduce intervertebral disc water content and height to in vivo levels. The distribution of compressive

P. Pollintine; A. S. Przybyla; P. Dolan; M. A. Adams



Subacute Combined Degeneration of the Cord: Putnam-Dana Syndrome  

Microsoft Academic Search

The association of anaemia and gastro-intestinal abnormalities with disorders of the brain, spinal cord, and peripheral nerves has been recognized since the mid 19th century. In early reports interpretable as subacute combined degeneration, anaemia was overlooked, and conversely in Addison’s and other early reports of pernicious anaemia, cord and nerve changes were not recorded. This paper shows that Lichtheim first

J. M. S. Pearce



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


The major causes of impaired vision in the elderly population of the United States are cataracts, macular degeneration, and open-angle glaucoma. Cataracts and macular degeneration usually reduce central vision, especially reading and near activities, whereas chronic glaucoma characteristically attacks peripheral vision in a silent way, impacting balance, walking, and driving. Untreated, these visual problems lead to issues with regard to taking medications, keeping track of finances and personal information, walking, watching television, and attending the theater, and often create social isolation. Thus, visually impaired individuals enter nursing homes 3 years earlier, have twice the risk of falling, and have 4× the risk of hip fracture. Consequently, many elderly with low vision exercise greater demands on community services. With the prospect of little improvement and sustained visual loss, in the face of poor tolerance of low-vision services and not accepting magnification as the only way to read, clinical depression is common. In many instances, however, early and accurate diagnosis can result in timely treatment and can preserve quality of life. This review will look at current diagnostic and therapeutic considerations. Currently, about 20.5 million people in the United States have cataracts. The number will reach 30 million by 2020. About 1.75 million Americans currently have some form of macular degeneration, and the number is estimated to increase to 2.95 million in 2020. Approximately 2.2 million Americans have glaucoma, and by 2020 that number is estimated to be close to 3.4 million people. It is projected that by 2030 there will be 72.1 million seniors. With some overlap of the above 3 groups conservatively estimated (if you add the 2030 cataract group to the macular degeneration and glaucoma groups), then about 1 in 2 senior individuals by 2030 may have some significant ocular disease, which could account for about 50% of the healthcare budget for the elderly. PMID:22499498

Eichenbaum, Joseph W


Retinal Degeneration in Choroideremia: Deficiency of Rab Geranylgeranyl Transferase  

Microsoft Academic Search

Rab geranylgeranyl transferase (GG transferase) is a two-component enzyme that attaches 20-carbon isoprenoid groups to cysteine residues in Rab proteins, a family of guanosine triphosphate-binding proteins that regulate vesicular traffic. The mutant gene in human choroideremia, an X-linked form of retinal degeneration, encodes a protein that resembles component A of rat Rab GG transferase. Lymphoblasts from choroideremia subjects showed a

Miguel C. Seabra; Michael S. Brown; Joseph L. Goldstein



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



Quantum degenerate mixture of ytterbium and lithium atoms  

NASA Astrophysics Data System (ADS)

We have produced a quantum degenerate mixture of fermionic alkali-metal 6Li and bosonic spin-singlet 174Yb gases. This was achieved using sympathetic cooling of lithium atoms by evaporatively cooled ytterbium atoms in a far-off-resonant optical dipole trap. We observe the coexistence of Bose-condensed (T/Tc?0.8) 174Yb with 2.3×104 atoms and Fermi degenerate (T/TF?0.3) 6Li with 1.2×104 atoms. Quasipure Bose-Einstein condensates of up to 3×104 174Yb atoms can be produced in single-species experiments. Our results mark a significant step toward studies of few- and many-body physics with mixtures of alkali-metal and alkaline-earth-metal-like atoms, and for the production of paramagnetic polar molecules in the quantum regime. Our methods also establish a convenient scheme for producing quantum degenerate ytterbium atoms in a 1064 nm optical dipole trap.

Hansen, Anders H.; Khramov, Alexander; Dowd, William H.; Jamison, Alan O.; Ivanov, Vladyslav V.; Gupta, Subhadeep



[Autosomal dominant spinocerebellar degeneration--new forms and pathomechanisms].  


In our country, hereditary spinocerebellar degeneration accounted for approximately 30% of the total cases. Most of them are autosomal dominant and include more than 20 diseases. The outlines of some new members, namely autosomal dominant cortical cerebellar atrophy linked to chromosome 16 (16q-ADCCA), SCA14, an ataxia caused by FGF14 mutation and a form of neuroferritinopathy were described. The etiology of many autosomal dominant SCDs has been identified as the abnormal expansion of CAG repeat. The latter three diseases are caused by missense mutations of the causative genes, which clearly shows the presence of other new mechanisms of cerebellar degeneration than repeat expansion. 16q-ADCCA is the most frequent after Machado-Joseph disease and SCA6 according to our genetic diagnosis of 185 SCD patients. The disease is characterized by Purkinje cell degeneration and atrophy with somatic sprouts as well as the halo-like structure surrounding the soma. The halo is positive for synaptophysin. These features are so unique that 16q-ADCCA may be diagnosed by neuropathology alone. PMID:15651290

Mizusawa, Hidehiro



[Vision rehabilitation of patients with old-age macular degeneration].  


Age-related degeneration of the macula retinae occurs in two forms: the serious form with invasion of blood vessels and leakage, and the atrophic form. Both forms ultimately lead to a central scotoma. The prevalence of the terminal stage of age-related macular degeneration varies from 1% in the age group 65-74 years to 11% in those 85 years or over. A total of 58,500 persons in the Netherlands have age-related macular degeneration and an estimated 22,000 persons depend on visual or optic aids. Aids for close vision are good illumination, magnification (reading glasses, magnifying glasses, telescopic lenses, television reading lenses (with possibility of changing contrast), large-letter books, playing cards with large symbols) and auditory aids. Aids for distant vision reduce troublesome light (sunglasses, filter) or enlarge the image (telescopic aids). Future new aids derive from modern computer technology (personal computer, integrated braille reader and speech synthesizer) or are based on opto-electronic image processing and presentation (mini-cameras with mini-VDUs in a sort of helmet). Effective use of aids depends on attention for the patient's desires and possibilities and on counselling in handling aids. Ophthalmological checkups remain useful for the prevention and (or) treatment of accessory disorders. PMID:9557020

Hoyng, C B; Verezen, C A; de Jong, P T



Quantum degenerate mixture of ytterbium and lithium atoms  

SciTech Connect

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

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



Remyelination protects axons from demyelination-associated axon degeneration.  


In multiple sclerosis, demyelination of the CNS axons is associated with axonal injury and degeneration, which is now accepted as the major cause of neurological disability in the disease. Although the kinetics and the extent of axonal damage have been described in detail, the mechanisms by which it occurs are as yet unclear; one suggestion is failure of remyelination. The goal of this study was to test the hypothesis that failure of prompt remyelination contributes to axonal degeneration following demyelination. Remyelination was inhibited by exposing the brain to 40 Gy of X-irradiation prior to cuprizone intoxication and this resulted in a significant increase in the extent of axonal degeneration and loss compared to non-irradiated cuprizone-fed mice. To exclude the possibility that this increase was a consequence of the X-irradiation and to highlight the significance of remyelination, we restored remyelinating capacity to the X-irradiated mouse brain by transplanting of GFP-expressing embryo-derived neural progenitors. Restoring the remyelinating capacity in these mice resulted in a significant increase in axon survival compared to non-transplanted, X-irradiated cuprizone-intoxicated mice. Our results support the concept that prompt remyelination protects axons from demyelination-associated axonal loss and that remyelination failure contributes to the axon loss that occurs in multiple sclerosis. PMID:18490361

Irvine, K A; Blakemore, W F



Mislocalization of neuronal mitochondria reveals regulation of Wallerian degeneration and NMNAT/WLD(S)-mediated axon protection independent of axonal mitochondria.  


Axon degeneration is a common and often early feature of neurodegeneration that correlates with the clinical manifestations and progression of neurological disease. Nicotinamide mononucleotide adenylytransferase (NMNAT) is a neuroprotective factor that delays axon degeneration following injury and in models of neurodegenerative diseases suggesting a converging molecular pathway of axon self-destruction. The underlying mechanisms have been under intense investigation and recent reports suggest a central role for axonal mitochondria in both degeneration and NMNAT/WLD(S) (Wallerian degeneration slow)-mediated protection. We used dorsal root ganglia (DRG) explants and Drosophila larval motor neurons (MNs) as models to address the role of mitochondria in Wallerian degeneration (WD). We find that expression of Drosophila NMNAT delays WD in human DRG neurons demonstrating evolutionary conservation of NMNAT function. Morphological comparison of mitochondria from WLD(S)-protected axons demonstrates that mitochondria shrink post-axotomy, though analysis of complex IV activity suggests that they retain their functional capacity despite this morphological change. To determine whether mitochondria are a critical site of regulation for WD, we genetically ablated mitochondria from Drosophila MN axons via the mitochondria trafficking protein milton. Milton loss-of-function did not induce axon degeneration in Drosophila larval MNs, and when axotomized WD proceeded stereotypically in milton distal axons although with a mild, but significant delay. Remarkably, the protective effects of NMNAT/WLD(S) were also maintained in axons devoid of mitochondria. These experiments unveil an axon self-destruction cascade governing WD that is not initiated by axonal mitochondria and for the first time illuminate a mitochondria-independent mechanism(s) regulating WD and NMNAT/WLD(S)-mediated axon protection. PMID:23314018

Kitay, Brandon M; McCormack, Ryan; Wang, Yunfang; Tsoulfas, Pantelis; Zhai, R Grace



Retinal degeneration increases susceptibility to myopia in mice  

PubMed Central

Purpose Retinal diseases are often associated with refractive errors, suggesting the importance of normal retinal signaling during emmetropization. For instance, retinitis pigmentosa, a disease characterized by severe photoreceptor degeneration, is associated with myopia; however, the underlying link between these conditions is not known. This study examines the influence of photoreceptor degeneration on refractive development by testing two mouse models of retinitis pigmentosa under normal and form deprivation visual conditions. Dopamine, a potential stop signal for refractive eye growth, was assessed as a potential underlying mechanism. Methods Refractive eye growth in mice that were homozygous for a mutation in Pde6b, Pde6brd1/rd1 (rd1), or Pde6brd10/rd10 (rd10) was measured weekly from 4 to 12 weeks of age and compared to age-matched wild-type (WT) mice. Refractive error was measured using an eccentric infrared photorefractor, and axial length was measured with partial coherence interferometry or spectral domain ocular coherence tomography. A cohort of mice received head-mounted diffuser goggles to induce form deprivation from 4 to 6 weeks of age. Dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) levels were measured with high-performance liquid chromatography in each strain after exposure to normal or form deprivation conditions. Results The rd1 and rd10 mice had significantly greater hyperopia relative to the WT controls throughout normal development; however, axial length became significantly longer only in WT mice starting at 7 weeks of age. After 2 weeks of form deprivation, the rd1 and rd10 mice demonstrated a faster and larger myopic shift (?6.14±0.62 and ?7.38±1.46 diopter, respectively) compared to the WT mice (?2.41±0.47 diopter). Under normal visual conditions, the DOPAC levels and DOPAC/dopamine ratios, a measure of dopamine turnover, were significantly lower in the rd1 and rd10 mice compared to the WT mice, while the dopamine levels were similar or higher than WT in the rd10 mice. Lower basal levels of DOPAC were highly correlated with increasing myopic shifts. Conclusions Refractive development under normal visual conditions was disrupted toward greater hyperopia from 4 to 12 weeks of age in these photoreceptor degeneration models, despite significantly lower DOPAC levels. However, the retinal degeneration models with low basal levels of DOPAC had increased susceptibility to form deprivation myopia. These results indicate that photoreceptor degeneration may alter dopamine metabolism, leading to increased susceptibility to myopia with an environmental visual challenge.

Park, Hanna; Tan, Christopher C.; Faulkner, Amanda; Jabbar, Seema B.; Schmid, Gregor; Abey, Jane; Iuvone, P. Michael



How Transcription Factors Identify Regulatory Sites in Genomic Sequence  

Microsoft Academic Search

\\u000a Binding of transcription factors to functional sites is a fundamental step in transcriptional regulation. In this chapter,\\u000a we discuss how transcription factors are thought to achieve specificity to their functional targets, despite their typically\\u000a low concentrations and degenerate binding specificities, and the fact that in large genomes their functional binding sites\\u000a must compete with their widespread alternative binding sites. We

Yair Field; Eilon Sharon; Eran Segal


The Local Type Ia Supernova Progenitors: One Double-Degenerate, No Symbiotics  

NASA Astrophysics Data System (ADS)

Although the basic mechanism responsible for Type Ia supernovae appears to be well understood (thermonuclear explosion of a carbon-oxygen white dwarf that has reached the Chandrasekhar mass limit), the identity of the progenitor system(s) remains a mystery. With implications from stellar evolution to frontline cosmology, it is critical to attack this problem from every possible angle. We present results from our study of three known historical Ia supernovae in the Large Magellanic Cloud (LMC) which allow us to eliminate possible progenitor candidates for at least the local population. We used archival Hubble Space Telescope images of SNR 0509-67.5, SNR 0509-68.7, and SNR 0519-69.0 to determine the site of each explosion and then search the surrounding area for potential ex-companion stars that were left behind. The search was carried out within an error ellipse that accounts for measurement error on the geometric center of the remnant, the orbital velocity of the pre-supernova binary system, and kicks from the actual explosion. For SNR 0509-67.5, the error ellipse is empty to the HST 5? limiting magnitude of V=26.9. Using an LMC distance modulus of 18.5, this implies that any single degenerate ex-companion must be fainter than MV=+8.4 (corresponding approximately to a K9 main sequence star), which eliminates all currently-published single-degenerate models and leads us to conclude that this system had a double-degenerate (double white dwarf) progenitor. For SNR 0509-68.7 and SNR 0519-69.0, we can eliminate the possibility of red giant and subgiant ex-companions. It has been shown that the two confident galactic Ia supernovae (Tycho's SN 1572 and SN 1006) also do not have red giant ex-companion stars. Combined with our three systems, this eliminates the symbiotic progenitor channel for all of the nearby Ia supernovae. This work was supported by the National Science Foundation (AST-1109420).

