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Sample records for 4-fold degenerate sites

  1. Efficient site-directed saturation mutagenesis using degenerate oligonucleotides.

    PubMed

    Steffens, David L; Williams, John G K

    2007-07-01

    We describe a reliable protocol for constructing single-site saturation mutagenesis libraries consisting of all 20 naturally occurring amino acids at a specific site within a protein. Such libraries are useful for structure-function studies and directed evolution. This protocol extends the utility of Stratagene's QuikChange Site-Directed Mutagenesis Kit, which is primarily recommended for single amino acid substitutions. Two complementary primers are synthesized, containing a degenerate mixture of the four bases at the three positions of the selected codon. These primers are added to starting plasmid template and thermal cycled to produce mutant DNA molecules, which are subsequently transformed into competent bacteria. The protocol does not require purification of mutagenic oligonucleotides or PCR products. This reduces both the cost and turnaround time in high-throughput directed evolution applications. We have utilized this protocol to generate over 200 site-saturation libraries in a DNA polymerase, with a success rate of greater than 95%. PMID:17595310

  2. Human cartilage endplate permeability varies with degeneration and intervertebral disc site.

    PubMed

    DeLucca, John F; Cortes, Daniel H; Jacobs, Nathan T; Vresilovic, Edward J; Duncan, Randall L; Elliott, Dawn M

    2016-02-29

    Despite the critical functions the human cartilage endplate (CEP) plays in the intervertebral disc, little is known about its structural and mechanical properties and their changes with degeneration. Quantifying these changes with degeneration is important for understanding how the CEP contributes to the function and pathology of the disc. Therefore the objectives of this study were to quantify the effect of disc degeneration on human CEP mechanical properties, determine the influence of superior and inferior disc site on mechanics and composition, and simulate the role of collagen fibers in CEP and disc mechanics using a validated finite element model. Confined compression data and biochemical composition data were used in a biphasic-swelling model to calculate compressive extrafibrillar elastic and permeability properties. Tensile properties were obtained by applying published tensile test data to an ellipsoidal fiber distribution. Results showed that with degeneration CEP permeability decreased 50-60% suggesting that transport is inhibited in the degenerate disc. CEP fibers are organized parallel to the vertebrae and nucleus pulposus and may contribute to large shear strains (0.1-0.2) and delamination failure of the CEP commonly seen in herniated disc tissue. Fiber-reinforcement also reduces CEP axial strains thereby enhancing fluid flux by a factor of 1.8. Collectively, these results suggest that the structure and mechanics of the CEP may play critical roles in the solute transport and disc mechanics. PMID:26874969

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

    PubMed

    Agu, Obekieze; Boardley, Dee; Adiseshiah, Mohan

    2008-01-01

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

  4. 4-fold photocurrent enhancement in ultrathin nanoplasmonic perovskite solar cells.

    PubMed

    Cai, Boyuan; Peng, Yong; Cheng, Yi-Bing; Gu, Min

    2015-11-30

    Although perovskite materials have been widely investigated for thin-film photovoltaic devices due to the potential for high efficiency, their high toxicity has pressed the development of a solar cell structure of an ultra-thin absorber layer. But insufficient light absorption could be a result of ultra-thin perovskite films. In this paper, we propose a new nanoplasmonic solar cell that integrates metal nanoparticles at its rear/front surfaces of the perovskite layer. Plasmon-enhanced light scattering and near-field enhancement effects from lumpy sliver nanoparticles result in the photocurrent enhancement for a 50 nm thick absorber, which is higher than that for a 300 nm thick flat perovskite solar cell. We also predict the 4-fold photocurrent enhancement in an ultrathin perovskite solar cell with the absorber thickness of 10 nm. Our results pave a new way for ultrathin high-efficiency solar cells with either a lead-based or a lead-free perovskite absorption layer. PMID:26698816

  5. Radial tensile properties of the lumbar annulus fibrosus are site and degeneration dependent.

    PubMed

    Fujita, Y; Duncan, N A; Lotz, J C

    1997-11-01

    We conducted an in vitro study of the radial tensile properties of the annulus fibrosus. The stress-strain response was nonlinear, with a mean tangent modulus of 0.19 MPa at zero strain and 0.47 MPa at 70% of the yield strain. We also investigated whether these properties varied as a function of location within the disc and degree of degeneration. Specimens harvested from the middle layers of the annulus were stiffer and failed at smaller strain magnitudes than those from the inner or outer annulus (analysis of covariance, p < 0.05). Differences due to degeneration were evident; degenerated discs had a 30% decrease in yield and ultimate stress compared with normal discs. Similarity between our data and those reported for the annulus in compression suggests that these values reflect the material behavior of the interlaminar matrix and are an order of magnitude smaller than values used in previous analytical representations of this tissue. We expect that awareness of these data will result in improved understanding of the physical behavior and tolerance to injury of the annulus fibrosus. PMID:9497805

  6. Macular degeneration

    MedlinePlus Videos and Cool Tools

    ... at the center of the field of vision. Macular degeneration results from a partial breakdown of the insulating ... choroid layer of blood vessels behind the retina. Macular degeneration results in the loss of central vision only.

  7. Cerebellar Degeneration

    MedlinePlus

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

  8. Optimization of the degenerated interfacial ATP binding site improves the function of disease-related mutant cystic fibrosis transmembrane conductance regulator (CFTR) channels.

    PubMed

    Tsai, Ming-Feng; Jih, Kang-Yang; Shimizu, Hiroyasu; Li, Min; Hwang, Tzyh-Chang

    2010-11-26

    The cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel, an ATP binding cassette (ABC) protein whose defects cause the deadly genetic disease cystic fibrosis (CF), encompasses two nucleotide binding domains (NBD1 and NBD2). Recent studies indicate that in the presence of ATP, the two NBDs coalesce into a dimer, trapping an ATP molecule in each of the two interfacial composite ATP binding sites (site 1 and site 2). Experimental evidence also suggests that CFTR gating is mainly controlled by ATP binding and hydrolysis in site 2, whereas site 1, which harbors several non-canonical substitutions in ATP-interacting motifs, is considered degenerated. The CF-associated mutation G551D, by introducing a bulky and negatively charged side chain into site 2, completely abolishes ATP-induced openings of CFTR. Here, we report a strategy to optimize site 1 for ATP binding by converting two amino acid residues to ABC consensus (i.e. H1348G) or more commonly seen residues in other ABC proteins (i.e. W401Y,W401F). Introducing either one or both of these mutations into G551D-CFTR confers ATP responsiveness for this disease-associated mutant channel. We further showed that the same maneuver also improved the function of WT-CFTR and the most common CF-associated ΔF508 channels, both of which rely on site 2 for gating control. Thus, our results demonstrated that the degenerated site 1 can be rebuilt to complement or support site 2 for CFTR function. Possible approaches for developing CFTR potentiators targeting site 1 will be discussed. PMID:20861014

  9. Optimization of the Degenerated Interfacial ATP Binding Site Improves the Function of Disease-related Mutant Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Channels*♦

    PubMed Central

    Tsai, Ming-Feng; Jih, Kang-Yang; Shimizu, Hiroyasu; Li, Min; Hwang, Tzyh-Chang

    2010-01-01

    The cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel, an ATP binding cassette (ABC) protein whose defects cause the deadly genetic disease cystic fibrosis (CF), encompasses two nucleotide binding domains (NBD1 and NBD2). Recent studies indicate that in the presence of ATP, the two NBDs coalesce into a dimer, trapping an ATP molecule in each of the two interfacial composite ATP binding sites (site 1 and site 2). Experimental evidence also suggests that CFTR gating is mainly controlled by ATP binding and hydrolysis in site 2, whereas site 1, which harbors several non-canonical substitutions in ATP-interacting motifs, is considered degenerated. The CF-associated mutation G551D, by introducing a bulky and negatively charged side chain into site 2, completely abolishes ATP-induced openings of CFTR. Here, we report a strategy to optimize site 1 for ATP binding by converting two amino acid residues to ABC consensus (i.e. H1348G) or more commonly seen residues in other ABC proteins (i.e. W401Y,W401F). Introducing either one or both of these mutations into G551D-CFTR confers ATP responsiveness for this disease-associated mutant channel. We further showed that the same maneuver also improved the function of WT-CFTR and the most common CF-associated ΔF508 channels, both of which rely on site 2 for gating control. Thus, our results demonstrated that the degenerated site 1 can be rebuilt to complement or support site 2 for CFTR function. Possible approaches for developing CFTR potentiators targeting site 1 will be discussed. PMID:20861014

  10. Brane brick models, toric Calabi-Yau 4-folds and 2d (0,2) quivers

    NASA Astrophysics Data System (ADS)

    Franco, Sebastián; Lee, Sangmin; Seong, Rak-Kyeong

    2016-02-01

    We introduce brane brick models, a novel type of Type IIA brane configurations consisting of D4-branes ending on an NS5-brane. Brane brick models are T-dual to D1-branes over singular toric Calabi-Yau 4-folds. They fully encode the infinite class of 2 d (generically) {N}=(0,2) gauge theories on the worldvolume of the D1-branes and streamline their connection to the probed geometries. For this purpose, we also introduce new combinatorial procedures for deriving the Calabi-Yau associated to a given gauge theory and vice versa.

  11. Ultrastructural observations on the progress of nerve degeneration and regeneration at the suture site following vagal-hypoglossal nerve coaptation in cats.

    PubMed

    Hu, Ming-E; Tyan, Yeu-Sheng; Hsu, Peng-Wei; Hsu, Jee-Ching; Chang, Hung-Ming; Ling, Eng-Ang; Lan, Chyn-Tair

    2009-01-01

    Nerve degeneration and regeneration have been investigated at the suture site following proximal-to-distal vagal-hypoglossal nerve coaptation (VHC) in cats at different time points (from 3 to 315 days postoperatively; dpo). Massive axonal degeneration and myelin breakdown and removal of degraded neural debris were observed during the first 2 weeks postoperatively. This was followed by active Schwann cell multiplication and inflammatory cell invasion at 14 dpo. Schwann cells appeared mobile, and were guided to the newly developed growth cones, dividing them into axonal sprout clusters. At 18 dpo, the migrating Schwann cells were confined to the preexisting basal lamina scaffolds, forming bands of Bungner. It is suggested that the latter may play a key role in navigating the regenerating axons to their newly acquired target organ at 22 dpo. Remyelination of axons was not observed till 46 dpo. Compared with the rapid axonal reaction in other models of nerve injury, the degeneration process in VHC was protracted and, furthermore, regeneration and remyelination were delayed. The subtle remodeling of the nerve in cross-coaptation may be far greater than previously recognized, and this may have clinical importance since patients undergoing nerve crossover microsurgery exhibit delayed motor rehabilitation, apparently as a direct result of a change in target innervation. Defining the mechanisms underlying the neuroplastic program could thus potentially improve the prognosis of crossover of two different peripheral nerves. PMID:19494480

  12. Remobilization causes site-specific cyst formation in immobilization-induced knee cartilage degeneration in an immobilized rat model.

    PubMed

    Nagai, Momoko; Ito, Akira; Tajino, Junichi; Iijima, Hirotaka; Yamaguchi, Shoki; Zhang, Xiangkai; Aoyama, Tomoki; Kuroki, Hiroshi

    2016-06-01

    An understanding of the articular cartilage degenerative process is necessary for the prevention and treatment of joint disease. The present study aimed to examine how long-term immobilization-induced cartilage degeneration is aggravated by remobilization. Sixty 8-week-old male Wistar rats were used in this study. The unilateral knee joint was immobilized using an external fixator for 8 weeks. The rats were killed at 0 and 3 days, and at 1, 2, 4 and 8 weeks after removing the fixator. After the rats were killed, the maximum knee extension angles were measured. Histological sections at the medial mid-condylar region (non-contact, transitional and contact regions of the femur and tibia) were prepared and scored. The cartilage thickness and number of chondrocytes were measured, and CD44 and Col2-3/4c expression levels were assessed immunohistochemically. The histological assessment revealed progressive aggravation of cartilage degeneration in the transitional region, with a decreased number of chondrocytes and CD44-positive chondrocytes as well as poor scoring over time, particularly in the tibia. Cyst formation was confirmed in the transitional region of the tibia at 8 weeks post-remobilization. The cartilage thickness in the transitional region was thicker than that in the contact region, particularly in the tibia. Col2-3/4c expression was observed in the non-contact and transitional regions, and the knee extension angle was recovered. In conclusion, immobilization-induced cartilage degeneration was aggravated by remobilization over time in the transitional region, followed by observations of a decreased number of chondrocytes and morphological disparity between different cartilage regions. PMID:26989984

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

    NASA Astrophysics Data System (ADS)

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  15. Macular Degeneration

    MedlinePlus

    ... common early symptom. Dry AMD happens when the light-sensitive cells in the macula slowly break down. Your gradually lose your central vision. A common early symptom is that straight lines appear crooked. Regular comprehensive eye exams can detect macular degeneration before the disease ...

  16. Synchrotron radiation circular dichroism spectroscopy study of recombinant T β4 folding

    NASA Astrophysics Data System (ADS)

    Huang, Yung-Chin; Chu, Hsueh-Liang; Chen, Peng-Jen; Chang, Chia-Ching

    Thymosin beta 4 (T β4) is a 43-amino acid small peptide, has been demonstrated that it can promote cardiac repair, wound repair, tissue protection, and involve in the proliferation of blood cell precursor stem cells of bone marrow. Moreover, T β4 has been identified as a multifunction intrinsically disordered protein, which is lacking the stable tertiary structure. Owing to the small size and disordered character, the T β4 protein degrades rapidly and the storage condition is critical. Therefore, it is not easy to reveal its folding mechanism of native T β4. However, recombinant T β4 protein (rT β4), which fused with a 5-kDa peptide in its amino-terminal, is stable and possesses identical function of T β4. Therefore, rT β4 can be used to study its folding mechanism. By using over-critical folding process, stable folding intermediates of rT β4 can be obtained. Structure analysis of folding intermediates by synchrotron radiation circular dichroism (SRCD) and fluorescence spectroscopies indicate that rT β4 is a random coli major protein and its hydrophobic region becomes compact gradually. Moreover, the rT β4 folding is a two state transition. Thermal denaturation analysis indicates that rT β4 lacks stable tertiary structure. These results indicated that rT β4, similar to T β4, is an intrinsically disordered protein. Research is supported by MOST, Taiwan. MOST 103-2112-M-009-011-MY3. Corresponding author: Chia-Ching Chang; ccchang01@faculty.nctu.edu.tw.

  17. Corticobasal degeneration.

    PubMed

    Gibb, W R; Luthert, P J; Marsden, C D

    1989-10-01

    Three patients with clinical and pathological features of corticobasal degeneration are described. They presented with a progressive disease bearing some clinical resemblance to Steele-Richardson-Olszewski syndrome and displaying some pathological features of Pick's disease. Their illness began at the age of 59 to 66 yrs with focal dystonia and myoclonus of an arm, the 'alien hand' sign, or an akinetic-rigid syndrome. They developed a supranuclear gaze palsy, parkinsonian features and mild cerebellar signs. Two patients showed constructional dyspraxia when using the arms. The duration of disease to death was 4 to 6 yrs. Pathological examination showed frontoparietal atrophy with cortical cell loss, gliosis and Pick cells, but there was no significant hippocampal disease or Pick bodies in this region. There was nerve cell loss and gliosis in the thalamus, lentiform nucleus, subthalamic nucleus, red nucleus, midbrain tegmentum, substantia nigra and locus coeruleus. Neuronal inclusions in the substantia nigra, termed corticobasal inclusions, were reminiscent of the globose neurofibrillary tangle of Steele-Richardson-Olszewski syndrome, and other pale inclusions resembled the pale body of Parkinson's disease, but Lewy bodies and neurofibrillary tangles were generally absent. Some nigral inclusions were similar to those in Pick's disease. Despite some pathological similarities to Pick's disease we suggest that the distribution of nerve cell loss and the corticobasal inclusion are unique to corticobasal degeneration. PMID:2478251

  18. Lipoprotein(A) with An Intact Lysine Binding Site Protects the Retina From an Age-Related Macular Degeneration Phenotype in Mice (An American Ophthalmological Society Thesis)

    PubMed Central

    Handa, James T.; Tagami, Mizuki; Ebrahimi, Katayoon; Leibundgut, Gregor; Janiak, Anna; Witztum, Joseph L.; Tsimikas, Sotirios

    2015-01-01

    Purpose: To test the hypothesis that the accumulation of oxidized phospholipids (OxPL) in the macula is toxic to the retina unless neutralized by a variety of mechanisms, including binding by lipoprotein(a) [Lp(a)], which is composed of apolipoprotein(a) [apo(a)] and apolipoprotein B-100 (apoB). Methods: Human maculas and eyes from two Lp(a) transgenic murine models were subjected to morphologic, ultrastructural, and immunohistochemical analysis. “Wild-type Lp(a)” mice, which express human apoB-100 and apo(a) that contains oxidized phospholipid, and “mutant LBS− Lp(a)” mice with a defective apo(a) lysine binding site (LBS) for oxidized phospholipid binding, were fed a chow or high-fat diet for 2 to 12 months. Oxidized phospholipid–containing lipoproteins were detected by immunoreactivity to E06, a murine monoclonal antibody binding to the phosphocholine headgroup of oxidized, but not native, phospholipids. Results: Oxidized phospholipids, apo(a), and apoB accumulate in maculas, including drusen, of age-related macular degeneration (AMD) samples and age-matched controls. Lp(a) mice fed a high-fat diet developed age-related changes. However, mutant LBS− Lp(a) mice fed a high-fat diet developed retinal pigment epithelial cell degeneration and drusen. These changes were associated with increased OxPL, decreased antioxidant defenses, increased complement, and decreased complement regulators. Conclusions: Human maculas accumulate Lp(a) and OxPL. Mutant LBS− Lp(a) mice, lacking the ability to bind E06-detectable oxidized phospholipid, develop AMD-like changes. The ability of Lp(a) to bind E06-detectable OxPL may play a protective role in AMD. PMID:26538774

  19. Macular degeneration (image)

    MedlinePlus

    Macular degeneration is a disease of the retina that affects the macula in the back of the eye. ... see fine details. There are two types of macular degeneration, dry and wet. Dry macular degeneration is more ...

  20. Macular Degeneration: An Overview.

    ERIC Educational Resources Information Center

    Chalifoux, L. M.

    1991-01-01

    This article presents information on macular degeneration for professionals helping persons with this disease adjust to their visual loss. It covers types of macular degeneration, the etiology of the disease, and its treatment. Also considered are psychosocial problems and other difficulties that persons with age-related macular degeneration face.…

  1. Intervertebral Disc Degeneration

    PubMed Central

    Rannou, François; Lee, Tzong-Shyuan; Zhou, Rui-Hai; Chin, Jennie; Lotz, Jeffrey C.; Mayoux-Benhamou, Marie-Anne; Barbet, Jacques Patrick; Chevrot, Alain; Shyy, John Y.-J.

    2004-01-01

    Degeneration of the intervertebral disk (IVD) is a major pathological process implicated in low back pain and is a prerequisite to disk herniation. Although mechanical stress is an important modulator of the degeneration, the underlying molecular mechanism remains unclear. The association of human IVD degeneration, assessed by magnetic resonance imaging, with annulus fibrosus cell apoptosis and anti-cytochrome c staining revealed that the activation of the mitochondria-dependent apoptosome was a major event in the degeneration process. Mouse models of IVD degeneration were used to investigate the role of the mechanical stress in this process. The application of mechanical overload (1.3 MPa) for 24 hours induced annulus fibrosus cell apoptosis and led to severe degeneration of the mouse disks. Immunostaining revealed cytochrome c release but not Fas-L generation. The role of the caspase-9-dependent mitochondrial pathway in annulus fibrosus cell apoptosis induced by overload was investigated further with the use of cultured rabbit IVD cells in a stretch device. Mechanical overload (15% area change) induced apoptosis with increased caspase-9 activity and decreased mitochondrial membrane potential. Furthermore, Z-LEHD-FMK, a caspase-9 inhibitor, but not Z-IETD-FMK, a caspase-8 inhibitor, attenuated the overload-induced apoptosis. Our results from human samples, mouse models, and annulus fibrosus culture experiments demonstrate that the mechanical overload-induced IVD degeneration is mediated through the mitochondrial apoptotic pathway in IVD cells. PMID:14982845

  2. Double Degenerate Binary Systems

    SciTech Connect

    Yakut, K.

    2011-09-21

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

  3. Biomechanics of Disc Degeneration

    PubMed Central

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

    2012-01-01

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

  4. Degenerate astigmatic cavities

    NASA Astrophysics Data System (ADS)

    Courtois, Jérémie; Mohamed, Ajmal; Romanini, Daniele

    2013-10-01

    At the output of a high-finesse cavity a succession of Lissajous patterns may be observed as the cavity length is finely tuned inside a “degenerate region” around a reentrant spherical configuration. This behavior is ascribed to a small parasitic astigmatism of the cavity mirrors. Simple geometrical optics modeling confirms this hypothesis, and then a more realistic analysis using transverse Gaussian modes reveals that the Lissajous patterns correspond to an organization of the astigmatism-split modes into a finer substructure of degenerate modes relative to that of a reentrant spherical cavity. This provides a thorough understanding of the field patterns observed in the degenerate region, including an intriguing spatial symmetry of the patterns corresponding to opposite displacements with respect to a specific central cavity length. This investigation represents a generalization of the theory of reentrant spherical cavities to the astigmatic case.

  5. Frontotemporal Lobar Degeneration

    PubMed Central

    Josephs, Keith A.

    2009-01-01

    Synopsis Frontotemporal lobar degeneration (FTLD) is a syndromic diagnosis that encompasses at least three different variants. Imaging modalities are clinically useful in FTLD while pathology remains the gold standard for definitive diagnosis. To date three different genes have been identified that account for FTLD. PMID:17659185

  6. Age-Related Macular Degeneration

    MedlinePlus

    ... this page please turn Javascript on. Age-related Macular Degeneration What is AMD? Click for more information Age-related macular degeneration, ... the macula allows you to see fine detail. AMD Blurs Central Vision AMD blurs the sharp central ...

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

    ClinicalTrials.gov

    2016-08-16

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

  8. Frontotemporal Lobar Degeneration

    PubMed Central

    Rabinovici, Gil D.; Miller, Bruce L.

    2010-01-01

    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

  9. Cortical basal ganglionic degeneration.

    PubMed

    Scarmeas, N; Chin, S S; Marder, K

    2001-10-01

    In this case study, we describe the symptoms, neuropsychological testing, and brain pathology of a retired mason's assistant with cortical basal ganglionic degeneration (CBGD). CBGD is an extremely rare neurodegenerative disease that is categorized under both Parkinsonian syndromes and frontal lobe dementias. It affects men and women nearly equally, and the age of onset is usually in the sixth decade of life. CBGD is characterized by Parkinson's-like motor symptoms and by deficits of movement and cognition, indicating focal brain pathology. Neuronal cell loss is ultimately responsible for the neurological symptoms. PMID:14602941

  10. Macular degeneration - age-related

    MedlinePlus

    Age-related macular degeneration (ARMD); AMD ... distorted and wavy. There may be a small dark spot in the center of your vision that ... leafy vegetables, may also decrease your risk of age-related macular degeneration. If you have wet AMD, ...

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

    SciTech Connect

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

    2010-03-12

    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.

  12. What Is Age-Related Macular Degeneration?

    MedlinePlus

    ... Degeneration Diagnosis: How is AMD diagnosed? Macular Degeneration Treatment: How is AMD Treated? Macular ... macular degeneration (AMD) is a deterioration or breakdown of the eye's macula. The macula is a small area in the ...

