Acute Axonal Degeneration Drives Development of Cognitive, Motor, and Visual Deficits after Blast-Mediated Traumatic Brain Injury in Mice

PubMed Central

Voorhees, Jaymie R.; Genova, Rachel M.; Britt, Jeremiah K.; McDaniel, Latisha; Harper, Matthew M.

2016-01-01

Abstract Axonal degeneration is a prominent feature of many forms of neurodegeneration, and also an early event in blast-mediated traumatic brain injury (TBI), the signature injury of soldiers in Iraq and Afghanistan. It is not known, however, whether this axonal degeneration is what drives development of subsequent neurologic deficits after the injury. The Wallerian degeneration slow strain (WldS) of mice is resistant to some forms of axonal degeneration because of a triplicated fusion gene encoding the first 70 amino acids of Ufd2a, a ubiquitin-chain assembly factor, that is linked to the complete coding sequence of nicotinamide mononucleotide adenylyltransferase 1 (NMAT1). Here, we demonstrate that resistance of WldS mice to axonal degeneration after blast-mediated TBI is associated with preserved function in hippocampal-dependent spatial memory, cerebellar-dependent motor balance, and retinal and optic nerve–dependent visual function. Thus, early axonal degeneration is likely a critical driver of subsequent neurobehavioral complications of blast-mediated TBI. Future therapeutic strategies targeted specifically at mitigating axonal degeneration may provide a uniquely beneficial approach to treating patients suffering from the effects of blast-mediated TBI. PMID:27822499

Acute Axonal Degeneration Drives Development of Cognitive, Motor, and Visual Deficits after Blast-Mediated Traumatic Brain Injury in Mice.

PubMed

Yin, Terry C; Voorhees, Jaymie R; Genova, Rachel M; Davis, Kevin C; Madison, Ashley M; Britt, Jeremiah K; Cintrón-Pérez, Coral J; McDaniel, Latisha; Harper, Matthew M; Pieper, Andrew A

2016-01-01

Axonal degeneration is a prominent feature of many forms of neurodegeneration, and also an early event in blast-mediated traumatic brain injury (TBI), the signature injury of soldiers in Iraq and Afghanistan. It is not known, however, whether this axonal degeneration is what drives development of subsequent neurologic deficits after the injury. The Wallerian degeneration slow strain ( WldS ) of mice is resistant to some forms of axonal degeneration because of a triplicated fusion gene encoding the first 70 amino acids of Ufd2a, a ubiquitin-chain assembly factor, that is linked to the complete coding sequence of nicotinamide mononucleotide adenylyltransferase 1 (NMAT1). Here, we demonstrate that resistance of WldS mice to axonal degeneration after blast-mediated TBI is associated with preserved function in hippocampal-dependent spatial memory, cerebellar-dependent motor balance, and retinal and optic nerve-dependent visual function. Thus, early axonal degeneration is likely a critical driver of subsequent neurobehavioral complications of blast-mediated TBI. Future therapeutic strategies targeted specifically at mitigating axonal degeneration may provide a uniquely beneficial approach to treating patients suffering from the effects of blast-mediated TBI.

The double-degenerate model for the progenitors of Type Ia supernovae

NASA Astrophysics Data System (ADS)

Liu, D.; Wang, B.; Han, Z.

2018-02-01

The double-degenerate (DD) model, involving the merging of massive double carbon-oxygen white dwarfs (CO WDs) driven by gravitational wave radiation, is one of the classical pathways for the formation of Type Ia supernovae (SNe Ia). Recently, it has been proposed that the WD+He subgiant channel has a significant contribution to the production of massive double WDs, in which the primary WD accumulates mass by accreting He-rich matter from an He subgiant. We evolved about 1800 CO WD+He star systems and obtained a large and dense grid for producing SNe Ia through the DD model. We then performed a series of binary population synthesis simulations for the DD model, in which the WD+He subgiant channel is calculated by interpolations in the SN Ia production grid. According to our standard model, the Galactic birth rate of SNe Ia is about 2.4 × 10- 3 yr- 1 for the WD+He subgiant channel of the DD model; the total birth rate is about 3.7 × 10- 3 yr- 1 for all channels, reproducing that of observations. Previous theoretical models still have deficit with the observed SNe Ia with delay times < 1 Gyr and > 8 Gyr. After considering the WD+He subgiant channel, we found that the delay time distributions are comparable with the observed results. Additionally, some recent studies proposed that the violent WD mergers are more likely to produce SNe Ia based on the DD model. We estimated that the violent mergers through the DD model may contribute to at most 16 per cent of all SNe Ia.

MAPK signaling promotes axonal degeneration by speeding the turnover of the axonal maintenance factor NMNAT2

PubMed Central

Walker, Lauren J; Summers, Daniel W; Sasaki, Yo; Brace, EJ; Milbrandt, Jeffrey; DiAntonio, Aaron

2017-01-01

Injury-induced (Wallerian) axonal degeneration is regulated via the opposing actions of pro-degenerative factors such as SARM1 and a MAPK signal and pro-survival factors, the most important of which is the NAD+ biosynthetic enzyme NMNAT2 that inhibits activation of the SARM1 pathway. Here we investigate the mechanism by which MAPK signaling facilitates axonal degeneration. We show that MAPK signaling promotes the turnover of the axonal survival factor NMNAT2 in cultured mammalian neurons as well as the Drosophila ortholog dNMNAT in motoneurons. The increased levels of NMNAT2 are required for the axonal protection caused by loss of MAPK signaling. Regulation of NMNAT2 by MAPK signaling does not require SARM1, and so cannot be downstream of SARM1. Hence, pro-degenerative MAPK signaling functions upstream of SARM1 by limiting the levels of the essential axonal survival factor NMNAT2 to promote injury-dependent SARM1 activation. These findings are consistent with a linear molecular pathway for the axonal degeneration program. DOI: http://dx.doi.org/10.7554/eLife.22540.001 PMID:28095293

Monitoring and modelling of white dwarfs with extremely weak magnetic fields. WD 2047+372 and WD 2359-434

NASA Astrophysics Data System (ADS)

Landstreet, J. D.; Bagnulo, S.; Valyavin, G.; Valeev, A. F.