Pagnotta, Ashley; Schaefer, B. E.



Combined effects of light and water availability on photosynthesis and growth of Arisaema heterophyllum in the forest understory and an open site  

Microsoft Academic Search

Photosynthetic characteristics, leaf longevity and biomass accumulation of a threatened herb species, Arisaema heterophyllum, were studied in the understory of a riparian forest and at a neighboring deforested open site for 3 years in order to understand\\u000a the combined effects of light and water availability. Light availability was 2- to 4-fold higher at the deforested than at\\u000a the forest site

H. Muraoka; Y. Tang; H. Koizumi; I. Washitani



Cerebellar degeneration in Lurcher mice under confocal laser scanning microscope.  


Lurcher mutant mice represent a natural model of genetically-determined olivocerebellar degeneration caused by a mutation in the ?2 glutamate receptor gene. They suffer from progressive postnatal loss of cerebellar Purkinje cells and a decrease of granule cells and inferior olive neurons. Their wild type littermates serve as healthy controls. A confocal laser scanning microscope was used aiming investigation the dynamics of changes in the cerebellar cortex of Lurcher and wild type mice derived from two strains during the period of 8-21 postnatal days. Fluorescent double-staining was used to visualize mainly the Purkinje cells in cerebellar slices. In wild types, only normal Purkinje cells of round or regular drop-shaped were present, when staining intensity of other individual cell structures differed in dependence on the age of the animal. In Lurcher mutants, there were still some normal-shaped cells. Nevertheless, depending on the animal's age, a wide variety of stages of the cell degeneration were depicted. The main characteristics of Purkinje cell degeneration in the early stage are: disruption of the continuity of the Purkinje cell layer, dark spots in cell nuclei and an irregular coloring of the cytoplasm. Later, the cells and their nuclei were deformed, often with two main dendrites sprouting from the cell body. Finally, the cell and nucleus margins were unclear, dendrites were significantly thickened, showing signs of shrinkage and fragmentation. Cell nucleoli underwent changes in number and appearance. No differences between the Lurcher mice of both strains (C3H and B6CBA) under examination were found. PMID:23463661

Purkartová, Zde?ka; Vožeh, František



Brain angiotensin and dopaminergic degeneration: relevance to Parkinson's disease  

PubMed Central

The pathogenic mechanism of Parkinson’s disease (PD) appears to be multifactorial. However, oxidative stress and neuroinflammation, including activation of NADPH-dependent oxidases, play a major role in the progression of dopaminergic cell death. The renin-angiotensin system (RAS) was described as a circulating humoral system that regulates blood pressure and water homeostasis. However, there exist local RAS in many tissues, and locally formed angiotensin activates NADPH-dependent oxidases, which are a major source of superoxide and are upregulated in major aging-related diseases such as hypertension, diabetes and atherosclerosis. Furthermore, an intracellular or intracrine RAS, with still unknown functions, has been identified in several cell types. The brain has an independent local RAS, which has been involved in several brain disorders, including neurodegenerative diseases. It is particularly interesting for PD the important interaction observed between angiotensin and dopamine, which counterregulate each other in renal cells and also in the striatum and substantia nigra. In recent studies, we have observed both a local and an intracellular RAS in the rodent, monkey and human substantia nigra, and that dopamine depletion induced RAS upregulation possibly as a compensatory mechanism. However, RAS hyperactivation also exacerbated oxidative stress and neuroinflammation, which contributed to progression of dopaminergic degeneration. In addition, we observed increased RAS activity in the nigra of animals with higher vulnerability of dopaminergic neurons to degeneration, such as aged males, menopausal females and rats subjected to chronic brain hypoperfusion. RAS activity and dopaminergic vulnerability were significantly reduced by treatment with angiotensin type I receptor antagonists. Manipulation of the brain RAS may constitute an effective neuroprotective strategy against dopaminergic degeneration in PD.

Labandeira-Garcia, Jose L; Rodriguez-Pallares, Jannette; Rodriguez-Perez, Ana I; Garrido-Gil, Pablo; Villar-Cheda, Begona; Valenzuela, Rita; Guerra, Maria J



Neurocognitive contributions to verbal fluency deficits in frontotemporal lobar degeneration  

PubMed Central

Objective: To test the hypothesis that different neurocognitive networks underlie verbal fluency deficits in frontotemporal lobar degeneration (FTLD). Methods: Letter (“FAS”) and semantic (“animal”) fluency tests were administered to patients with a behavioral/dysexecutive disorder (bvFTLD; n = 71), semantic dementia (SemD; n = 21), and progressive nonfluent aphasia (PNFA; n = 26). Tests measuring working memory, naming/lexical retrieval, and semantic knowledge were also obtained. MRI voxel-based morphometry (VBM) studies were obtained on a subset of these patients (bvFTLD, n = 51; PNFA, n = 11; SemD, n = 10). Results: Patients with SemD were disproportionately impaired on the semantic fluency measure. Reduced output on this test was correlated with impaired performance on naming/lexical retrieval tests. VBM analyses related reduced letter and semantic fluency to anterior and inferior left temporal lobe atrophy. Patients with bvFTLD were equally impaired on both fluency tests. Poor performance on both fluency tests was correlated with low scores on working memory and naming/lexical retrieval measures. In this group, MRI-VBM analyses related letter fluency to bilateral frontal atrophy and semantic fluency to left frontal/temporal atrophy. Patients with PNFA were also equally impaired on fluency tests. Reduced semantic fluency output was correlated with reduced performance on naming/lexical retrieval tests. MRI-VBM analyses related semantic fluency to the right frontal lobe and letter fluency to left temporal atrophy. Conclusions: Distinct neurocognitive networks underlie impaired performance on letter and semantic fluency tests in frontotemporal lobar degeneration subgroups. GLOSSARY AD = Alzheimer disease; ANOVA = analysis of variance; bvFTLD = behavioral/dysexecutive subgroup; FTLD = frontotemporal lobar degeneration; MMSE = Mini-Mental State Examination; MNI = Montreal Neurological Institute; MR = magnetic resonance; PNFA = progressive nonfluent aphasia; SemD = semantic dementia; TE = echo time; TR = repetition time; VBM = voxel-based morphometry.

Libon, D J.; McMillan, C; Gunawardena, D; Powers, C; Massimo, L; Khan, A; Morgan, B; Farag, C; Richmond, L; Weinstein, J; Moore, P; Coslett, H B.; Chatterjee, A; Aguirre, G; Grossman, M



Quantum and semiclassical description of a triply degenerate anharmonic oscillator  

SciTech Connect

Quantum and semiclassical energies are compared as a function of anharmonicity using the Hecht Hamiltonian for the triply degenerate anharmonic oscillator for octahedral and tetrahedral molecules. Semiclassical energies are found by turning on the potential adiabatically and the corresponding classical trajectories are described in terms of an adiabatic vibrational energy (VE) surface. Accurate semiclassical energies are obtained for chaotic trajectories near the separatrix of the VE surface. The quantum wave functions corresponding to the semiclassical trajectories after the onset of chaos are used to disprove a recently proposed quantum analog to classical quasiperiodic motion.

Patterson, C.W.



Double-degenerate Bose-Fermi mixture of strontium  

NASA Astrophysics Data System (ADS)

We report on the attainment of a double-degenerate Bose-Fermi mixture of strontium. A sample of fermionic ^87Sr atoms is spin-polarized and sympathetically cooled by interisotope collisions with the bosonic isotope ^84Sr. A degeneracy with T/TF=0.30(5) is reached for a ^87Sr Fermi sea of 2x10^4 atoms together with an almost pure ^84Sr BEC of 10^5 atoms. The rich electronic structure and the large nuclear spin of ^87Sr make it a promising candidate for quantum simulation of SU(N) magnetism and quantum information processing.

Schreck, Florian



Observational prospects for massive stars with degenerate neutron cores  

NASA Astrophysics Data System (ADS)

In this paper we present observable characteristics of massive stars with degenerate neutron cores, or Thorne-Zytkow objects, which would distinguish them from other stars. Spectroscopically these stars are red supergiants, but they have peculiar surface abundances compared with 'normal' red supergiants. This is due to the convection of rp-process products from the nuclear burning region to the surface. We present predictions of surface abundances of elelments heavier than iron. In particular, Mo should have an abundance greater than 1000 times solar. We estimate that several of the about 100 red supergiants within 5 kpc of the Sun are Thorne-Zytkow objects.

Biehle, Garrett T.



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



Endogenous glucocorticoids participate in retinal degeneration during continuous illumination.  


Continuous illumination (CI) induces an oxidative stress of the retina which is involved in light-induced retinal degeneration (LIRD). As the increase of glucocorticoids (GC) could also collaborate in the damage, adrenalectomized (ADX) and sham-operated rats (control, CTL) were submitted to CI, and their eyes were studied at light and electron microscopic levels. After CI, ADX retinas were significantly thicker than CTL retinas. Retinal alterations appeared earlier and were severer in CTL than in ADX retinas. Corticosterone levels increased gradually in the sera of CTL rats along CI. These results suggest that adrenalectomy attenuates LIRD, supporting the hypothesis. PMID:18937116

López, Ester María; Julián, Lilian Karina; Capani, Francisco; Cymeryng, Cora Beatriz; Coirini, Hector; López-Costa, Juan José



Electron thermal conductivity owing to collisions between degenerate electrons  

SciTech Connect

We calculate the thermal conductivity of electrons produced by electron-electron Coulomb scattering in a strongly degenerate electron gas taking into account the Landau damping of transverse plasmons. The Landau damping strongly reduces this conductivity in the domain of ultrarelativistic electrons at temperatures below the electron plasma temperature. In the inner crust of a neutron star at temperatures T < or approx. 10{sup 7} K this thermal conductivity completely dominates over the electron conductivity due to electron-ion (electron-phonon) scattering and becomes competitive with the the electron conductivity due to scattering of electrons by impurity ions.

Shternin, P. S.; Yakovlev, D. G. [Ioffe Physical Technical Institute, Politekhnicheskaya 26, 194021 St. Petersburg (Russian Federation)



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

Johnson, G J



Arthroscopic management of mucoid degeneration of anterior cruciate ligament  

PubMed Central

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

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



Ascending aortic dissection in weight lifters with cystic medial degeneration.  


We report 4 cases of ascending aortic dissection in patients with long histories of weight lifting. In 2 of the patients, the initial symptoms of dissection developed while they were lifting weights. Two patients had a history of hypertension and 2 had previously used anabolic steroids. All 4 were successfully treated surgically. Histopathology showed aortic medial changes in all 4. We believe that the hemodynamic stresses of weight lifting, namely, a rapid increase in systemic arterial blood pressure without a decrease in total peripheral vascular resistance, in combination with aortic medial degeneration may have contributed to the development of the aortic dissection. PMID:2322060

de Virgilio, C; Nelson, R J; Milliken, J; Snyder, R; Chiang, F; MacDonald, W D; Robertson, J M




PubMed Central

Recent findings assessing the utility of biomarkers are reviewed that help identify the basis for disease in patients with frontotemporal lobar degeneration (FTLD) spectrum pathology. Biofluid studies identify about 15% of patients with FTLD due to a genetic mutation that is associated with the specific histopathologic features of TDP-43 or a tauopathy. Other genetically-based risk factors and targeted proteomic searches of plasma and cerebrospinal fluid have suggested additional markers that may be useful in sporadic cases of FTLD. While progress has been made in developing biomarkers for FTLD, additional work is needed to extend these advances so that the histopathologic abnormality causing FTLD can be specified in an individual patient.

Grossman, Murray



Managing differences: care of the person with frontotemporal degeneration.  


Caring for people with non-Alzheimer's dementias is particularly challenging for families and care providers. This is especially true for those with frontotemporal degeneration (FTD) who exhibit profound changes in personality, behavior, language, and movement. Initial symptoms are often misdiagnosed as psychiatric disorders or early-onset Alzheimer's disease, and typically do not respond to pharmacological and nonpharmacological interventions designed for people with other dementias. Using individual examples, this article illustrates common features of two subtypes of FTD: behavioral variant FTD and non-fluent primary progressive aphasia. PMID:23394488

Hall, Geri R; Shapira, Jill; Gallagher, Maribeth; Denny, Sharon S



Paraneoplastic cerebellar degeneration mimicking acute post-infectious cerebellitis.  


Acute cerebellitis is a monophasic non-progressive encephalitis restricted to the cerebellum, while paraneoplastic cerebellar degeneration is a subacute progressive disorder, which may either accompany or herald Hodgkin's disease. In the present report, we describe a young man with clinical and laboratory features of acute post-infectious cerebellitis in whom the progressive relapsing course subsequently led to the diagnosis of Hodgkin's disease. Dynamic changes observed on repeated MRIs during the protracted clinical course imply the presence of early active inflammation and subsequent neuronal atrophy. PMID:19727999

Karmon, Yuval; Inbar, Edna; Cordoba, Mario; Gadoth, Natan



Coupling and degenerating modes in longitudinal-torsional step horns.  