  13. Salzmann's Nodular Degeneration.

    PubMed

    Maharana, Prafulla K; Sharma, Namrata; Das, Sujata; Agarwal, Tushar; Sen, Seema; Prakash, Gaurav; Vajpayee, Rasik B

    2016-01-01

    Salzmann's nodular degeneration (SND) is a rare, noninflammatory, slowly progressive degenerative disease of the cornea that is characterized by the appearance of nodular bluish gray opacities that vary in number and size. It is usually bilateral; most commonly occurring in people aged 50-60 years old, with a female preponderance; and often associated with a history of prior corneal inflammation. The clinical features usually depend on the location of the nodules. Generally, the nodules of SND are bluish white to gray in color, 1-2 mm in size, and round, conical or prismatic in shape. The overlying Bowman's layer is usually absent from the nodular areas and is partially replaced by granular Periodic Acid Schiff-positive eosinophilic material resembling the basement membrane. Diagnostic investigations include ultrasonic pachymetry, anterior segment optical coherence tomography, ultrasound biomicroscopy, and confocal microscopy. The majority of patients respond well to conservative management with topical lubricants; severe cases may require surgical intervention. The various surgical modalities described include superficial keratectomy, which may be combined with phototherapeutic keratectomy and keratoplasty. Various modifications of these procedures include the use of alcohol-assisted epithelial delamination, intraoperative mitomycin-C or amniotic membrane transplantation to make the procedure easy, reduce the risk of recurrence and improve postoperative comfort. Recurrences are rarely reported; overall, the visual prognosis following treatment is optimal. PMID:26462409

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

    PubMed Central

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

    2014-01-01

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

  15. Nutrition and retinal degenerations.

    PubMed

    Berson, E L

    2000-01-01

    Considerable progress has been made in the understanding and management of degenerative diseases of the retina involving photoreceptors. Nutritional approaches to treatment have proved successful in the case of the common forms of retinitis pigmentosa (supplementation with vitamin A), Bassen-Kornzweig disease (supplementation with vitamins A, E, and K), gyrate atrophy (low-protein, low-arginine diet and/or supplementation with vitamin B6), and Refsum disease (low-phytol, low-phytanic acid diet). The night blindness associated with Sorsby fundus dystrophy can be reversed over the short term with vitamin A. A significant trend for decreased risk for advanced or exudative ARMD has been reported among those whose diets contain a higher content of carotenoids, such as spinach and collard greens. A randomized trial is in progress to determine whether beta-carotene, vitamin C, and vitamin E as well as trace minerals, particularly zinc, will modify the course of ARMD. The difficulties that patients with retinal degenerations face as a result of their diminishing vision, sometimes over decades, cannot be underestimated. Nutritional therapy has proved effective in modifying the course of a number of these conditions; the therapeutic benefit of nutritional modification in diseases that have a genetic basis is of particular interest. Further research is warranted to determine the mechanisms by which these treatments provide their benefit as well as to identify other conditions that may yield to nutritional intervention. Risk-factor analyses of well-defined populations followed over time with food-frequency questionnaires in conjunction with careful assessments of visual function may reveal other dietary constituents that can modify the course of degenerative diseases of the retina. PMID:11064860

  16. Frontotemporal lobar degeneration: current perspectives

    PubMed Central

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

    2014-01-01

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

  17. Chondroadherin Fragmentation Mediated by the Protease HTRA1 Distinguishes Human Intervertebral Disc Degeneration from Normal Aging*

    PubMed Central

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

    2013-01-01

    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

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

    PubMed

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

    2013-03-01

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

  19. The crystal structure of ferritin from Chlorobium tepidum reveals a new conformation of the 4-fold channel for this protein family.

    PubMed

    Arenas-Salinas, Mauricio; Townsend, Philip D; Brito, Christian; Marquez, Valeria; Marabolli, Vanessa; Gonzalez-Nilo, Fernando; Matias, Cata; Watt, Richard K; López-Castro, Juan D; Domínguez-Vera, José; Pohl, Ehmke; Yévenes, Alejandro

    2014-11-01

    Ferritins are ubiquitous iron-storage proteins found in all kingdoms of life. They share a common architecture made of 24 subunits of five α-helices. The recombinant Chlorobium tepidum ferritin (rCtFtn) is a structurally interesting protein since sequence alignments with other ferritins show that this protein has a significantly extended C-terminus, which possesses 12 histidine residues as well as several aspartate and glutamic acid residues that are potential metal ion binding residues. We show that the macromolecular assembly of rCtFtn exhibits a cage-like hollow shell consisting of 24 monomers that are related by 4-3-2 symmetry; similar to the assembly of other ferritins. In all ferritins of known structure the short fifth α-helix adopts an acute angle with respect to the four-helix bundle. However, the crystal structure of the rCtFtn presented here shows that this helix adopts a new conformation defining a new assembly of the 4-fold channel of rCtFtn. This conformation allows the arrangement of the C-terminal region into the inner cavity of the protein shell. Furthermore, two Fe(III) ions were found in each ferroxidase center of rCtFtn, with an average FeA-FeB distance of 3 Å; corresponding to a diferric μ-oxo/hydroxo species. This is the first ferritin crystal structure with an isolated di-iron center in an iron-storage ferritin. The crystal structure of rCtFtn and the biochemical results presented here, suggests that rCtFtn presents similar biochemical properties reported for other members of this protein family albeit with distinct structural plasticity. PMID:25079050

  20. [Neuropsychological exploration in frontotemporal degeneration].

    PubMed

    Peña-Casanova, J; Böhm, P

    2000-01-01

    The present paper discusses the neuropsychological assessment in fronto-temporal lobe degeneration. Having established the neuroanatomical and functional basis for the discussion the major syndromes included in the concept of frontotemporal degeneration are reviewed from a neuropsychological standpoint. With reference to fronto-temporal dementia the different frontal or executive function tests and their limitations are discussed. With reference to progressive aphasia and semantic dementia we differentiate the distinct language profiles as observed in aphasia batteries and general neuropsychological tests. Reference is made to especially useful tests for the differentiation of the two syndromes from each other, as well as from other primary progressive disorders. Concluding remarks postulate a series of axis of cognitive function in fronto-temporal lobe degenerations, which exist at the functional as well as the anatomical level and along which the different syndromes evolve. PMID:10723171

  1. Degenerate approach to the mean field Bose-Hubbard Hamiltonian

    NASA Astrophysics Data System (ADS)

    Belemuk, Alexander M.; Ryzhov, Valentin N.

    2016-04-01

    A degenerate variant of mean field perturbation theory for the on-site Bose-Hubbard Hamiltonian is presented. We split the perturbation into two terms and perform exact diagonalization in the two-dimensional subspace corresponding to the degenerate states. The final relations for the second order ground state energy and first order wave function do not contain singularities at integer values of the chemical potentials. The resulting equation for the phase boundary between superfluid and Mott states coincides with the prediction from the conventional mean field perturbation approach.

  2. Macular Degeneration - Multiple Languages: MedlinePlus

    MedlinePlus

    ... Are Here: Home → Multiple Languages → All Health Topics → Macular Degeneration URL of this page: https://www.nlm.nih. ... V W XYZ List of All Topics All Macular Degeneration - Multiple Languages To use the sharing features on ...

  3. Ataxias and Cerebellar or Spinocerebellar Degeneration

    MedlinePlus

    ... Awards Enhancing Diversity Find People About NINDS NINDS Ataxias and Cerebellar or Spinocerebellar Degeneration Information Page Synonym(s): ... Publications and Information Publicaciones en Español What are Ataxias and Cerebellar or Spinocerebellar Degeneration? Ataxia often occurs ...

  4. Nutritional supplements for macular degeneration.

    PubMed

    2006-02-01

    Age-related macular degeneration is the commonest cause of blindness in developed countries and the third most common worldwide. Each year in the UK, around 17,000 people become blind or partially sighted as a result of this condition, and its prevalence is likely to increase with an ageing population. Laser therapy and rarely surgery, can slow disease progression in a minority of patients but is unlikely to restore lost vision. A wide range of nutritional supplements are now on sale with promotional claims that they improve eye health. While some specialists recommend their use to patients with advanced disease, these supplements are also increasingly promoted to people with early or no signs of disease. Consequently, GPs come under pressure from patients to recommend, or even prescribe, a nutritional supplement. Here we examine the evidence for nutritional supplements in the management of age-related macular degeneration and consider which, if any, can be recommended. PMID:16550811

  5. Solitons in Degenerate Electron-Phonon Systems

    NASA Astrophysics Data System (ADS)

    Foell, Charles; Clougherty, Dennis

    2004-03-01

    We consider a 1øplus 1-dimensional model describing the coupling between degenerate electron states under local Jahn-Teller interactions. In the adiabatic approximation, the equations of motion are shown to reduce to a set of coupled non-linear Schrödinger equations in the electron fields. We demonstrate that in the continuum limit solitary waves of the wave-daughter wave type are stable for sufficiently strong on-site Coulomb repulsion. Our results may have relevance to describing the electronic and optical properties of quasi-one-dimensional systems such as halogen-bridged mixed-valence transition-metal linear-chain complexes (MX chains) and polymeric fullerides.

  6. The degeneration of Y chromosomes.

    PubMed

    Charlesworth, B; Charlesworth, D

    2000-11-29

    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. PMID:11127901

  7. Radial keratotomy associated endothelial degeneration

    PubMed Central

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

    2012-01-01

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

  8. Light scattering of degenerate fermions

    NASA Astrophysics Data System (ADS)

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

    2006-05-01

    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.

  9. General pathophysiology in retinal degeneration.

    PubMed

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

    2014-01-01

    Retinal degeneration, including that seen in age-related macular degeneration and retinitis pigmentosa (RP), is the most common form of neural degenerative disease in the world. There is great genetic and allelic heterogeneity of the various retinal dystrophies. Classifications of these diseases can be ambiguous, as there are similar clinical presentations in retinal degenerations arising from different genetic mechanisms. As would be expected, alterations in the activity of the phototransduction cascade, such as changes affecting the renewal and shedding of the photoreceptor OS, visual transduction, and/or retinol metabolism have a great impact on the health of the retina. Mutations within any of the molecules responsible for these visual processes cause several types of retinal and retinal pigment epithelium degenerative diseases. Apoptosis has been implicated in the rod cell loss seen in a mouse model of RP, but the precise mechanisms that connect the activation of these pathways to the loss of phosphodiesterase (PDE6β) function has yet to be defined. Additionally, the activation of apoptosis by CCAAT/-enhancer-binding protein homologous protein (CHOP), after activation of the unfolded protein response pathway, may be responsible for cell death, although the mechanism remains unknown. However, the mechanisms of cell death after loss of function of PDE6, which is a commonly studied mammalian model in research, may be generalizable to loss of function of different key proteins involved in the phototransduction cascade. PMID:24732759

  10. General Pathophysiology in Retinal Degeneration

    PubMed Central

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

    2015-01-01

    Retinal degeneration, including that seen in age-related macular degeneration and retinitis pigmentosa (RP), is the most common form of neural degenerative disease in the world. There is great genetic and allelic heterogeneity of the various retinal dystrophies. Classifications of these diseases can be ambiguous, as there are similar clinical presentations in retinal degenerations arising from different genetic mechanisms. As would be expected, alterations in the activity of the phototransduction cascade, such as changes affecting the renewal and shedding of the photoreceptor OS, visual transduction, and/ or retinol metabolism have a great impact on the health of the retina. Mutations within any of the molecules responsible for these visual processes cause several types of retinal and retinal pigment epithelium degenerative diseases. Apoptosis has been implicated in the rod cell loss seen in a mouse model of RP, but the precise mechanisms that connect the activation of these pathways to the loss of phosphodiesterase (PDE6β) function has yet to be defined. Additionally, the activation of apoptosis by CCAAT/-enhancer-binding protein homologous protein (CHOP), after activation of the unfolded protein response pathway, may be responsible for cell death, although the mechanism remains unknown. However, the mechanisms of cell death after loss of function of PDE6, which is a commonly studied mammalian model in research, may be generalizable to loss of function of different key proteins involved in the phototransduction cascade. PMID:24732759

  11. Decreased Transcription Factor Binding Levels Nearby Primate Pseudogenes Suggest Regulatory Degeneration

    PubMed Central

    Douglas, Gavin M.; Wilson, Michael D.; Moses, Alan M.

    2016-01-01

    Characteristics of pseudogene degeneration at the coding level are well-known, such as a shift toward neutral rates of nonsynonymous substitutions and gain of frameshift mutations. In contrast, degeneration of pseudogene transcriptional regulation is not well understood. Here, we test two predictions of regulatory degeneration along a pseudogenized lineage: 1) Decreased transcription factor (TF) binding and 2) accelerated evolution in putative cis-regulatory regions. We find evidence for decreased TF binding levels nearby two primate pseudogenes compared with functional liver genes. However, the majority of TF-bound sequences nearby pseudogenes do not show evidence for lineage-specific accelerated rates of evolution. We conclude that decreases in TF binding level could be a marker for regulatory degeneration, while sequence degeneration in primate cis-regulatory modules may be obscured by background rates of TF binding site turnover. PMID:26882985

  12. Decreased Transcription Factor Binding Levels Nearby Primate Pseudogenes Suggest Regulatory Degeneration.

    PubMed

    Douglas, Gavin M; Wilson, Michael D; Moses, Alan M

    2016-06-01

    Characteristics of pseudogene degeneration at the coding level are well-known, such as a shift toward neutral rates of nonsynonymous substitutions and gain of frameshift mutations. In contrast, degeneration of pseudogene transcriptional regulation is not well understood. Here, we test two predictions of regulatory degeneration along a pseudogenized lineage: 1) Decreased transcription factor (TF) binding and 2) accelerated evolution in putative cis-regulatory regions.We find evidence for decreased TF binding levels nearby two primate pseudogenes compared with functional liver genes. However, the majority of TF-bound sequences nearby pseudogenes do not show evidence for lineage-specific accelerated rates of evolution. We conclude that decreases in TF binding level could be a marker for regulatory degeneration, while sequence degeneration in primate cis-regulatory modules may be obscured by background rates of TF binding site turnover. PMID:26882985

  13. Microsphere embolization of nerve capillaries and fiber degeneration.

    PubMed Central

    Nukada, H.; Dyck, P. J.

    1984-01-01

    Polystyrene microspheres, the size chosen to plug capillaries and precapillaries, were injected into the arterial supply of rat sciatic nerves. They produced widespread segmental occlusion of capillaries in lower limb nerves. The clinical and pathologic effect was dose-related. One million microspheres produced selective capillary occlusion but no nerve fiber degeneration; approximately 6 million microspheres also produced selective capillary occlusion and associated foot and leg weakness, sensory loss, and fiber degeneration, beginning in a central core of the distal sciatic nerve; 30 million microspheres caused both capillary and arterial occlusion and a greater neuropathologic deficit. From these observations it is inferred that 1) occlusion of isolated precapillaries and capillaries does not produce ischemic fiber degeneration; 2) occlusion of many microvessels results in central fascicular fiber degeneration, indicating that these cores are watershed regions of poor perfusion; and 3) stereotyped pathologic alterations of nerve fibers and Schwann cells are related to dose, anatomic site, and time elapsed since injection. Images Figure 1 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 PMID:6326580

  14. Ultraviolet spectrophotometry of degenerate stars

    NASA Technical Reports Server (NTRS)

    Greenstein, J. L.; Oke, J. B.

    1979-01-01

    Observations of one helium- and three hydrogen-atmosphere degenerates made with the International Ultraviolet Explorer are discussed. Fluxes in the UV give temperatures in good accordance with those determined from the ground and from the ANS satellite data. Profiles of the strong L-alpha absorption in two DA's fit predictions for the expected temperatures. Gravity determination is vitiated by their steep temperature dependence. If one accepts that theoretical predictions should be correct, corrections to the absolute IUE calibration derived are an upward shift of 3-5%, with irregular residuals attaining + or - 7%.

  15. Degeneration of a Nonrecombining Chromosome

    NASA Astrophysics Data System (ADS)

    Rice, William R.

    1994-01-01

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

  16. [Age-related macular degeneration].

    PubMed

    Budzinskaia, M V

    2014-01-01

    The review provides an update on the pathogenesis and new treatment modalities for neovascular age-related macular degeneration (AMD). The impact of polymorphism in particular genes, including complement factor H (CFH), age-related maculopathy susceptibility 2 (ARMS2/LOC387715), and serine peptidase (HTRA1), on AMD development is discussed. Clinical presentations of different forms of exudative AMD, that is classic, occult, or more often mixed choroidal neovascularization, retinal angiomatous proliferation, and choroidal polypoidal vasculopathy, are described. Particular attention is paid to the results of recent clinical trials and safety issues around the therapy. PMID:25715554

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

    PubMed Central

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

    2013-01-01

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

  18. Mathematical glimpse on the Y chromosome degeneration

    NASA Astrophysics Data System (ADS)

    Lobo, M. P.

    2006-04-01

    The Y chromosomes are genetically degenerate and do not recombine with their matching partners X. Non-recombination of XY pairs has been pointed out as the key factor for the degeneration of the Y chromosome. The aim here is to show that there is a mathematical asymmetry in sex chromosomes which leads to the degeneration of Y chromosomes even in the absence of XX and XY recombination. A model for sex-chromosome evolution in a stationary regime is proposed. The consequences of their asymmetry are analyzed and lead us to a couple of conclusions. First, Y chromosome degeneration shows up sqrt{2} more often than X chromosome degeneration. Second, if nature prohibits female mortalities from beeing exactly 50%, then Y chromosome degeneration is inevitable.

  19. New mouse primary retinal degeneration (rd-3)

    SciTech Connect

    Chang, B.; Hawes, N.L.; Roderick, T.H. ); Heckenlively, J.R. )

    1993-04-01

    A new mouse retinal degeneration that appears to be an excellent candidate for modeling human retinitis pigmentosa is reported. In this degeneration, called rd-3, differentiation proceeds postnatally through 2 weeks, and photoreceptor degeneration starts by 3 weeks. The rod photoreceptor loss is essentially complete by 5 weeks, whereas remnant cone cells are seen through 7 weeks. This is the only mouse homozygous retinal degeneration reported to date in which photoreceptors are initially normal. Crosses with known mouse retinal degenerations rd, Rds, nr, and pcd are negative for retinal degeneration in offspring, and linkage analysis places rd-3 on mouse chromosome 1 at 10 [+-]2.5 cM distal to Akp-1. Homology mapping suggests that the homologous human locus should be on chromosome 1q. 32 refs., 3 figs., 3 tabs.

  20. Axon degeneration: context defines distinct pathways.

    PubMed

    Geden, Matthew J; Deshmukh, Mohanish

    2016-08-01

    Axon degeneration is an essential part of development, plasticity, and injury response and has been primarily studied in mammalian models in three contexts: 1) Axotomy-induced Wallerian degeneration, 2) Apoptosis-induced axon degeneration (axon apoptosis), and 3) Axon pruning. These three contexts dictate engagement of distinct pathways for axon degeneration. Recent advances have identified the importance of SARM1, NMNATs, NAD+ depletion, and MAPK signaling in axotomy-induced Wallerian degeneration. Interestingly, apoptosis-induced axon degeneration and axon pruning have many shared mechanisms both in signaling (e.g. DLK, JNKs, GSK3α/β) and execution (e.g. Puma, Bax, caspase-9, caspase-3). However, the specific mechanisms by which caspases are activated during apoptosis versus pruning appear distinct, with apoptosis requiring Apaf-1 but not caspase-6 while pruning requires caspase-6 but not Apaf-1. PMID:27197022

  1. [Age-related macular degeneration].

    PubMed

    Garcia Layana, A

    1998-01-01

    Age-related macular degeneration (ARMD) is the leading cause of blindness in the occidental world. Patients suffering this process have an important reduction on their quality of life being handicapped to read, to write, to recognise faces of their friends, or even to watch the television. One of the main problems of that disease is the absence of an effective treatment able to revert the process. Laser treatment is only useful in a limited number of patients, and even in these cases recurrent lesions are frequent. These facts and the progressive ageing of our society establish the ARMD as one of the biggest aim of medical investigations for the next century, and currently is focus of attention in the most industrialised countries. One of the most promising pieces of research is focused in the investigation of the risk factors associated with the age-related macular degeneration, in order to achieve a prophylactic treatment avoiding its appearance. Diet elements such as fat ingestion or reduced antioxidant intakes are being investigated as some of these factors, what open a new possibility for a prophylactic treatment. Finally, research is looking for new therapeutic modalities such as selective radiotherapy in order to improve or maintain the vision of these patients. PMID:10420956

  2. Photoreceptor Cells Influence Retinal Vascular Degeneration in Mouse Models of Retinal Degeneration and Diabetes

    PubMed Central

    Liu, Haitao; Tang, Jie; Du, Yunpeng; Saadane, Aicha; Tonade, Deoye; Samuels, Ivy; Veenstra, Alex; Palczewski, Krzysztof; Kern, Timothy S.

    2016-01-01

    Purpose Loss of photoreceptor cells is associated with retinal vascular degeneration in retinitis pigmentosa, whereas the presence of photoreceptor cells is implicated in vascular degeneration in diabetic retinopathy. To investigate how both the absence and presence of photoreceptors could damage the retinal vasculature, we compared two mouse models of photoreceptor degeneration (opsin−/− and RhoP23H/P23H ) and control C57Bl/5J mice, each with and without diabetes. Methods Retinal thickness, superoxide, expression of inflammatory proteins, ERG and optokinetic responses, leukocyte cytotoxicity, and capillary degeneration were evaluated at 1 to 10 months of age using published methods. Results Retinal photoreceptor cells degenerated completely in the opsin mutants by 2 to 4 months of age, and visual function subsided correspondingly. Retinal capillary degeneration was substantial while photoreceptors were still present, but slowed after the photoreceptors degenerated. Diabetes did not further exacerbate capillary degeneration in these models of photoreceptor degeneration, but did cause capillary degeneration in wild-type animals. Photoreceptor cells, however, did not degenerate in wild-type diabetic mice, presumably because the stress responses in these cells were less than in the opsin mutants. Retinal superoxide and leukocyte damage to retinal endothelium contributed to the degeneration of retinal capillaries in diabetes, and leukocyte-mediated damage was increased in both opsin mutants during photoreceptor cell degeneration. Conclusions Photoreceptor cells affect the integrity of the retinal microvasculature. Deterioration of retinal capillaries in opsin mutants was appreciable while photoreceptor cells were present and stressed, but was less after photoreceptors degenerated. This finding proves relevant to diabetes, where persistent stress in photoreceptors likewise contributes to capillary degeneration. PMID:27548901

  3. Hot subdwarfs with degenerate companions

    NASA Astrophysics Data System (ADS)

    Mereghetti, Sandro

    2010-10-01

    Stellar evolutionary models predict that most of the hot sub-dwarfs in close binary systems have white dwarf companions. In a few cases even more massive compact objects (neutron stars or black holes) are suggested by the optical mass functions. The X-ray emission expected from accretion of the sub-dwarf's wind can reveal the nature of the compact companions and be used to derive other important information on these post-common envelope systems, as recently demonstrated by the discovery of a massive WD in HD 49798. We selected 3 promising targets from a sample of hot subdwarfs suspected to have degenerate companions. This proposal was accepted in AO9 with C priority.

  4. Laser therapy and macular degeneration

    NASA Astrophysics Data System (ADS)

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

    2001-10-01

    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.

  5. Genetics of Frontotemporal Lobar Degeneration

    PubMed Central

    Galimberti, Daniela; Scarpini, Elio

    2012-01-01

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

  6. Degenerate doping of metallic anodes

    DOEpatents

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

    2015-05-12

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

  7. Degenerate adiabatic perturbation theory: Foundations and applications

    NASA Astrophysics Data System (ADS)

    Rigolin, Gustavo; Ortiz, Gerardo

    2014-08-01

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

  8. A Monte Carlo algorithm for degenerate plasmas

    SciTech Connect

    Turrell, A.E. Sherlock, M.; Rose, S.J.