2017-11-01

Magnetic fields are detected in a few percent of white dwarfs. The number of such magnetic white dwarfs known is now some hundreds. Fields range in strength from a few kG to several hundred MG. Almost all the known magnetic white dwarfs have a mean field modulus ≥1 MG. We are trying to fill a major gap in observational knowledge at the low field limit (≤200 kG) using circular spectro-polarimetry. In this paper we report the discovery and monitoring of strong, periodic magnetic variability in two previously discovered "super-weak field" magnetic white dwarfs, WD 2047+372 and WD 2359-434. WD 2047+372 has a mean longitudinal field that reverses between about -12 and + 15 kG, with a period of 0.243 d, while its mean field modulus appears nearly constant at 60 kG. The observations can be interpreted in terms of a dipolar field tilted with respect to the stellar rotation axis. WD 2359-434 always shows a weak positive longitudinal field with values between about 0 and + 12 kG, varying only weakly with stellar rotation, while the mean field modulus varies between about 50 and 100 kG. The rotation period is found to be 0.112 d using the variable shape of the Hα line core, consistent with available photometry. The field of this star appears to be much more complex than a dipole, and is probably not axisymmetric. Available photometry shows that WD 2359-434 is a light variable with an amplitude of only 0.005 mag; our own photometry shows that if WD 2047+372 is photometrically variable, the amplitude is below about 0.01 mag. These are the first models for magnetic white dwarfs with fields below about 100 kG based on magnetic measurements through the full stellar rotation. They reveal two very different magnetic surface configurations, and that, contrary to simple ohmic decay theory, WD 2359-434 has a much more complex surface field than the much younger WD 2047+372. Based, in part, on observations collected at the European Organisation for Astronomical Research in the

A Method for WD40 Repeat Detection and Secondary Structure Prediction

PubMed Central

Wang, Yang; Jiang, Fan; Zhuo, Zhu; Wu, Xian-Hui; Wu, Yun-Dong

2013-01-01

WD40-repeat proteins (WD40s), as one of the largest protein families in eukaryotes, play vital roles in assembling protein-protein/DNA/RNA complexes. WD40s fold into similar β-propeller structures despite diversified sequences. A program WDSP (WD40 repeat protein Structure Predictor) has been developed to accurately identify WD40 repeats and predict their secondary structures. The method is designed specifically for WD40 proteins by incorporating both local residue information and non-local family-specific structural features. It overcomes the problem of highly diversified protein sequences and variable loops. In addition, WDSP achieves a better prediction in identifying multiple WD40-domain proteins by taking the global combination of repeats into consideration. In secondary structure prediction, the average Q3 accuracy of WDSP in jack-knife test reaches 93.7%. A disease related protein LRRK2 was used as a representive example to demonstrate the structure prediction. PMID:23776530

Is WD 1437-008 a cataclysmic variable?

NASA Astrophysics Data System (ADS)

Shimansky, V. V.; Nurtdinova, D. N.; Borisov, N. V.; Spiridonova, O. I.

2011-10-01

Comprehensive observations of a close binary candidate WD 1437-008 are performed. The shape and amplitude of the observed brightness variations are shown to be inconsistent with the hypothesis of reflection effects, and the photometric period of the system, P phot = 0. d 2775, is found to differ from the period of spectral variations, P sp = 0. d 272060. As a result, WD 1437-008 has been preliminarily classified as a low-inclination cataclysmic variable.

Intracellular calcium release through IP3R or RyR contributes to secondary axonal degeneration.

PubMed

Orem, Ben C; Pelisch, Nicolas; Williams, Joshua; Nally, Jacqueline M; Stirling, David P

2017-10-01

Severed CNS axons often retract or dieback away from the injury site and fail to regenerate. The precise mechanisms underlying acute axonal dieback and secondary axonal degeneration remain poorly understood. Here we investigate the role of Ca 2+ store mediated intra-axonal Ca 2+ release in acute axonal dieback and secondary axonal degeneration. To differentiate between primary (directly transected) and "bystander" axonal injury (axons spared by the initial injury but then succumb to secondary degeneration) in real-time we use our previously published highly focal laser-induced spinal cord injury (LiSCI) ex vivo model. Ascending spinal cord dorsal column axons that express YFP were severed using an 800 nm laser pulse while being imaged continuously using two-photon excitation microscopy. We inhibited two major intra-axonal Ca 2+ store channels, ryanodine receptors (RyR) and IP 3 R, with ryanodine or 2-APB, respectively, to individually determine their role in axonal dieback and secondary axonal degeneration. Each antagonist was dissolved in artificial CSF and applied 1h post-injury alone or in combination, and continuously perfused for the remainder of the imaging session. Initially following LiSCI, transected axons retracted equal distances both distal and proximal to the lesion. However, by 4h after injury, the distal axonal segments that are destined for Wallerian degeneration had significantly retracted further than their proximal counterparts. We also found that targeting either RyR or IP 3 R using pharmacological and genetic approaches significantly reduced proximal axonal dieback and "bystander" secondary degeneration of axons compared to vehicle controls at 6h post-injury. Combined treatment effects on secondary axonal degeneration were similar to either drug in isolation. Together, these results suggest that intra-axonal Ca 2+ store mediated Ca 2+ release through RyR or IP 3 R contributes to secondary axonal degeneration following SCI. Copyright © 2017

Evolving ONe WD+He star systems to intermediate-mass binary pulsars

NASA Astrophysics Data System (ADS)

Liu, D.; Wang, B.; Chen, W.; Zuo, Z.; Han, Z.