Longitudinal-torsional vibration is used and proposed for a variety of ultrasonic applications including motors, welding, and rock-cutting. To obtain this behavior in an ultrasonic step horn one can either, (i) couple the longitudinal and torsional modes of the horn by incorporating a ring of diagonal slits in the thick base section or, (ii) place helical flutes in the thin stem section to degenerate the longitudinal mode into a modified behavior with a longitudinal-torsional motion. This paper compares the efficacy of these two design approaches using both numerical and experimental techniques. PMID:22770885

Harkness, Patrick; Lucas, Margaret; Cardoni, Andrea



Vitreomacular adhesion and neovascular age-related macular degeneration.  


We explore the hypothesis that vitreomacular adhesion (VMA) and vitreomacular traction (VMT) play a role in the pathogenesis and clinical course of neovascular ("wet") age-related macular degeneration (AMD). Several biological theories are offered to explain this possible association, including direct tractional force, altered vitreous oxygenation, altered diffusion coefficients of intravitreal molecules, and alterations in the pharmacokinetics of intravitreal drugs. Release of VMT may improve the clinical course of neovascular AMD, and a few case series suggest that vitrectomy can lead to both a functional and anatomic improvement. A large, randomized, controlled clinical trial is underway, investigating pharmacologic release of VMA in eyes with neovascular AMD. PMID:23068973

Simpson, Andrew R H; Petrarca, Robert; Jackson, Timothy L




PubMed Central

Frontotemporal lobar degeneration (FTLD) is a neurodegenerative disease that affects frontal and temporal regions of the brain. Two proteins indicated in the pathology are tau and the recently discovered TDP-43. Major manifestations include progressive aphasia and a disorder of social comportment. The diagnosis of a patient includes a detailed cognitive exam, clinical testing and neuroimaging techniques. The current goal of therapy for FTLD is symptomatic management with medications borrowed from other conditions. Non-pharmacologic management such as behavioral interventions and environmental engineering are also efficacious in optimizing quality of life.

Massimo, Lauren; Grossman, Murray



Magnetic order and dynamics in an orbitally degenerate ferromagnetic insulator.  


Neutron scattering was used to determine the spin structure and the magnon spectrum of the Mott-Hubbard insulator YTiO3. The magnetic structure is complex, comprising substantial G-type and A-type antiferromagnetic components in addition to the predominant ferromagnetic component. The magnon spectrum, on the other hand, is gapless and nearly isotropic. We show that these findings are inconsistent with the orbitally ordered states thus far proposed for YTiO3 and discuss general implications for a theoretical description of exchange interactions in orbitally degenerate systems. PMID:12398750

Ulrich, C; Khaliullin, G; Okamoto, S; Reehuis, M; Ivanov, A; He, H; Taguchi, Y; Tokura, Y; Keimer, B



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)



Unilateral superior pellucid marginal degeneration in a case with ichthyosis.  


A 47-year-old man with ichthyosis vulgaris presented to our hospital complaining of reduced visual acuity and ocular discomfort in the left eye. Slit-lamp biomicroscopy revealed a thinning about 2mm from the superior limbus and superficial punctate corneal lesions in the left eyes. Corneal topography was 'butterfly-like' in an area of increased elevation in the left eye. Although ichthyosis vulgaris and unilateral superior pellucid marginal degeneration are both uncommon conditions, this is first report about these two conditions in studied together. PMID:21084217

Dundar, Huseyin; Kara, Necip; Kaya, Vedat; Bozkurt, Ercument; Yazici, Ahmet Taylan; Hekimhan, Pelin Kaynak



Chemically reacting mixtures in terms of degenerated parabolic setting  

NASA Astrophysics Data System (ADS)

The paper analyzes basic mathematical questions for a model of chemically reacting mixtures. We derive a model of several (finite) component compressible gas taking rigorously into account the thermodynamical regime. Mathematical description of the model leads to a degenerate parabolic equation with hyperbolic deviation. The thermodynamics implies that the diffusion terms are non-symmetric, not positively defined, and cross-diffusion effects must be strongly marked. The mathematical goal is to establish the existence of weak solutions globally in time for arbitrary number of reacting species. A key point is an entropy-like estimate showing possible renormalization of the system.

Mucha, P. B.; Pokorný, M.; Zatorska, E.



Structural Basis for Degenerate Recognition of Natural HIV Peptide Variants by Cytotoxic Lymphocytes  

SciTech Connect

It is well established that even small changes in amino acid side chains of antigenic peptide bound to MHC protein may completely abrogate recognition of the peptide-MHC (pMHC) complex by the T-cell receptor (TCR). Often, however, several non-conservative substitutions in the peptide antigen are accommodated and do not impair its recognition by TCR. For example, a preponderance of natural sequence variants of the HIV p17 Gag-derived peptide SLYNTVATL (SL9) are recognized by cytotoxic T lymphocytes (CTL), which implies that interactions with SL9 variants are degenerate both with respect to the class I MHC molecule and with respect to TCR. Here we study the molecular basis for this degenerate recognition of SL9 variants. We show that several SL9 variants bind comparably well to soluble HLA-A2 and to a particular soluble TCR and that these variants are active in the cognate cytotoxicity assay. Natural SL9 variation is restricted by its context in the HIV p17 matrix protein, and we have used synthetic variants to explore the wider spectrum of recognition. High-resolution crystal structures of seven selected SL9 variants bound to HLA-A2 all have remarkably similar peptide conformations and side-chain dispositions outside sites of substitution. This preservation of the peptide conformation despite epitope variations suggests a mechanism for the observed degeneracy in pMHC recognition by TCR, and may contribute to the persistence of SL9-mediated immune responses in chronically infected individuals.

Martinez-Hackert,E.; Anikeeva, N.; Kalams, S.; Walker, B.; Hendrickson, W.; Sykulev, Y.



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.

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



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

PubMed Central

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

Rallis, Andrew; Lu, Bingwei; Ng, Julian



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



Axonal Degeneration Is Blocked by Nicotinamide Mononucleotide Adenylyltransferase (Nmnat) Protein Transduction into Transected Axons*  

PubMed Central

Axonal degeneration is an early and important component of many neurological disorders. Overexpression of nicotinamide mononucleotide adenylyltransferase (Nmnat), a component of the slow Wallerian degeneration (Wlds) protein, protects axons from a variety of insults. We found that transduction of Nmnat protein into severed axons via virus-like particles prevented axonal degeneration. The post-injury efficacy of Nmnat indicates that its protective effects occur locally within the axon and provides an opportunity to develop novel agents to treat axonal damage.

Sasaki, Yo; Milbrandt, Jeffrey



Growth Factors and Anticatabolic Substances for Prevention and Management of Intervertebral Disc Degeneration  

PubMed Central

Intervertebral disc (IVD) degeneration is frequent, appearing from the second decade of life and progressing with age. Conservative management often fails, and patients with IVD degeneration may need surgical intervention. Several treatment strategies have been proposed, although only surgical discectomy and arthrodesis have been proved to be predictably effective. Biological strategies aim to prevent and manage IVD degeneration, improving the function and anabolic and reparative capabilities of the nucleus pulposus and annulus fibrosus cells and inhibiting matrix degradation. At present, clinical applications are still in their infancy. Further studies are required to clarify the role of growth factors and anticatabolic substances for prevention and management of intervertebral disc degeneration.

Longo, Umile Giuseppe; Petrillo, Stefano; Franceschetti, Edoardo; Maffulli, Nicola; Denaro, Vincenzo



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.



Axonal degeneration in the peripheral nervous system: implications for the pathogenesis of amyotrophic lateral sclerosis.  


Axons are the anatomical link between neuronal cell bodies and their target organs, and thus axonal degeneration is the pathological substrate that underlies neurological dysfunction in a large number of neurological conditions. Recent advances in the field of axonal biology demonstrate that axons possess programs for survival and degeneration that are distinct from those of the cell body, indicating that therapeutic strategies must consider protection of both the cell body and the axon. This review discusses axonal degeneration in the peripheral nervous system (PNS) with a focus on amyotrophic lateral sclerosis, examining both the underlying mechanisms, and the cellular and disease models of axonal degeneration that relate to disease pathogenesis. PMID:23664960

Fischer-Hayes, Lindsey R; Brotherton, Terrell; Glass, Jonathan D



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)



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

PubMed Central

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 in dopaminergic neuron degeneration, the effects of ?-synuclein on dopamine homeostasis and its contribution to dopaminergic neuron degeneration in C. elegans have not been reported. Here, we examined the effects of ?-synuclein overexpression on worm dopamine homeostasis. We found that ?-synuclein expression results in upregulation of dopamine synthesis and content, and redistribution of dopaminergic synaptic vesicles, which significantly contribute to dopaminergic neuron degeneration. These results provide in vivo evidence supporting a critical role for dopamine homeostasis in supporting dopaminergic neuron integrity.

Pehek, Elizabeth A.; Moise, Alex R.; Huang, Ying; Palczewski, Krzysztof; Feng, Zhaoyang



Mesenchymal Stem Cell for Prevention and Management of Intervertebral Disc Degeneration  

PubMed Central

Intervertebral disc degeneration (IVD) is a frequent pathological condition. Conservative management often fails, and patients with IVD degeneration may require surgical intervention. Several treatment strategies have been proposed, although only surgical discectomy and arthrodesis have been proved to be predictably effective. The aim of biological strategies is to prevent and manage IVD degeneration, improve the function, the anabolic and reparative capabilities of the nucleus pulposus and annulus fibrosus cells, and inhibit matrix degradation. At present, clinical applications are still in their infancy. Further studies are required to clarify the role of mesenchymal stem cells and gene therapy for the prevention and treatment of IVD degeneration.

Longo, Umile Giuseppe; Papapietro, Nicola; Petrillo, Stefano; Franceschetti, Edoardo; Maffulli, Nicola; Denaro, Vincenzo



Atorvastatin treatment attenuates motor neuron degeneration in wobbler mice.  


We aimed to study whether atorvastatin treatment can retard motor neuron degeneration in wobbler mice. Wobbler mice and their normal littermates were fed 0.01% atorvastatin-mixed food (10 mg/kg/day) or regular food from age 3-4 weeks of disease onset for four weeks (n=10/group) or more than eight weeks (n=10/group). Motor function was evaluated by pull-strength and deformity scale of the forelimbs. For those symptomatic assessment and body weight were measured weekly. Neuropathological and biochemical changes of the biceps muscle and the cervical cord were analyzed at four weeks after treatment. Compared to vehicle, atorvastatin-treated wobbler mice delayed progression of forelimb motor deficits by more than four weeks. Wobbler mice significantly increased body weight from three weeks post-treatment of atorvastatin, compared with vehicle (p<0.05). Atorvastatin administration suppressed denervation atrophy at 30% (p<0.01), maintained choline acetyl transferase activities of the biceps muscle (p<0.05), and attenuated approximately 30% loss of motor neurons in wobbler mice (p<0.01). Atorvastatin fed to normal littermates did not influence body weight gain, neuropathological and biochemical findings. These data suggest that atorvastatin has neuroprotective effects on denervating muscles and degenerating motor neurons in wobbler mice. PMID:19922131

Iwamoto, Konosuke; Yoshii, Yasuhiro; Ikeda, Ken


Network oscillations in rod-degenerated mouse retinas.  


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



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.



Emotional reactivity and emotion recognition in frontotemporal lobar degeneration  

PubMed Central

Background Frontotemporal lobar degeneration (FTLD) is associated with a profound decline in social and emotional behavior; however, current understanding regarding the specific aspects of emotional functioning that are preserved and disrupted is limited. Objective To assess preservation of function and deficits in two aspects of emotional processing (emotional reactivity and emotion recognition) in FTLD. Methods Twenty-eight FTLD patients were compared with 16 controls in emotional reactivity (self-reported emotional experience, emotional facial behavior, and autonomic nervous system response to film stimuli) and emotion recognition (ability to identify a target emotion of fear, happy, or sad experienced by film characters). Additionally, the neural correlates of emotional reactivity and emotion recognition were investigated. Results FTLD patients were comparable to controls in 1) emotional reactivity to the fear, happy, and sad film clips and 2) emotion recognition for the happy film clip. However, FTLD patients were significantly impaired compared with controls in emotion recognition for the fear and sad film clips. Volumetric analyses revealed that deficits in emotion recognition were associated with decreased lobar volumes in the frontal and temporal lobes. Conclusions The socioemotional decline typically seen in frontotemporal lobar degeneration patients may result more from an inability to process certain emotions in other people than from deficits in emotional reactivity.

Werner, K.H.; Roberts, N.A.; Rosen, H.J.; Dean, D.L.; Kramer, J.H.; Weiner, M.W.; Miller, B.L.; Levenson, R.W.



Encounters between degenerate stars and extrasolar comet clouds  

NASA Astrophysics Data System (ADS)

Under the assumption that the presence of comet clouds around otherwise normal stars is a common occurrence in the Galaxy, the observational consequences of random penetration encounters between the general Galactic population of degenerate stars and these comet clouds is considered. The only case considered is where the compact stars is a single star. For this scenario, encounters involving neutron stars (NSs) result in impact rates 1000-10,000 times slower than in the model of Tremaine and Zytkow (1986). The rate for white dwarfs (WDs) is larger than the one for NSs by a factor of about 30 times the ratio of the degenerate star number densities. The mean impact rate is significantly increased if the number of comets in a cloud is nearly independent of the mass of the central star. It is concluded that some of the observed gamma-ray bursts may be caused by accretion of comets onto NSs and that this scenario, but with a WD as the accretor, probably contributes to the optical flash background rate.