    2013-09-15

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

  9. Total absorption by degenerate critical coupling

    SciTech Connect

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

    2014-06-23

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

  10. Advances in the management of macular degeneration

    PubMed Central

    2014-01-01

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

  11. Live Imaging of Calcium Dynamics during Axon Degeneration Reveals Two Functionally Distinct Phases of Calcium Influx

    PubMed Central

    Yamagishi, Yuya; Tessier-Lavigne, Marc

    2015-01-01

    Calcium is a key regulator of axon degeneration caused by trauma and disease, but its specific spatial and temporal dynamics in injured axons remain unclear. To clarify the function of calcium in axon degeneration, we observed calcium dynamics in single injured neurons in live zebrafish larvae and tested the temporal requirement for calcium in zebrafish neurons and cultured mouse DRG neurons. Using laser axotomy to induce Wallerian degeneration (WD) in zebrafish peripheral sensory axons, we monitored calcium dynamics from injury to fragmentation, revealing two stereotyped phases of axonal calcium influx. First, axotomy triggered a transient local calcium wave originating at the injury site. This initial calcium wave only disrupted mitochondria near the injury site and was not altered by expression of the protective WD slow (WldS) protein. Inducing multiple waves with additional axotomies did not change the kinetics of degeneration. In contrast, a second phase of calcium influx occurring minutes before fragmentation spread as a wave throughout the axon, entered mitochondria, and was abolished by WldS expression. In live zebrafish, chelating calcium after the first wave, but before the second wave, delayed the progress of fragmentation. In cultured DRG neurons, chelating calcium early in the process of WD did not alter degeneration, but chelating calcium late in WD delayed fragmentation. We propose that a terminal calcium wave is a key instructive component of the axon degeneration program. SIGNIFICANCE STATEMENT Axon degeneration resulting from trauma or neurodegenerative disease can cause devastating deficits in neural function. Understanding the molecular and cellular events that execute axon degeneration is essential for developing treatments to address these conditions. Calcium is known to contribute to axon degeneration, but its temporal requirements in this process have been unclear. Live calcium imaging in severed zebrafish neurons and temporally controlled

  12. Dispersion relations in weakly degenerate plasmas

    NASA Astrophysics Data System (ADS)

    Rocchi, F.; Molinari, V. G.; Mostacci, D.; Sumini, M.

    2001-06-01

    From a quantum mechanical point of view, electrons in laser produced plasmas can be regarded as weakly degenerate. For instance, for a plasma with electron density of 10 22 cm -3 and electron temperature of 1 eV, Sommerfeld's parameter is between 1 and 2. Under these conditions the usual dispersion relations for waves in plasmas need be corrected to account for degeneracy. In the present work, starting from the transport equation with a simplified version of the Boltzmann-Uehling-Uhlenbeck collision kernel the propagation of waves impinging on a plasma with weakly degenerate electrons is investigated and dispersion relations accounting for degeneracy are derived. These dispersion relations give the classical ones in the limit for Sommerfeld's parameter approaching zero. A shift of the wavenumber value and a non-collisional damping due to degeneracy effects are predicted which render a weakly degenerate plasma more opaque to radiation than a non-degenerate one.

  13. Degenerate neuronal systems sustaining cognitive functions

    PubMed Central

    Noppeney, Uta; Friston, Karl J; Price, Cathy J

    2004-01-01

    The remarkable resilience of cognitive functions to focal brain damage suggests that multiple degenerate neuronal systems can sustain the same function either via similar mechanisms or by implementing different cognitive strategies. In degenerate functional neuroanatomy, multiple degenerate neuronal systems might be present in a single brain where they are either co-activated or remain latent during task performance. In degeneracy over subjects, a particular function may be sustained by only one neuronal system within a subject, but by different systems over subjects. Degeneracy over subjects might have arisen from (ab)normal variation in neurodevelopmental trajectories or long-term plastic changes following structural lesions. We discuss how degenerate neuronal systems can be revealed using (1) intersubject variability, (2) multiple lesion studies and (3) an iterative approach integrating information from lesion and functional imaging studies. PMID:15610392

  14. Quantitative Pfirrmann Disc Degeneration Grading System to Overcome the Limitation of Pfirrmann Disc Degeneration Grade

    PubMed Central

    2016-01-01

    Objective Pfirrmann disc degeneration grade is one of morphologic disc degeneration grading system and it was reliable on routine T2-weighted magnetic resonance (MR) images. The purpose of this study was to evaluate the agreement of Pfirrmann disc degeneration grade, and check the alternative technique of disc degeneration grading system. Methods Fifteen volunteers (4 medical doctors related to spinal disease, 2 medical doctors not related to spinal disease, 6 nurses in spinal hospital, and 3 para-medicines) were included in this study. Three different digitalized MR images were provided all volunteers, and they checked Pfirrmann disc degeneration grade of each disc levels after careful listening to explanation. Indeed, all volunteers checked the signal intensity of disc degeneration at the points of nucleus pulposus (NP), disc membrane, ligaments, fat, and air to modify the quantitative Pfirrmann disc degeneration grade. Results Total 225 grade results of Pfirrmann disc degeneration grade and 405 signal intensity results of quantitative Pfirrmann disc degeneration grade were analyzed. Average interobserver agreement was "moderate (mean±standard deviation, 0.575±0.251)" from poor to excellent. Completely agreed levels of Pfirrmann disc degeneration grade were only 4 levels (26.67%), and the disagreement levels were observed in 11 levels; two different grades in 8 levels (53.33%) and three different grades in 3 levels (20%). Quantitative Pfirrmann disc degeneration showed relatively cluster distribution with the interobserver deviations of 0.41-1.56 at the ratio of NP and disc membrane, and it showed relatively good cluster and distribution indicating that the proposed grading system has good discrimination ability. Conclusion Pfirrmann disc degeneration grade showed the limitation of different interobserver results, but this limitation could be overcome by using quantitative techniques of MR signal intensity. Further evaluation is needed to access its advantage

  15. Microscopic Observation of Pauli Blocking in Degenerate Fermionic Lattice Gases.

    PubMed

    Omran, Ahmed; Boll, Martin; Hilker, Timon A; Kleinlein, Katharina; Salomon, Guillaume; Bloch, Immanuel; Gross, Christian

    2015-12-31

    The Pauli exclusion principle is one of the most fundamental manifestations of quantum statistics. Here, we report on its local observation in a spin-polarized degenerate gas of fermions in an optical lattice. We probe the gas with single-site resolution using a new generation quantum gas microscope avoiding the common problem of light induced losses. In the band insulating regime, we measure a strong local suppression of particle number fluctuations and a low local entropy per atom. Our work opens a new avenue for studying quantum correlations in fermionic quantum matter both in and out of equilibrium. PMID:26764988

  16. Microscopic Observation of Pauli Blocking in Degenerate Fermionic Lattice Gases

    NASA Astrophysics Data System (ADS)

    Omran, Ahmed; Boll, Martin; Hilker, Timon A.; Kleinlein, Katharina; Salomon, Guillaume; Bloch, Immanuel; Gross, Christian

    2015-12-01

    The Pauli exclusion principle is one of the most fundamental manifestations of quantum statistics. Here, we report on its local observation in a spin-polarized degenerate gas of fermions in an optical lattice. We probe the gas with single-site resolution using a new generation quantum gas microscope avoiding the common problem of light induced losses. In the band insulating regime, we measure a strong local suppression of particle number fluctuations and a low local entropy per atom. Our work opens a new avenue for studying quantum correlations in fermionic quantum matter both in and out of equilibrium.

  17. Prospectives for Gene Therapy of Retinal Degenerations

    PubMed Central

    Thumann, Gabriele

    2012-01-01

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

  18. Antioxidative nanofullerol prevents intervertebral disk degeneration

    PubMed Central

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

    2014-01-01

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

  19. Optic pathway degeneration in Japanese black cattle

    PubMed Central

    CHIBA, Shiori; FUNATO, Shingo; HORIUCHI, Noriyuki; MATSUMOTO, Kotaro; INOKUMA, Hisashi; FURUOKA, Hidefumi; KOBAYASHI, Yoshiyasu

    2014-01-01

    Degeneration of the optic pathway has been reported in various animal species including cattle. We experienced a case of bilateral optic tract degeneration characterized by severe gliosis in a Japanese black cattle without any obvious visual defects. To evaluate the significance, pathological nature and pathogenesis of the lesions, we examined the optic pathway in 60 cattle (41 Japanese black, 13 Holstein and 6 crossbreed) with or without ocular abnormalities. None of these animals had optic canal stenosis. Degenerative changes with severe gliosis in the optic pathway, which includes the optic nerve, optic chiasm and optic tract, were only observed in 8 Japanese black cattle with or without ocular abnormalities. Furthermore, strong immunoreactivity of glial fibrillary acidic protein was observed in the retinal stratum opticum and ganglion cell layer in all 5 cattle in which the optic pathway lesions could be examined. As etiological research, we also examined whether the concentrations of vitamin A and vitamin B12 or bovine viral diarrhea virus (BVDV) infection was associated with optic pathway degeneration. However, our results suggested that the observed optic pathway degeneration was probably not caused by these factors. These facts indicate the presence of optic pathway degeneration characterized by severe gliosis that has never been reported in cattle without bilateral compressive lesions in the optic pathway or bilateral severe retinal atrophy. PMID:25421501

  20. The cell stress machinery and retinal degeneration.

    PubMed

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

    2013-06-27

    Retinal degenerations are a group of clinically and genetically heterogeneous disorders characterised by progressive loss of vision due to neurodegeneration. The retina is a highly specialised tissue with a unique architecture and maintaining homeostasis in all the different retinal cell types is crucial for healthy vision. The retina can be exposed to a variety of environmental insults and stress, including light-induced damage, oxidative stress and inherited mutations that can lead to protein misfolding. Within retinal cells there are different mechanisms to cope with disturbances in proteostasis, such as the heat shock response, the unfolded protein response and autophagy. In this review, we discuss the multiple responses of the retina to different types of stress involved in retinal degenerations, such as retinitis pigmentosa, age-related macular degeneration and glaucoma. Understanding the mechanisms that maintain and re-establish proteostasis in the retina is important for developing new therapeutic approaches to fight blindness. PMID:23684651

  1. Potential Outcome Factors in Subacute Combined Degeneration

    PubMed Central

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

    2006-01-01

    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. PMID:16970556

  2. Pathogenesis of tendinopathies: inflammation or degeneration?

    PubMed Central

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

    2009-01-01

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

  3. Retinal Cell Degeneration in Animal Models

    PubMed Central

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

    2016-01-01

    The aim of this review is to provide an overview of various retinal cell degeneration models in animal induced by chemicals (N-methyl-d-aspartate- and CoCl2-induced), autoimmune (experimental autoimmune encephalomyelitis), mechanical stress (optic nerve crush-induced, light-induced) and ischemia (transient retinal ischemia-induced). The target regions, pathology and proposed mechanism of each model are described in a comparative fashion. Animal models of retinal cell degeneration provide insight into the underlying mechanisms of the disease, and will facilitate the development of novel effective therapeutic drugs to treat retinal cell damage. PMID:26784179

  4. Ion acoustic shock waves in degenerate plasmas

    SciTech Connect

    Akhtar, N.; Hussain, S.

    2011-07-15

    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.

  5. Kinematic control of robot with degenerate wrist

    NASA Technical Reports Server (NTRS)

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

    1984-01-01

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

  6. CT of sarcomatous degeneration in neurofibromatosis

    SciTech Connect

    Coleman, B.G.; Arger, P.H.; Dalinka, M.K.; Obringer, A.C.; Raney, B.R.; Meadows, A.T.

    1983-02-01

    Neurofibromatosis is a relatively common disorder that often involves many organ systems. One of the least understood aspects of this malady is a well documented potential for sarcomatous degeneration of neurofibromas. The inability to identify patients at risk and the lack of noninvasive screening methods for symptomatic patients often leads to late diagnosis. In six of seven subsequently proven neurofibrosarcomas, CT demonstrated low-density areas that histopathologically appeared to be due to necrosis, hemorrhage, and/or cystic degeneration. The density differences within these sarcomas were enhanced by the intravenous adminstration of iodinated contrast agents.

  7. Microscopic Observation of Pauli Blocking in Degenerate Fermionic Lattice Gases

    NASA Astrophysics Data System (ADS)

    Hilker, Timon; Omran, Ahmed; Boll, Martin; Salomon, Guillaume; Bloch, Immanuel; Gross, Christian

    2016-05-01

    Ultracold atoms in optical lattices provide a powerful platform for the controlled study of quantum many-body physics. We present here the first studies with a new generation quantum gas microscope, which allows to observe the full atom number statistics on every site. The common problem of light induced losses during imaging is avoided by an additional small scale ``pinning lattice'' used for Raman sideband cooling in the imaging process. We report the local observation of the Pauli exclusion principle in a spin-polarized degenerate gas of 6 Li fermions in an optical lattice. In the band insulating regime, we measure a tenfold suppression of particle number fluctuations per site compared to classical particles. From the remaining fluctuations we extract a local entropy as low as 0.3 kB per atom. Our work opens an exciting avenue for studying local density and even magnetic correlations in fermionic quantum matter both in and out of equilibrium.

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

    PubMed

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

    2012-08-01

    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

  9. Driving and Age-Related Macular Degeneration

    PubMed Central

    Owsley, Cynthia; McGwin, Gerald

    2009-01-01

    This article reviews the research literature on driving and age-related macular degeneration, which is motivated by the link between driving and the quality of life of older adults and their increased collision rate. It addresses the risk of crashes, driving performance, driving difficulty, self-regulation, and interventions to enhance, safety, and considers directions for future research. PMID:20046818

  10. A family of degenerate Lie algebras

    NASA Astrophysics Data System (ADS)

    Cruz, I.

    1999-08-01

    We show that almost all the real Lie algebras with only zero- and two-dimensional coadjoint orbits are degenerate in both the smooth and analytic category. The only exceptions are the already known cases (studied for example by Dufour and Weinstein).

  11. Driving and Age-Related Macular Degeneration

    ERIC Educational Resources Information Center

    Owsley, Cynthia; McGwin, Gerald, Jr.

    2008-01-01

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

  12. Depression in Age-Related Macular Degeneration

    ERIC Educational Resources Information Center

    Casten, Robin; Rovner, Barry

    2008-01-01

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

  13. Spectroscopic observations of cool degenerate star candidates

    NASA Technical Reports Server (NTRS)

    Hintzen, P.

    1986-01-01

    Spectroscopic observations are reported for 23 Luyten Half-Second degenerate star candidates and for 13 Luyten-Palomar common proper-motion pairs containing possible degenerate star components. Twenty-five degenerate stars are identified, 20 of which lack previous spectroscopy. Most of these stars are cool - Luyten color class g or later. One star, LP 77-57, shows broad continuum depressions similar to those in LHS 1126, which Liebert and Dahn attributed to pressure-shifted C2. A second degenerate star, LHS 290, exhibits apparent strong Swan bands which are blueshifted about 75 A. Further observations, including polarimetry and photometry, are required to appraise the spectroscopic peculiarities of these stars. Finally, five cool, sharp-lined DA white dwarfs have been observed to detect lines of metals and to determine line strengths. None of these DAs show signs of Mg b or the G band, and four show no evidence of Ca II K. The attempt to detect Ca MI in the fifth star, G199-71, was inconclusive.

  14. Tenascin-C and human tendon degeneration.

    PubMed Central

    Riley, G. P.; Harrall, R. L.; Cawston, T. E.; Hazleman, B. L.; Mackie, E. J.

    1996-01-01

    We investigated the distribution of tenascin in supraspinatus tendons to determine whether an alteration in tenascin expression was associated with human tendon degeneration. Tenascin was present in all of the tendons studied, although with two distinct patterns of expression. First, tenascin was associated with organized, fibrous regions of the tendon matrix that were typical of the normal tendon structure. This distribution is consistent with a role for tenascin in collagen fibril organization, perhaps maintaining the interface between fibrils and adjacent structures. Second, although tenascin was generally absent from poorly organized matrix in degenerate tendons, it was strongly associated with some rounded cells in disorganized fibrocartilaginous regions that were more abundant in pathological specimens. Tenascin was also found around infiltrating blood vessels, with more intense staining associated with a mononuclear cell infiltrate. Western blotting of tendon extracts showed differences in tenascin isoform expression, with only the small (200-kd) tenascin isoform found in normal tendons. Degenerate tendons also expressed the 300-kd isoform, consistent with a role for the larger tenascin isoform in tendon disease, potentially stimulating tenocyte proliferation, cell rounding, and fibrocartilaginous change. Proteolytic fragments of tenascin were detected but only in ruptured tendons, an indication of matrix remodeling in degenerate tendons, with fragment sizes consistent with the activity of matrix metalloproteinase enzymes. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:8780397

  15. Purinergic signaling in retinal degeneration and regeneration.

    PubMed

    Reichenbach, Andreas; Bringmann, Andreas

    2016-05-01

    Purinergic signaling is centrally involved in mediating the degeneration of the injured and diseased retina, the induction of retinal gliosis, and the protection of the retinal tissue from degeneration. Dysregulated calcium signaling triggered by overactivation of P2X7 receptors is a crucial step in the induction of neuronal and microvascular cell death under pathogenic conditions like ischemia-hypoxia, elevated intraocular pressure, and diabetes, respectively. Overactivation of P2X7 plays also a pathogenic role in inherited and age-related photoreceptor cell death and in the age-related dysfunction and degeneration of the retinal pigment epithelium. Gliosis of micro- and macroglial cells, which is induced and/or modulated by purinergic signaling and associated with an impaired homeostatic support to neurons, and the ATP-mediated propagation of retinal gliosis from a focal injury into the surrounding noninjured tissue are involved in inducing secondary cell death in the retina. On the other hand, alterations in the glial metabolism of extracellular nucleotides, resulting in a decreased level of ATP and an increased level of adenosine, may be neuroprotective in the diseased retina. Purinergic signals stimulate the proliferation of retinal glial cells which contributes to glial scarring which has protective effects on retinal degeneration and adverse effects on retinal regeneration. Pharmacological modulation of purinergic receptors, e.g., inhibition of P2X and activation of adenosine receptors, may have clinical importance for the prevention of photoreceptor, neuronal, and microvascular cell death in diabetic retinopathy, retinitis pigmentosa, age-related macular degeneration, and glaucoma, respectively, for the clearance of retinal edema, and the inhibition of dysregulated cell proliferation in proliferative retinopathies. This article is part of a Special Issue entitled 'Purines in Neurodegeneration and Neuroregeneration'. PMID:25998275

  16. Molecular pharmacodynamics of emixustat in protection against retinal degeneration.

    PubMed

    Zhang, Jianye; Kiser, Philip D; Badiee, Mohsen; Palczewska, Grazyna; Dong, Zhiqian; Golczak, Marcin; Tochtrop, Gregory P; Palczewski, Krzysztof

    2015-07-01

    Emixustat is a visual cycle modulator that has entered clinical trials as a treatment for age-related macular degeneration (AMD). This molecule has been proposed to inhibit the visual cycle isomerase RPE65, thereby slowing regeneration of 11-cis-retinal and reducing production of retinaldehyde condensation byproducts that may be involved in AMD pathology. Previously, we reported that all-trans-retinal (atRAL) is directly cytotoxic and that certain primary amine compounds that transiently sequester atRAL via Schiff base formation ameliorate retinal degeneration. Here, we have shown that emixustat stereoselectively inhibits RPE65 by direct active site binding. However, we detected the presence of emixustat-atRAL Schiff base conjugates, indicating that emixustat also acts as a retinal scavenger, which may contribute to its therapeutic effects. Using agents that lack either RPE65 inhibitory activity or the capacity to sequester atRAL, we assessed the relative importance of these 2 modes of action in protection against retinal phototoxicity in mice. The atRAL sequestrant QEA-B-001-NH2 conferred protection against phototoxicity without inhibiting RPE65, whereas an emixustat derivative incapable of atRAL sequestration was minimally protective, despite direct inhibition of RPE65. These data indicate that atRAL sequestration is an essential mechanism underlying the protective effects of emixustat and related compounds against retinal phototoxicity. Moreover, atRAL sequestration should be considered in the design of next-generation visual cycle modulators. PMID:26075817

  17. Molecular pharmacodynamics of emixustat in protection against retinal degeneration

    PubMed Central

    Zhang, Jianye; Kiser, Philip D.; Badiee, Mohsen; Palczewska, Grazyna; Dong, Zhiqian; Golczak, Marcin; Tochtrop, Gregory P.; Palczewski, Krzysztof

    2015-01-01

    Emixustat is a visual cycle modulator that has entered clinical trials as a treatment for age-related macular degeneration (AMD). This molecule has been proposed to inhibit the visual cycle isomerase RPE65, thereby slowing regeneration of 11-cis-retinal and reducing production of retinaldehyde condensation byproducts that may be involved in AMD pathology. Previously, we reported that all-trans-retinal (atRAL) is directly cytotoxic and that certain primary amine compounds that transiently sequester atRAL via Schiff base formation ameliorate retinal degeneration. Here, we have shown that emixustat stereoselectively inhibits RPE65 by direct active site binding. However, we detected the presence of emixustat-atRAL Schiff base conjugates, indicating that emixustat also acts as a retinal scavenger, which may contribute to its therapeutic effects. Using agents that lack either RPE65 inhibitory activity or the capacity to sequester atRAL, we assessed the relative importance of these 2 modes of action in protection against retinal phototoxicity in mice. The atRAL sequestrant QEA-B-001-NH2 conferred protection against phototoxicity without inhibiting RPE65, whereas an emixustat derivative incapable of atRAL sequestration was minimally protective, despite direct inhibition of RPE65. These data indicate that atRAL sequestration is an essential mechanism underlying the protective effects of emixustat and related compounds against retinal phototoxicity. Moreover, atRAL sequestration should be considered in the design of next-generation visual cycle modulators. PMID:26075817

  18. Pollen Tube Discharge Completes the Process of Synergid Degeneration That Is Initiated by Pollen Tube-Synergid Interaction in Arabidopsis1[OPEN

    PubMed Central

    Leydon, Alexander R.; Tsukamoto, Tatsuya; Dunatunga, Damayanthi; Qin, Yuan; Johnson, Mark A.; Palanivelu, Ravishankar

    2015-01-01

    In flowering plant reproduction, pollen tube reception is the signaling system that results in pollen tube discharge, synergid degeneration, and successful delivery of male gametes (two sperm cells) to the site where they can fuse with female gametes (egg cell and central cell). Some molecules required for this complex and essential signaling exchange have been identified; however, fundamental questions about the nature of the interactions between the pollen tube and the synergid cells remain to be clarified. Here, we monitor pollen tube arrival, pollen tube discharge, and synergid degeneration in Arabidopsis (Arabidopsis thaliana) wild type and in male and female gametophytic mutants that disrupt development and function of the gametophytes. By combining assays used previously to study these interactions and an assay that facilitates simultaneous analysis of pollen tube discharge and synergid degeneration, we find that synergid degeneration could be initiated without pollen tube discharge. Our data support the hypothesis that pollen tube-synergid contact, or signaling via secreted molecules, initiates receptive synergid degeneration. We also find that when pollen tubes successfully burst, they always discharge into a degenerated synergid. In addition to this pollen tube-dependent promotion of synergid degeneration, we also show that a basal developmental pathway mediates synergid degeneration in the absence of pollination. Our results are consistent with the model that a complex set of interactions between the pollen tube and synergid cells promote receptive synergid degeneration. PMID:26229050

  19. NEUTRINO PROCESSES IN PARTIALLY DEGENERATE NEUTRON MATTER

    SciTech Connect

    Bacca, S.; Hally, K.; Liebendoerfer, M.; Perego, A.; Pethick, C. J.; Schwenk, A.