2018-06-01

It has been suggested that accretion-induced collapse (AIC) is a non-negligible path for the formation of the observed neutron stars (NSs). An ONe white dwarf (WD) that accretes material from a He star may experience AIC process and eventually produce intermediate-mass binary pulsars (IMBPs), named as the ONe WD+He star scenario. Note that previous studies can only account for part of the observed IMBPs with short orbital periods. In this work, we investigate the evolution of about 900 ONe WD+He star binaries to explore the distribution of IMBPs. We found that the ONe WD+He star scenario could form IMBPs including pulsars with 5-340 ms spin periods and 0.75-1.38 M_{⊙} WD companions, in which the orbital periods range from 0.04 to 900 d. Compared with the 20 observed IMBPs, this scenario can cover the parameters of 13 sources in the final orbital period-WD mass plane and the Corbet diagram, most of which have short orbital periods. We found that the ONe WD+He star scenario can explain almost all the observed IMBPs with short orbital periods. This work can well match the observed parameters of PSR J1802-2124 (one of the two precisely observed IMBPs), providing a possible evolutional path for its formation. We also speculate that the compact companion of HD 49798 (a hydrogen depleted sdO6 star) may be not a NS based on this work.

Activity-dependent degeneration of axotomized neuromuscular synapses in WldS mice

PubMed Central

Brown, R.; Hynes-Allen, A.; Swan, A.J.; Dissanayake, K.N.; Gillingwater, T.H.; Ribchester, R.R.

2015-01-01

Activity and disuse of synapses are thought to influence progression of several neurodegenerative diseases in which synaptic degeneration is an early sign. Here we tested whether stimulation or disuse renders neuromuscular synapses more or less vulnerable to degeneration, using axotomy as a robust trigger. We took advantage of the slow synaptic degeneration phenotype of axotomized neuromuscular junctions in flexor digitorum brevis (FDB) and deep lumbrical (DL) muscles of Wallerian degeneration-Slow (WldS) mutant mice. First, we maintained ex vivo FDB and DL nerve-muscle explants at 32 °C for up to 48 h. About 90% of fibers from WldS mice remained innervated, compared with about 36% in wild-type muscles at the 24-h checkpoint. Periodic high-frequency nerve stimulation (100 Hz: 1 s/100 s) reduced synaptic protection in WldS preparations by about 50%. This effect was abolished in reduced Ca2+ solutions. Next, we assayed FDB and DL innervation after 7 days of complete tetrodotoxin (TTX)-block of sciatic nerve conduction in vivo, followed by tibial nerve axotomy. Five days later, only about 9% of motor endplates remained innervated in the paralyzed muscles, compared with about 50% in 5 day-axotomized muscles from saline-control-treated WldS mice with no conditioning nerve block. Finally, we gave mice access to running wheels for up to 4 weeks prior to axotomy. Surprisingly, exercising WldS mice ad libitum for 4 weeks increased about twofold the amount of subsequent axotomy-induced synaptic degeneration. Together, the data suggest that vulnerability of mature neuromuscular synapses to axotomy, a potent neurodegenerative trigger, may be enhanced bimodally, either by disuse or by hyperactivity. PMID:25617654

The physical properties of double degenerate common proper motion binaries

NASA Technical Reports Server (NTRS)

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

1991-01-01

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

The Work Disability Functional Assessment Battery (WD-FAB): Feasibility and Psychometric Properties

PubMed Central

Meterko, Mark; Marfeo, Elizabeth E.; McDonough, Christine M.; Jette, Alan M.; Ni, Pengsheng; Bogusz, Kara; Rasch, Elizabeth K; Brandt, Diane E.; Chan, Leighton

2015-01-01

Objectives To assess the feasibility and psychometric properties of eight scales covering two domains of the newly developed Work Disability Functional Assessment Battery (WD-FAB): physical function (PF) and behavioral health (BH) function. Design Cross-sectional. Setting Community. Participants Adults unable to work due to a physical (n=497) or mental (n=476) disability. Interventions None. Main Outcome Measures Each disability group responded to a survey consisting of the relevant WD-FAB scales and existing measures of established validity. The WD-FAB scales were evaluated with regard to data quality (score distribution; percent “I don’t know” responses), efficiency of administration (number of items required to achieve reliability criterion; time required to complete the scale) by computerized adaptive testing (CAT), and measurement accuracy as tested by person fit. Construct validity was assessed by examining both convergent and discriminant correlations between the WD-FAB scales and scores on same-domain and cross-domain established measures. Results Data quality was good and CAT efficiency was high across both WD-FAB domains. Measurement accuracy was very good for the PF scales; BH scales demonstrated more variability. Construct validity correlations, both convergent and divergent, between all WD-FAB scales and established measures were in the expected direction and range of magnitude. Conclusions The data quality, CAT efficacy, person fit and construct validity of the WD-FAB scales were well supported and suggest that the WD-FAB could be used to assess physical and behavioral health function related to work disability. Variation in scale performance suggests the need for future work on item replenishment and refinement, particularly regarding the Self-Efficacy scale. PMID:25528263

A neuroprotective agent that inactivates prodegenerative TrkA and preserves mitochondria

PubMed Central

Feinberg, Konstantin; Kolaj, Adelaida; Wu, Chen; Grinshtein, Natalie; Krieger, Jonathan R.; Moran, Michael F.; Rubin, Lee L.