Pineault, Serge; Poisson, Eric



Vitamin E deficiency induces axonal degeneration in mouse hippocampal neurons.  


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



Clenbuterol reduces degeneration of exercised or aged dystrophic (mdx) muscle.  


Evidence of dystrophic muscle degeneration in the hind limb muscles of young (20-week-old) treadmill-exercised or aged (87-week-old) sedentary mdx mice was greatly reduced by treatment with clenbuterol, a beta(2)-adrenoceptor agonist. Daily treadmill exercise for 10 weeks increased the size of regions within the mdx plantaris but not the soleus or gastrocnemius muscles, in which necrotic muscle fibers or the absence of fibers was observed. Clenbuterol reduced the size of these abnormal regions from 21% of total muscle cross-sectional area to levels (4%) found in sedentary mdx mice. In addition, the muscles obtained from aged clenbuterol-treated mdx or wild-type mice did not display the extensive fibrosis or fiber loss observed in untreated mdx mice. These observations are consistent with a mechanism of dystrophic muscle degeneration caused by work load-induced injury that is cumulative with aging and is opposed by beta(2)-adrenoceptor activation. Optimization of beta(2)-agonist treatment of muscular dystrophy in mdx mice may lead to a useful therapeutic modality for human forms of the disease. PMID:10716762

Zeman, R J; Peng, H; Danon, M J; Etlinger, J D



Rare earth nanoparticles prevent retinal degeneration induced by intracellular peroxides.  


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. PMID:18654167

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



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)



APP cleavage dependent and independent axonal degeneration programs share a common Nmnat1-sensitive pathway  

PubMed Central

Axonal degeneration is a hallmark of many debilitating neurological disorders and is thought to be regulated by mechanisms distinct from those governing cell body death. Recently, caspase 6 activation via APP cleavage and activation of DR6 was discovered to induce axon degeneration after NGF withdrawal. We tested whether this pathway is involved in axonal degeneration caused by withdrawal of other trophic support, axotomy or vincristine exposure. Neurturin deprivation, like NGF withdrawal activated this APP/DR6/caspase 6 pathway and resulted in axonal degeneration, however, APP cleavage and caspase 6 activation were not involved in axonal degeneration induced by mechanical or toxic insults. However, loss of surface APP (sAPP) and caspase 6 activation were observed during axonal degeneration induced by dynactin 1(Dctn1) dysfunction, which disrupts axonal transport. Mutations in Dctn1 are associated with motor neuron disease and frontal temporal dementia, thus suggesting that the APP/caspase 6 pathway could be important in specific types of disease-associated axonal degeneration. The NGF deprivation paradigm, with its defined molecular pathway, was used to examine the context of Nmnat-mediated axonal protection. We found that although Nmnat blocks axonal degeneration after trophic factor withdrawal, it did not prevent loss of axon sAPP or caspase 6 activation within the axon, suggesting it acts downstream of caspase 6. These results indicate that diverse insults induce axonal degeneration via multiple pathways and that these degeneration signals converge on a common, Nmnat-sensitive program that is uniquely involved in axonal, but not cell body, degeneration.

Vohra, Bhupinder P.S.; Sasaki, Yo; Miller, Bradley R; Chang, Jufang; DiAntonio, Aaron; Milbrandt, Jeffrey



Striatal degeneration impairs language learning: evidence from Huntington's disease.  


Although the role of the striatum in language processing is still largely unclear, a number of recent proposals have outlined its specific contribution. Different studies report evidence converging to a picture where the striatum may be involved in those aspects of rule-application requiring non-automatized behaviour. This is the main characteristic of the earliest phases of language acquisition that require the online detection of distant dependencies and the creation of syntactic categories by means of rule learning. Learning of sequences and categorization processes in non-language domains has been known to require striatal recruitment. Thus, we hypothesized that the striatum should play a prominent role in the extraction of rules in learning a language. We studied 13 pre-symptomatic gene-carriers and 22 early stage patients of Huntington's disease (pre-HD), both characterized by a progressive degeneration of the striatum and 21 late stage patients Huntington's disease (18 stage II, two stage III and one stage IV) where cortical degeneration accompanies striatal degeneration. When presented with a simplified artificial language where words and rules could be extracted, early stage Huntington's disease patients (stage I) were impaired in the learning test, demonstrating a greater impairment in rule than word learning compared to the 20 age- and education-matched controls. Huntington's disease patients at later stages were impaired both on word and rule learning. While spared in their overall performance, gene-carriers having learned a set of abstract artificial language rules were then impaired in the transfer of those rules to similar artificial language structures. The correlation analyses among several neuropsychological tests assessing executive function showed that rule learning correlated with tests requiring working memory and attentional control, while word learning correlated with a test involving episodic memory. These learning impairments significantly correlated with the bicaudate ratio. The overall results support striatal involvement in rule extraction from speech and suggest that language acquisition requires several aspects of memory and executive functions for word and rule learning. PMID:18842608

De Diego-Balaguer, R; Couette, M; Dolbeau, G; Dürr, A; Youssov, K; Bachoud-Lévi, A-C



Degeneration of the Injured Cervical Cord Is Associated with Remote Changes in Corticospinal Tract Integrity and Upper Limb Impairment  

PubMed Central

Background Traumatic spinal cord injury (SCI) leads to disruption of axons and macroscopic tissue loss. Using diffusion tensor imaging (DTI), we assessed degeneration of the corticospinal tract (CST) in the cervical cord above a traumatic lesion and explored its relationship with cervical atrophy, remote axonal changes within the cranial CST and upper limb function. Methods Nine cervical injured volunteers with bilateral motor and sensory impairment and ten controls were studied. DTI of the cervical cord and brain provided measurements of fractional anisotropy (FA), while anatomical MRI assessed cross-sectional spinal cord area (i.e. cord atrophy). Spinal and central regions of interest (ROI) included the bilateral CST in the cervical cord and brain. Regression analysis identified correlations between spinal FA and cranial FA in the CST and disability. Results In individuals with SCI, FA was significantly lower in both CSTs throughout the cervical cord and brain when compared with controls (p?0.05). Reduced FA of the cervical cord in patients with SCI was associated with smaller cord area (p?=?0.002) and a lower FA of the cranial CST at the internal capsule level (p?=?0.001). Lower FA in the cervical CST also correlated with impaired upper limb function, independent of cord area (p?=?0.03). Conclusion Axonal degeneration of the CST in the atrophic cervical cord, proximal to the site of injury, parallels cranial CST degeneration and is associated with disability. This DTI protocol can be used in longitudinal assessment of microstructural changes immediately following injury and may be utilised to predict progression and monitor interventions aimed at promoting spinal cord repair.

Nagy, Zoltan; Hutton, Chloe; Weiskopf, Nikolaus; Friston, Karl; Wheeler-Kingshott, Claudia A.; Thompson, Alan J.



Detecting Double Degenerate Progenitors of SNe Ia with LISA  

NASA Astrophysics Data System (ADS)

The Galactic population of close white dwarf binaries is expected to provide the largest number of gravitational wave sources for low frequency detectors such as the Laser Interferometer Space Antenna (LISA). Current data analysis techniques have demonstrated the capability of resolving on the order of 104 white dwarf binaries from a 2 year observation. Resolved binaries are either at high frequencies or large amplitudes. Such systems are more likely to be high-mass binaries, a subset of which will be progenitors of SNe Ia in the double degenerate scenario. We report on results of a study of the properties of resolved binaries using a population synthesis model of the Galactic white dwarf binaries and a LISA data analysis algorithm using Mock LISA Data Challenge tools.

Stroeer, Alexander; Benacquista, Matthew; Ceballos, Frank



High Energy Radiative Transfer Processes in the Superdense Degenerate Plasma  

NASA Astrophysics Data System (ADS)

The closed-form system for Kinetic equations has been obtained to describe the multiple interaction processes between high energy photons and particles, nuclei, as well as ions, taking into consideration the possible micro-processes which are typical for “n,p,e”, “A,n,e” and “A,e” phases of superdense degenerate plasma within the neutron stars and white dwarfs. Especially, the role of particle-antiparticle pairs' production and photo-ionization processes are discussed both in single- and multi-photon approaches. The considered system for Kinetic equations of the diffuse fields of photons and particles has been generalized to describe the neutrino-antineutrino beams' transfer problem, especially to estimate their expected flow based on the “secondary side-effects” observation - mainly due to photons, as well as other detectable particles.

Avetissian, Ara K.; Pikichyan, Hovhannes V.



Lipids, Lipoproteins, and Age-Related Macular Degeneration  

PubMed Central

Age-related macular degeneration (AMD) is the leading cause of blindness among the elderly. While excellent treatment has emerged for neovascular disease, treatment for early AMD is lacking due to an incomplete understanding of the early molecular events. A prominent age-related change is the accumulation of neutral lipid in normal Bruch's membrane (BrM) throughout adulthood and also disease-related BrM accumulations called basal deposits and drusen. AMD lesion formation has thus been conceptualized as sharing mechanisms with atherosclerotic plaque formation, where low-density lipoprotein (LDL) retention within the arterial wall initiates a cascade of pathologic events. However, we do not yet understand how lipoproteins contribute to AMD. This paper explores how systemic and local production of lipoproteins might contribute to the pathogenesis of AMD.

Ebrahimi, Katayoon B.; Handa, James T.



Speech and language findings associated with paraneoplastic cerebellar degeneration.  


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 dysarthria is often part of the initial presentation. A retrospective study was conducted of the speech, language, and swallowing concerns of patients with PCD evaluated at the Mayo Clinic in Rochester, MN, between 1990 and 2001. Prospective speech and language assessments were then conducted with 5 patients who had PCD. While ataxic dysarthria was the most common speech diagnosis, a spastic component was recognized frequently enough to suggest that the subacute (days to weeks) emergence and progression of an ataxic or mixed ataxic-spastic dysarthria in the setting of a more diffuse cerebellar ataxia should raise suspicions about PCD and justify further investigation of a possible immune-related etiology. PMID:16229671

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



Fundus autofluorescence and progression of age-related macular degeneration.  


Fundus autofluorescence imaging is an imaging method that provides additional information compared to conventional imaging techniques. It permits to topographically map lipofuscin distribution of the retinal pigment epithelial cell monolayer. Excessive accumulation of lipofuscin granules in the lysosomal compartment of retinal pigment epithelium cells represents a common downstream pathogenetic pathway in various hereditary and complex retinal diseases including age-related macular degeneration (AMD). This comprehensive review contains an introduction in fundus autofluorescence imaging, including basic considerations, the origin of the signal, different imaging methods, and a brief overview of fundus autofluorescence findings in normal subjects. Furthermore, it summarizes cross-sectional and longitudinal fundus autofluorescence findings in patients with AMD, addresses the pathophysiological significance of increased fundus autofluorescence, and characterizes different fundus autofluorescence phenotypes as well as fundus autofluorescence alterations with disease progression. PMID:19171212

Schmitz-Valckenberg, Steffen; Fleckenstein, Monika; Scholl, Hendrik P N; Holz, Frank G


The Relationship between Subclinical Asperger's Syndrome and Frontotemporal Lobar Degeneration  

PubMed Central

Background/Aims The existence of the behavioral variant of frontotemporal dementia (bv-FTD), including senile Asperger's syndrome (AS), has been proposed. However, there are no empirical case reports to support the proposal. In this report, we present 3 patients who showed symptoms of bv-FTD and demonstrated signs of autistic spectrum disorder, especially AS. Methods We evaluated 3 subjects using the diagnostic criteria for bv-FTD, and their caregivers retrospectively provided data to calculate the Autism-Spectrum Quotient, Japanese version [Wakabayashi et al.: Shinrigaku Kenkyu 2004;75:78–84]. We also compared these data with those obtained from 3 individuals with Alzheimer's disease. Results All 3 patients met the criteria for bv-FTD and had a higher Autism-Spectrum Quotient score than did comparable Alzheimer's disease subjects. Conclusion It is possible that some senile persons with frontotemporal lobar degeneration-like maladaptive behavior may suffer from subclinical AS.

Midorikawa, Akira; Kawamura, Mitsuru



Self-phase-locked degenerate femtosecond optical parametric oscillator.  


We demonstrated a stable degenerate synchronously pumped femtosecond optical parametric oscillator (SPOPO) as a divide-by-2 subharmonic generator. The SPOPO exhibited passive all-optical self-phase-locking between the pump and signal/idler and thus required no external electronic feedback to produce the phase-locked subharmonic. We employed a type I phase-matched, 1-mm-long, periodically poled MgO:LiNbO3 crystal as the nonlinear gain element and an 80 MHz mode-locked Ti:sapphire laser with 180 fs pulses tuned at 775 nm as the pump. The SPOPO generated transform-limited 70 fs phase-locked output pulses centered at 1550 nm. The self-phase-locking operation was confirmed by separate beat-note measurement techniques with respect to the pump laser and with respect to an external cw laser. PMID:18709125

Wong, Samuel T; Plettner, Tomas; Vodopyanov, Konstantin L; Urbanek, Karel; Digonnet, Michel; Byer, Robert L



Broadband degenerate OPO for mid-infrared frequency comb generation.  