    2012-10-10

    We investigate neutrino processes for conditions reached in simulations of core-collapse supernovae. In regions where neutrino-matter interactions play an important role, matter is partially degenerate, and we extend earlier work that addressed the degenerate regime. We derive expressions for the spin structure factor in neutron matter, which is a key quantity required for evaluating rates of neutrino processes. We show that, for essentially all conditions encountered in the post-bounce phase of core-collapse supernovae, it is a very good approximation to calculate the spin relaxation rates in the nondegenerate limit. We calculate spin relaxation rates based on chiral effective field theory interactions and find that they are typically a factor of two smaller than those obtained using the standard one-pion-exchange interaction alone.

  20. Inflammation in intervertebral disc degeneration and regeneration

    PubMed Central

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

    2015-01-01

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

  1. Shell nuclear explosions in degenerate dwarfs

    NASA Astrophysics Data System (ADS)

    Kuznetsov, O. A.; Tutukov, A. V.; Chechetkin, V. M.

    1989-08-01

    Numerical gas dynamics simulations are used to study shell nuclear explosions of degenerate carbon-oxygen dwarfs with masses of 1.17, 1.36, and 1.42 solar masses. It is assumed that the calorific capacity of the burning shell matter is between 5 X 10 to the 17th and 5 X 10 to the 18th erg/g. It is shown that, at a low calorific capacity, a remnant may form if the mass of the shell is less than 90 percent of the mass of the degenerate dwarf. In the case of high calorific capacity, a remnant may form only if the mass of the shell is less than half of the dwarf's mass.

  2. Degeneration and regeneration of ganglion cell axons.

    PubMed

    Weise, J; Ankerhold, R; Bähr, M

    2000-01-15

    The retino-tectal system has been used to study developmental aspects of axon growth, synapse formation and the establishment of a precise topographic order as well as degeneration and regeneration of adult retinal ganglion cell (RGC) axons after axonal lesion. This paper reviews some novel findings that provide new insights into the mechanisms of developmental RGC axon growth, pathfinding, and target formation. It also focuses on the cellular and molecular cascades that underlie RGC degeneration following an axonal lesion and on some therapeutic strategies to enhance survival of axotomized RGCs in vivo. In addition, this review deals with problems related to the induction of regeneration after axonal lesion in the adult CNS using the retino-tectal system as model. Different therapeutic approaches to promote RGC regeneration and requirements for specific target formation of regenerating RGCs in vitro and in vivo are discussed. PMID:10649506

  3. Macular degeneration in an arc welder.

    PubMed

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

    2007-04-01

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

  4. Calabi-Yau manifolds and their degenerations.

    PubMed

    Tosatti, Valentino

    2012-07-01

    Calabi-Yau manifolds are geometric objects of central importance in several branches of mathematics, including differential geometry, algebraic geometry, and mathematical physics. In this paper, we give a brief introduction to the subject aimed at a general mathematical audience and present some of our results that shed some light on the possible ways in which families of Calabi-Yau manifolds can degenerate. PMID:22257362

  5. Degenerate Bose gases with uniform loss

    NASA Astrophysics Data System (ADS)

    Grišins, Pjotrs; Rauer, Bernhard; Langen, Tim; Schmiedmayer, Jörg; Mazets, Igor E.

    2016-03-01

    We theoretically investigate a weakly interacting degenerate Bose gas coupled to an empty Markovian bath. We show that in the universal phononic limit the system evolves towards an asymptotic state where an emergent temperature is set by the quantum noise of the outcoupling process. For situations typically encountered in experiments, this mechanism leads to significant cooling. Such dissipative cooling supplements conventional evaporative cooling and dominates in settings where thermalization is highly suppressed, such as in a one-dimensional quasicondensate.

  6. Effect of trapping in degenerate quantum plasmas

    SciTech Connect

    Shah, H. A.; Qureshi, M. N. S.; Tsintsadze, N.

    2010-03-15

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

  7. Dichromatic Langmuir waves in degenerate quantum plasma

    SciTech Connect

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

    2015-06-15

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

  8. Recombination-generation currents in degenerate semiconductors

    NASA Technical Reports Server (NTRS)

    Von Roos, O.

    1978-01-01

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

  9. Equilibrium configurations of degenerate fluid spheres

    SciTech Connect

    Whitman, P.G.

    1985-04-01

    Equilibrium configurations of degenerate fluid spheres which assume a polytropic form in the ultrahigh-density regime are considered. We show that analytic solutions more general than those of Misner and Zapolsky exist which possess the asymptotic equation of state. Simple expressions are derived which indicate this nature of the fluids in the extreme relativistic limit, and the stability of these interiors is considered in the asymptotic region.

  10. Asymmetrical alien hands in corticobasal degeneration.

    PubMed

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

    2007-03-15

    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

  11. Buoyancy instabilities in degenerate, collisional, magnetized plasmas

    NASA Astrophysics Data System (ADS)

    Chang, Philip; Quataert, Eliot

    2010-03-01

    In low-collisionality plasmas, anisotropic heat conduction due to a magnetic field leads to buoyancy instabilities for any non-zero temperature gradient. We study analogous instabilities in degenerate collisional plasmas, i.e. when the electron collision frequency is large compared to the electron cyclotron frequency. Although heat conduction is nearly isotropic in this limit, the small residual anisotropy ensures that collisional degenerate plasmas are also convectively unstable independent of the sign of the temperature gradient. We show that the range of wavelengths that are unstable is independent of the magnetic field strength, while the growth time increases with decreasing magnetic field strength. We discuss the application of these collisional buoyancy instabilities to white dwarfs and neutron stars. Magnetic tension and the low specific heat of a degenerate plasma significantly limit their effectiveness; the most promising venues for growth are in the liquid oceans of young, weakly magnetized neutron stars (B <~ 109 G) and in the cores of young, high magnetic field white dwarfs (B ~ 109 G).

  12. Inertial fusion features in degenerate plasmas

    NASA Astrophysics Data System (ADS)

    León, Pablo T.; Eliezer, Shalom; Piera, Mireia; Martínez-Val, José M.

    2005-04-01

    Very high plasma densities can be obtained at the end of the implosion phase in inertial fusion targets, particularly in the so-called fast-ignition scheme (Tabak et al., 1994; Mulser & Bauer, 2004), where a central hot spark is not needed at all. By properly tailoring the fuel compression stage, degenerate states can be reached (Azechi et al., 1991; Nakai et al., 1991; McCory, 1998). In that case, most of the relevant energy transfer mechanisms involving electrons are affected (Honrubia & Tikhonchuk, 2004; Bibi & Matte, 2004; Bibi et al., 2004). For instance, bremsstrahlung emission is highly suppressed (Eliezer et al., 2003). In fact, a low ignition-temperature regime appears at very high plasma densities, due to radiation leakage reduction (León et al., 2001). Stopping power and ion-electron coulomb collisions are also changed in this case, which are important mechanisms to trigger ignition by the incoming fast jet, and to launch the fusion wave from the igniting region into the colder, degenerate plasma. All these points are reviewed in this paper. Although degenerate states would not be easy to obtain by target implosion, they present a very interesting upper limit that deserves more attention in order to complete the understanding on the different domains for inertial confinement fusion.

  13. Propagation of disturbances in degenerate quantum systems

    NASA Astrophysics Data System (ADS)

    Chancellor, Nicholas; Haas, Stephan

    2011-07-01

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

  14. The progressive nature of Wallerian degeneration in wild-type and slow Wallerian degeneration (WldS) nerves

    PubMed Central

    Beirowski, Bogdan; Adalbert, Robert; Wagner, Diana; Grumme, Daniela S; Addicks, Klaus; Ribchester, Richard R; Coleman, Michael P

    2005-01-01

    Background The progressive nature of Wallerian degeneration has long been controversial. Conflicting reports that distal stumps of injured axons degenerate anterogradely, retrogradely, or simultaneously are based on statistical observations at discontinuous locations within the nerve, without observing any single axon at two distant points. As axon degeneration is asynchronous, there are clear advantages to longitudinal studies of individual degenerating axons. We recently validated the study of Wallerian degeneration using yellow fluorescent protein (YFP) in a small, representative population of axons, which greatly improves longitudinal imaging. Here, we apply this method to study the progressive nature of Wallerian degeneration in both wild-type and slow Wallerian degeneration (WldS) mutant mice. Results In wild-type nerves, we directly observed partially fragmented axons (average 5.3%) among a majority of fully intact or degenerated axons 37–42 h after transection and 40–44 h after crush injury. Axons exist in this state only transiently, probably for less than one hour. Surprisingly, axons degenerated anterogradely after transection but retrogradely after a crush, but in both cases a sharp boundary separated intact and fragmented regions of individual axons, indicating that Wallerian degeneration progresses as a wave sequentially affecting adjacent regions of the axon. In contrast, most or all WldS axons were partially fragmented 15–25 days after nerve lesion, WldS axons degenerated anterogradely independent of lesion type, and signs of degeneration increased gradually along the nerve instead of abruptly. Furthermore, the first signs of degeneration were short constrictions, not complete breaks. Conclusions We conclude that Wallerian degeneration progresses rapidly along individual wild-type axons after a heterogeneous latent phase. The speed of progression and its ability to travel in either direction challenges earlier models in which clearance of

  15. Transneuronal Degeneration of Thalamic Nuclei following Middle Cerebral Artery Occlusion in Rats

    PubMed Central

    2016-01-01

    Objective. Postinfarction transneuronal degeneration refers to secondary neuronal death that occurs within a few days to weeks following the disruption of input or output to synapsed neurons sustaining ischemic insults. The thalamus receives its blood supply from the posterior circulation; however, infarctions of the middle cerebral arterial may cause secondary transneuronal degeneration in the thalamus. In this study, we presented the areas of ischemia and associated transneuronal degeneration following MCAo in a rat model. Materials and Methods. Eighteen 12-week-old male Sprague-Dawley rats were randomly assigned to receive middle cerebral artery occlusion surgery for 1, 7, and 14 days. Cerebral atrophy was assessed by 2,3,5-triphenyltetrazolium hydrochloride staining. Postural reflex and open field tests were performed prior to animal sacrifice to assess the effects of occlusion on behavior. Results. Myelin loss was observed at the lesion site following ischemia. Gliosis was also observed in thalamic regions 14 days following occlusion. Differential degrees of increased vascular endothelial growth factor expression were observed at each stage of infarction. Increases in myelin basic protein levels were also observed in the 14-day group. Conclusion. The present rat model of ischemia provides evidence of transneuronal degeneration within the first 14 days of occlusion. The observed changes in protein expression may be associated with self-repair mechanisms in the damaged brain. PMID:27597962

  16. TGF-β1 is critical for Wallerian degeneration after rat sciatic nerve injury.

    PubMed

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

    2015-01-22

    Wallerian degeneration (WD) is a process of axonal degeneration distal to the injury site followed by a robust regenerative response. It involves degeneration and regeneration which can be directly induced by nerve injury and activated by transcription factors. Although WD has been studied extensively, the precise mechanisms of transcription factors regulating WD are still elusive. In this study, we reported the effect of transforming growth factor-β1 (TGF-β1) on WD after rat sciatic nerve injury. The data showed that TGF-β1 may express in injured rat sciatic nerve and cultured Schwann cells (SCs). Knock down of TGF-β1 expressions resulted in the reduction of SC proliferation and apoptosis, up regulation of cytokines and Smad2, 4. Enhanced expression of TGF-β1 could promote SC proliferation and apoptosis, down regulation of cytokines and Smad2, 4. Altered expressions of TGF-β1 may affect Smad and AKT but not c-Jun and extracellular regulated protein kinase (ERK) pathways. Our results revealed the role of TGF-β1 on WD and provided the basis for the molecular mechanisms of TGF-β1-regulated nerve degeneration and/or regeneration. PMID:25451291

  17. Transneuronal Degeneration of Thalamic Nuclei following Middle Cerebral Artery Occlusion in Rats.

    PubMed

    Chang, Shu-Jen; Cherng, Juin-Hong; Wang, Ding-Han; Yu, Shu-Ping; Liou, Nien-Hsien; Hsu, Ming-Lun

    2016-01-01

    Objective. Postinfarction transneuronal degeneration refers to secondary neuronal death that occurs within a few days to weeks following the disruption of input or output to synapsed neurons sustaining ischemic insults. The thalamus receives its blood supply from the posterior circulation; however, infarctions of the middle cerebral arterial may cause secondary transneuronal degeneration in the thalamus. In this study, we presented the areas of ischemia and associated transneuronal degeneration following MCAo in a rat model. Materials and Methods. Eighteen 12-week-old male Sprague-Dawley rats were randomly assigned to receive middle cerebral artery occlusion surgery for 1, 7, and 14 days. Cerebral atrophy was assessed by 2,3,5-triphenyltetrazolium hydrochloride staining. Postural reflex and open field tests were performed prior to animal sacrifice to assess the effects of occlusion on behavior. Results. Myelin loss was observed at the lesion site following ischemia. Gliosis was also observed in thalamic regions 14 days following occlusion. Differential degrees of increased vascular endothelial growth factor expression were observed at each stage of infarction. Increases in myelin basic protein levels were also observed in the 14-day group. Conclusion. The present rat model of ischemia provides evidence of transneuronal degeneration within the first 14 days of occlusion. The observed changes in protein expression may be associated with self-repair mechanisms in the damaged brain. PMID:27597962

  18. Kramers-degenerated NV+113C spin systems in diamond: analytical description

    NASA Astrophysics Data System (ADS)

    Nizovtsev, Alexander P.; Kilin, Sergei Y.; Pushkarchuk, Alexander L.; Kuten, Semen A.

    2013-02-01

    Spin systems consisted of single electronic spin S=1 of the NV center and nearby nuclear spins I=1/2 of 13C atoms disposed in diamond lattice near the center can be used as a small register of a quantum computer or as a sensor of a magnetic field. At odd number of nuclear spins eigenvalues of the spin systems at zero external magnetic field are at least twofold degenerated (Kramers degeneration) due to time reversal invariance of the spin Hamiltonian. This degeneracy is lifted only by external magnetic field regardless of the presence of any electric (crystal) field which can also lift the degeneracy thus hindering measurement of the magnetic field. Therefore, the Kramers-degenerated spin systems can be very perspective for measurement of a local magnetic field by the NV-based single-spin quantum magnetometer. Here, we are considering analytically the simplest Kramers-degenerated spin system NV+113C consisting of a single electron spin S=1 of the NV сenter coupled by hyperfine interaction with a single nuclear spin I=1/2 of 13C atom disposed in arbitrary site of diamond lattice. Simple approximate analytical expressions are obtained for eigenvalues and eigenstates of the spin system.

  19. Asymptotic behavior of degenerate logistic equations

    NASA Astrophysics Data System (ADS)

    Arrieta, José M.; Pardo, Rosa; Rodríguez-Bernal, Aníbal

    2015-12-01

    We analyze the asymptotic behavior of positive solutions of parabolic equations with a class of degenerate logistic nonlinearities of the type λu - n (x)uρ. An important characteristic of this work is that the region where the logistic term n (ṡ) vanishes, that is K0 = { x : n (x) = 0 }, may be non-smooth. We analyze conditions on λ, ρ, n (ṡ) and K0 guaranteeing that the solution starting at a positive initial condition remains bounded or blows up as time goes to infinity. The asymptotic behavior may not be the same in different parts of K0.

  20. Vector polarons in a degenerate electron system

    NASA Astrophysics Data System (ADS)

    Clougherty, Dennis P.; Foell, Charles A.

    2004-08-01

    We consider a one-dimensional model of an electron in a doubly (or nearly) degenerate band that interacts with elastic distortions. We show that the electron equations of motion reduce to a set of coupled nonlinear Schrödinger equations. For the case of interband electron-phonon coupling stemming from local Jahn-Teller interactions, multicomponent self-localized polaron solutions-vector polarons- are described and classified. The phase diagram for the different types of vector polarons in this model is presented. By interpreting the components of the orbital doublet as those of spin- (1)/(2) , our results can also be used to describe bound magnetic polarons.

  1. Degenerate Fermi Gas of {sup 87}Sr

    SciTech Connect

    DeSalvo, B. J.; Yan, M.; Mickelson, P. G.; Martinez de Escobar, Y. N.; Killian, T. C.

    2010-07-16

    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.

  2. Pharmacogenetics and age-related macular degeneration.

    PubMed

    Schwartz, Stephen G; Brantley, Milam A

    2011-01-01

    Pharmacogenetics seeks to explain interpatient variability in response to medications by investigating genotype-phenotype correlations. There is a small but growing body of data regarding the pharmacogenetics of both nonexudative and exudative age-related macular degeneration. Most reported data concern polymorphisms in the complement factor H and age-related maculopathy susceptibility 2 genes. At this time, the data are not consistent and no definite conclusions may be drawn. As clinical trials data continue to accumulate, these relationships may become more apparent. PMID:22046503

  3. Relativistic Bernstein waves in a degenerate plasma

    SciTech Connect

    Ali, Muddasir; Hussain, Azhar; Murtaza, G.

    2011-09-15

    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.

  4. The non-directional pattern of axonal changes in Wallerian degeneration: a computer-aided morphometric analysis.

    PubMed Central

    Malbouisson, A M; Ghabriel, M N; Allt, G

    1984-01-01

    Wallerian degeneration was investigated to determine whether axonal changes occur progressively in a somatofugal or somatopetal direction or simultaneously along the length of the axon. Microtubule density was used as a measure of the extent of axonal degeneration and was assessed by a computer-aided analysis of electron micrographs. The left sural nerves of ten rats were crushed and 30 hours later axonal areas and axonal microtubule numbers were recorded from a large sample of axons at two sites 1 cm and 3 cm distal to the crush. The same recordings were made from the right unoperated nerve at two comparable sites. Statistical analysis of all the data provided no evidence for a somatofugal or reverse direction of degeneration. It is concluded therefore that in Wallerian degeneration axonal changes, as indicated by microtubule dissolution, occur simultaneously along the length of the axon. It is proposed that to interpret the conflicting published data on the direction of fibre degeneration, Schwann cell changes (e.g. myelin ovoid formation) and axonal changes (e.g. microtubule dissolution) should be considered independently since they have different aetiological mechanisms which may account for the differing experimental results reported. Images Fig. 1 Figs. 7-8 Figs. 9-10 PMID:6469853

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

    PubMed Central

    Goñi, Sandra Elizabeth; Lozano, Mario Enrique

    2013-01-01

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

  6. MRI and MR tractography in bilateral hypertrophic olivary degeneration

    PubMed Central

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

    2014-01-01

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

  7. Changes in ganglion cells during retinal degeneration.

    PubMed

    Saha, Susmita; Greferath, Ursula; Vessey, Kirstan A; Grayden, David B; Burkitt, Anthony N; Fletcher, Erica L

    2016-08-01

    Inherited retinal degeneration such as retinitis pigmentosa (RP) is associated with photoreceptor loss and concomitant morphological and functional changes in the inner retina. It is not known whether these changes are associated with changes in the density and distribution of synaptic inputs to retinal ganglion cells (RGCs). We quantified changes in ganglion cell density in rd1 and age-matched C57BL/6J-(wildtype, WT) mice using the immunocytochemical marker, RBPMS. Our data revealed that following complete loss of photoreceptors, (∼3months of age), there was a reduction in ganglion cell density in the peripheral retina. We next examined changes in synaptic inputs to A type ganglion cells by performing double labeling experiments in mice with the ganglion cell reporter lines, rd1-Thy1 and age-matched wildtype-Thy1. Ribbon synapses were identified by co-labelling with CtBP2 (RIBEYE) and conventional synapses with the clustering molecule, gephyrin. ON RGCs showed a significant reduction in RIBEYE-immunoreactive synapse density while OFF RGCs showed a significant reduction in the gephyrin-immmunoreactive synapse density. Distribution patterns of both synaptic markers across the dendritic trees of RGCs were unchanged. The change in synaptic inputs to RGCs was associated with a reduction in the number of immunolabeled rod bipolar and ON cone bipolar cells. These results suggest that functional changes reported in ganglion cells during retinal degeneration could be attributed to loss of synaptic inputs. PMID:27132232

  8. Nodular fasciitis with degeneration and regression.

    PubMed

    Yanagisawa, Akihiro; Okada, Hideki

    2008-07-01

    Nodular fasciitis is a benign reactive proliferation that is frequently misdiagnosed as a sarcoma. This article describes a case of nodular fasciitis of 6-month duration located in the cheek, which degenerated and spontaneously regressed after biopsy. The nodule was fixed to the zygoma but was free from the overlying skin. The mass was 3.0 cm in diameter and demonstrated high signal intensity on T2-weighted magnetic resonance imaging. A small part of the lesion was biopsied. Pathological and immunohistochemical examinations identified the nodule as nodular fasciitis with myxoid histology. One month after the biopsy, the mass showed decreased signal intensity on T2-weighted images and measured 2.2 cm in size. The signal on T2-weighted images showed time-dependent decreases, and the mass continued to reduce in size throughout the follow-up period. The lesion presented as hypointense to the surrounding muscles on T2-weighted images and was 0.4 cm in size at 2 years of follow-up. This case demonstrates that nodular fasciitis with myxoid histology can change to that with fibrous appearance gradually with time, thus bringing about spontaneous regression. Degeneration may be involved in the spontaneous regression of nodular fasciitis with myxoid appearance. The mechanism of regression, unclarified at present, should be further studied. PMID:18650753

  9. Degenerate parametric oscillation in quantum membrane optomechanics

    NASA Astrophysics Data System (ADS)

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

    2016-02-01

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

  10. Metabolic anatomy of paraneoplastic cerebellar degeneration

    SciTech Connect

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

    1988-06-01

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

  11. Progressive retinal degeneration in ranch mink.

    PubMed

    Hadlow, W J

    1984-01-01

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

  12. Intra-axonal calcium changes after axotomy in wild-type and slow Wallerian degeneration axons.

    PubMed

    Adalbert, R; Morreale, G; Paizs, M; Conforti, L; Walker, S A; Roderick, H L; Bootman, M D; Siklós, L; Coleman, M P

    2012-12-01

    Calcium accumulation induces the breakdown of cytoskeleton and axonal fragmentation in the late stages of Wallerian degeneration. In the early stages there is no evidence for any long-lasting, extensive increase in intra-axonal calcium but there does appear to be some redistribution. We hypothesized that changes in calcium distribution could have an early regulatory role in axonal degeneration in addition to the late executionary role of calcium. Schmidt-Lanterman clefts (SLCs), which allow exchange of metabolites and ions between the periaxonal and extracellular space, are likely to have an increased role when axon segments are separated from the cell body, so we used the oxalate-pyroantimonate method to study calcium at SLCs in distal stumps of transected wild-type and slow Wallerian degeneration (Wld(S)) mutant sciatic nerves, in which Wallerian degeneration is greatly delayed. In wild-type nerves most SLCs show a step gradient of calcium distribution, which is lost at around 20% of SLCs within 3mm of the lesion site by 4-24h after nerve transection. To investigate further the association with Wallerian degeneration, we studied nerves from Wld(S) rats. The step gradient of calcium distribution in Wld(S) is absent in around 20% of the intact nerves beneath SLCs but 4-24h following injury, calcium distribution in transected axons remained similar to that in uninjured nerves. We then used calcium indicators to study influx and buffering of calcium in injured neurites in primary culture. Calcium penetration and the early calcium increase in this system were indistinguishable between Wld(S) and wild-type axons. However, a significant difference was observed during the following hours, when calcium increased in wild-type neurites but not in Wld(S) neurites. We conclude that there is little relationship between calcium distribution and the early stages of Wallerian degeneration at the time points studied in vivo or in vitro but that Wld(S) neurites fail to show a later

  13. Differential Modulation of Retinal Degeneration by Ccl2 and Cx3cr1 Chemokine Signalling

    PubMed Central

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

    2012-01-01

    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

  14. Functional Rescue of Retinal Degeneration-Associated Mutant RPE65 Proteins.

    PubMed

    Jin, Minghao; Li, Songhua; Hu, Jane; Jin, Heather H; Jacobson, Samuel G; Bok, Dean

    2016-01-01

    More than 100 different mutations in the RPE65 gene are associated with inherited retinal degeneration. Although some missense mutations have been shown to abolish isomerase activity of RPE65, the molecular bases leading to loss of function and retinal degeneration remain incompletely understood. Here we show that several missense mutations resulted in significant decrease in expression level of RPE65 in the human retinal pigment epithelium cells. The 26S proteasome non-ATPase regulatory subunit 13, a newly identified negative regulator of RPE65, mediated degradation of mutant RPE65s, which were misfolded and formed aggregates in the cells. Many mutations, including L22P, T101I, and L408P, were mapped on nonactive sites of RPE65. Enzyme activities of these mutant RPE65s were significantly rescued at low temperature, whereas mutant RPE65s with a distinct active site mutation could not be rescued under the same conditions. 4-phenylbutyrate (PBA) displayed a significant synergistic effect on the low temperature-mediated rescue of the mutant RPE65s. Our results suggest that a low temperature eye mask and PBA, a FDA-approved oral medicine, may provide a promising "protein repair therapy" that can enhance the efficacy of gene therapy for delaying retinal degeneration caused by RPE65 mutations. PMID:26427455

  15. A COMPUTATIONAL MODEL OF MOTOR NEURON DEGENERATION

    PubMed Central

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

    2014-01-01

    SUMMARY To explore the link between bioenergetics and motor neuron degeneration, we used a computational model in which detailed morphology and ion conductance are paired with intracellular ATP production and consumption. We found that reduced ATP availability increases the metabolic cost of a single action potential and disrupts K+/Na+ homeostasis, resulting in a chronic depolarization. The magnitude of the ATP shortage at which this ionic instability occurs depends on the morphology and intrinsic conductance characteristic of the neuron. If ATP shortage is confined to the distal part of the axon, the ensuing local ionic instability eventually spreads to the whole neuron and involves fasciculation-like spiking events. A shortage of ATP also causes a rise in intracellular calcium. Our modeling work supports the notion that mitochondrial dysfunction can account for salient features of the paralytic disorder amyotrophic lateral sclerosis, including motor neuron hyperexcitability, fasciculation, and differential vulnerability of motor neuron subpopulations. PMID:25088365

  16. Hypocoercivity of linear degenerately dissipative kinetic equations

    NASA Astrophysics Data System (ADS)

    Duan, Renjun

    2011-08-01

    In this paper we develop a general approach of studying the hypocoercivity for a class of linear kinetic equations with both transport and degenerately dissipative terms. As concrete examples, the relaxation operator, Fokker-Planck operator and linearized Boltzmann operator are considered when the spatial domain takes the whole space or torus and when there is a confining force or not. The key part of the developed approach is to construct some equivalent temporal energy functionals for obtaining time rates of the solution trending towards equilibrium in some Hilbert spaces. The result in the case of the linear Boltzmann equation with confining forces is new. The proof mainly makes use of the macro-micro decomposition combined with Kawashima's argument on dissipation of the hyperbolic-parabolic system. At the end, a Korn-type inequality with probability measure is provided to deal with dissipation of momentum components.