2017-01-01

Axon degeneration is an early event and pathological in neurodegenerative conditions and nerve injuries. To discover agents that suppress neuronal death and axonal degeneration, we performed drug screens on primary rodent neurons and identified the pan-kinase inhibitor foretinib, which potently rescued sympathetic, sensory, and motor wt and SOD1 mutant neurons from trophic factor withdrawal-induced degeneration. By using primary sympathetic neurons grown in mass cultures and Campenot chambers, we show that foretinib protected neurons by suppressing both known degenerative pathways and a new pathway involving unliganded TrkA and transcriptional regulation of the proapoptotic BH3 family members BimEL, Harakiri,and Puma, culminating in preservation of mitochondria in the degenerative setting. Foretinib delayed chemotherapy-induced and Wallerian axonal degeneration in culture by preventing axotomy-induced local energy deficit and preserving mitochondria, and peripheral Wallerian degeneration in vivo. These findings identify a new axon degeneration pathway and a potentially clinically useful therapeutic drug. PMID:28877995

The LuWD40-1 gene encoding WD repeat protein regulates growth and pollen viability in flax (Linum Usitatissimum L.).

PubMed

Kumar, Santosh; Jordan, Mark C; Datla, Raju; Cloutier, Sylvie

2013-01-01

As a crop, flax holds significant commercial value for its omega-3 rich oilseeds and stem fibres. Canada is the largest producer of linseed but there exists scope for significant yield improvements. Implementation of mechanisms such as male sterility can permit the development of hybrids to assist in achieving this goal. Temperature sensitive male sterility has been reported in flax but the leakiness of this system in field conditions limits the production of quality hybrid seeds. Here, we characterized a 2,588 bp transcript differentially expressed in male sterile lines of flax. The twelve intron gene predicted to encode a 368 amino acid protein has five WD40 repeats which, in silico, form a propeller structure with putative nucleic acid and histone binding capabilities. The LuWD40-1 protein localized to the nucleus and its expression increased during the transition and continued through the vegetative stages (seed, etiolated seedling, stem) while the transcript levels declined during reproductive development (ovary, anthers) and embryonic morphogenesis of male fertile plants. Knockout lines for LuWD40-1 in flax failed to develop shoots while overexpression lines showed delayed growth phenotype and were male sterile. The non-viable flowers failed to open and the pollen grains from these flowers were empty. Three independent transgenic lines overexpressing the LuWD40-1 gene had ∼80% non-viable pollen, reduced branching, delayed flowering and maturity compared to male fertile genotypes. The present study provides new insights into a male sterility mechanism present in flax.

The axon-protective WLD(S) protein partially rescues mitochondrial respiration and glycolysis after axonal injury.

PubMed

Godzik, Katharina; Coleman, Michael P

2015-04-01

The axon-protective Wallerian degeneration slow (WLD(S)) protein can ameliorate the decline in axonal ATP levels after neurite transection. Here, we tested the hypothesis that this effect is associated with maintenance of mitochondrial respiration and/or glycolysis. We used isolated neurites of superior cervical ganglion (SCG) cultures in the Seahorse XF-24 Metabolic Flux Analyser to determine mitochondrial respiration and glycolysis under different conditions. We observed that both mitochondrial respiration and glycolysis declined significantly during the latent phase of Wallerian degeneration. WLD(S) partially reduced the decline both in glycolysis and in mitochondrial respiration. In addition, we found that depleting NAD levels in uncut cultures led to changes in mitochondrial respiration and glycolysis similar to those rescued by WLD(S) after cut, suggesting that the maintenance of NAD levels in Wld(S) neurites after axonal injury at least partially underlies the maintenance of ATP levels. However, by using another axon-protective mutation (Sarm1(-/-)), we could demonstrate that rescue of basal ECAR (and hence probably glycolysis) rather than basal OCR (mitochondrial respiration) may be part of the protective phenotype to delay Wallerian degeneration. These findings open new routes to study glycolysis and the connection between NAD and ATP levels in axon degeneration, which may help to eventually develop therapeutic strategies to treat neurodegenerative diseases.

WD+RG systems as the progenitors of type Ia supernovae

NASA Astrophysics Data System (ADS)

Wang, Bo; Han, Zhan-Wen

2010-03-01

Type Ia supernovae (SNe Ia) play an important role in the study of cosmic evolution, especially in cosmology. There are several progenitor models for SNe Ia proposed in the past years. By considering the effect of accretion disk instability on the evolution of white dwarf (WD) binaries, we performed detailed binary evolution calculations for the WD + red-giant (RG) channel of SNe Ia, in which a carbon-oxygen WD accretes material from a RG star to increase its mass to the Chandrasekhar mass limit. According to these calculations, we mapped out the initial and final parameters for SNe Ia in the orbital period-secondary mass (log Pi - Mi2) plane for various WD masses for this channel. We discussed the influence of the variation of the duty cycle value on the regions for producing SNe Ia. Similar to previous studies, this work also indicates that the long-period dwarf novae offer possible ways for producing SNe Ia. Meanwhile, we find that the surviving companion stars from this channel have a low mass after the SN explosion, which may provide a means for the formation of the population of single low-mass WDs (<0.45 Modot).

Constraining the Single-degenerate Channel of Type Ia Supernovae with Stable Iron-group Elements in SNR 3C 397

NASA Astrophysics Data System (ADS)

Dave, Pranav; Kashyap, Rahul; Fisher, Robert; Timmes, Frank; Townsley, Dean; Byrohl, Chris

2017-05-01

Recent Suzaku X-ray spectra of supernova remnant (SNR) 3C 397 indicate enhanced stable iron group element abundances of Ni, Mn, Cr, and Fe. Seeking to address key questions about the progenitor and explosion mechanism of 3C 397, we compute nucleosynthetic yields from a suite of multidimensional hydrodynamics models in the near-Chandrasekhar-mass, single-degenerate paradigm for Type Ia supernovae (SNe Ia). Varying the progenitor white dwarf (WD) internal structure, composition, ignition, and explosion mechanism, we find that the best match to the observed iron peak elements of 3C 397 are dense (central density ≥6 × 109 g cm-3), low-carbon WDs that undergo a weak, centrally ignited deflagration, followed by a subsequent detonation. The amount of 56Ni produced is consistent with a normal or bright normal SNe Ia. A pure deflagration of a centrally ignited, low central density (≃2 × 109 g cm-3) progenitor WD, frequently considered in the literature, is also found to produce good agreement with 3C 397 nucleosynthetic yields, but leads to a subluminous SN Ia event, in conflict with X-ray line width data. Additionally, in contrast to prior work that suggested a large supersolar metallicity for the WD progenitor for SNR 3C 397, we find satisfactory agreement for solar- and subsolar-metallicity progenitors. We discuss a range of implications our results have for the single-degenerate channel.