We present a new technique suitable for generating broadband phase- and frequency-locked frequency combs in the mid-infrared. Our source is based on a degenerate optical parametric oscillator (OPO) which rigorously both down-converts and augments the spectrum of a pump frequency comb provided by a commercial mode-locked near-IR laser. Low intracavity dispersion, combined with extensive cross-mixing of comb components, results in extremely broad instantaneous mid-IR bandwidths. We achieve an output power of 60 mW and 20 dB bandwidth extending from 2500 to 3800 nm. Among other applications, such a source is well-suited for coherent Fourier-transform spectroscopy in the absorption-rich mid-IR 'molecular fingerprint' region. PMID:21451655

Leindecker, Nick; Marandi, Alireza; Byer, Robert L; Vodopyanov, Konstantin L



Lipid degeneration in pheochromocytomas mimicking adrenal cortical tumors.  


A case of bilateral adrenal pheochromocytomas with unusual morphologic features is reported in a 27-year-old man with a family history of von Hippel-Lindau disease. In both glands, the medulla was replaced by neoplasms with two distinct gross and microscopic appearances. There was typical pheochromocytoma in areas of dusky red tissue. The yellow nodules noted on gross examination were microscopically composed of large cells with vacuolated cytoplasm. Fat stains confirmed the presence of lipid in these areas. Immunohistochemistry revealed positivity for neuron-specific enolase and chromogranin in the cytoplasm of pheochromocytes, as well as in the perinuclear cytoplasm and processes of cells scattered in the yellow nodules. Ultrastructural examination of the yellow lesions showed characteristics of pheochromocytoma and an extensive accumulation of lipid. Although gross and light-microscopic examination of the yellow tissue suggested adrenal cortical nodules, immunohistochemistry and electon microscopy elucidated lipid degeneration within pheochromocytoma, a finding not previously described. PMID:3592062

Ramsay, J A; Asa, S L; van Nostrand, A W; Hassaram, S T; de Harven, E P



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)



Origins of Band-Gap Renormalization in Degenerately Doped Semiconductors  

SciTech Connect

Degenerate n-type doping of semiconductors results in optical band-gap widening through occupation of the conduction band, which is partially offset by the so-called band-gap renormalization. From investigation of the magnitude and origin of these shifts through density-functional band-structure theory, we demonstrate that the key contribution to renormalization arises from the nonparabolic nature of the host conduction band but not the rigid shift of the band edges, as is the current paradigm. Furthermore, the carrier dependence of the band-gap widening is highly sensitive to the electronic states of the dopant ion, which can be involved in a significant reconstruction of the lower conduction band.

Walsh, A.; Da Silva, J.L.F.; Wei, S.-H.



Bietti's tapetoretinal degeneration with marginal corneal dystrophy crystalline retinopathy.  

PubMed Central

In 1937 Bietti reported a tapetoretinal degeneration with associated corneal deposits at the limbus. The hallmark of the disease was the crystalline characteristics of the retinal spots as well as those at the corneal limbus. Bagolini and Ioli-Spade in 1968 presented a 30 year follow-up on Bietti's cases and presented six additional cases. The present report delas with this entity in Orientals, a Chinese woman and a Japanese man. Corneal and conjunctival biopsy from the female patient revelaed a lipid deposition in both fibroblasts and epithelium. The term "crystalline retinopathy" has been added to the description of this entity since it defines the most characteristic feature of the syndrome. Images FIGURE 7 A FIGURE 7 B FIGURE 1 A FIGURE 1 B FIGURE 1 C FIGURE 2 A FIGURE 2 B FIGURE 2 C FIGURE 3 FIGURE 4 A FIGURE 4 B FIGURE 5 FIGURE 6 A FIGURE 6 B FIGURE 6 C FIGURE 8

Welch, R B



A novel noise optimization technique for inductively degenerated CMOS LNA  

NASA Astrophysics Data System (ADS)

This paper proposes a novel noise optimization technique. The technique gives analytical formulae for the noise performance of inductively degenerated CMOS low noise amplifier (LNA) circuits with an ideal gate inductor for a fixed bias voltage and nonideal gate inductor for a fixed power dissipation, respectively, by mathematical analysis and reasonable approximation methods. LNA circuits with required noise figure can be designed effectively and rapidly just by using hand calculations of the proposed formulae. We design a 1.8 GHz LNA in a TSMC 0.25 ?m CMOS process. The measured results show a noise figure of 1.6 dB with a forward gain of 14.4 dB at a power consumption of 5 mW, demonstrating that the designed LNA circuits can achieve low noise figure levels at low power dissipation.

Zhiqing, Geng; Haiyong, Wang; Nanjian, Wu



Age-related macular degeneration and the aging eye  

PubMed Central

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

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



Effects of axon degeneration on oligodendrocyte lineage cells: Dorsal rhizotomy evokes a repair response while axon degeneration rostral to spinal contusion induces both repair and apoptosis  

PubMed Central

Wallerian degeneration in the dorsal columns (DC) after spinal cord injury (SCI) is associated with microglial activation and prolonged oligodendrocyte (OL) apoptosis that may contribute to demyelination and dysfunction after SCI. But, there is an increase in OL lineage cells after SCI that may represent a reparative response, and there is evidence for remyelination after SCI. To assess the role of axonal degeneration per se in OL apoptosis and proliferation, we cut the L2-S2 dorsal roots producing massive axonal degeneration and microglial activation in the DC, and found no evidence of OL loss or apoptosis. Rather, the numbers of OL-lineage cells positive for NG2 and APC (CC1) increased, and BrdU studies suggested new OL formation. We then tested contusion SCI (cSCI) that results in comparable degeneration in the DC rostral to the injury, microglial activation, and apoptosis of DC OLs by 8 days. NG2+ cell proliferation and oligodendrogenesis was seen as after rhizotomy. The net result of this combination of proliferation and apoptosis was a reduction in DC OLs, confirming earlier studies. Using an antibody to oxidized nucleic acids, we found rapid and prolonged RNA oxidation in OLs rostral to cSCI, but no evidence of oxidative stress in DC OLs after rhizotomy. These results suggest that signals associated with axonal degeneration are sufficient to induce OL proliferation, and that secondary injury processes associated with the central SCI, including oxidative stress, rather than axonal degeneration per se, are responsible for OL apoptosis.

Sun, Fang; Lin, Chien-Liang Glenn; McTigue, Dana; Shan, Xiu; Tovar, C Amy; Bresnahan, Jacqueline C.; Beattie, Michael S.



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


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



Mechanical properties of active and degenerating eclosion muscles of the flesh fly, Sarcophaga bullata  

Microsoft Academic Search

Holometabolous insects use specialized muscles to eclose from the pupa. Many of these muscles are supercontracting, and most of them undergo programmed degeneration shortly after eclosion. We describe mechanical properties of the dorsal anterior eclosion muscle (DAEM) of the flesh fly, Sarcophaga bullata, and changes during the degeneration process. Skinned fibers from active DAEM show a steep sigmoidal relationship (Hill

Gerald W. M. Bothe; Stefan Galler



The relevance of long head biceps degeneration in the presence of rotator cuff tears  

Microsoft Academic Search

BACKGROUND: Long head biceps (LHB) degeneration in combination with rotator cuff tears can be a source of chronic shoulder pain. LHB tenotomy is an approved surgical procedure for pain reduction and improvement of joint function, however, the pathophysiology of LHB degeneration is not fully understood. In the literature, neoangiogenesis in tendon tissue has previously been shown to be associated with

Stefan Lakemeier; Johannes JA Reichelt; Nina Timmesfeld; Susanne Fuchs-Winkelmann; Juergen RJ Paletta; Markus D Schofer



Clinicopathological correlation in exudative age related macular degeneration: histological differentiation between classic and occult choroidal neovascularisation  

Microsoft Academic Search

AIMSTo analyse the histopathology of classic and occult choroidal neovascular membrane surgical specimens in age related macular degeneration.METHODS35 membranes, from a consecutive series of surgically removed choroidal neovascular membranes in age related macular degeneration, were classified as classic or occult following the guidelines of the Macular Photocoagulation Study. Membranes with classic as well as occult components were considered as mixed

B A Lafaut; K U Bartz-Schmidt; C Vanden Broecke; S Aisenbrey; J J De Laey; K Heimann



Mesenchymal Stem Cells Arrest Intervertebral Disc Degeneration Through Chondrocytic Differentiation and Stimulation of Endogenous Cells  

Microsoft Academic Search

Degenerative disc disease (DDD) is a common disease which affects millions of people. Autograft of the bone marrow derived mesenchymal stem cells (BMSCs) have been shown to have the ability to arrest degeneration in rabbit and canine intervertebral discs. In this study, we have used the mouse model to investigate the mechanism of degeneration arrest. BMSC from Egfp transgenic mice

Fan Yang; Victor YL Leung; Keith DK Luk; Danny Chan; Kenneth MC Cheung



Phototoxic retinal degeneration and toxicokinetics of sitafloxacin, a quinolone antibacterial agent, in mice  

Microsoft Academic Search

We examined drug concentrations and the incidence of retinal degeneration in the eyes of albino BALB\\/c mice after a single intravenous administration of sitafloxacin plus a 4 h period of UVA irradiation. Retinal degeneration was induced at 40 mg\\/kg or more plus UVA irradiation, and there was little decrease in ocular sitafloxacin concentration under UVA irradiation. We then examined the

Kohji Shimoda; Satoshi Okawara; Michiyuki Kato



Genetic Linkage of Snowflake Vitreoretinal Degeneration to Chromosome 2q36  

Microsoft Academic Search

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

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



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

Microsoft Academic Search

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

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



In vivo evidence for the selective subcortical degeneration in Huntington's disease  

Microsoft Academic Search

Although Huntington's disease is largely considered to be a subcortical disease, there is no clear consensus on whether all deep grey matter loss is a direct downstream consequence of the massive degeneration of the medium-size spiny neurons in the striatum. Our aim was to characterise in vivo such preferential degeneration by analysing various distinct diffusion imaging measures including mean diffusivity,

Gwenaëlle Douaud; Timothy E. Behrens; Cyril Poupon; Yann Cointepas; Saâd Jbabdi; Véronique Gaura; Narly Golestani; Pierre Krystkowiak; Christophe Verny; Philippe Damier; Anne-Catherine Bachoud-Lévi; Philippe Hantraye; Philippe Remy



bcl-2 Overexpression Reduces Apoptotic Photoreceptor Cell Death in Three Different Retinal Degenerations  

Microsoft Academic Search

Apoptosis of photoreceptors occurs infrequently in adult retina but can be triggered in inherited and environmentally induced retinal degenerations. The protooncogene bcl-2 is known to be a potent regulator of cell survival in neurons. We created lines of transgenic mice overexpressing bcl-2 to test for its ability to increase photoreceptor survival. Bcl-2 increased photoreceptor survival in mice with retinal degeneration

Jeannie Chen; John G. Flannery; Matthew M. Lavail; Roy H. Steinberg; Jun Xu; Melvin I. Simon



Quality of life in age-related macular degeneration: a review of the literature  

Microsoft Academic Search

BACKGROUND: The Age-related Macular Degeneration Alliance International commissioned a review of the literature on quality of life (QoL) in macular degeneration (MD) with a view to increasing awareness of MD, reducing its impact and improving services for people with MD worldwide. METHOD: A systematic review was conducted using electronic databases, conference proceedings and key journal hand search checks. The resulting

Jan Mitchell; Clare Bradley



Simulating the Double-Degenerate Channel for Type Ia Supernovae  

NASA Astrophysics Data System (ADS)

Type Ia Supernovae (SNe Ia) are the thermonuclear explosions of white dwarfs, and are of fundamental importance to the study of many phenomena, including the expansion of the universe and dark energy. For many years, it was suspected that that SNe Ia occur in binary systems, but the identity of the white dwarf’s companion could not be determined. A leading hypothesis, the single-degenerate (SD) channel, suggests that the companion is either on the main sequence or a red giant, and that the white dwarf accretes matter off of its companion until it nears the Chandrasekhar limit of 1.4 solar masses, causing the white dwarf to detonate shortly thereafter. Another hypothesis, the double-degenerate (DD) channel, proposes that both stars in the system are white dwarfs and that they merge together, resulting in a central, rapidly spinning white dwarf, surrounded by a thick disk of remnant material. Precisely how this triggers a detonation remains unclear; early spherically-symmetric models by Nomoto et al. indicated that merged white dwarfs would collapse to neutron stars instead of producing supernovae. Recent observations of two supernovae discovered last year by the Palomar Transient Factory (PTF), SN 2011 fe and SN PTF11k, have provided evidence that suggests that both the SD and DD channels coexist in nature. Consequently, it is important to develop simulations that can resolve the mystery of the DD channel’s detonation mechanism. To this end, we use a smoothed-particle hydrodynamics (SPH) code, GADGET-1, to model the rotating flows characteristic of merged DD systems and study how they evolve with time.

Jumper, Kevin; Fisher, R. T.