  17. [Epidemiology of age-related macular degeneration].

    PubMed

    Brandl, C; Stark, K J; Wintergerst, M; Heinemann, M; Heid, I M; Finger, R P

    2016-09-01

    Age-related macular degeneration (AMD) is the main cause of blindness in industrialized societies. Population-based epidemiological investigations generate important data on prevalence, incidence, risk factors, and future trends. This review summarizes the most important epidemiological studies on AMD with a focus on their transferability to Germany including existing evidence for the main risk factors for AMD development and progression. Future tasks, such as the standardization of grading systems and the use of recent retinal imaging technology in epidemiological studies are discussed. In Germany, epidemiological data on AMD are scarce. However, the need for epidemiological research in ophthalmology is currently being addressed by several recently started population-based studies. PMID:27541733

  18. Therapeutic interventions in parkinsonism: Corticobasal degeneration.

    PubMed

    Marsili, Luca; Suppa, Antonio; Berardelli, Alfredo; Colosimo, Carlo

    2016-01-01

    Corticobasal degeneration (CBD) is a progressive neurodegenerative disorder resulting from pathological accumulation of tau protein and is included in the spectrum of Atypical Parkinsonism. The typical clinical phenotype of CBD is characterized by the Corticobasal syndrome (CBS). In recent years it has become clear that the clinical picture of CBS may be caused by different pathological conditions, resulting in frequent misdiagnosis. CBD has high morbidity and poor prognosis with no effective therapies. In this review, we will discuss the symptomatic treatment, the palliative care and the disease modifying strategies currently in use. Symptomatic treatment in patients with CBD may sometimes be useful for improving motor (parkinsonism, dystonia and myoclonus) and non-motor (cognitive-behavioral) symptoms, but the effects are often unsatisfactory. In addition, non-pharmacological strategies and palliative care are useful integrating components of the multidisciplinary therapeutic approach for patients with CBD. Despite many efforts, a disease-modifying treatment is still unavailable for CBD. PMID:26382843

  19. Cartilage degeneration in different human joints.

    PubMed

    Kuettner, K E; Cole, A A

    2005-02-01

    Variations among joints in the initiation and progression of degeneration may be explained, in part, by metabolic, biochemical and biomechanical differences. Compared to the cartilage in the knee joint, ankle cartilage has a higher content of proteoglycans and water, as well as an increased rate of proteoglycan turnover and synthesis, all of which are responsible for its increased stiffness and reduced permeability. Chondrocytes within ankle cartilage have a decreased response to catabolic factors such as interleukin-1 and fibronectin fragments, compared to the chondrocytes of knee cartilage. Moreover, in response to damage, ankle chondrocytes synthesize proteoglycans at a higher rate than that found in knee cartilage chondrocytes, which suggests a greater capacity for repair. In addition to the cartilages of the two joints, the underlying bones also respond differently to degenerative changes. Taken together, these metabolic, biochemical and biomechanical differences may provide protection to the ankle. PMID:15694570

  20. The muon g - 2 and degenerate supersymmetry

    NASA Astrophysics Data System (ADS)

    Chowdhury, Debtosh; Patel, Ketan M.; Tata, Xerxes; Vempati, Sudhir K.

    2016-04-01

    A degenerate supersymmetric particle spectrum can escape constraints from flavor physics and at the same time evade limits from the direct searches. If such a spectrum is light enough, it can also account for the observed value of the anomalous magnetic moment of the muon. Inspired by this, we consider a scenario where all the soft terms have approximately a common mass scale while allowing for small splittings. We study this scenario considering the constraints from Higgs mass, various B meson decays and the dark matter relic density. We find that, with superpartners ~ 800 - 1000 GeV, it is still possible to escape the present limits from the first run of LHC and flavor physics and can account for muon g - 2 within 2σ.

  1. Quantum Walk in Degenerate Spin Environments

    NASA Astrophysics Data System (ADS)

    Carlström, Johan; Prokof'ev, Nikolay; Svistunov, Boris

    2016-06-01

    We study the propagation of a hole in degenerate (paramagnetic) spin environments. This canonical problem has important connections to a number of physical systems, and is perfectly suited for experimental realization with ultracold atoms in an optical lattice. At the short-to-intermediate time scale that we can access using a stochastic-series-type numeric scheme, the propagation turns out to be distinctly nondiffusive with the probability distribution featuring minima in both space and time due to quantum interference, yet the motion is not ballistic, except at the beginning. We discuss possible scenarios for long-term evolution that could be explored with an unprecedented degree of detail in experiments with single-atom resolved imaging.

  2. Spectroscopic temperature determination of degenerate Fermi gases

    SciTech Connect

    Kostrun, Marijan; Cote, Robin

    2003-12-01

    We suggest a simple method for measuring the temperature of ultracold gases made of fermions. We show that by using a two-photon Raman probe, it is possible to obtain line shapes which reveal properties of the degenerate sample, notably its temperature T. The proposed method could be used with identical fermions in different hyperfine states interacting via s-wave scattering or identical fermions in the same hyperfine state via p-wave scattering. We illustrate the applicability of the method in realistic conditions for {sup 6}Li prepared in two different hyperfine states. We find that temperatures down to 0.05T{sub F} can be determined by this in situ method.

  3. Subwavelength total acoustic absorption with degenerate resonators

    NASA Astrophysics Data System (ADS)

    Yang, Min; Meng, Chong; Fu, Caixing; Li, Yong; Yang, Zhiyu; Sheng, Ping

    2015-09-01

    We report the experimental realization of perfect sound absorption by sub-wavelength monopole and dipole resonators that exhibit degenerate resonant frequencies. This is achieved through the destructive interference of two resonators' transmission responses, while the matching of their averaged impedances to that of air implies no backscattering, thereby leading to total absorption. Two examples, both using decorated membrane resonators (DMRs) as the basic units, are presented. The first is a flat panel comprising a DMR and a pair of coupled DMRs, while the second one is a ventilated short tube containing a DMR in conjunction with a sidewall DMR backed by a cavity. In both examples, near perfect absorption, up to 99.7%, has been observed with the airborne wavelength up to 1.2 m, which is at least an order of magnitude larger than the composite absorber. Excellent agreement between theory and experiment is obtained.

  4. Degenerate R-S perturbation theory

    NASA Technical Reports Server (NTRS)

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

    1973-01-01

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

  5. MicroRNA in intervertebral disc degeneration.

    PubMed

    Li, Zheng; Yu, Xin; Shen, Jianxiong; Chan, Matthew T V; Wu, William Ka Kei

    2015-06-01

    Aetiology of intervertebral disc degeneration (IDD) is complex, with genetic, developmental, biochemical and biomechanical factors contributing to the disease process. It is becoming obvious that epigenetic processes influence evolution of IDD as strongly as the genetic background. Deregulated phenotypes of nucleus pulposus cells, including differentiation, migration, proliferation and apoptosis, are involved in all stages of progression of human IDD. Non-coding RNAs, including microRNAs, have recently been recognized as important regulators of gene expression. Research into roles of microRNAs in IDD has been very active over the past 5 years. Our review summarizes current research enlightenment towards understanding roles of microRNAs in regulating nucleus pulposus cell functions in IDD. These exciting findings support the notion that specific modulation of microRNAs may represent an attractive approach for management of IDD. PMID:25736871

  6. Age-related macular degeneration: current treatments

    PubMed Central

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

    2009-01-01

    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. PMID:19668560

  7. Topological superradiance in a degenerate Fermi gas

    NASA Astrophysics Data System (ADS)

    Pan, Jian-Song; Liu, Xiong-Jun; Zhang, Wei; Yi, Wei; Guo, Guang-Can; Yi's Group Team; Liu's Group Team; Zhang's Group Team

    2015-05-01

    We predict the existence of a topological superradiant state in a two-component degenerate Fermi gas in a cavity. The superradiant light generation in the transversely driven cavity mode induces a cavity-assisted spin-orbit coupling in the system and opens a bulk gap at half filling. This mechanism can simultaneously drive a topological phase transition in the system, yielding a topological superradiant state. We map out the steady-state phase diagram of the system in the presence of an effective Zeeman field, and identify a critical tetracritical point beyond which the topological and the conventional superraidiant phase boundaries separate. We propose to detect the topological phase transition based on its signatures in either the momentum distribution of the atoms or in the cavity photon occupation.

  8. 9 CFR 311.35 - Muscular inflammation, degeneration, or infiltration.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

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

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

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Muscular inflammation, degeneration, or infiltration. 311.35 Section 311.35 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE... PARTS § 311.35 Muscular inflammation, degeneration, or infiltration. (a) If muscular lesions are...

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

    PubMed

    Narváez, Yamile Reveiz; Gómez-Restrepo, Carlos

    2012-09-01

    Age-related macular degeneration is a cause for disability in the elderly since it greatly affects their quality of life and increases depression likelihood. This article discusses the negative effect depression has on patients with age-related macular degeneration and summarizes the interventions available for decreasing their depression index. PMID:26572116

  11. 9 CFR 311.35 - Muscular inflammation, degeneration, or infiltration.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Muscular inflammation, degeneration, or infiltration. 311.35 Section 311.35 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE... PARTS § 311.35 Muscular inflammation, degeneration, or infiltration. (a) If muscular lesions are...

  12. 9 CFR 311.35 - Muscular inflammation, degeneration, or infiltration.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Muscular inflammation, degeneration, or infiltration. 311.35 Section 311.35 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE... PARTS § 311.35 Muscular inflammation, degeneration, or infiltration. (a) If muscular lesions are...

  13. 9 CFR 311.35 - Muscular inflammation, degeneration, or infiltration.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Muscular inflammation, degeneration, or infiltration. 311.35 Section 311.35 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE... PARTS § 311.35 Muscular inflammation, degeneration, or infiltration. (a) If muscular lesions are...

  14. Retinas in a Dish Peek into Inherited Retinal Degeneration.

    PubMed

    Duong, Thu T; Vasireddy, Vidyullatha; Mills, Jason A; Bennett, Jean

    2016-06-01

    Human retinal degeneration can cause blindness, and the lack of relevant model systems has made identifying underlying mechanisms challenging. Parfitt et al. (2016) generate three-dimensional retinal tissue from patient-derived induced pluripotent stem cells to identify how CEP290 mutations cause retinal degeneration, and show an antisense approach can correct disease-associated phenotypes. PMID:27257755

  15. Does lumbar facet arthrosis precede disc degeneration? A postmortem study.

    PubMed

    Eubanks, Jason David; Lee, Michael J; Cassinelli, Ezequiel; Ahn, Nicholas U

    2007-11-01

    It is believed lumbar degeneration begins in the disc, where desiccation and collapse lead to instability and compensatory facet arthrosis. We explored the contrary contention that facet degeneration precedes disc degeneration by examining 647 skeletal lumbar spines. Using facet osteophytosis as a measure of facet degeneration and vertebral rim osteophytosis as a measure of disc degeneration, we assumed bone degeneration in both locations equally reflected the progression of those in the soft tissues. We graded arthrosis Grade 0 to 4 on a continuum from no arthritis to ankylosis. The data were analyzed for different age groups to examine patterns of degeneration with age. Specimens younger than 30 years of age had a higher prevalence of facet osteophytosis compared with vertebral rim osteophotosis at L1-L2 and L2-L3. Specimens aged 30 to 39 years showed more facet osteophytosis than vertebral rim osteophytosis at L4-L5. Specimens older than 40 years, however, showed more vertebral rim osteophytosis compared with facet osteophytosis at all levels except L4-L5 and L5-S1. This skeletal study suggests facet osteophytosis appears early in the degenerative process, preceding vertebral rim osteophytosis of degenerating intervertebral discs. However, once facets begin deteriorating with age, vertebral rim osteophytosis overtakes continued facet osteophytosis. These data challenge the belief that facet osteophytosis follows vertebral rim osteophytosis; rather, it appears vertebral rim osteophytosis progresses more rapidly in later years, but facet osteophotosis occurs early, predominating in younger individuals. PMID:17767079

  16. Transurethral resection and degeneration of bladder tumour

    PubMed Central

    Li, Aihua; Fang, Wei; Zhang, Feng; Li, Weiwu; Lu, Honghai; Liu, Sikuan; Wang, Hui; Zhang, Binghui

    2013-01-01

    Introduction: We evaluate the efficacy and safety of transurethral resection and degeneration of bladder tumour (TURD-Bt). Methods: In total, 56 patients with bladder tumour were treated by TURD-Bt. The results in these patients were compared with 32 patients treated by current transurethral resection of bladder tumour (TUR-Bt). Patients with or without disease progressive factors were respectively compared between the 2 groups. The factors included recurrent tumour, multiple tumours, tumour ≥3 cm in diameter, clinical stage T2, histological grade 3, adenocarcinoma, and ureteral obstruction or hydronephrosis. Results: Follow-up time was 48.55 ± 23.74 months in TURD-Bt group and 56.28 ± 17.61 months in the TUR-Bt group (p > 0.05). In patients without progressive factors, no tumour recurrence was found and overall survival was 14 (100%) in the TURD-Bt group; 3 (37.50%) patients had recurrence and overall survival was 5 (62.5%) in the TUR-Bt group. In patients with progressive factors, 8 (19.05%) patients had tumour recurrence, overall survival was 32 (76.19%) and cancer death was 3 (7.14%) in TURD-Bt group; 18 (75.00%) patients had tumour recurrence (p < 0.05), overall survival was 12 (50.00%) (p < 0.01) and cancer death was 8 (33.33%) (p < 0.05) in TUR-Bt group. No significant complication was found in TURD-Bt group. Conclusion: This study suggests that complete resection and degeneration of bladder tumour can be expected by TURD-Bt. The surgical procedure is safe and efficacious, and could be predictable and controllable before and during surgery. We would conclude that for bladder cancers without lymph node metastasis and distal metastasis, TURD-Bt could be performed to replace radical TUR-Bt and preserve the bladder. PMID:24475002

  17. Ouabain-induced cochlear degeneration in rat

    PubMed Central

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

    2012-01-01

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

  18. Crystallization and collapse in relativistically degenerate matter

    SciTech Connect

    Akbari-Moghanjoughi, M.

    2013-04-15

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

  19. Ouabain-induced cochlear degeneration in rat.

    PubMed

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

    2012-08-01

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

  20. Preservation of retinotopic map in retinal degeneration.

    PubMed

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

    2012-05-01

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

  1. Retrograde Axonal Degeneration in Parkinson Disease

    PubMed Central

    Tagliaferro, Patricia; Burke, Robert E.

    2016-01-01

    In spite of tremendous research efforts we have not yet achieved two of our principal therapeutic goals in the treatment of Parkinson’s disease (PD), to prevent its onward progression and to provide restoration of systems that have already been damaged by the time of diagnosis. There are many possible reasons for our inability to make progress. One possibility is that our efforts thus far may not have been directed towards the appropriate cellular compartments. Up until now research has been largely focused on the loss of neurons in the disease. Thus, neuroprotection approaches have been largely aimed at blocking mechanisms that lead to destruction of the neuronal cell body. Attempts to provide neurorestoration have been almost entirely focused on replacement of neurons. We herein review the evidence that the axonal component of diseased neuronal systems merit more of our attention. Evidence from imaging studies, from postmortem neurochemical studies, and from genetic animal models suggests that the axons of the dopaminergic system are involved predominantly and early in PD. Since the mechanisms of axonal destruction are distinct from those of neuron cell body degeneration, a focus on axonal neurobiology will offer new opportunities for preventing their degeneration. At present these mechanisms remain largely obscure. However, defining them is likely to offer new opportunities for neuroprotection. In relation to neurorestoration, while it has been classically believed that neurons of the adult central nervous system are incapable of new axon growth, recent evidence shows that this is not true for the dopaminergic projection. In conclusion, the neurobiology of axons is likely to offer many new approaches to protective and restorative therapeutics. PMID:27003783

  2. Accelerated cellular senescence in degenerate intervertebral discs: a possible role in the pathogenesis of intervertebral disc degeneration

    PubMed Central

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

    2007-01-01

    Current evidence implicates intervertebral disc degeneration as a major cause of low back pain, although its pathogenesis is poorly understood. Numerous characteristic features of disc degeneration mimic those seen during ageing but appear to occur at an accelerated rate. We hypothesised that this is due to accelerated cellular senescence, which causes fundamental changes in the ability of disc cells to maintain the intervertebral disc (IVD) matrix, thus leading to IVD degeneration. Cells isolated from non-degenerate and degenerate human tissue were assessed for mean telomere length, senescence-associated β-galactosidase (SA-β-gal), and replicative potential. Expression of P16INK4A (increased in cellular senescence) was also investigated in IVD tissue by means of immunohistochemistry. RNA from tissue and cultured cells was used for real-time polymerase chain reaction analysis for matrix metalloproteinase-13, ADAMTS 5 (a disintegrin and metalloprotease with thrombospondin motifs 5), and P16INK4A. Mean telomere length decreased with age in cells from non-degenerate tissue and also decreased with progressive stages of degeneration. In non-degenerate discs, there was an age-related increase in cellular expression of P16INK4A. Cells from degenerate discs (even from young patients) exhibited increased expression of P16INK4A, increased SA-β-gal staining, and a decrease in replicative potential. Importantly, there was a positive correlation between P16INK4A and matrix-degrading enzyme gene expression. Our findings indicate that disc cell senescence occurs in vivo and is accelerated in IVD degeneration. Furthermore, the senescent phenotype is associated with increased catabolism, implicating cellular senescence in the pathogenesis of IVD degeneration. PMID:17498290

  3. Accelerated cellular senescence in degenerate intervertebral discs: a possible role in the pathogenesis of intervertebral disc degeneration.

    PubMed

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

    2007-01-01

    Current evidence implicates intervertebral disc degeneration as a major cause of low back pain, although its pathogenesis is poorly understood. Numerous characteristic features of disc degeneration mimic those seen during ageing but appear to occur at an accelerated rate. We hypothesised that this is due to accelerated cellular senescence, which causes fundamental changes in the ability of disc cells to maintain the intervertebral disc (IVD) matrix, thus leading to IVD degeneration. Cells isolated from non-degenerate and degenerate human tissue were assessed for mean telomere length, senescence-associated beta-galactosidase (SA-beta-gal), and replicative potential. Expression of P16INK4A (increased in cellular senescence) was also investigated in IVD tissue by means of immunohistochemistry. RNA from tissue and cultured cells was used for real-time polymerase chain reaction analysis for matrix metalloproteinase-13, ADAMTS 5 (a disintegrin and metalloprotease with thrombospondin motifs 5), and P16INK4A. Mean telomere length decreased with age in cells from non-degenerate tissue and also decreased with progressive stages of degeneration. In non-degenerate discs, there was an age-related increase in cellular expression of P16INK4A. Cells from degenerate discs (even from young patients) exhibited increased expression of P16INK4A, increased SA-beta-gal staining, and a decrease in replicative potential. Importantly, there was a positive correlation between P16INK4A and matrix-degrading enzyme gene expression. Our findings indicate that disc cell senescence occurs in vivo and is accelerated in IVD degeneration. Furthermore, the senescent phenotype is associated with increased catabolism, implicating cellular senescence in the pathogenesis of IVD degeneration. PMID:17498290

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

    PubMed

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

    2000-10-01

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

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

    PubMed Central

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

    2015-01-01

    Axon degeneration is an intrinsic self-destruction program that underlies axon loss during injury and disease. Sterile alpha and TIR motif containing 1 (SARM1) protein is an essential mediator of axon degeneration. We report that SARM1 initiates a local destruction program involving rapid breakdown of NAD+ after injury. We used an engineered protease-sensitized SARM1 to demonstrate that SARM1 activity is required after axon injury to induce axon degeneration. Dimerization of the Toll-Interleukin Receptor (TIR) domain of SARM1 alone was sufficient to induce locally-mediated axon degeneration. Formation of the SARM1 TIR dimer triggered rapid breakdown of NAD+, whereas SARM1-induced axon destruction could be counteracted by increased NAD+ synthesis. SARM1-induced depletion of NAD+ may explain the potent axon protection in Wallerian Degeneration slow (Wlds) mutant mice. PMID:25908823

  6. Anomalous skin effects in a weakly magnetized degenerate electron plasma

    NASA Astrophysics Data System (ADS)

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

    2014-09-01

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

  7. Progranulin Knockout Accelerates Intervertebral Disc Degeneration in Aging Mice

    PubMed Central

    Zhao, Yun-peng; Tian, Qing-yun; Liu, Ben; Cuellar, Jason; Richbourgh, Brendon; Jia, Tang-hong; Liu, Chuan-ju

    2015-01-01

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

  8. Anomalous skin effects in a weakly magnetized degenerate electron plasma

    SciTech Connect

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

    2014-09-15

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

  9. Versal unfolding of planar Hamiltonian systems at fully degenerate equilibrium

    NASA Astrophysics Data System (ADS)

    Tang, Yilei; Zhang, Weinian

    2016-07-01

    In this paper we study bifurcations of a planar Hamiltonian system at a fully degenerate equilibrium, which has a zero linearization. Since the Poincaré normal form theory is not applicable to such a degenerate system, we investigate its restrictive normal forms in the class of Hamiltonian fields and prove that such a degenerate system is of codimension 3 degeneracy in the class, so that we introduce three parameters to versally unfold the degenerate system in the class. In order to discuss further the qualitative properties of the versal unfolding, we use the Poincaré index to determine the number and distribution of hyperbolic sectors near the degenerate equilibrium. We display its all bifurcations such as pitchfork bifurcation, saddle-center bifurcation and the Bogdanov-Takens bifurcation within Hamiltonian systems.