GROWING WHITE DWARFS TO THE CHANDRASEKHAR LIMIT: THE PARAMETER SPACE OF THE SINGLE DEGENERATE SN Ia CHANNEL

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hillman, Y.; Prialnik, D.; Kovetz, A.

Can a white dwarf (WD), accreting hydrogen-rich matter from a non-degenerate companion star, ever exceed the Chandrasekhar mass and explode as a SN Ia? We explore the range of accretion rates that allow a WD to secularly grow in mass, and derive limits on the accretion rate and on the initial mass that will allow it to reach 1.4M{sub ⊙}—the Chandrasekhar mass. We follow the evolution through a long series of hydrogen flashes, during which a thick helium shell accumulates. This determines the effective helium mass accretion rate for long-term, self-consistent evolutionary runs with helium flashes. We find that netmore » mass accumulation always occurs despite helium flashes. Although the amount of mass lost during the first few helium shell flashes is a significant fraction of that accumulated prior to the flash, that fraction decreases with repeated helium shell flashes. Eventually no mass is ejected at all during subsequent flashes. This unexpected result occurs because of continual heating of the WD interior by the helium shell flashes near its surface. The effect of heating is to lower the electron degeneracy throughout the WD, especially in the outer layers. This key result yields helium burning that is quasi-steady state, instead of explosive. We thus find a remarkably large parameter space within which long-term, self-consistent simulations show that a WD can grow in mass and reach the Chandrasekhar limit, despite its helium flashes.« less

Betacellulin regulates schwann cell proliferation and myelin formation in the injured mouse peripheral nerve.

PubMed

Vallières, Nicolas; Barrette, Benoit; Wang, Linda Xiang; Bélanger, Erik; Thiry, Louise; Schneider, Marlon R; Filali, Mohammed; Côté, Daniel; Bretzner, Frédéric; Lacroix, Steve

2017-04-01

When a nerve fiber is cut or crushed, the axon segment that is separated from the soma degenerates distal from the injury in a process termed Wallerian degeneration (WD). C57BL/6OlaHsd-Wld S (Wld S ) mutant mice exhibit significant delays in WD. This results in considerably delayed Schwann cell and macrophage responses and thus in impaired nerve regenerations. In our previous work, thousands of genes were screened by DNA microarrays and over 700 transcripts were found to be differentially expressed in the injured sciatic nerve of Wld S compared with wild-type (WT) mice. One of these transcripts, betacellulin (Btc), was selected for further analysis since it has yet to be characterized in the nervous system, despite being known as a ligand of the ErbB receptor family. We show that Btc mRNA is strongly upregulated in immature and dedifferentiated Sox2 + Schwann cells located in the sciatic nerve distal stump of WT mice, but not Wld S mutants. Transgenic mice ubiquitously overexpressing Btc (Tg-Btc) have increased numbers of Schmidt-Lantermann incisures compared with WT mice, as revealed by Coherent anti-Stokes Raman scattering (CARS). Tg-Btc mice also have faster nerve conduction velocity. Finally, we found that deficiency in Btc reduces the proliferation of myelinating Schwann cells after sciatic nerve injury, while Btc overexpression induces Schwann cell proliferation and improves recovery of locomotor function. Taken together, these results suggest a novel regulatory role of Btc in axon-Schwann cell interactions involved in myelin formation and nerve repair. GLIA 2017 GLIA 2017;65:657-669. © 2017 Wiley Periodicals, Inc.

Genomic survey, expression profile and co-expression network analysis of OsWD40 family in rice

PubMed Central

2012-01-01

Background WD40 proteins represent a large family in eukaryotes, which have been involved in a broad spectrum of crucial functions. Systematic characterization and co-expression analysis of OsWD40 genes enable us to understand the networks of the WD40 proteins and their biological processes and gene functions in rice. Results In this study, we identify and analyze 200 potential OsWD40 genes in rice, describing their gene structures, genome localizations, and evolutionary relationship of each member. Expression profiles covering the whole life cycle in rice has revealed that transcripts of OsWD40 were accumulated differentially during vegetative and reproductive development and preferentially up or down-regulated in different tissues. Under phytohormone treatments, 25 OsWD40 genes were differentially expressed with treatments of one or more of the phytohormone NAA, KT, or GA3 in rice seedlings. We also used a combined analysis of expression correlation and Gene Ontology annotation to infer the biological role of the OsWD40 genes in rice. The results suggested that OsWD40 genes may perform their diverse functions by complex network, thus were predictive for understanding their biological pathways. The analysis also revealed that OsWD40 genes might interact with each other to take part in metabolic pathways, suggesting a more complex feedback network. Conclusions All of these analyses suggest that the functions of OsWD40 genes are diversified, which provide useful references for selecting candidate genes for further functional studies. PMID:22429805

Constraining the Single-degenerate Channel of Type Ia Supernovae with Stable Iron-group Elements in SNR 3C 397

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dave, Pranav; Kashyap, Rahul; Fisher, Robert