Renin angiotensin system and gender differences in dopaminergic degeneration  

PubMed Central

Background There are sex differences in dopaminergic degeneration. Men are approximately two times as likely as premenopausal women of the same age to develop Parkinson's disease (PD). It has been shown that the local renin angiotensin system (RAS) plays a prominent role in sex differences in the development of chronic renal and cardiovascular diseases, and there is a local RAS in the substantia nigra and dopaminergic cell loss is enhanced by angiotensin via type 1 (AT1) receptors. Results In the present study, we observed that intrastriatal injection of 6-hydroxydopamine induced a marked loss of dopaminergic neurons in the substantia nigra of male rats, which was significantly higher than the loss induced in ovariectomized female rats given estrogen implants (i.e. rats with estrogen). However, the loss of dopaminergic neurons was significantly lower in male rats treated with the AT1 antagonist candesartan, and similar to that observed in female rats with estrogen. The involvement of the RAS in gender differences in dopaminergic degeneration was confirmed with AT1a-null mice lesioned with the dopaminergic neurotoxin MPTP. Significantly higher expression of AT1 receptors, angiotensin converting enzyme activity, and NADPH-oxidase complex activity, and much lower levels of AT2 receptors were observed in male rats than in female rats with estrogen. Conclusions The results suggest that brain RAS plays a major role in the increased risk of developing PD in men, and that manipulation of brain RAS may be an efficient approach for neuroprotective treatment of PD in men, without the feminizing effects of estrogen.



A novel grading scale for striatonigral degeneration (multiple system atrophy).  


Striatonigral degeneration (SND) is commonly thought to represent the neuropathological substrate of L-Dopa unresponsive parkinsonism in patients with multiple system atrophy (MSA). Other neuropathological hallmarks of MSA include olivopontocerebellar atrophy (OPCA) and preganglionic sympathetic spinal cord lesions. Clinicopathological evaluation of MSA patients recruited into ongoing natural history studies or neuroprotective intervention trials will require standardized grading of MSA pathology. Based on 25 autopsy cases of MSA, we propose a novel SND grading scale which allows semiquantitative assessment of lesion severity based on neuronal loss, astrogliosis and presence of alpha-synuclein positive glial cytoplasmic inclusions (GCIs) in substantia nigra, putamen, caudate nucleus, and globus pallidus. SND grade I is defined as degeneration of the substantia nigra pars compacta (SNC) with relative preservation of the striatum except for minimal gliosis and GCIs in the posterior putamen ("minimal change MSA"). SND grade II is characterized by neuronal loss, astrogliosis and presence of GCIs in SNC and posterior/dorsolateral putamen. Caudate nucleus and external globus pallidus may exhibit slight gliosis. Striatal pathology is severe and extends to anterior ventromedial subregions in SND grade III. There is neuronal loss in caudate nucleus and globus pallidus. GCIs are more abundant in grade II than grade III SNC and putamen. Preliminary clinicopathologic correlation studies suggest milder parkinsonian disability and better initial L-Dopa responsiveness in SND grade I and II cases compared to grade III cases. Prospective clinicopathologic studies are required to validate the proposed SND grading scale and may result in further subdivisions, particularly of SND grade III. PMID:11956953

Wenning, G K; Seppi, K; Tison, F; Jellinger, K



Genetic susceptibility of intervertebral disc degeneration among young Finnish adults  

PubMed Central

Background Disc degeneration (DD) is a common condition that progresses with aging. Although the events leading to DD are not well understood, a significant genetic influence has been found. This study was undertaken to assess the association between relevant candidate gene polymorphisms and moderate DD in a well-defined and characterized cohort of young adults. Focusing on young age can be valuable in determining genetic predisposition to DD. Methods We investigated the associations of existing candidate genes for DD among 538 young adults with a mean age of 19 belonging to the 1986 Northern Finland Birth Cohort. Nineteen single nucleotide polymorphisms (SNP) in 16 genes were genotyped. We evaluated lumbar DD using the modified Pfirrmann classification and a 1.5-T magnetic resonance scanner for imaging. Results Of the 538 individuals studied, 46% had no degeneration, while 54% had DD and 51% of these had moderate DD. The risk of DD was significantly higher in subjects with an allele G of IL6 SNPs rs1800795 (OR 1.45, 95% CI 1.07-1.96) and rs1800797 (OR 1.37, 95% CI 1.02-1.85) in the additive inheritance model. The role of IL6 was further supported by the haplotype analysis, which resulted in an association between the GGG haplotype (SNPs rs1800797, rs1800796 and rs1800795) and DD with an OR of 1.51 (95% CI 1.11-2.04). In addition, we observed an association between DD and two other polymorphisms, SKT rs16924573 (OR 0.27 95% CI 0.07-0.96) and CILP rs2073711 in women (OR 2.04, 95% CI 1.07-3.89). Conclusion Our results indicate that IL6, SKT and CILP are involved in the etiology of DD among young adults.



Age-related macular degeneration: Evidence of a major gene  

SciTech Connect

Age-related macular degeneration is a major cause of blindness in developing countries. It remains a very poorly understood disorder. Although environmental and genetic factors have been implicated in its pathogenesis, none have been firmly implicated. The purpose of this study was to use pedigree analysis to evaluate the possible role of a major gene as a determinant of familial aggregation. Information was collected regarding occupation, smoking, sun exposure, associated medical problems and family history. 50 probands with age-related macular degeneration (ARMD) and 39 age, race and sex-matched controls were included in the study. In the ARMD group 15/50 (30%) of probands reported a positive family history; 22 out of 222 first degree relatives over age 60 were reported to be affected. In the control groups, none of the 138 first degree relatives over age 50 had a history of ARMD. This difference is statistically significant (p = 0.0003), indicating that genetic factors may play an important role in the pathogenesis of ARMD. In the ARMD group more siblings as compared to parents (16/127 vs. 5/82) were affected. 5/50 (10%) of the ARMD probands also gave a history of a second degree relative affected with ARMD, compared to none known among the relatives of controls. Data from 50 pedigrees were analyzed by complex segregation analysis under a class A regressive logistic model using the REGD program implemented in the SAGE package. Preliminary results allow rejection of a polygenic model and suggest there is a major gene for ARMD in these families. The inheritance model most compatible with the observed familial aggregation is autosomal recessive. In conclusion, these results are suggestive of a major gene effect in the etiology of ARMD. Identification of a major gene effect is a first step to further pursue linkage analysis and to search for the gene(s) involved in the causation of ARMD.

Bhatt, S.; Warren, C.; Yang, H. [UCLA School of Medicine, Los Angeles, CA (United States)] [and others



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


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

Carpentier, Pierre; Foquin, Annie; Dorandeu, Frédéric



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.


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.



Screening UBQLN-2 in French frontotemporal lobar degeneration and frontotemporal lobar degeneration-amyotrophic lateral sclerosis patients.  


The ubiquilin-2 gene (UBQLN-2) is the only amyotrophic lateral sclerosis (ALS)-related gene mapping on the X chromosome. Mutations in the PXX domain of UBQLN-2 have been first described in ALS patients with a mutational frequency of 2.6% in familial ALS cases with no evidence of male-to-male transmission. Different populations have been further tested with mutations largely distributed in the gene and lower frequency of positive cases. To determine the genetic contribution of UBQLN-2 in frontotemporal lobar degeneration (FTLD) and FTLD-ALS, we screened a cohort of 136 French patients, identifying a missense variant (c.1006A>G; p.T336A) in 1 FTLD patient whose biological relevance to disease is questionable. We conclude that UBQLN-2 mutations related to ALS/FTLD are extremely rare in French FTLD and FTLD-ALS patients and should not be analyzed systematically. PMID:23582661

Lattante, Serena; Le Ber, Isabelle; Camuzat, Agnès; Pariente, Jérémie; Brice, Alexis; Kabashi, Edor



Orientation of a Novel DNA Binding Site Affects Human Papillomavirus-Mediated Transcription and Replication  

Microsoft Academic Search

A consensus binding site for the human papillomavirus (HPV) E2 protein was determined from an unbiased set of degenerate oligonucleotides using cyclic amplification and selection of targets (CASTing). Detectable DNA-protein complexes were formed after six to nine cycles of CASTing. A population of selected binding sites was cloned, and a consensus was determined by statistical analysis of the DNA sequences





EPA Science Inventory

Site rank is formulated for ranking the relative hazard of contamination sources and vulnerability of drinking water wells. Site rank can be used with a variety of groundwater flow and transport models....


Anecortave acetate in the treatment of age-related macular degeneration  

PubMed Central

RETAANE® 15mg (anecortave acetate suspension) is under investigation to treat exudative age-related macular degeneration (AMD), the single largest cause of blindness in the Western world, affecting over 15 million people in the USA. RETAANE suspension is a unique synthetic cortisene and has antiangiogenic properties that were established in multiple experimental models of angiogenesis. The molecule acts at multiple sites of the angiogenic cascade. Clinical trials in patients with exudative AMD have demonstrated the excellent safety record of both the drug anecortave acetate and the posterior juxtascleral depot (PJD) administration procedure. A pivotal study comparing RETAANE suspension with placebo showed a significantly higher chance of maintaining vision in the treatment (73%) as compared with placebo (47%). Another study compared RETAANE suspension with Visudyne® photodynamic therapy, revealing no statistically significant differences between the two treatments over 24 months. AMD is a multi-faceted disease and therefore a molecule such as RETAANE suspension with a unique mechanism of action, demonstrated clinical efficacy, and retreatment every six months is an important potential treatment option which should be further investigated both as a monotherapy or in combination with other treatment strategies.

Augustin, Albert



Deafness and retinal degeneration in a novel USH1C knock-in mouse model.  


Usher syndrome is the leading cause of combined deaf-blindness, but the molecular mechanisms underlying the auditory and visual impairment are poorly understood. Usher I is characterized by profound congenital hearing loss, vestibular dysfunction, and progressive retinitis pigmentosa beginning in early adolescence. Using the c.216G>A cryptic splice site mutation in Exon 3 of the USH1C gene found in Acadian Usher I patients in Louisiana, we constructed the first mouse model that develops both deafness and retinal degeneration. The same truncated mRNA transcript found in Usher 1C patients is found in the cochleae and retinas of these knock-in mice. Absent auditory-evoked brainstem responses indicated that the mutant mice are deaf at 1 month of age. Cochlear histology showed disorganized hair cell rows, abnormal bundles, and loss of both inner and outer hair cells in the middle turns and at the base. Retinal dysfunction as evident by an abnormal electroretinogram was seen as early as 1 month of age, with progressive loss of rod photoreceptors between 6 and 12 months of age. This knock-in mouse reproduces the dual sensory loss of human Usher I, providing a novel resource to study the disease mechanism and the development of therapies. PMID:20095043

Lentz, Jennifer J; Gordon, William C; Farris, Hamilton E; MacDonald, Glen H; Cunningham, Dale E; Robbins, Carol A; Tempel, Bruce L; Bazan, Nicolas G; Rubel, Edwin W; Oesterle, Elizabeth C; Keats, Bronya J



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.

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.; Mannikko, Minna; Makela, Pirkka; Karppinen, Jaro; Jarvelin, 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



Differential proteomic analysis of the mouse retina: The induction of crystallin proteins by retinal degeneration in the rd1 mouse  

Microsoft Academic Search

We have applied proteomic analysis to the degeneration of photoreceptors. In the rd1 mouse, a recessive mutation in the PDE6B gene leads to rapid loss of rods through apoptosis. By 5 wk postnatal, virtually all rod photorecep- tors have degenerated, leaving one row of cones that degenerates secondarily. In order to assess comparative protein expression, proteins extracted from whole retina

Nukhet Cavusoglu; Saddek Mohand-Saõ; Olivier Poch; Alain Van-Dorsselaer; Thierry Leveillard



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.

Graham, Stuart L.; Klistorner, Alexander



Degenerate dispersive equations arising in the study of magma dynamics  

NASA Astrophysics Data System (ADS)

An outstanding problem in Earth science is understanding the method of transport of magma in the Earth's mantle. Two proposed methods for this transport are percolation through porous rock and flow up conduits. Under reasonable assumptions and simplifications, both means of transport can be described by a class of degenerate nonlinear dispersive partial differential equations of the form: \\[ \\begin{equation*}\\phi_{t}+(\\phi^{n})_{z}-(\\phi^{n}(\\phi^{-m}\\phi_{t})_{z})_{z}=0,\\end{equation*} \\] where phi(z, 0) > 0 and phi(z, t) ? 1 as z ? ±?. Although we treat arbitrary n and m, the exponents are physically expected to be between 2 and 5 and 0 and 1, respectively. In the case of percolation, the magma moves via the buoyant ascent of a less dense phase, treated as a fluid, through a denser, porous phase, treated as a matrix. In contrast to classical porous media problems where the matrix is fixed and the fluid is compressible, here the matrix is deformable, with a viscous constitutive relation, and the fluid is incompressible. Moreover, the matrix is modelled as a second, immiscible, compressible fluid to mimic the process of dilation of the pores. Flow via a conduit is modelled as a viscously deformable pipe of magma, fed from below. Analogue and numerical experiments suggest that these equations behave akin to KdV and BBM; initial conditions evolve into a collection of solitary waves and dispersive radiation. As phi ? 0, the equations become degenerate. A general local well-posedness existence theory is given for a physical class of data (roughly H1) via fixed point methods. The strategy requires positive lower bounds on phi(z, t). The key to global existence is the persistence of these bounds for all time. Furthermore, we construct a Lyapunov energy functional, which is locally convex about the uniform porosity state, phi ? 1, and prove (global in time) nonlinear dynamic stability of the uniform state for any m and n. For data which are large perturbations of the uniform state, we prove global in time well-posedness for restricted ranges of m and n. This includes, for example, the case n = 4,m = 0, where an appropriate uniform in time lower global on phi can be proved using the conservation laws. We compare the dynamics with that of other problems and discuss open questions concerning a larger range of exponents, for which we conjecture global existence.

Simpson, G.; Spiegelman, M.; Weinstein, M. I.



Distinct pathways mediate axon degeneration during apoptosis and axon-specific pruning.  