  10. Quantum degenerate atomic gases in controlled optical lattice potentials

    NASA Astrophysics Data System (ADS)

    Gemelke, Nathan D.

    2007-12-01

    Since the achievement of Bose Einstein condensation in cold atomic gases, mean-field treatments of the condensed phase have provided an excellent description for the static and dynamic properties observed in experiments. Recent experimental efforts have focused on studying deviations from mean-field behavior. I will describe work on two experiments which introduce controlled single particle degeneracies with time-dependent optical potentials, aiming to induce correlated motion and nontrivial statistics in the gas. In the first experiment, an optical lattice with locally rotating site potentials is produced to investigate fractional quantum Hall effects (FQHE) in rotating Bose gases. Here, the necessary gauge potential is provided by the rotating reference frame of the gas, which, in direct analogy to the electronic system, organizes single particle states into degenerate Landau levels. At low temperatures the repulsive interaction provided by elastic scattering is expected to produce ground states with structure nearly identical to those in the FQHE. I will discuss how these effects are made experimentally feasible by working at small particle numbers in the tight trapping potentials of an optical lattice, and present first results on the use of photoassociation to probe correlation in this system. In the second experiment, a vibrated optical lattice potential alters the single-particle dispersion underlying a condensed Bose gas and offers tailored phase-matching for nonlinear atom optical processes. I will demonstrate how this leads to parametric instability in the condensed gas, and draw analogy to an optical parametric oscillator operating above threshold.

  11. Differential Light-induced Responses in Sectorial Inherited Retinal Degeneration*

    PubMed Central

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

    2014-01-01

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

  12. Phosphorylated TDP-43 in frontotemporal lobar degeneration and ALS

    PubMed Central

    Hasegawa, Masato; Arai, Tetsuaki; Nonaka, Takashi; Kametani, Fuyuki; Yoshida, Mari; Hashizume, Yoshio; Beach, Thomas G.; Buratti, Emanuele; Baralle, Francisco; Morita, Mitsuya; Nakano, Imaharu; Oda, Tatsuro; Tsuchiya, Kuniaki; Akiyama, Haruhiko

    2009-01-01

    Objective TDP-43 is deposited as cytoplasmic and intranuclear inclusions in brains of subjects with frontotemporal lobar degeneration with ubiquitinated inclusions (FTLD-U) and amyotrophic lateral sclerosis (ALS). Previous studies reported that abnormal phosphorylation takes place in deposited TDP-43. The aim of this study was to identify the phosphorylation sites and responsible kinases, and to clarify the pathological significance of phosphorylation of TDP-43. Methods We generated multiple antibodies specific to phosphorylated TDP-43 by immunizing phosphopeptides of TDP-43, and analyzed FTLD-U and ALS brains by immunohistochemistry, immunoelectron microscopy and immunoblots. Additionally, we performed investigations aimed at identifying the responsible kinases and we assessed the effects of phosphorylation on TDP-43 oligomerization and fibrillization. Results We identified multiple phosphorylation sites in carboxyl-terminal regions of deposited TDP-43. Phosphorylation-specific antibodies stained more inclusions than antibodies to ubiquitin and, unlike existing commercially-available anti-TDP-43 antibodies, did not stain normal nuclei. Ultrastructurally, these antibodies labeled abnormal fibers of 15 nm diameter, and on immunoblots recognized hyperphosphorylated TDP-43 at 45 kDa, with additional 22–28 kDa fragments in sarkosyl-insoluble fractions from FTLD-U and ALS brains. The phosphorylated epitopes were generated by casein kinase 1 and 2, and phosphorylation led to increased oligomerization and fibrillization of TDP-43. Interpretation These results suggest that phosphorylated TDP-43 is a major component of the inclusions, and that abnormal phosphorylation of TDP-43 is a critical step in the pathogenesis of FTLD-U and ALS. Phosphorylation-specific antibodies will be powerful tools for the investigation of these disorders. PMID:18546284

  13. Widespread cytoskeletal pathology characterizes corticobasal degeneration.

    PubMed Central

    Feany, M. B.; Dickson, D. W.

    1995-01-01

    Corticobasal degeneration (CBD) is a rare, progressive neurological disorder characterized by widespread neuronal and glial pathology. Using immunohistochemistry and laser confocal microscopy, we demonstrate that the nonamyloid cortical plaques of CBD are actually collections of abnormal tau in the distal processes of astrocytes. These glial cells express both vimentin and CD44, markers of astrocyte activation. Glial pathology also includes tau-positive cytoplasmic inclusions, here localized to Leu 7-expressing oligodendrocytes. In addition, a wide array of neuronal pathology is defined with tau-positive inclusions in multiple domains of a variety of cortical neurons. CBD thus exhibits widespread glial and neuronal cytoskeletal pathology, including a novel structure, the astrocytic plaque. CBD is a disease of generalized cytoskeletal disruption affecting several cell types and multiple domains of these cells. The further definition of CBD pathology refines the diagnosis and pathophysiological understanding of this unique disease and has important implications for other neurodegenerative diseases, like Alzheimer's disease, characterized by abnormal tau deposition. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:7778678

  14. CERKL Knockdown Causes Retinal Degeneration in Zebrafish

    PubMed Central

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

    2013-01-01

    The human CERKL gene is responsible for common and severe forms of retinal dystrophies. Despite intense in vitro studies at the molecular and cellular level and in vivo analyses of the retina of murine knockout models, CERKL function remains unknown. In this study, we aimed to approach the developmental and functional features of cerkl in Danio rerio within an Evo-Devo framework. We show that gene expression increases from early developmental stages until the formation of the retina in the optic cup. Unlike the high mRNA-CERKL isoform multiplicity shown in mammals, the moderate transcriptional complexity in fish facilitates phenotypic studies derived from gene silencing. Moreover, of relevance to pathogenicity, teleost CERKL shares the two main human protein isoforms. Morpholino injection has been used to generate a cerkl knockdown zebrafish model. The morphant phenotype results in abnormal eye development with lamination defects, failure to develop photoreceptor outer segments, increased apoptosis of retinal cells and small eyes. Our data support that zebrafish Cerkl does not interfere with proliferation and neural differentiation during early developmental stages but is relevant for survival and protection of the retinal tissue. Overall, we propose that this zebrafish model is a powerful tool to unveil CERKL contribution to human retinal degeneration. PMID:23671706

  15. Statistical physics of age related macular degeneration

    NASA Astrophysics Data System (ADS)

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

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

  16. Physics of Age Related Macular Degeneration

    NASA Astrophysics Data System (ADS)

    Family, Fereydoon

    2009-11-01

    Age-related macular degeneration (AMD) is the leading cause of blindness beyond the age of 50 years. The most common pathogenic mechanism that leads to AMD is choroidal neovascularization (CNV). CNV is produced by accumulation of residual material caused by aging of retinal pigment epithelium cells (RPE). The RPE is a phagocytic system that is essential for renewal of photoreceptors (rods and cones). With time, incompletely degraded membrane material builds up in the form of lipofuscin. Lipofuscin is made of free-radical-damaged protein and fat, which forms not only in AMD, but also Alzheimer's disease, and Parkinson's disease. The study of lipofuscin formation and growth is important, because of their association with cellular aging. In this talk I will discuss a model of non-equilibrium cluster growth that we have developed for studying the formation and growth of lipofuscin in AMD [K.I. Mazzitello, C.M. Arizmendi, Fereydoon Family, H. E. Grossniklaus, Physical Review E (2009)]. I will also present an overview of our theoretical and computational efforts in modeling some other aspects of the physics of AMD, including CNV and the breakdown of Bruch's membrane [Ongoing collaboration with Abbas Shirinifard and James A. Glazier, Biocomplexity Institute and Department of Physics, Indiana University, Y. Jiang, Los Alamos, and Hans E. Grossniklaus, Department of Ophthalmology, Emory University].

  17. [Multiple system atrophy - synuclein and neuronal degeneration].

    PubMed

    Yoshida, Mari

    2011-11-01

    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 α-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

  18. Linear stochastic degenerate Sobolev equations and applications†

    NASA Astrophysics Data System (ADS)

    Liaskos, Konstantinos B.; Pantelous, Athanasios A.; Stratis, Ioannis G.

    2015-12-01

    In this paper, a general class of linear stochastic degenerate Sobolev equations with additive noise is considered. This class of systems is the infinite-dimensional analogue of linear descriptor systems in finite dimensions. Under appropriate assumptions, the mild and strong well-posedness for the initial value problem are studied using elements of the semigroup theory and properties of the stochastic convolution. The final value problem is also examined and it is proved that this is uniquely strongly solvable and the solution is continuously dependent on the final data. Based on the results of the forward and backward problem, the conditions for the exact controllability are investigated for a special but important class of these equations. The abstract results are illustrated by applications in complex media electromagnetics, in the one-dimensional stochastic Dirac equation in the non-relativistic limit and in a potential application in input-output analysis in economics. Dedicated to Professor Grigoris Kalogeropoulos on the occasion of his seventieth birthday.

  19. Disruption in dopaminergic innervation during photoreceptor degeneration.

    PubMed

    Ivanova, Elena; Yee, Christopher W; Sagdullaev, Botir T

    2016-04-15

    Dopaminergic amacrine cells (DACs) release dopamine in response to light-driven synaptic inputs, and are critical to retinal light adaptation. Retinal degeneration (RD) compromises the light responsiveness of the retina and, subsequently, dopamine metabolism is impaired. As RD progresses, retinal neurons exhibit aberrant activity, driven by AII amacrine cells, a primary target of the retinal dopaminergic network. Surprisingly, DACs are an exception to this physiological change; DACs exhibit rhythmic activity in healthy retina, but do not burst in RD. The underlying mechanism of this divergent behavior is not known. It is also unclear whether RD leads to structural changes in DACs, impairing functional regulation of AII amacrine cells. Here we examine the anatomical details of DACs in three mouse models of human RD to determine how changes to the dopaminergic network may underlie physiological changes in RD. By using rd10, rd1, and rd1/C57 mice we were able to dissect the impacts of genetic background and the degenerative process on DAC structure in RD retina. We found that DACs density, soma size, and primary dendrite length are all significantly reduced. Using a novel adeno-associated virus-mediated technique to label AII amacrine cells in mouse retina, we observed diminished dopaminergic contacts to AII amacrine cells in RD mice. This was accompanied by changes to the components responsible for dopamine synthesis and release. Together, these data suggest that structural alterations of the retinal dopaminergic network underlie physiological changes during RD. PMID:26356010

  20. [Criteria for the diagnosis of corticobasal degeneration].

    PubMed

    Shimohata, Takayoshi; Aiba, Ikuko; Nishizawa, Masatoyo

    2015-04-01

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

  1. Diagnoses of corticobasal syndrome and corticobasal degeneration.

    PubMed

    Shimohata, Takayoshi; Aiba, Ikuko; Nishizawa, Masatoyo

    2016-03-30

    Experts use the term corticobasal syndrome (CBS) for patients with a clinical diagnosis of corticobasal degeneration (CBD), and reserve CBD for those whose conditions have been diagnosed on the basis of neuropathological analyses. Several studies demonstrated that patients with CBD may also present with progressive supranuclear syndrome (PSPS), aphasia, Alzheimer disease-like dementia or behavioral change, suggesting that CBS is merely one of the presenting phenotypes of CBD. Although previous CBD diagnostic criteria reflected only CBS, the international consortium proposed new diagnostic criteria for CBD in 2013 (Armstrong's criteria). The new criteria include 4 CBD subtypes; CBS, frontal behavioral-spatial syndrome (FBS), nonfluent/agrammatic variant of primary progressive aphasia (naPPA),and PSPS. These subtypes were combined to create 2 sets of criteria: more specific clinical research criteria for probable CBD (cr-CBD) and broader criteria for possible CBD that are more inclusive but have a higher chance to detect other tau-based pathologies (p-CBD). Two studies have already revealed that the sensitivity and specificity of the criteria were not high. Because therapeutic interventions that target abnormally-phosphorylated tau have started, further refinement of the criteria is needed via biomarker researches with prospective study designs. PMID:26876110

  2. Age-related macular degeneration: choroidal ischaemia?

    PubMed Central

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

    2013-01-01

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

  3. Animal models of age related macular degeneration

    PubMed Central

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

    2013-01-01

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

  4. An Interferometric Harvest of Double Degenerates

    NASA Astrophysics Data System (ADS)

    Nelan, Edmund

    2001-07-01

    The white dwarf {WD} mass and age distributions hold clues to the star formation history of our Galaxy and the age of the disk. To extract this information we need to carefully calibrate the WD mass-radius relation and the WD cooling curve. But to do so, we must directly determine the masses for a variety of WDs of different sub-types. The only direct method is through the orbital analysis of resolved WDs in non- interacting binary systems. Sadly, this has been done, with varying quality, for only 4 WDs {40 Eri B, Sirius B, Procyon B, and Stien 2051B}, mainly because it is extremely difficult to resolve WDs in binary systems with periods less than 50 years. We propose a high angular resolution Snapshot survey with FGS1r to observe cool WDs with the objective of discovering {resolving} double degenerate systems with modest separations and periods as short as 25 years, ideal binaries for follow up mass determinations. By carefully selecting our targets, about 10 such systems should be revealed. This will dramatically increase the number of WDs available for dynamical mass measurements {its 2 for 1.}, enabling a better calibration the WD mass-radius relation.

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

    PubMed

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

    2014-11-01

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

  6. Bmp6 Regulates Retinal Iron Homeostasis and Has Altered Expression in Age-Related Macular Degeneration

    PubMed Central

    Hadziahmetovic, Majda; Song, Ying; Wolkow, Natalie; Iacovelli, Jared; Kautz, Leon; Roth, Marie-Paule; Dunaief, Joshua L.

    2011-01-01

    Iron-induced oxidative stress causes hereditary macular degeneration in patients with aceruloplasminemia. Similarly, retinal iron accumulation in age-related macular degeneration (AMD) may exacerbate the disease. The cause of retinal iron accumulation in AMD is poorly understood. Given that bone morphogenetic protein 6 (Bmp6) is a major regulator of systemic iron, we examined the role of Bmp6 in retinal iron regulation and in AMD pathogenesis. Bmp6 was detected in the retinal pigment epithelium (RPE), a major site of pathology in AMD. In cultured RPE cells, Bmp6 was down-regulated by oxidative stress and up-regulated by iron. Intraocular Bmp6 protein injection in mice up-regulated retinal hepcidin, an iron regulatory hormone, and altered retinal labile iron levels. Bmp6−/− mice had age-dependent retinal iron accumulation and degeneration. Postmortem RPE from patients with early AMD exhibited decreased Bmp6 levels. Because oxidative stress is associated with AMD pathogenesis and down-regulates Bmp6 in cultured RPE cells, the diminished Bmp6 levels observed in RPE cells in early AMD may contribute to iron build-up in AMD. This may in turn propagate a vicious cycle of oxidative stress and iron accumulation, exacerbating AMD and other diseases with hereditary or acquired iron excess. PMID:21703414

  7. [Multi-infarct disorder presenting as corticobasal degeneration (DCB): vascular pseudo-corticobasal degeneration?].

    PubMed

    Kreisler, A; Mastain, B; Tison, F; Fénelon, G; Destée, A

    2007-12-01

    We report on five patients with a clinical presentation of corticobasal degeneration (CBD), including gradually progressive, asymmetric, L-DOPA-resistant parkinsonism associated variously with apraxia, focal action myoclonus, focal dystonia, cortical sensory loss and alien limb phenomenon. Some patients also presented an atypical CBD clinical history or signs - notably sudden onset. The disease was however not suggestive of another diagnosis. Magnetic resonance imaging of the brain revealed extensive vascular lesions. Only five similar cases have been published to our knowledge. Although we cannot exclude underlying CBD pathology, our cases illustrate the fact that multi-infarct pathology can masquerade as CBD or alter the clinical phenotype of the disease. PMID:18355466

  8. Deletion of autophagy inducer RB1CC1 results in degeneration of the retinal pigment epithelium

    PubMed Central

    Yao, Jingyu; Jia, Lin; Khan, Naheed; Lin, Chengmao; Mitter, Sayak K; Boulton, Michael E; Dunaief, Joshua L; Klionsky, Daniel J; Guan, Jun-Lin; Thompson, Debra A; Zacks, David N

    2015-01-01

    Autophagy regulates cellular homeostasis and response to environmental stress. Within the retinal pigment epithelium (RPE) of the eye, the level of autophagy can change with both age and disease. The purpose of this study is to determine the relationship between reduced autophagy and age-related degeneration of the RPE. The gene encoding RB1CC1/FIP200 (RB1-inducible coiled-coil 1), a protein essential for induction of autophagy, was selectively knocked out in the RPE by crossing Best1-Cre mice with mice in which the Rb1cc1 gene was flanked with Lox-P sites (Rb1cc1flox/flox). Ex vivo and in vivo analyses, including western blot, immunohistochemistry, transmission electron microscopy, fundus photography, optical coherence tomography, fluorescein angiography, and electroretinography were performed to assess the structure and function of the retina as a function of age. Deletion of Rb1cc1 resulted in multiple autophagy defects within the RPE including decreased conversion of LC3-I to LC3-II, accumulation of autophagy-targeted precursors, and increased numbers of mitochondria. Age-dependent degeneration of the RPE occurred, with formation of atrophic patches, subretinal migration of activated microglial cells, subRPE deposition of inflammatory and oxidatively damaged proteins, subretinal drusenoid deposits, and occasional foci of choroidal neovascularization. There was secondary loss of photoreceptors overlying the degenerated RPE and reduction in the electroretinogram. These observations are consistent with a critical role of autophagy in the maintenance of normal homeostasis in the aging RPE, and indicate that disruption of autophagy leads to retinal phenotypes associated with age-related degeneration. PMID:26075877

  9. Delivery systems for the treatment of degenerated intervertebral discs.

    PubMed

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

    2015-04-01

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

  10. Degenerate higher derivative theories beyond Horndeski: evading the Ostrogradski instability

    NASA Astrophysics Data System (ADS)

    Langlois, David; Noui, Karim

    2016-02-01

    Theories with higher order time derivatives generically suffer from ghost-like instabilities, known as Ostrogradski instabilities. This fate can be avoided by considering ``degenerate'' Lagrangians, whose kinetic matrix cannot be inverted, thus leading to constraints between canonical variables and a reduced number of physical degrees of freedom. In this work, we derive in a systematic way the degeneracy conditions for scalar-tensor theories that depend quadratically on second order derivatives of a scalar field. We thus obtain a classification of all degenerate theories within this class of scalar-tensor theories. The quartic Horndeski Lagrangian and its extension beyond Horndeski belong to these degenerate cases. We also identify new families of scalar-tensor theories with the property that they are degenerate despite the nondegeneracy of the purely scalar part of their Lagrangian.

  11. An Unusual Case of Extensive Lattice Degeneration and Retinal Detachment

    PubMed Central

    Sarma, Saurabh Kumar; Basaiawmoit, Jennifer V.

    2016-01-01

    Lattice degeneration of the retina is not infrequently encountered on a dilated retinal examination and many of them do not need any intervention. We report a case of atypical lattice degeneration variant with peripheral retinal detachment. An asymptomatic 35-year-old lady with minimal refractive error was found to have extensive lattice degeneration, peripheral retinal detachment and fibrotic changes peripherally with elevation of retinal vessels on dilated retinal examination. There were also areas of white without pressure, chorioretinal scarring and retinal breaks. All the changes were limited to beyond the equator but were found to span 360 degrees. She was treated with barrage laser all around to prevent extension of the retinal detachment posteriorly. She remained stable till her latest follow-up two years after the barrage laser. This case is reported for its rarity with a discussion of the probable differential diagnoses. To the best of our knowledge, this is the first report of such findings in lattice degeneration.

  12. Construction of nonregular pointwise degenerate delay-differential systems

    NASA Technical Reports Server (NTRS)

    Choudhury, A. K.

    1978-01-01

    Pointwise degenerate delay-differential systems (degeneracy at t = 2h) are reduced to Popov's construction under the regularity assumption. Necessary and sufficient conditions for the degeneracy are outlined.

  13. Degenerations of generalized Krichever-Novikov algebras on tori

    NASA Astrophysics Data System (ADS)

    Schlichenmaier, Martin

    1993-08-01

    Degenerations of Lie algebras of meromorphic vector fields on elliptic curves (i.e., complex tori) which are holomorphic outside a certain set of points (markings) are studied. By an algebraic geometric degeneration process certain subalgebras of Lie algebras of meromorphic vector fields on P1, the Riemann sphere, are obtained. In case of some natural choices of the markings these subalgebras are explicitly determined. It is shown that the number of markings can change.

  14. Single-degenerate Type Ia Supernovae Are Preferentially Overluminous

    NASA Astrophysics Data System (ADS)

    Fisher, Robert; Jumper, Kevin

    2015-06-01

    Recent observational and theoretical progress has favored merging and helium-accreting sub-Chandrasekhar mass white dwarfs (WDs) in the double-degenerate and the double-detonation channels, respectively, as the most promising progenitors of normal Type Ia supernovae (SNe Ia). Thus the fate of rapidly accreting Chandrasekhar mass WDs in the single-degenerate channel remains more mysterious then ever. In this paper, we clarify the nature of ignition in Chandrasekhar-mass single-degenerate SNe Ia by analytically deriving the existence of a characteristic length scale which establishes a transition from central ignitions to buoyancy-driven ignitions. Using this criterion, combined with data from three-dimensional simulations of convection and ignition, we demonstrate that the overwhelming majority of ignition events within Chandrasekhar-mass WDs in the single-degenerate channel are buoyancy-driven, and consequently lack a vigorous deflagration phase. We thus infer that single-degenerate SNe Ia are generally expected to lead to overluminous 1991T-like SNe Ia events. We establish that the rates predicted from both the population of supersoft X-ray sources (SSSs) and binary population synthesis models of the single-degenerate channel are broadly consistent with the observed rates of overluminous SNe Ia, and suggest that the population of SSSs are the dominant stellar progenitors of SNe 1991T-like events. We further demonstrate that the single-degenerate channel contribution to the normal and failed 2002cx-like rates is not likely to exceed 1% of the total SNe Ia rate. We conclude with a range of observational tests of overluminous SNe Ia which will either support or strongly constrain the single-degenerate scenario.