Recent Suzaku X-ray spectra of supernova remnant (SNR) 3C 397 indicate enhanced stable iron group element abundances of Ni, Mn, Cr, and Fe. Seeking to address key questions about the progenitor and explosion mechanism of 3C 397, we compute nucleosynthetic yields from a suite of multidimensional hydrodynamics models in the near-Chandrasekhar-mass, single-degenerate paradigm for Type Ia supernovae (SNe Ia). Varying the progenitor white dwarf (WD) internal structure, composition, ignition, and explosion mechanism, we find that the best match to the observed iron peak elements of 3C 397 are dense (central density ≥6 × 10{sup 9} g cm{sup −3}), low-carbon WDsmore » that undergo a weak, centrally ignited deflagration, followed by a subsequent detonation. The amount of {sup 56}Ni produced is consistent with a normal or bright normal SNe Ia. A pure deflagration of a centrally ignited, low central density (≃2 × 10{sup 9} g cm{sup −3}) progenitor WD, frequently considered in the literature, is also found to produce good agreement with 3C 397 nucleosynthetic yields, but leads to a subluminous SN Ia event, in conflict with X-ray line width data. Additionally, in contrast to prior work that suggested a large supersolar metallicity for the WD progenitor for SNR 3C 397, we find satisfactory agreement for solar- and subsolar-metallicity progenitors. We discuss a range of implications our results have for the single-degenerate channel.« less

A single-degenerate channel for the progenitors of Type Ia supernovae with different metallicities

NASA Astrophysics Data System (ADS)

Meng, X.; Chen, X.; Han, Z.

2009-06-01

A single-degenerate channel for the progenitors of Type Ia supernovae (SNe Ia) is currently accepted, in which a carbon-oxygen white dwarf (CO WD) accretes hydrogen-rich material from its companion, increases its mass to the Chandrasekhar mass limit and then explodes as a SN Ia. Incorporating the prescription of Hachisu et al. for the accretion efficiency into Eggleton's stellar evolution code, and assuming that the prescription is valid for all metallicities, we performed binary stellar evolution calculations for more than 25000 close WD binaries with metallicities Z = 0.06, 0.05, 0.04, 0.03, 0.02, 0.01, 0.004, 0.001, 0.0003 and 0.0001. For our calculations, the companions are assumed to be unevolved or slightly evolved stars (WD + MS). As a result, the initial parameter spaces for SNe Ia at various Z are presented in the orbital period-secondary mass (logPi, Mi2) plane. Our study shows that both the initial mass of the secondary and the initial orbital period increase with metallicity. Thus, the minimum mass of the CO WD for SNe Ia decreases with metallicity Z. The difference in the minimum mass may be as large as 0.24Msolar for different Z. Adopting the results above, we studied the birth rate of SNe Ia for various Z via a binary population synthesis approach. If a single starburst is assumed, SNe Ia occur systemically earlier and the peak value of the birth rate is larger for a high Z. The Galactic birth rate from the WD + MS channel is lower than (but comparable to) that inferred from observations. Our study indicates that supernovae like SN2002ic will not occur in extremely low-metallicity environments, if the delayed dynamical-instability model is appropriate.

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

NASA Astrophysics Data System (ADS)

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

1995-01-01

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

THE FIRST DISTANCE CONSTRAINT ON THE RENEGADE HIGH-VELOCITY CLOUD COMPLEX WD

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peek, J. E. G.; Roman-Duval, Julia; Tumlinson, Jason

2016-09-10

We present medium-resolution, near-ultraviolet Very Large Telescope/FLAMES observations of the star USNO-A0600-15865535. We adapt a standard method of stellar typing to our measurement of the shape of the Balmer ϵ absorption line to demonstrate that USNO-A0600-15865535 is a blue horizontal branch star, residing in the lower stellar halo at a distance of 4.4 kpc from the Sun. We measure the H and K lines of singly ionized calcium and find two isolated velocity components, one originating in the disk, and one associated with the high-velocity cloud complex WD. This detection demonstrated that complex WD is closer than ∼4.4 kpc andmore » is the first distance constraint on the +100 km s{sup −1} Galactic complex of clouds. We find that complex WD is not in corotation with the Galactic disk, which has been assumed for decades. We examine a number of scenarios and find that the most likely scenario is that complex WD was ejected from the solar neighborhood and is only a few kiloparsecs from the Sun.« less

Wld S protein requires Nmnat activity and a short N-terminal sequence to protect axons in mice.

PubMed

Conforti, Laura; Wilbrey, Anna; Morreale, Giacomo; Janeckova, Lucie; Beirowski, Bogdan; Adalbert, Robert; Mazzola, Francesca; Di Stefano, Michele; Hartley, Robert; Babetto, Elisabetta; Smith, Trevor; Gilley, Jonathan; Billington, Richard A; Genazzani, Armando A; Ribchester, Richard R; Magni, Giulio; Coleman, Michael

2009-02-23

The slow Wallerian degeneration (Wld(S)) protein protects injured axons from degeneration. This unusual chimeric protein fuses a 70-amino acid N-terminal sequence from the Ube4b multiubiquitination factor with the nicotinamide adenine dinucleotide-synthesizing enzyme nicotinamide mononucleotide adenylyl transferase 1. The requirement for these components and the mechanism of Wld(S)-mediated neuroprotection remain highly controversial. The Ube4b domain is necessary for the protective phenotype in mice, but precisely which sequence is essential and why are unclear. Binding to the AAA adenosine triphosphatase valosin-containing protein (VCP)/p97 is the only known biochemical property of the Ube4b domain. Using an in vivo approach, we show that removing the VCP-binding sequence abolishes axon protection. Replacing the Wld(S) VCP-binding domain with an alternative ataxin-3-derived VCP-binding sequence restores its protective function. Enzyme-dead Wld(S) is unable to delay Wallerian degeneration in mice. Thus, neither domain is effective without the function of the other. Wld(S) requires both of its components to protect axons from degeneration.

Genome-wide investigation and expression analyses of WD40 protein family in the model plant foxtail millet (Setaria italica L.).