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 deprivation, microfluidic chamber experiments reveal that Caspase-6 deficiency only protects axons during axon-specific but not whole-cell (apoptotic) nerve growth factor deprivation. Strikingly, axon-selective degeneration requires the apoptotic proteins Caspase-9 and Caspase-3 but, in contrast to apoptosis, not apoptotic protease activating factor-1. Additionally, cell bodies of degenerating axons are protected from caspase activation by proteasome activity and X-linked inhibitor of apoptosis protein. 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; Hampton Henley, W; Michael Ramsey, J; Deshmukh, Mohanish



Mitochondrial swelling and microtubule depolymerization are associated with energy depletion in axon degeneration.  


Although mitochondrial dysfunction is intimately related to axonal degeneration following nerve injury, the molecular mechanisms of mitochondrial swelling and its mechanistic relation to axonal degeneration are largely unknown. Previous studies have demonstrated that axonal degeneration in the injured peripheral nerves shows two morphologically distinct phases: (1) A latency period (?24h), in which the morphology of axonal cytoskeletons seems unchanged, followed by (2) an execution period (36-48h), which shows a catastrophic granular degeneration of most axonal structures in rodent axons. In the present study, we found that, in the sciatic nerve axotomy model, energy failure and microtubule depolymerization occurred during the latency period whereas mitochondrial swelling and neurofilament degradation started in the execution period. The energy repletion with NAD or an NAD/pyruvate mixture inhibited microtubule depolymerization, mitochondrial swelling and axonal degeneration in transected sciatic nerve axons. In addition, microtubule perturbing agents enhanced axonal degeneration and mitochondrial swelling. Extracellular calcium chelation did not affect energy failure, microtubule depolymerization or mitochondrial swelling, but it did prevent neurofilament degradation. These findings suggest that an early disturbance in energy dynamics regardless of mitochondrial swelling might be a key trigger for the initiation of axonal degeneration and that extracellular calcium influx is a late effector for neurofilament degradation. PMID:23485808

Park, J Y; Jang, S Y; Shin, Y K; Koh, H; Suh, D J; Shinji, T; Araki, T; Park, H T



dnc-1/dynactin 1 knockdown disrupts transport of autophagosomes and induces motor neuron degeneration.  


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

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



Cell degeneration is not a primary causer for Connexin26 (GJB2) deficiency associated hearing loss.  


Connexin26 (Cx26, GJB2) mutations can induce congenital deafness and are responsible for ?50% of nonsyndromic hearing loss in children. Mouse models show that Cx26 deficiency induces cochlear development disorder, hair cell loss, and spiral ganglion (SG) neuron degeneration. Hair cell loss and cell degeneration have been considered as a primary causer responsible for Cx26 deficiency associated hearing loss. In this study, by coincidental examination of cochlear postnatal development with recording of auditory brainstem response (ABR) and hair cell function, we found that occurrence of hearing loss in Cx26 knockout (KO) mice was ahead of hair cell loss and cochlear cell degeneration. ABR was absent at the whole-frequency range (8-40 kHz) after birth. However, cochlear cells including SG neurons had no significant degeneration throughout postnatal development. Severe cochlear hair cell loss and SG neuron degeneration were only visible in middle and basal turns, i.e., in middle and high frequency regions, in the adult Cx26 KO mouse cochlea. Functional tests show that hair cells in Cx26 KO mice functioned normally; outer hair cells retained electromotility. These data suggest that cell degeneration is not a primary causer of Cx26 deficiency associated hearing loss. Some mechanisms other than cell degeneration, such as cochlear development disorders, may play an essential role in this common hereditary deafness. PMID:22975134

Liang, Chun; Zhu, Yan; Zong, Liang; Lu, Guang-Jin; Zhao, Hong-Bo



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


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



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


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



NMR based structure–activity relationship analysis of an antimicrobial peptide, thanatin, engineered by site-specific chemical modification: Activity improvement and spectrum alteration  

Microsoft Academic Search

Activity improvement of an antimicrobial peptide, thanatin, has been achieved up to 4-fold higher than natural original one by site-specific chemical modifications with tert-butyl group at two cysteine residues which form an intramoleular disulfide bridge. The chemically modified thanatin (C11tBu\\/C18tBu) exhibited improved antimicrobial activity toward Gram-positive bacteria, Micrococcus luteus, whereas lowered activity toward Gram-negative bacteria, Escherichia coli. This finding suggests

Tomohiro Imamura; Naoki Yamamoto; Atsuo Tamura; Shinji Murabayashi; Shigeki Hashimoto; Hiroaki Shimada; Seiichi Taguchi



Molecular mechanisms of retinal pigment epithelium damage and development of age-related macular degeneration.  


Age-related macular degeneration (AMD) is attributed to a complex interaction of genetic and environmental factors. It is characterized by degeneration involving the retinal photoreceptors, retinal pigment epithelium (RPE) and Bruch's membrane, as well as alterations in choroidal capillaries. AMD pathogenesis is strongly associated with chronic oxidative stress and inflammation that ultimately lead to protein damage, aggregation and degeneration of RPE. Specific degenerative findings for AMD are accumulation of intracellular lysosomal lipofuscin and extracellular drusens. In this review, we discuss thoroughly RPE-derived mechanisms in AMD pathology. PMID:22112056

Kinnunen, Kati; Petrovski, Goran; Moe, Morten C; Berta, András; Kaarniranta, Kai



Renormalization-group effects on scenario with nearly degenerate neutrino masses and bi-maximal mixing  

NASA Astrophysics Data System (ADS)

The renormalization-group effects on the scenario with nearly degenerate mass and bi-maximal mixing of neutrinos are analysed. Consequently, we show explicitly in the SO(3) gauge model that the renormalization-group effects could modify the fitting values of the relevant basic parameters of the model, but leave the nearly degenerate neutrino mass and bi-maximal mixing scenario stable for reconciling both solar and atmospheric neutrino data. The approximately degenerate Majorana neutrino masses are allowed to be large enough to play a significant cosmological role without conflicting with the current neutrinoless double beta decay.

Wu, Yue-Liang



Atypical presentation of Salzmann nodular degeneration diagnosed with ultra-high-resolution optical coherence tomography.  


A 59-year-old woman presented with bilateral, peripheral, circular corneal infiltrates. There was a clear zone separating the outer margin of the degeneration from the limbus in both eyes. The inner margins were indistinct. Ultra-high-resolution optical coherence tomography (UHR-OCT) imaging demonstrated subepithelial infiltrations with epithelial thinning and corneal surface elevation. The infiltrate was accompanied by significant stromal scarring, which reached deep layers of the corneal stroma. UHR-OCT findings were consistent with Salzmann nodular degeneration. UHR-OCT can be used as an optical biopsy to diagnose atypical corneal degenerations without tissue sampling. PMID:22150601

Hurmeric, Volkan; Yoo, Sonia H; Galor, Anat; Canto, Ana Paula; Wang, Jianhua



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

NASA Astrophysics Data System (ADS)

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

Stepanova, Ekaterina V.; Shishkov, Andrey E.



Integrin - Dependent Mechanotransduction in Mechanically Stimulated Human Annulus Fibrosus Cells: Evidence for an Alternative Mechanotransduction Pathway Operating with Degeneration  

PubMed Central

Intervertebral disc (IVD) cells derived from degenerate tissue respond aberrantly to mechanical stimuli, potentially due to altered mechanotransduction pathways. Elucidation of the altered, or alternative, mechanotransduction pathways operating with degeneration could yield novel targets for the treatment of IVD disease. Our aim here was to investigate the involvement of RGD-recognising integrins and associated signalling molecules in the response to cyclic tensile strain (CTS) of human annulus fibrosus (AF) cells derived from non-degenerate and degenerate IVDs. AF cells from non-degenerate and degenerate human IVDs were cyclically strained with and without function blocking RGD – peptides with 10% strain, 1.0 Hz for 20 minutes using a Flexercell® strain device. QRT-PCR and Western blotting were performed to analyse gene expression of type I collagen and ADAMTS -4, and phosphorylation of focal adhesion kinase (FAK), respectively. The response to 1.0 Hz CTS differed between the two groups of AF cells, with decreased ADAMTS -4 gene expression and decreased type I collagen gene expression post load in AF cells derived from non-degenerate and degenerate IVDs, respectively. Pre-treatment of non-degenerate AF cells with RGD peptides prevented the CTS-induced decrease in ADAMTS -4 gene expression, but caused an increase in expression at 24 hours, a response not observed in degenerate AF cells where RGD pre-treatment failed to inhibit the mechano-response. In addition, FAK phosphorylation increased in CTS stimulated AF cells derived from non-degenerate, but not degenerate IVDs, with RGD pre-treatment inhibiting the CTS – dependent increase in phosphorylated FAK. Our findings suggest that RGD -integrins are involved in the 1.0 Hz CTS – induced mechano-response observed in AF cells derived from non-degenerate, but not degenerate IVDs. This data supports our previous work, suggesting an alternative mechanotransduction pathway may be operating in degenerate AF cells.

Gilbert, Hamish T. J.; Nagra, Navraj S.; Freemont, Anthony J.; Millward-Sadler, Sarah J.; Hoyland, Judith A.



Integrin - dependent mechanotransduction in mechanically stimulated human annulus fibrosus cells: evidence for an alternative mechanotransduction pathway operating with degeneration.  


Intervertebral disc (IVD) cells derived from degenerate tissue respond aberrantly to mechanical stimuli, potentially due to altered mechanotransduction pathways. Elucidation of the altered, or alternative, mechanotransduction pathways operating with degeneration could yield novel targets for the treatment of IVD disease. Our aim here was to investigate the involvement of RGD-recognising integrins and associated signalling molecules in the response to cyclic tensile strain (CTS) of human annulus fibrosus (AF) cells derived from non-degenerate and degenerate IVDs. AF cells from non-degenerate and degenerate human IVDs were cyclically strained with and without function blocking RGD - peptides with 10% strain, 1.0 Hz for 20 minutes using a Flexercell® strain device. QRT-PCR and Western blotting were performed to analyse gene expression of type I collagen and ADAMTS -4, and phosphorylation of focal adhesion kinase (FAK), respectively. The response to 1.0 Hz CTS differed between the two groups of AF cells, with decreased ADAMTS -4 gene expression and decreased type I collagen gene expression post load in AF cells derived from non-degenerate and degenerate IVDs, respectively. Pre-treatment of non-degenerate AF cells with RGD peptides prevented the CTS-induced decrease in ADAMTS -4 gene expression, but caused an increase in expression at 24 hours, a response not observed in degenerate AF cells where RGD pre-treatment failed to inhibit the mechano-response. In addition, FAK phosphorylation increased in CTS stimulated AF cells derived from non-degenerate, but not degenerate IVDs, with RGD pre-treatment inhibiting the CTS - dependent increase in phosphorylated FAK. Our findings suggest that RGD -integrins are involved in the 1.0 Hz CTS - induced mechano-response observed in AF cells derived from non-degenerate, but not degenerate IVDs. This data supports our previous work, suggesting an alternative mechanotransduction pathway may be operating in degenerate AF cells. PMID:24039840

Gilbert, Hamish T J; Nagra, Navraj S; Freemont, Anthony J; Millward-Sadler, Sarah J; Hoyland, Judith A



Anterior temporal lobe degeneration produces widespread network-driven dysfunction.  


The neural organization of semantic memory remains much debated. A 'distributed-only' view contends that semantic knowledge is represented within spatially distant, modality-selective primary and association cortices. Observations in semantic variant primary progressive aphasia have inspired an alternative model featuring the anterior temporal lobe as an amodal hub that supports semantic knowledge by linking distributed modality-selective regions. Direct evidence has been lacking, however, to support intrinsic functional interactions between an anterior temporal lobe hub and upstream sensory regions in humans. Here, we examined the neural networks supporting semantic knowledge by performing a multimodal brain imaging study in healthy subjects and patients with semantic variant primary progressive aphasia. In healthy subjects, the anterior temporal lobe showed intrinsic connectivity to an array of modality-selective primary and association cortices. Patients showed focal anterior temporal lobe degeneration but also reduced physiological integrity throughout distributed modality-selective regions connected with the anterior temporal lobe in healthy controls. Physiological deficits outside the anterior temporal lobe correlated with scores on semantic tasks and with anterior temporal subregion atrophy, following domain-specific and connectivity-based predictions. The findings provide a neurophysiological basis for the theory that semantic processing is orchestrated through interactions between a critical anterior temporal lobe hub and modality-selective processing nodes. PMID:24072486

Guo, Christine C; Gorno-Tempini, Maria Luisa; Gesierich, Benno; Henry, Maya; Trujillo, Andrew; Shany-Ur, Tal; Jovicich, Jorge; Robinson, Simon D; Kramer, Joel H; Rankin, Katherine P; Miller, Bruce L; Seeley, William W



Radiation therapy for neovascular age-related macular degeneration  

PubMed Central

Antivascular endothelial growth factor (anti-VEGF) therapies represent the standard of care for most patients presenting with neovascular (wet) age-related macular degeneration (neovascular AMD). Anti-VEGF drugs require repeated injections and impose a considerable burden of care, and not all patients respond. Radiation targets the proliferating cells that cause neovascular AMD, including fibroblastic, inflammatory, and endothelial cells. Two new neovascular AMD radiation treatments are being investigated: epimacular brachytherapy and stereotactic radiosurgery. Epimacular brachytherapy uses beta radiation, delivered to the lesion via a pars plana vitrectomy. Stereotactic radiosurgery uses low voltage X-rays in overlapping beams, directed onto the lesion. Feasibility data for epimacular brachytherapy show a greatly reduced need for anti-VEGF therapy, with a mean vision gain of 8.9 ETDRS letters at 12 months. Pivotal trials are underway (MERLOT, CABERNET). Preliminary stereotactic radiosurgery data suggest a mean vision gain of 8 to 10 ETDRS letters at 12 months. A large randomized sham controlled stereotactic radiosurgery feasibility study is underway (CLH002), with pivotal trials to follow. While it is too early to conclude on the safety and efficacy of epimacular brachytherapy and stereotactic radiosurgery, preliminary results are positive, and these suggest that radiation offers a more durable therapeutic effect than intraocular injections.