  15. Simulation of biological therapies for degenerated intervertebral discs.

    PubMed

    Zhu, Qiaoqiao; Gao, Xin; Temple, H Thomas; Brown, Mark D; Gu, Weiyong

    2016-04-01

    The efficacy of biological therapies on intervertebral disc repair was quantitatively studied using a three-dimensional finite element model based on a cell-activity coupled multiphasic mixture theory. In this model, cell metabolism and matrix synthesis and degradation were considered. Three types of biological therapies-increasing the cell density (Case I), increasing the glycosaminoglycan (GAG) synthesis rate (Case II), and decreasing the GAG degradation rate (Case III)-to the nucleus pulposus (NP) of each of two degenerated discs [one mildly degenerated (e.g., 80% viable cells in the NP) and one severely degenerated (e.g., 30% viable cells in the NP)] were simulated. Degenerated discs without treatment were also simulated as a control. The cell number needed, nutrition level demanded, time required for the repair, and the long-term outcomes of these therapies were analyzed. For Case I, the repair process was predicted to be dependent on the cell density implanted and the nutrition level at disc boundaries. With sufficient nutrition supply, this method was predicted to be effective for treating both mildly and severely degenerated discs. For Case II, the therapy was predicted to be effective for repairing the mildly degenerated disc, but not for the severely degenerated disc. Similar results were predicted for Case III. No change in cell density for Cases II and III were predicted under normal nutrition level. This study provides a quantitative guide for choosing proper strategies of biological therapies for different degenerated discs. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:699-708, 2016. PMID:26425965

  16. Distinct optical properties of relativistically degenerate matter

    SciTech Connect

    Akbari-Moghanjoughi, M.

    2014-06-15

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

  17. Distinct optical properties of relativistically degenerate matter

    NASA Astrophysics Data System (ADS)

    Akbari-Moghanjoughi, M.

    2014-06-01

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

  18. Frontotemporal Lobar Degeneration and MicroRNAs

    PubMed Central

    Piscopo, Paola; Albani, Diego; Castellano, Anna E.; Forloni, Gianluigi; Confaloni, Annamaria

    2016-01-01

    Frontotemporal lobar degeneration (FTLD) includes a spectrum of disorders characterized by changes of personality and social behavior and, often, a gradual and progressive language dysfunction. In the last years, several efforts have been fulfilled in identifying both genetic mutations and pathological proteins associated with FTLD. The molecular bases undergoing the onset and progression of the disease remain still unknown. Recent literature prompts an involvement of RNA metabolism in FTLD, particularly microRNAs (miRNAs). Dysregulation of miRNAs in several disorders, including neurodegenerative diseases, and increasing importance of circulating miRNAs in different pathologies has suggested to implement the study of their possible application as biological markers and new therapeutic targets; moreover, miRNA-based therapy is becoming a powerful tool to deepen the function of a gene, the mechanism of a disease, and validate therapeutic targets. Regarding FTLD, different studies showed that miRNAs are playing an important role. For example, several reports have evaluated miRNA regulation of the progranulin gene suggesting that it is under their control, as described for miR-29b, miR-107, and miR-659. More recently, it has been demonstrated that TMEM106B gene, which protein is elevated in FTLD-TDP brains, is repressed by miR-132/212 cluster; this post-transcriptional mechanism increases intracellular levels of progranulin, affecting its pathways. These findings if confirmed could suggest that these microRNAs have a role as potential targets for some related-FTLD genes. In this review, we focus on the emerging roles of the miRNAs in the pathogenesis of FTLD. PMID:26903860

  19. Gene expression profile analysis of human intervertebral disc degeneration

    PubMed Central

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

    2013-01-01

    In this study, we used microarray analysis to investigate the biogenesis and progression of intervertebral disc degeneration. The gene expression profiles of 37 disc tissue samples obtained from patients with herniated discs and degenerative disc disease collected by the National Cancer Institute Cooperative Tissue Network were analyzed. Differentially expressed genes between more and less degenerated discs were identified by significant analysis of microarray. A total of 555 genes were 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 β-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. PMID:24130454

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

    PubMed

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

    2014-04-01

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

  1. Development of Animal Models of Local Retinal Degeneration

    PubMed Central

    Lorach, Henri; Kung, Jennifer; Beier, Corinne; Mandel, Yossi; Dalal, Roopa; Huie, Philip; Wang, Jenny; Lee, Seungjun; Sher, Alexander; Jones, Bryan William; Palanker, Daniel

    2015-01-01

    Purpose Development of nongenetic animal models of local retinal degeneration is essential for studies of retinal pathologies, such as chronic retinal detachment or age-related macular degeneration. We present two different methods to induce a highly localized retinal degeneration with precise onset time, that can be applied to a broad range of species in laboratory use. Methods A 30-μm thin polymer sheet was implanted subretinally in wild-type (WT) rats. The effects of chronic retinal separation from the RPE were studied using histology and immunohistochemistry. Another approach is applicable to species with avascular retina, such as rabbits, where the photoreceptors and RPE were thermally ablated over large areas, using a high power scanning laser. Results Photoreceptors above the subretinal implant in rats degenerated over time, with 80% of the outer nuclear layer disappearing within a month, and the rest by 3 months. Similar loss was obtained by selective photocoagulation with a scanning laser. Cells in the inner nuclear layer and ganglion cell layer were preserved in both cases. However, there were signs of rewiring and decrease in the size of the bipolar cell terminals in the damaged areas. Conclusions Both methods induce highly reproducible degeneration of photoreceptors over a defined area, with complete preservation of the inner retinal neurons during the 3-month follow-up. They provide a reliable platform for studies of local retinal degeneration and development of therapeutic strategies in a wide variety of species. PMID:26207299

  2. Electron microscopic studies of macrophages in Wallerian degeneration of rat optic nerve after intravenous injection of colloidal carbon.

    PubMed Central

    Ling, E A

    1978-01-01

    The origin of macrophages in the degenerating optic nerve of rats after eye enucleation was investigated electron microscopically following intravenous labelling of mononuclear leucoytes with colloidal carbon. In the various post-operative periods studied carbon-labelled macrophages were seen at the site of lesion. At 4 and 7 days after enucleation carbon-labelled cells were seen at the site of Wallerian degeneration of the optic nerve over 4 mm distal to the site of the lesion. In the electron microscope these cells showed a flattened nucleus bearing coarse chromatin clumps, their cytoplasm contained a prominent Golgi complex and long isolate profiles of rough endoplasmic reticulum. Clusters of carbon particles in the cytoplasms were membrane-bound. Lysosomal bodies embedded with carbon particles were also observed. In relation to the blood vessels of the optic nerve, endothelial cells and pericytes with ingested carbon were seen. Macrophages in the meninges covering the optic nerve were also labelled. The results suggest that some macrophages in the region of Wallerian degeneration in the optic nerve, as well as those at the actual site of the lesion, were transformed blood leucocytes. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 PMID:649492

  3. From hidden symmetry to extra dimensions: A five-dimensional formulation of the degenerate BESS model

    SciTech Connect

    Coradeschi, Francesco; De Curtis, Stefania; Dominici, Daniele

    2010-07-01

    We consider the continuum limit of a moose model corresponding to a generalization to N sites of the degenerate BESS model. The five-dimensional formulation emerging in this limit is a realization of a RS1 type model with SU(2){sub L} x SU(2){sub R} in the bulk, broken by boundary conditions and a vacuum expectation value on the infrared brane. A low-energy effective Lagrangian is derived by means of the holographic technique and corresponding bounds on the model parameters are obtained.

  4. From hidden symmetry to extra dimensions: A five-dimensional formulation of the degenerate BESS model

    NASA Astrophysics Data System (ADS)

    Coradeschi, Francesco; de Curtis, Stefania; Dominici, Daniele

    2010-07-01

    We consider the continuum limit of a moose model corresponding to a generalization to N sites of the degenerate BESS model. The five-dimensional formulation emerging in this limit is a realization of a RS1 type model with SU(2)L⊗SU(2)R in the bulk, broken by boundary conditions and a vacuum expectation value on the infrared brane. A low-energy effective Lagrangian is derived by means of the holographic technique and corresponding bounds on the model parameters are obtained.

  5. Lipofuscin accumulation, abnormal electrophysiology, and photoreceptor degeneration in mutant ELOVL4 transgenic mice: a model for macular degeneration.

    PubMed

    Karan, G; Lillo, C; Yang, Z; Cameron, D J; Locke, K G; Zhao, Y; Thirumalaichary, S; Li, C; Birch, D G; Vollmer-Snarr, H R; Williams, D S; Zhang, K

    2005-03-15

    Macular degeneration is a heterogeneous group of disorders characterized by photoreceptor degeneration and atrophy of the retinal pigment epithelium (RPE) in the central retina. An autosomal dominant form of Stargardt macular degeneration (STGD) is caused by mutations in ELOVL4, which is predicted to encode an enzyme involved in the elongation of long-chain fatty acids. We generated transgenic mice expressing a mutant form of human ELOVL4 that causes STGD. In these mice, we show that accumulation by the RPE of undigested phagosomes and lipofuscin, including the fluorophore, 2-[2,6-dimethyl-8-(2,6,6-trimethyl-1-cyclohexen-1-yl)-1E,3E,5E,7E-octatetraenyl]-1-(2-hyydroxyethyl)-4-[4-methyl-6-(2,6,6,-trimethyl-1-cyclohexen-1-yl)-1E,3E,5E-hexatrienyl]-pyridinium (A2E) is followed by RPE atrophy. Subsequently, photoreceptor degeneration occurs in the central retina in a pattern closely resembling that of human STGD and age-related macular degeneration. The ELOVL4 transgenic mice thus provide a good model for both STGD and dry age-related macular degeneration, and represent a valuable tool for studies on therapeutic intervention in these forms of blindness. PMID:15749821

  6. Tyro3 Modulates Mertk-Associated Retinal Degeneration

    PubMed Central

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

    2015-01-01

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

  7. Potential regenerative treatment strategies for intervertebral disc degeneration in dogs

    PubMed Central

    2014-01-01

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

  8. Statins for age-related macular degeneration

    PubMed Central

    Gehlbach, Peter; Li, Tianjing; Hatef, Elham

    2016-01-01

    Background Age-related macular degeneration (AMD) is a progressive late onset disorder of the macula affecting central vision. Age-related macular degeneration is the leading cause of blindness in people over 65 years in industrialized countries. Recent epidemiologic, genetic, and pathological evidence has shown AMD shares a number of risk factors with atherosclerosis, leading to the hypothesis that statins may exert protective effects in AMD. Objectives The objective of this review was to examine the effectiveness of statins compared with other treatments, no treatment, or placebo in delaying the onset and progression of AMD. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2014, Issue 6), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to June 2014), EMBASE (January 1980 to June 2014), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to June 2014), PubMed (January 1946 to June 2014), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov), and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 5 June 2014. Selection criteria We included randomized controlled trials (RCTs) that compared statins with other treatments, no treatment, or placebo in participants who were either susceptible to or diagnosed as having early stages of AMD. Data collection and analysis We used standard methodological procedures expected by The Cochrane Collaboration. Two authors independently evaluated the search results against the selection criteria, abstracted data, and assessed risk of bias. We did not perform meta-analysis due to heterogeneity in the interventions and outcomes among the

  9. Genetics Home Reference: Stargardt macular degeneration

    MedlinePlus

    ... or Free article on PubMed Central Walia S, Fishman GA. Natural history of phenotypic changes in Stargardt macular ... 23, 2016 The resources on this site should not be used as a substitute for professional medical care or advice. Users with ...

  10. Notochord Cells in Intervertebral Disc Development and Degeneration

    PubMed Central

    McCann, Matthew R.; Séguin, Cheryle A.

    2016-01-01

    The intervertebral disc is a complex structure responsible for flexibility, multi-axial motion, and load transmission throughout the spine. Importantly, degeneration of the intervertebral disc is thought to be an initiating factor for back pain. Due to a lack of understanding of the pathways that govern disc degeneration, there are currently no disease-modifying treatments to delay or prevent degenerative disc disease. This review presents an overview of our current understanding of the developmental processes that regulate intervertebral disc formation, with particular emphasis on the role of the notochord and notochord-derived cells in disc homeostasis and how their loss can result in degeneration. We then describe the role of small animal models in understanding the development of the disc and their use to interrogate disc degeneration and associated pathologies. Finally, we highlight essential development pathways that are associated with disc degeneration and/or implicated in the reparative response of the tissue that might serve as targets for future therapeutic approaches. PMID:27252900

  11. Biologic Treatment of Mild and Moderate Intervertebral Disc Degeneration

    PubMed Central

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

    2014-01-01

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

  12. Transplantation and Stem Cell Therapy for Cerebellar Degenerations.

    PubMed

    Cendelin, Jan

    2016-02-01

    Stem cell-based and regenerative therapy may become a hopeful treatment for neurodegenerative diseases including hereditary cerebellar degenerations. Neurotransplantation therapy mainly aims to substitute lost cells, but potential effects might include various mechanisms including nonspecific trophic effects and stimulation of endogenous regenerative processes and neural plasticity. Nevertheless, currently, there remain serious limitations. There is a wide spectrum of human hereditary cerebellar degenerations as well as numerous cerebellar mutant mouse strains that serve as models for the development of effective therapy. By now, transplantation has been shown to ameliorate cerebellar function, e.g. in Purkinje cell degeneration mice, Lurcher mutant mice and mouse models of spinocerebellar ataxia type 1 and type 2 and Niemann-Pick disease type C. Despite the lack of direct comparative studies, it appears that there might be differences in graft development and functioning between various types of cerebellar degeneration. Investigation of the relation of graft development to specific morphological, microvascular or biochemical features of the diseased host tissue in various cerebellar degenerations may help to identify factors determining the fate of grafted cells and potential of their functional integration. PMID:26155762

  13. Mechanisms of distal axonal degeneration in peripheral neuropathies.

    PubMed

    Cashman, Christopher R; Höke, Ahmet

    2015-06-01

    Peripheral neuropathy is a common complication of a variety of diseases and treatments, including diabetes, cancer chemotherapy, and infectious causes (HIV, hepatitis C, and Campylobacter jejuni). Despite the fundamental difference between these insults, peripheral neuropathy develops as a combination of just six primary mechanisms: altered metabolism, covalent modification, altered organelle function and reactive oxygen species formation, altered intracellular and inflammatory signaling, slowed axonal transport, and altered ion channel dynamics and expression. All of these pathways converge to lead to axon dysfunction and symptoms of neuropathy. The detailed mechanisms of axon degeneration itself have begun to be elucidated with studies of animal models with altered degeneration kinetics, including the slowed Wallerian degeneration (Wld(S)) and Sarm knockout animal models. These studies have shown axonal degeneration to occur through a programmed pathway of injury signaling and cytoskeletal degradation. Insights into the common disease insults that converge on the axonal degeneration pathway promise to facilitate the development of therapeutics that may be effective against other mechanisms of neurodegeneration. PMID:25617478

  14. Human Annulus Fibrosus Dynamic Tensile Modulus Increases with Degeneration.

    PubMed

    Sen, Sounok; Jacobs, Nathan T; Boxberger, John I; Elliott, Dawn M

    2012-01-01

    The annulus fibrosus (AF) of the intervertebral disc experiences cyclic tensile loading in vivo at various states of mechanical equilibrium. Disc degeneration is associated with alterations in the biochemical composition of the AF including decreased water content, decreased proteoglycan concentration, and increased collagen deposition that affect mechanical function of the AF in compression and shear. Such changes may also affect the dynamic viscoelastic properties of the AF and thus alter the disc's ability to dissipate energy under physiologic loading. The objectives of this study were to quantify the dynamic viscoelastic properties of human AF in circumferential tension and to determine the effect of degeneration on these properties. Nondegenerated and degenerated human AF tensile samples were tested in uniaxial tension over a spectrum of loading frequencies spanning 0.01Hz to 2Hz at several states of equilibrium strain to determine the dynamic viscoelastic properties (dynamic modulus, phase angle) using a linear viscoelastic model. The AF dynamic modulus increased at higher equilibrium strain levels. The AF behaved more elastically at higher frequencies with a decreased phase angle. Degeneration resulted in a higher dynamic modulus at all strain levels but had no effect on phase angle. The findings from this study elucidate the effect of degeneration on the dynamic viscoelastic properties of human AF and lend insight into the mechanical role of the AF in cyclic loading conditions. PMID:22247579

  15. RADIOLOGICAL ANALYSIS OF EXPERIMENTAL DISC DEGENERATION IN RABBITS

    PubMed Central

    Vialle, Emiliano; Vialle, Luiz Roberto; Arruda, André de Oliveira; Riet, Ricardo Nascimento; Krieger, Antônio Bernardo de Queiroz

    2015-01-01

    Objective: To validate radiographic evaluation of a rabbit model for disc degeneration. Methods: Lumbar intervertebral discs of New Zealand rabbits were stabbed three times with a 18G needle at a limited depth of 5mm, through lateral approach. Serial radiographic images were taken on the early pre-and postoperative periods, and after four, eight and 12 weeks of the procedure, with subsequent analysis of disc height, osteophyte formation, endplate sclerosis, and presence of disc degeneration. The statistical analysis of data was validated by the Kappa coefficient, with a confidence interval (CI) of 95%. Results: A significant reduction of disc space was found on AP X-ray images after 12 postoperative weeks, with Kappa = 0.489 for CI 95% (0.25-0.72) with p < 0.001. X-ray signs of disc degeneration also presented Kappa = 0.63 for CI 95% (0.39-0.86) with p < 0.001. The remaining assessed criteria showed positive results, but with a lower Kappa value. Conclusion: The disc degeneration model using rabbits as proposed in this study was shown to be feasible, with positive X-ray correlation between pre- and postoperative images, validating the potential to induce disc degeneration in this animal model for future studies. PMID:27022512

  16. Mechanisms of Distal Axonal Degeneration in Peripheral Neuropathies

    PubMed Central

    Cashman, Christopher R.; Höke, Ahmet

    2015-01-01

    Peripheral neuropathy is a common complication of a variety of diseases and treatments, including diabetes, cancer chemotherapy, and infectious causes (HIV, hepatitis C, and Campylobacter jejuni). Despite the fundamental difference between these insults, peripheral neuropathy develops as a combination of just six primary mechanisms: altered metabolism, covalent modification, altered organelle function and reactive oxygen species formation, altered intracellular and inflammatory signaling, slowed axonal transport, and altered ion channel dynamics and expression. All of these pathways converge to lead to axon dysfunction and symptoms of neuropathy. The detailed mechanisms of axon degeneration itself have begun to be elucidated with studies of animal models with altered degeneration kinetics, including the slowed Wallerian degeneration (Wlds) and Sarmknockout animal models. These studies have shown axonal degeneration to occur througha programmed pathway of injury signaling and cytoskeletal degradation. Insights into the common disease insults that converge on the axonal degeneration pathway promise to facilitate the development of therapeutics that may be effective against other mechanisms of neurodegeneration. PMID:25617478

  17. Femoral head shape differences during development may identify hips at risk of degeneration.

    PubMed

    Vanden Berg-Foels, Wendy S; Schwager, Steven J; Todhunter, Rory J; Reeves, Anthony P

    2011-12-01

    Developmental dysplasia of the hip (DDH) is a common cause of elevated contact stress and early onset osteoarthritis (OA). We hypothesized that adaptation to focal loading during postnatal development would result in signature changes to the shape of the femoral head secondary center of ossification (SCO). SCO shape was evaluated in a canine model of DDH at ages 14 and 32 weeks. The evolving 3D morphology of the SCO was captured using serial quantitative computed tomography. A discrete medial representation shape model was fit to each SCO and served as the basis for quantitative thickness and bending measurements. Shape measurements were tested for associations with hip subluxation and degeneration. At 32 weeks, the SCO was thinner (flatter) in the perifoveal region, the site of focal loading; a greater bend to the SCO was present lateral to the site of thinning; SCO thinning and bending were associated with less femoral head coverage and with a higher probability of degeneration. Shape changes were not detected at 14 weeks. Measurement and visualization of SCO shape changes due to altered loading may provide a basis for identifying hips at risk of early onset OA and a tool for surgical planning of hip restructuring. PMID:21909817

  18. Synaptic remodeling of neuronal circuits in early retinal degeneration

    PubMed Central

    Soto, Florentina; Kerschensteiner, Daniel

    2015-01-01

    Photoreceptor degenerations are a major cause of blindness and among the most common forms of neurodegeneration in humans. Studies of mouse models revealed that synaptic dysfunction often precedes photoreceptor degeneration, and that abnormal synaptic input from photoreceptors to bipolar cells causes circuits in the inner retina to become hyperactive. Here, we provide a brief overview of frequently used mouse models of photoreceptor degenerations. We then discuss insights into circuit remodeling triggered by early synaptic dysfunction in the outer and hyperactivity in the inner retina. We discuss these insights in the context of other experimental manipulations of synaptic function and activity. Knowledge of the plasticity and early remodeling of retinal circuits will be critical for the design of successful vision rescue strategies. PMID:26500497

  19. Reprogramming of adult rod photoreceptors prevents retinal degeneration

    PubMed Central

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

    2013-01-01

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

  20. Electromagnetic wave equations for relativistically degenerate quantum magnetoplasmas.

    PubMed

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

    2010-06-01

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

  1. Autophagy: A double-edged sword in intervertebral disk degeneration.

    PubMed

    Zhang, Shu-Jun; Yang, Wei; Wang, Cheng; He, Wen-Si; Deng, Hai-Yang; Yan, Yi-Guo; Zhang, Jian; Xiang, Yong-Xiao; Wang, Wen-Jun

    2016-06-01

    Autophagy is a homeostatic mechanism through which intracellular damaged organelles and proteins are degraded and recycled in response to increased metabolic demands or stresses. Although primarily cytoprotective, dysfunction of autophagy is often associated with many degenerative diseases, including intervertebral disc (IVD) degeneration (IDD). As a main contributing factor to low back pain, IDD is the pathological basis for various debilitating spinal diseases. Either higher or lower levels of autophagy are observed in degenerative IVD cells. Despite the precise role of autophagy in disc degeneration that is still controversial, with difference from protection to aggravation, targeting autophagy has shown promise for mitigating disc degeneration. In the current review, we summarize the changes of autophagy in degenerative IVD cells and mainly discuss the relationship between autophagy and IDD. With continued efforts, modulation of the autophagic process could be a potential and attractive therapeutic strategy for degenerative disc disease. PMID:27018178

  2. Molecular mechanisms of cell death in intervertebral disc degeneration (Review).

    PubMed

    Zhang, Fan; Zhao, Xueling; Shen, Hongxing; Zhang, Caiguo

    2016-06-01

    Intervertebral discs (IVDs) are complex structures that consist of three parts, namely, nucleus pulposus, annulus fibrosus and cartilage endplates. With aging, IVDs gradually degenerate as a consequence of many factors, such as microenvironment changes and cell death. Human clinical trial and animal model studies have documented that cell death, particularly apoptosis and autophagy, significantly contribute to IVD degeneration. The mechanisms underlying this phenomenon include the activation of apoptotic pathways and the regulation of autophagy in response to nutrient deprivation and multiple stresses. In this review, we briefly summarize recent progress in understanding the function and regulation of apoptosis and autophagy signaling pathways. In particular, we focus on studies that reveal the functional mechanisms of these pathways in IVD degeneration. PMID:27121482

  3. Molecular mechanisms of cell death in intervertebral disc degeneration (Review)

    PubMed Central

    ZHANG, FAN; ZHAO, XUELING; SHEN, HONGXING; ZHANG, CAIGUO

    2016-01-01

    Intervertebral discs (IVDs) are complex structures that consist of three parts, namely, nucleus pulposus, annulus fibrosus and cartilage endplates. With aging, IVDs gradually degenerate as a consequence of many factors, such as microenvironment changes and cell death. Human clinical trial and animal model studies have documented that cell death, particularly apoptosis and autophagy, significantly contribute to IVD degeneration. The mechanisms underlying this phenomenon include the activation of apoptotic pathways and the regulation of autophagy in response to nutrient deprivation and multiple stresses. In this review, we briefly summarize recent progress in understanding the function and regulation of apoptosis and autophagy signaling pathways. In particular, we focus on studies that reveal the functional mechanisms of these pathways in IVD degeneration. PMID:27121482