PubMed

Mishra, Awdhesh Kumar; Muthamilarasan, Mehanathan; Khan, Yusuf; Parida, Swarup Kumar; Prasad, Manoj

2014-01-01

WD40 proteins play a crucial role in diverse protein-protein interactions by acting as scaffolding molecules and thus assisting in the proper activity of proteins. Hence, systematic characterization and expression profiling of these WD40 genes in foxtail millet would enable us to understand the networks of WD40 proteins and their biological processes and gene functions. In the present study, a genome-wide survey was conducted and 225 potential WD40 genes were identified. Phylogenetic analysis categorized the WD40 proteins into 5 distinct sub-families (I-V). Gene Ontology annotation revealed the biological roles of the WD40 proteins along with its cellular components and molecular functions. In silico comparative mapping with sorghum, maize and rice demonstrated the orthologous relationships and chromosomal rearrangements including duplication, inversion and deletion of WD40 genes. Estimation of synonymous and non-synonymous substitution rates revealed its evolutionary significance in terms of gene-duplication and divergence. Expression profiling against abiotic stresses provided novel insights into specific and/or overlapping expression patterns of SiWD40 genes. Homology modeling enabled three-dimensional structure prediction was performed to understand the molecular functions of WD40 proteins. Although, recent findings had shown the importance of WD40 domains in acting as hubs for cellular networks during many biological processes, it has invited a lesser research attention unlike other common domains. Being a most promiscuous interactors, WD40 domains are versatile in mediating critical cellular functions and hence this genome-wide study especially in the model crop foxtail millet would serve as a blue-print for functional characterization of WD40s in millets and bioenergy grass species. In addition, the present analyses would also assist the research community in choosing the candidate WD40s for comprehensive studies towards crop improvement of millets and

Genome-Wide Investigation and Expression Analyses of WD40 Protein Family in the Model Plant Foxtail Millet (Setaria italica L.)

PubMed Central

Mishra, Awdhesh Kumar; Muthamilarasan, Mehanathan; Khan, Yusuf; Parida, Swarup Kumar; Prasad, Manoj

2014-01-01

WD40 proteins play a crucial role in diverse protein-protein interactions by acting as scaffolding molecules and thus assisting in the proper activity of proteins. Hence, systematic characterization and expression profiling of these WD40 genes in foxtail millet would enable us to understand the networks of WD40 proteins and their biological processes and gene functions. In the present study, a genome-wide survey was conducted and 225 potential WD40 genes were identified. Phylogenetic analysis categorized the WD40 proteins into 5 distinct sub-families (I–V). Gene Ontology annotation revealed the biological roles of the WD40 proteins along with its cellular components and molecular functions. In silico comparative mapping with sorghum, maize and rice demonstrated the orthologous relationships and chromosomal rearrangements including duplication, inversion and deletion of WD40 genes. Estimation of synonymous and non-synonymous substitution rates revealed its evolutionary significance in terms of gene-duplication and divergence. Expression profiling against abiotic stresses provided novel insights into specific and/or overlapping expression patterns of SiWD40 genes. Homology modeling enabled three-dimensional structure prediction was performed to understand the molecular functions of WD40 proteins. Although, recent findings had shown the importance of WD40 domains in acting as hubs for cellular networks during many biological processes, it has invited a lesser research attention unlike other common domains. Being a most promiscuous interactors, WD40 domains are versatile in mediating critical cellular functions and hence this genome-wide study especially in the model crop foxtail millet would serve as a blue-print for functional characterization of WD40s in millets and bioenergy grass species. In addition, the present analyses would also assist the research community in choosing the candidate WD40s for comprehensive studies towards crop improvement of millets and

Necroplanetology: Disrupted Planetary Material Transiting WD 1145+017

NASA Astrophysics Data System (ADS)

Manideep Duvvuri, Girish; Redfield, Seth; Veras, Dimitri

2018-06-01

The WD 1145+017 system shows irregular transit features that are consistent with the tidal disruption of differentiated asteroids with bulk densities < 4 g cm-3 and bulk masses < 1021 kg. We use the open-source N-body code REBOUND to simulate this disruption with different internal structures: varying the core volume fraction, mantle/core density ratio, and the presence/absence of a thin low-density crust. We show that these parameters have observationally distinguishable effects on the transit light curve as the asteroid is disrupted and fit the simulation-generated lightcurves to data. We find that an asteroid with a low core fraction, low mantle/density ratio, and without a crust is most consistent with the A1 feature present for multiple weeks circa April 2017. This combination of observations and simulations to study the interior structure and chemistry of exoplanetary bodies via their destruction in action is an early example of necroplanetology, a field that will hopefully grow with the discovery of other systems like WD 1145+017.

Molecular mapping of qBK1 WD , a major QTL for bakanae disease resistance in rice.

PubMed

Lee, Sais-Beul; Hur, Yeon-Jae; Cho, Jun-Hyeon; Lee, Jong-Hee; Kim, Tae-Heon; Cho, Soo-Min; Song, You-Chun; Seo, Young-Su; Lee, Jungkwan; Kim, Tae-Sung; Park, Yong-Jin; Oh, Myung-Kyu; Park, Dong-Soo