Petrarca, Robert; Jackson, Timothy L



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.



Mice lacking complex gangliosides develop Wallerian degeneration and myelination defects.  


Gangliosides are a family of sialic acid-containing glycosphingolipids highly enriched in the mammalian nervous system. Although they are the major sialoglycoconjugates in the brain, their neurobiological functions remain poorly defined. By disrupting the gene for a key enzyme in complex ganglioside biosynthesis (GM2/GD2 synthase; EC we generated mice that express only simple gangliosides (GM3/GD3) and examined their central and peripheral nervous systems. The complex ganglioside knockout mice display decreased central myelination, axonal degeneration in both the central and peripheral nervous systems, and demyelination in peripheral nerves. The pathological features of their nervous system closely resemble those reported in mice with a disrupted gene for myelin-associated glycoprotein (MAG), a myelin receptor that binds to complex brain gangliosides in vitro. Furthermore, GM2/GD2 synthase knockout mice have reduced MAG expression in the central nervous system. These results indicate that complex gangliosides function in central myelination and maintaining the integrity of axons and myelin. They also support the theory that complex gangliosides are endogenous ligands for MAG. The data extend and clarify prior observations on a similar mouse model, which reported only subtle conduction defects in their nervous system [Takamiya, K., Yamamoto, A., Furukawa, K., Yamashiro, S., Shin, M., Okada, M., Fukumoto, S., Haraguchi, M., Takeda, N., Fujimura, K., et al. (1996) Proc. Natl. Acad. Sci. USA 93, 10662-10667]. PMID:10377449

Sheikh, K A; Sun, J; Liu, Y; Kawai, H; Crawford, T O; Proia, R L; Griffin, J W; Schnaar, R L



A local moment approach to the degenerate Anderson impurity model.  


The local moment approach is extended to the orbitally degenerate (SU(2N)) Anderson impurity model (AIM). Single-particle dynamics are obtained over the full range of energy scales, focusing on particle-hole symmetry in the strongly-correlated regime where the onsite Coulomb interaction leads to many-body Kondo physics with entangled spin and orbital degrees of freedom. The approach captures many-body broadening of the Hubbard satellites and recovers the correct exponential vanishing of the Kondo scale for all N, and its universal scaling spectra are found to be in very good agreement with numerical renormalization group (NRG) results. In particular the high-frequency logarithmic decays of the scaling spectra, obtained here in closed form for arbitrary N, coincide essentially perfectly with available numerics from the NRG. A particular case of an anisotropic Coulomb interaction, in which the model represents a system of N 'capacitively coupled' SU(2) AIMs, is also discussed. Here the model is generally characterized by two low-energy scales, the crossover between which is seen directly in its dynamics. PMID:21832350

Galpin, Martin R; Gilbert, Anne B; Logan, David E



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



Aberrant septin 11 is associated with sporadic frontotemporal lobar degeneration  

PubMed Central

Background Detergent-insoluble protein accumulation and aggregation in the brain is one of the pathological hallmarks of neurodegenerative diseases. Here, we describe the identification of septin 11 (SEPT11), an enriched component of detergent-resistant fractions in frontotemporal lobar degeneration with ubiquitin-immunoreactive inclusions (FTLD-U), using large-scale unbiased proteomics approaches. Results We developed and applied orthogonal quantitative proteomic strategies for the unbiased identification of disease-associated proteins in FTLD-U. Using these approaches, we proteomically profiled detergent-insoluble protein extracts prepared from frontal cortex of FTLD-U cases, unaffected controls, or neurologic controls (i.e. Alzheimer's disease; AD). Among the proteins altered specifically in FTLD-U, we identified TAR DNA binding protein-43 (TDP-43), a known component of ubiquitinated inclusions. Moreover, we identified additional proteins enriched in detergent-resistant fractions in FTLD-U, and characterized one of them, SEPT11, in detail. Using independent highly sensitive targeted proteomics approaches, we confirmed the enrichment of SEPT11 in FTLD-U extracts. We further showed that SEPT11 is proteolytically cleaved into N-terminal fragments and, in addition to its prominent glial localization in normal brain, accumulates in thread-like pathology in affected cortex of FTLD-U patients. Conclusions The proteomic discovery of insoluble SEPT11 accumulation in FTLD-U, along with novel pathological associations, highlights a role for this cytoskeleton-associated protein in the pathogenesis of this complex disorder.



Seven new loci associated with age-related macular degeneration.  


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

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



Development of polypoidal lesions in age-related macular degeneration  

PubMed Central

Purpose To investigate the development of polypoidal lesions using indocyanine green angiography (IA) in eyes with typical age-related macular degeneration (AMD). Methods We retrospectively reviewed the medical records of 47 consecutive patients (47 eyes) with typical AMD who had been followed up with IA for at least 2 years. Results At the initial visit, although all eyes showed classic and/or occult choroidal neovascularization (CNV) associated with AMD, no eyes showed polypoidal lesions by IA. However, during follow-up, 13 (27.7%) of the 47 eyes did show polypoidal lesions. All polypoidal lesions developed at the edge of persistent CNV or, more often, at the terminus of recently progressed CNV. Of 12 eyes with a final lesion area >8 disc area, 7 (58.3%) showed newly developed polypoidal lesions. In the eyes with these newly developed polypoidal lesions, the mean area of the vascular lesion had extended significantly from 10.50±7.88?mm2 to 20.87±10.21?mm2 during follow-up (P=0.0018). Conclusion The current observation suggests that IA of active AMD sometimes reveals polypoidal lesions if there is progression of the CNV in the subretinal pigment epithelium space.

Tsujikawa, A; Ojima, Y; Yamashiro, K; Ooto, S; Tamura, H; Nakata, I; Yoshimura, N



Neuroanatomical profiles of personality change in frontotemporal lobar degeneration  

PubMed Central

Background The neurobiological basis of personality is poorly understood. Frontotemporal lobar degeneration (FTLD) frequently presents with complex behavioural changes, and therefore potentially provides a disease model in which to investigate brain substrates of personality. Aims To assess neuroanatomical correlates of personality change in a cohort of individuals with FTLD using voxel-based morphometry (VBM). Method Thirty consecutive individuals fulfilling consensus criteria for FTLD were assessed. Each participant’s carer completed a Big Five Inventory (BFI) questionnaire on five key personality traits; for each trait, a change score was derived based on current compared with estimated premorbid characteristics. All participants underwent volumetric brain magnetic resonance imaging. A VBM analysis was implemented regressing change score for each trait against regional grey matter volume across the FTLD group. Results The FTLD group showed a significant decline in extraversion, agreeableness, conscientiousness and openness and an increase in neuroticism. Change in particular personality traits was associated with overlapping profiles of grey matter loss in more anterior cortical areas and relative preservation of grey matter in more posterior areas; the most robust neuroanatomical correlate was identified for reduced conscientiousness in the region of the posterior superior temporal gyrus. Conclusions Quantitative measures of personality change in FTLD can be correlated with changes in regional grey matter. The neuroanatomical profiles for particular personality traits overlap brain circuits previously implicated in aspects of social cognition and suggest that dysfunction at the level of distributed cortical networks underpins personality change in FTLD.

Mahoney, Colin J.; Rohrer, Jonathan D.; Omar, Rohani; Rossor, Martin N.; Warren, Jason D.



Selenium induces cholinergic motor neuron degeneration in Caenorhabditis elegans  

PubMed Central

Selenium is an essential micronutrient required for cellular antioxidant systems, yet at higher doses it induces oxidative stress. Additionally, in vertebrates environmental exposures to toxic levels of selenium can cause paralysis and death. Here we show that selenium-induced oxidative stress leads to decreased cholinergic signaling and degeneration of cholinergic neurons required for movement and egg-laying in Caenorhabditis elegans. Exposure to high levels of selenium leads to proteolysis of a soluble muscle protein through mechanisms suppressible by two pharmacological agents, levamisole and aldicarb which enhance cholinergic signaling in muscle. In addition, animals with reduction-of-function mutations in genes encoding post-synaptic levamisole-sensitive acetylcholine receptor subunits or the vesicular acetylcholine transporter developed impaired forward movement faster during selenium-exposure than normal animals, again confirming that selenium reduces cholinergic signaling. Finally, the antioxidant reduced glutathione, inhibits selenium-induced reductions in egg-laying through a cellular protective mechanism dependent on the C. elegans glutaredoxin, GLRX-21. These studies provide evidence that the environmental toxicant selenium induces neurodegeneration of cholinergic neurons through depletion of glutathione, a mechanism linked to the neuropathology of Alzheimer’s disease, amyotrophic lateral sclerosis, and Parkinson’s disease.

Estevez, Annette O.; Mueller, Catherine L.; Morgan, Kathleen L.; Szewczyk, Nathaniel J.; Teece, Luke; Miranda-Vizuete, Antonio; Estevez, Miguel



[Mechanism of neuronal degeneration of multiple system atrophy].  


Multiple system atrophy (MSA) is a sporadic neurodegenerative disorder that encompasses olivopontocerebellar atrophy (OPCA), striatonigral degeneration (SND) and Shy-Drager syndrome (SDS). The histopathological hallmarks are alpha-synuclein (AS) positive glial cytoplasmic inclusions (GCIs) in oligodendroglias. AS aggregation is also found in glial nuclear inclusions (GNIs), neuronal cytoplasmic inclusions (NCIs), neuronal nuclear inclusions (NNIs) and dystrophic neurites. Reviewing the pathological features in 102 MSA cases revealed that the, OPCA-type was relatively more frequent and SND-type was less frequent in Japanese MSA cases. The frequency of the SND-type is relatively high in Western countries. This different in the dominant type suggests that the phenotypic patterns of MSA may vary with the race. In early stages of MSA, in addition to GCIs, NNIs, NCIs, and diffuse homogenous stain of AS in neuronal nuclei and cytoplasm were observed in various vulnerable lesions including the pontine nuclei, putamen, substantia nigra, locus ceruleus, inferior olivary nucleus, intermediolateral column of the thoracic cord, lower motor neurons, and cortical pyramidal neurons. These findings indicated that the primary nonfibrillar and fibrillar AS aggregation also occurred in neurons. Therefore, both the direct involvement of neurons themselves and the oligodendroglia-myelin-axon mechanism may synergistically accelerate the degenerative process of MSA. PMID:19803404

Yoshida, Mari; Sone, Mie



Cognitive impairments in cerebellar degeneration: a comparison with Huntington's disease.  


To determine the specificity of cognitive impairments in patients with cerebellar degeneration (CD), the neuropsychological test performance of 31 CD patients was compared to that of 21 patients with Huntington's disease (HD) and 29 normal adults. The CD and HD groups did not differ in age, education, or duration of illness, and their overall severity on a quantified neurological examination was similar. Fifteen neuropsychological test variables were reduced to five underlying domains: motor, verbal, spatial, memory, and executive functioning. The CD patients had their greatest impairment in the executive domain and their least in the memory domain. In contrast, the HD patients had very substantial spatial deficits and significant memory impairment, in addition to executive dysfunction. The findings indicate that 1) the cognitive impairment in CD is not as severe as in HD, and 2) the pattern of deficits in CD, while consistent with a subcortical dementia, differs in important ways from that in HD. These differences may reflect the involvement of the cerebellar dentate nucleus and the striatal nuclei in separate "loops" or closed circuits, linking them with specific areas of cerebral neocortex. PMID:15260369

Brandt, Jason; Leroi, Iracema; O'Hearn, Elizabeth; Rosenblatt, Adam; Margolis, Russell L



Changes of dopamine receptors in mice with olivocerebellar degeneration.  


Lurcher mutants are mice with functional mutation in the 82 glutamate receptor (GluRdelta2) that is predominantly expressed in cerebellar Purkinje cells and plays a crucial role in cerebellar functions. These mice display ataxia and impaired motor-related learning tasks. In order to elucidate the role of dopaminergic receptor system in coping with mutation in delta2 glutamate receptor the behavioral effect (spatial learning) of D1 dopamine receptor activation and inhibition and changes in D1-like and D2-like dopamine receptors in striatum, hippocampus and cerebellum in C57BI/7 and C3H Lurcher mutants and wild type mice were studied. We have found that Lurcher mutants were worse in the spatial learning but mice of both types reacted similarly to D1 dopamine receptor agonist (without effect) and antagonist (worsening). Moreover, Lurchers revealed substantial higher density of both D1-like and D2-like dopamine receptors in hippocampus in C57BI/7 strain, while in C3H strain only D1-like dopamine receptors were higher. In C57BI/7 strain, D-like dopamine receptors were lower in cerebellum; D2-like dopamine receptors were not affected. In the striatum, the receptor densities were similar to the wild type counterparts. Our results suggest specific participation of dopamine receptor system in coping with olivocerebellar degeneration. PMID:17682727

Myslivecek, J; Cendelín, J; Korelusová, I; Kunová, M; Markvartová, V; Vozeh, F