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

    PubMed

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

    2014-06-01

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

  5. NAD(+) and axon degeneration revisited: Nmnat1 cannot substitute for Wld(S) to delay Wallerian degeneration.

    PubMed

    Conforti, L; Fang, G; Beirowski, B; Wang, M S; Sorci, L; Asress, S; Adalbert, R; Silva, A; Bridge, K; Huang, X P; Magni, G; Glass, J D; Coleman, M P

    2007-01-01

    The slow Wallerian degeneration protein (Wld(S)), a fusion protein incorporating full-length nicotinamide mononucleotide adenylyltransferase 1 (Nmnat1), delays axon degeneration caused by injury, toxins and genetic mutation. Nmnat1 overexpression is reported to protect axons in vitro, but its effect in vivo and its potency remain unclear. We generated Nmnat1-overexpressing transgenic mice whose Nmnat activities closely match that of Wld(S) mice. Nmnat1 overexpression in five lines of transgenic mice failed to delay Wallerian degeneration in transected sciatic nerves in contrast to Wld(S) mice where nearly all axons were protected. Transected neurites in Nmnat1 transgenic dorsal root ganglion explant cultures also degenerated rapidly. The delay in vincristine-induced neurite degeneration following lentiviral overexpression of Nmnat1 was significantly less potent than for Wld(S), and lentiviral overexpressed enzyme-dead Wld(S) still displayed residual neurite protection. Thus, Nmnat1 is significantly weaker than Wld(S) at protecting axons against traumatic or toxic injury in vitro, and has no detectable effect in vivo. The full protective effect of Wld(S) requires more N-terminal sequences of the protein. PMID:16645633

  6. Lumbar intervertebral disc degeneration and related factors in Korean firefighters

    PubMed Central

    Jang, Tae-Won; Ahn, Yeon-Soon; Byun, Junsu; Lee, Jong-In; Kim, Kun-Hyung; Kim, Youngki; Song, Han-Soo; Lee, Chul-Gab; Kwon, Young-Jun; Yoon, Jin-Ha; Jeong, Kyoungsook

    2016-01-01

    Objectives The job of firefighting can cause lumbar burden and low back pain. This study aimed to identify the association between age and lumbar intervertebral disc degeneration and whether the association differs between field and administrative (non-field) firefighters. Methods Subjects were selected using a stratified random sampling method. Firefighters were stratified by geographic area, gender, age and type of job. First, 25 fire stations were randomly sampled considering regional distribution. Then firefighters were stratified by gender, age and their job and randomly selected among the strata. A questionnaire survey and MRI scans were performed, and then four radiologists used Pfirrmann classification methods to determine the grade of lumbar intervertebral disc degeneration. Results Pfirrmann grade increased with lumbar intervertebral disc level. Analysis of covariance showed that age was significantly associated with lumbar intervertebral disc degeneration (p<0.05). The value of β (parameter estimate) was positive at all lumbar intervertebral disc levels and was higher in the field group than in the administrative group at each level. In logistic regression analysis, type of job was statistically significant only with regard to the L4–5 intervertebral disc (OR 3.498, 95% CI 1.241 to 9.860). Conclusions Lumbar intervertebral disc degeneration is associated with age, and field work such as firefighting, emergency and rescue may accelerate degeneration in the L4–5 intervertebral disc. The effects of field work on lumbar intervertebral disc degeneration were not clear in discs other than at the level L4–5. PMID:27354080

  7. Key emerging issues in progressive supranuclear palsy and corticobasal degeneration.

    PubMed

    Josephs, Keith A

    2015-03-01

    It has been approximately 50 years since neurologists were introduced to the entities, "progressive supranuclear palsy" and "corticobasal degeneration". Since the two seminal publications, there have been significant advancements in our understanding of these two neurodegenerative diseases, particularly the fact that both are associated with tau. Recent advances over the past 3 years that are notable to the field are discussed in this review that covers clinical diagnosis, pathological features, neuroimaging and CSF biomarkers, genetic associations and clinical trials related to progressive supranuclear palsy and corticobasal degeneration. PMID:25701010

  8. Extended Hellmann-Feynman theorem for degenerate eigenstates

    NASA Astrophysics Data System (ADS)

    Zhang, G. P.; George, Thomas F.

    2004-04-01

    In a previous paper, we reported a failure of the traditional Hellmann-Feynman theorem (HFT) for degenerate eigenstates. This has generated enormous interest among different groups. In four independent papers by Fernandez, by Balawender, Hola, and March, by Vatsya, and by Alon and Cederbaum, an elegant method to solve the problem was devised. The main idea is that one has to construct and diagonalize the force matrix for the degenerate case, and only the eigenforces are well defined. We believe this is an important extension to HFT. Using our previous example for an energy level of fivefold degeneracy, we find that those eigenforces correctly reflect the symmetry of the molecule.

  9. The macroscopic quantum phase of ultracold degenerate gases in the asymmetrical two-dimensional magnetic lattice

    NASA Astrophysics Data System (ADS)

    Abdelrahman, A.; Vasiliev, M.; Alameh, K.

    2011-06-01

    We investigate the existence of the macroscopic quantum phase in trapped ultracold quantum degenerate gases in an asymmetrical two-dimensional magnetic lattice. We show the key to adiabatically control the tunneling in the new two-dimensional magnetic lattice by means of external magnetic bias fields. In solving the system of coupled time-dependent differential equations, described here by the Boson Josephson Junctions (BJJs), we used an order parameter that includes both time-dependent variational parameters to describe the fractional population at each lattice site and the phase difference to quantify the macroscopic quantum phase signature. A dynamical oscillation of the fractional population and the phase difference at each individual lattice site is observed when solving the BJJs system.

  10. Effects of Subretinal Gene Transfer at Different Time Points in a Mouse Model of Retinal Degeneration

    PubMed Central

    Dai, Xufeng; Zhang, Hua; Han, Juanjuan; He, Ying; Zhang, Yangyang; Qi, Yan; Pang, Ji-jing

    2016-01-01

    Lysophosphatidylcholine acyltransferase 1 (LPCAT1) is necessary for photoreceptors to generate an important lipid component of their membranes. The absence of LPCAT1 results in early and rapid rod and cone degeneration. Retinal degeneration 11 (rd11) mice carry a mutation in the Lpcat1 gene, and are an excellent model of early-onset rapid retinal degeneration (RD). To date, no reports have documented gene therapy administration in the rd11 mouse model at different ages. In this study, the AAV8 (Y733F)-smCBA-Lpcat1 vector was subretinally injected at postnatal day (P) 10, 14, 18, or 22. Four months after injection, immunohistochemistry and analysis of retinal morphology showed that treatment at P10 rescued about 82% of the wild-type retinal thickness. However, the diffusion of the vector and the resulting rescue were limited to an area around the injection site that was only 31% of the total retinal area. Injection at P14 resulted in vector diffusion that covered approximately 84% of the retina, and we found that gene therapy was more effective against RD when exposure to light was limited before and after treatment. We observed long-term preservation of electroretinogram (ERG) responses, and preservation of retinal structure, indicating that early treatment followed by limited light exposure can improve gene therapy effectiveness for the eyes of rd11 mice. Importantly, delayed treatment still partially preserved M-cones, but not S-cones, and M-cones in the rd11 retina appeared to have a longer window of opportunity for effective preservation with gene therapy. These results provide important information regarding the effects of subretinal gene therapy in the mouse model of LPCAT1-deficiency. PMID:27228218

  11. Protective effects of hydrogen-rich saline against N-methyl-N-nitrosourea-induced photoreceptor degeneration.

    PubMed

    Chen, Tao; Tao, Ye; Yan, Weiming; Yang, Guoqing; Chen, Xuemin; Cao, Ruidan; Zhang, Lei; Xue, Junhui; Zhang, Zuoming

    2016-07-01

    The N-methyl-N-nitrosourea (MNU)-treated rat is typically used as an animal model of chemically-induced retinitis pigmentosa (RP). Reactive oxygen species (ROS) have been recognized as the crucial contributor to the retinal photoreceptor apoptosis seen in MNU-treated rats. In the present study, we explored the therapeutic effects of hydrogen-rich saline (HRS), a selective ROS scavenger, on MNU-induced photoreceptor degeneration. Intraperitoneal (IP) administration of HRS ameliorated MNU-induced photoreceptor degeneration in terms of morphology and function: Sharply decreased thickness of the retinal outer nuclear layer (ONL) and flattened photopic and scotopic electroretinogram (ERG) waveforms, typically seen in response to MNU treatment, were substantially rescued in rats cotreated with MNU and HRS (MNU + HRS). Moreover, the terminal deoxyuridine triphosphate nick-end labeling (TUNEL) assay revealed a smaller number of apoptotic photoreceptors in the MNU + HRS group compared that in the MNU group. Compared to MNU-treated rats, retinal malondialdehyde (MDA) content in MNU + HRS rats significantly decreased while superoxide dismutase (SOD) activity significantly increased. Morphological and multi-electrode array (MEA) analyses revealed more efficient preservation of the architecture and field potential waveforms in particularly the peripheral regions of the retinas within the MNU + HRS group, compared to that in the MNU group. However, this enhanced protection of structure and function in the peripheral retina is unlikely the result of site-dependent variation in the efficacy of HRS; rather, it is most likely due to reduced susceptibility of peripheral photoreceptors to MNU-induced degeneration. Inner retinal neuron function in the MNU + HRS rats was better preserved, with fewer apoptotic photoreceptors in the ONL. Collectively, these results support the rationale for future clinical evaluation of HRS as a therapeutic agent for human RP. PMID:27215478

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

    PubMed Central

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

    2014-01-01

    Ultrastructural studies of oocyte degeneration in the oocyte, and the functions of follicle cells during oocyte degeneration are described to clarify the reproductive mechanism on oocyte degeneration of Mactra chinensis using cytological methods. Commonly, the follicle cells are attached to the oocyte. Follicle cells play an important role in oocyte degeneration. In particular, the functions of follicle cells during oocyte degeneration are associated with phagocytosis and the intracellular digestion of products. In this study, morphologically similar degenerated phagosomes (various lysosomes), which were observed in the degenerated oocytes, appeared in the follicle cells. After the spawning of the oocytes, the follicle cells were involved in oocyte degeneration through phagocytosis by phagolysosomes. Therefore, it can be assumed that follicle cells reabsorb phagosomes from degenerated oocytes. In this study, the presence of lipid granules, which occurred from degenerating yolk granules, gradually increased in degenerating oocytes. The function of follicle cells can accumulate reserves of lipid granules and glycogen in the cytoplasm, which can be employed by the vitellogenic oocyte. Based on observations of follicle cells attached to degenerating oocytes after spawning, the follicle cells of this species are involved in the lysosomal induction of oocyte degeneration for the reabsorption of phagosomes (phagolysosomes) in the cytoplasm for nutrient storage, as seen in other bivalves. PMID:25949203

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

    PubMed

    Mazzarello, Paolo

    2011-01-01

    Cesare Lombroso (1835-1909) was a prominent Italian medical doctor and intellectual in the second half of the nineteenth century. He became world famous for his theory that criminality, madness and genius were all sides of the same psychobiological condition: an expression of degeneration, a sort of regression along the phylogenetic scale, and an arrest at an early stage of evolution. Degeneration affected criminals especially, in particular the "born delinquent" whose development had stopped at an early stage, making them the most "atavistic" types of human being. Lombroso also advocated the theory that genius was closely linked with madness. A man of genius was a degenerate, an example of retrograde evolution in whom madness was a form of "biological compensation" for excessive intellectual development. To confirm this theory, in August 1897, Lombroso, while attending the Twelfth International Medical Congress in Moscow, decided to meet the great Russian writer Lev Tolstoy in order to directly verify, in him, his theory of degeneration in the genius. Lombroso's anthropological ideas fuelled a heated debate on the biological determinism of human behaviour. PMID:21729591

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

    PubMed

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

    2014-01-01

    Degeneration of intervertebral discs (IVDs) is associated with back pain and elevated levels of inflammatory cells. It has been hypothesised that discogenic pain is a direct result of vascular and neural ingrowth along annulus fissures, which may expose the avascular nucleus pulposus (NP) to the systemic circulation and induce an autoimmune reaction. In this study, we confirmed our previous observation of antibodies in human degenerated and post-traumatic IVDs cultured in vitro. We hypothesised that the presence of antibodies was due to an autoimmune reaction against specific proteins of the disc. Furthermore we identified antigens which possibly trigger an autoimmune response in degenerative disc diseases. We demonstrated that degenerated and post-traumatic IVDs contain IgG antibodies against typical extracellular proteins of the disc, particularly proteins of the NP. We identified IgGs against collagen type II and aggrecan, confirming an autoimmune reaction against the normally immune privileged NP. We also found specific IgGs against collagens types I and V, but not against collagen type III. In conclusion, this study confirmed the association between disc degeneration and autoimmunity, and may open the avenue for future studies on developing prognostic, diagnostic and therapy-monitoring markers for degenerative disc diseases. PMID:24706108

  15. The Effects of Simulated Microgravity on Intervertebral Disc Degeneration

    PubMed Central

    Jin, Li; Feng, Gang; Reames, Davis L; Shimer, Adam L; Shen, Francis H; Li, Xudong

    2012-01-01

    BACKGROUND CONTEXT Astronauts experience back pain, particularly low back pain, during and after spaceflight. Recent studies have described histological and biochemical changes in rat intervertebral discs after space travel, but there is still no in vitro model to investigate the effects of microgravity on disc metabolism. PURPOSE To study the effects of microgravity on disc degeneration and to establish an in vitro simulated microgravity study model STUDY DESIGN Discs were cultured in static and rotating conditions in bioreactor, and the characteristics of disc degeneration were evaluated METHODS The mice discs were cultured in a rotating wall vessel bioreactor where the microgravity condition was simulated. Intervertebral discs were cultured in static and microgravity condition. Histology, biochemistry, and immunohistochemical assays were performed to evaluate the characteristics of the discs in microgravity condition. RESULTS Intervertebral discs cultured in rotating bioreactors were found to develop changes of disc degeneration manifested by reduced red Safranin-o staining within the annulus fibrosus, downregulated GAG content and GAG/Hypro ratio, increased MMP-3 expression, and upregulated apoptosis. CONCLUSIONS We conclude that simulated microgravity induces the molecular changes of disc degeneration. The rotating bioreactor model will provide a foundation to investigate the effects of microgravity on disc metabolism. PMID:23537452

  16. Anisotropic uniqueness classes for a degenerate parabolic equation

    SciTech Connect

    Vil'danova, V F; Mukminov, F Kh

    2013-11-30

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

  17. Dystonia and Cerebellar Degeneration in the Leaner Mouse Mutant

    PubMed Central

    Raike, Robert S.; Hess, Ellen J.; Jinnah, H.A.

    2015-01-01

    Cerebellar degeneration is traditionally associated with ataxia. Yet, there are examples of both ataxia and dystonia occurring in individuals with cerebellar degeneration. There is also substantial evidence suggesting that cerebellar dysfunction alone may cause dystonia. The types of cerebellar defects that may cause ataxia, dystonia, or both have not been delineated. In the current study, we explored the relationship between cerebellar degeneration and dystonia using the leaner mouse mutant. Leaner mice have severe dystonia that is associated with dysfunctional and degenerating cerebellar Purkinje cells. Whereas the density of Purkinje cells was not significantly reduced in 4 week-old leaner mice, approximately 50% of the neurons were lost by 34 weeks of age. On the other hand, the dystonia and associated functional disability became significantly less severe during this same interval. In other words, dystonia improved as Purkinje cells were lost, suggesting that dysfunctional Purkinje cells, rather than Purkinje cell loss, contribute to the dystonia. These results provide evidence that distorted cerebellar function may cause dystonia and support the concept that different types of cerebellar defects can have different functional consequences. PMID:25791619

  18. Electron–ion relaxation time in moderately degenerate plasma

    SciTech Connect

    Vronskii, M. A. Koryakina, Yu. V.

    2015-09-15

    A formula is derived for the electron–ion relaxation time in a partially degenerate plasma with electron-ion interaction via a central field. The resulting expression in the form of an integral of the transport cross section generalizes the well-known Landau and Brysk approximations.

  19. Cesare Lombroso: an anthropologist between evolution and degeneration

    PubMed Central

    Mazzarello, Paolo

    Summary Cesare Lombroso (1835–1909) was a prominent Italian medical doctor and intellectual in the second half of the nineteenth century. He became world famous for his theory that criminality, madness and genius were all sides of the same psychobiological condition: an expression of degeneration , a sort of regression along the phylogenetic scale, and an arrest at an early stage of evolution. Degeneration affected criminals especially, in particular the “born delinquent” whose development had stopped at an early stage, making them the most “atavistic” types of human being. Lombroso also advocated the theory that genius was closely linked with madness. A man of genius was a degenerate, an example of retrograde evolution in whom madness was a form of “biological compensation” for excessive intellectual development. To confirm this theory, in August 1897, Lombroso, while attending the Twelfth International Medical Congress in Moscow, decided to meet the great Russian writer Lev Tolstoy in order to directly verify, in him, his theory of degeneration in the genius. Lombroso’s anthropological ideas fuelled a heated debate on the biological determinism of human behaviour. PMID:21729591

  20. The Experience of Age-Related Macular Degeneration

    ERIC Educational Resources Information Center

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

    2004-01-01

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

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

    ERIC Educational Resources Information Center

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

    2012-01-01

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

  2. Emerging monochromatic fluxes and colors of red degenerate stars

    NASA Technical Reports Server (NTRS)

    Kapranidis, S.

    1985-01-01

    The emerging monochromatic fluxes and the B-V, V-I, J-H, and V-K color indices are presented for red degenerate stars with helium atmospheres which were calculated using an equation of state and opacities based on a hot Thomas-Fermi model of the helium gas. The effective temperature range is 4500-2500 K. It is found that although the emerging fluxes resemble blackbody curves, red degenerates emit more radiation than blackbodies in the short wavelength range and less in the long wavelength range. Thus, red degenerates appear bluer than blackbodies of the same temperature. The calculated colors of these models are compared to the colors of some of the coolest known non-DA degenerate stars. In particular it is found that the B-V and V-I colors of the cool white dwarf VB 11, whose temperature had been previously estimated to be higher than 4000 K, suggest a temperature of 3750 K. If this result is correct, then VB 11 is probably the coolest known white dwarf.

  3. Gestural Imitation and Limb Apraxia in Corticobasal Degeneration

    ERIC Educational Resources Information Center

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

    2004-01-01

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

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

    ClinicalTrials.gov

    2016-04-29

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

  5. Therapeutic Approaches to Histone Reprogramming in Retinal Degeneration

    PubMed Central

    Kleinman, Mark E.

    2016-01-01

    Recent data have revealed epigenetic derangements and subsequent chromatin remodeling as a potent biologic switch for chronic inflammation and cell survival which are important therapeutic targets in the pathogenesis of several retinal degenerations. Histone deacetylases (HDACs) are a major component of this system and serve as a unique control of the chromatin remodeling process. With a multitude of targeted HDAC inhibitors now available, their use in both basic science and clinical studies has widened substantially. In the field of ocular biology, there are data to suggest that HDAC inhibition may suppress neovascularization and may be a possible treatment for retinitis pigmentosa and dry age-related macular degeneration (AMD). However, the effects of these inhibitors on cell survival and chemokine expression in the chorioretinal tissues remain very unclear. Here, we review the multifaceted biology of HDAC activity and pharmacologic inhibition while offering further insight into the importance of this epigenetic pathway in retinal degenerations. Our laboratory investigations aim to open translational avenues to advance dry AMD therapeutics while exploring the role of acetylation on inflammatory gene expression in the aging and degenerating retina. PMID:26427391

  6. Parainflammation, chronic inflammation, and age-related macular degeneration.

    PubMed

    Chen, Mei; Xu, Heping

    2015-11-01

    Inflammation is an adaptive response of the immune system to noxious insults to maintain homeostasis and restore functionality. The retina is considered an immune-privileged tissue as a result of its unique anatomic and physiologic properties. During aging, the retina suffers from a low-grade chronic oxidative insult, which sustains for decades and increases in level with advancing age. As a result, the retinal innate-immune system, particularly microglia and the complement system, undergoes low levels of activation (parainflammation). In many cases, this parainflammatory response can maintain homeostasis in the healthy aging eye. However, in patients with age-related macular degeneration, this parainflammatory response becomes dysregulated and contributes to macular damage. Factors contributing to the dysregulation of age-related retinal parainflammation include genetic predisposition, environmental risk factors, and old age. Dysregulated parainflammation (chronic inflammation) in age-related macular degeneration damages the blood retina barrier, resulting in the breach of retinal-immune privilege, leading to the development of retinal lesions. This review discusses the basic principles of retinal innate-immune responses to endogenous chronic insults in normal aging and in age-related macular degeneration and explores the difference between beneficial parainflammation and the detrimental chronic inflammation in the context of age-related macular degeneration. PMID:26292978

  7. Speech and Language Findings Associated with Paraneoplastic Cerebellar Degeneration

    ERIC Educational Resources Information Center

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

    2005-01-01

    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…

  8. MicroRNAs: New players in intervertebral disc degeneration.

    PubMed

    Wang, Cheng; Wang, Wen-Jun; Yan, Yi-Guo; Xiang, Yong-Xiao; Zhang, Jian; Tang, Zhi-Han; Jiang, Zhi-Sheng

    2015-10-23

    Chronic low back pain is generally attributed to intervertebral disc (IVD) degeneration (IDD), which is closely associated with apoptosis, extracellular matrix (ECM) disruption, cell proliferation and inflammatory response. Currently, there is no clinical therapy targeting the pathophysiology of disc degeneration. microRNAs (miRNAs) are a class of small noncoding RNA molecules that negatively regulate gene expression at the post-transcriptional levels. miRNAs not only regulate many normal physiological processes, but also play an important role in the development of most disorders, including degenerative disc disease. A variety of miRNAs are differentially expressed in degenerative human IVD tissues and cells. Among these, some of the miRNAs have been shown to be involved in multiple pathological processes during disc degeneration, including apoptosis, ECM degradation, cell proliferation and inflammatory response. This review will mainly focus on the expression profiles, roles, and therapeutic implications of miRNAs in IDD. With continued efforts, restoration of dysregulated miRNA expression may represent a promising biological treatment approach for mitigating or reversing IVD degeneration. PMID:26368266

  9. Inflammatory Mediators in Intervertebral Disk Degeneration and Discogenic Pain

    PubMed Central

    Wuertz, Karin; Haglund, Lisbet

    2013-01-01

    Although degeneration of the intervertebral disk has historically been described as a misbalance between anabolic and catabolic factors, the role of inflammatory mediators has long been neglected. However, past research clearly indicates that inflammatory mediators such as interleukin (IL)-1β, IL-6, IL-8 and tumor necrosis factor-α are expressed at higher levels in “diseased” intervertebral disks. Both disk cells as well as invading macrophages can be the source of the detected cytokines. Importantly, occurrence of inflammatory mediators in the disk can worsen the progress of degeneration by inducing the expression of matrix degrading enzymes as well as by inhibiting extracellular matrix synthesis. In addition, inflammatory mediators play a crucial role in pain development during intervertebral disk herniation (i.e., sciatica) and disk degeneration (i.e., discogenic pain). This review provides information on the most relevant inflammatory mediators during different types of disk diseases and explains how these factors can induce disk degeneration and the development of discogenic and sciatic/radiculopathic pain. PMID:24436868

  10. Nonlinear isothermal waves in a degenerate electron plasma

    SciTech Connect

    Dubinov, A. E.; Dubinova, A. A.

    2008-05-15

    A nonlinear differential equation describing oscillations of the chemical potential in a one-dimensional steady-state wave propagating in a degenerate electron gas against an immobile neutralizing ion background is derived, investigated, and solved exactly. It is found that the wave phase velocity is bounded below by a critical velocity, whose exact value is obtained.