2018-01-10

Bakanae or foot rot disease is a prominent disease of rice caused by Gibberella fujikuroi. This disease may infect rice plants from the pre-emergence stage to the mature stage. In recent years, raising rice seedlings in seed boxes for mechanical transplanting has increased the incidence of many seedling diseases; only a few rice varieties have been reported to exhibit resistance to bakanae disease. In this study, we attempted to identify quantitative trait loci (QTLs) conferring bakanae disease resistance from the highly resistant japonica variety Wonseadaesoo. A primary QTL study using the genotypes/phenotypes of the recombinant inbred lines (RILs) indicated that the locus qBK1 WD conferring resistance to bakanae disease from Wonseadaesoo was located in a 1.59 Mb interval delimited on the physical map between chr01_13542347 (13.54 Mb) and chr01_15132528 (15.13 Mb). The log of odds (LOD) score of qBK1 WD was 8.29, accounting for 20.2% of the total phenotypic variation. We further identified a gene pyramiding effect of two QTLs, qBK WD and previously developed qBK1. The mean proportion of healthy plant for 31 F 4 RILs that had no resistance genes was 35.3%, which was similar to that of the susceptible check variety Ilpum. The proportion of healthy plants for the lines with only qBK WD or qBK1 was 66.1% and 55.5%, respectively, which was significantly higher than that of the lines without resistance genes and that of Ilpum. The mean proportion of the healthy plant for 15 F 4 RILs harboring both qBK WD and qBK1 was 80.2%, which was significantly higher than that of the lines with only qBK WD or qBK1. Introducing qBK WD or pyramiding the QTLs qBK WD and qBK1 could provide effective tools for breeding rice with bakanae disease resistance. To our knowledge, this is the first report on a gene pyramiding effect that provides higher resistance against bakanae disease.

Improving Assessment of Work Related Mental Health Function Using the Work Disability Functional Assessment Battery (WD-FAB).

PubMed

Marfeo, Elizabeth E; Ni, Pengsheng; McDonough, Christine; Peterik, Kara; Marino, Molly; Meterko, Mark; Rasch, Elizabeth K; Chan, Leighton; Brandt, Diane; Jette, Alan M

2018-03-01

Purpose To improve the mental health component of the Work Disability Functional Assessment Battery (WD-FAB), developed for the US Social Security Administration's (SSA) disability determination process. Specifically our goal was to expand the WD-FAB scales of mood & emotions, resilience, social interactions, and behavioral control to improve the depth and breadth of the current scales and expand the content coverage to include aspects of cognition & communication function. Methods Data were collected from a random, stratified sample of 1695 claimants applying for the SSA work disability benefits, and a general population sample of 2025 working age adults. 169 new items were developed to replenish the WD-FAB scales and analyzed using factor analysis and item response theory (IRT) analysis to construct unidimensional scales. We conducted computer adaptive test (CAT) simulations to examine the psychometric properties of the WD-FAB. Results Analyses supported the inclusion of four mental health subdomains: Cognition & Communication (68 items), Self-Regulation (34 items), Resilience & Sociability (29 items) and Mood & Emotions (34 items). All scales yielded acceptable psychometric properties. Conclusions IRT methods were effective in expanding the WD-FAB to assess mental health function. The WD-FAB has the potential to enhance work disability assessment both within the context of the SSA disability programs as well as other clinical and vocational rehabilitation settings.

The Prp19 WD40 Domain Contains a Conserved Protein Interaction Region Essential for its Function

PubMed Central

Vander Kooi, Craig W.; Ren, Liping; Xu, Ping; Ohi, Melanie D.; Gould, Kathleen L.; Chazin, Walter J.

2010-01-01

Summary Prp19 is a member of the WD40-repeat family of E3 ubiquitin ligases and a conserved eukaryotic RNA splicing factor essential for activation and stabilization of the spliceosome. To understand the role of the WD40 repeat domain of Prp19 we have determined its structure using X-ray crystallography. The domain has a distorted seven bladed WD40 architecture with significant asymmetry due to irregular packing of blades one and seven into the core of the WD40 domain. Structure-based mutagenesis identified a highly conserved surface centered around blade five that is required for the physical interaction between Prp19 and Cwc2, another essential splicing factor. This region is found to be required for Prp19 function and yeast viability. Experiments in vitro and in vivo demonstrate that two molecules of Cwc2 bind to the Prp19 tetramer. These coupled structural and functional studies provide a model for the functional architecture of Prp19. PMID:20462492

Viral neurotropism, peripheral neuropathy and other morphological abnormalities in bovine ephemeral fever virus-infected downer cattle.

PubMed

Barigye, R; Davis, S; Hunt, R; Hunt, N; Walsh, S; Elliott, N; Burnup, C; Aumann, S; Day, C; Dyrting, K; Weir, R; Melville, L F

2016-10-01

This study assessed the neurotropism of bovine ephemeral fever (BEF) virus (BEFV) and described histomorphological abnormalities of the brain, spinal cord and peripheral nerves that may causally contribute to paresis or paralysis in BEF. Four paralysed and six asymptomatic but virus-infected cattle were monitored, and blood and serum samples screened by qRT-PCR, virus isolation and neutralisation tests. Fresh brain, spinal cord, peripheral nerve and other tissues were qRT-PCR-tested for viral RNA, while formalin-fixed specimens were processed routinely and immunohistochemically evaluated for histomorphological abnormalities and viral antigen distribution, respectively. The neurotropism of BEFV was immunohistochemically confirmed in the brain and peripheral nerves and peripheral neuropathy was demonstrated in three paralysed but not the six aneurological but virus-infected animals. Wallerian degeneration (WD) was present in the ventral funicular white matter of the lumbar spinal cord of a paralysed steer and in cervical and thoracic spinal cord segments of three paralysed animals. Although no spinal cord lesions were seen in the steer euthanased within 7 days of illness, peripheral neuropathy was present and more severe in nerves of the brachial plexuses than in the gluteal or fibular nerves. The only steer with WD in the lumbar spinal cord also showed intrahistiocytic cell viral antigen that was spatially distributed within areas of moderate brain stem encephalitis. The data confirmed neurotropism of BEFV in cattle and documented histomorphological abnormalities in peripheral nerves and brain which, together with spinal cord lesions, may contribute to chronic paralysis in BEFV-infected downer cattle. © 2016 Australian Veterinary Association.

Leucine-Rich Repeat Kinase 2 Binds to Neuronal Vesicles through Protein Interactions Mediated by Its C-Terminal WD40 Domain

PubMed Central

Piccoli, Giovanni; Onofri, Franco; Cirnaru, Maria Daniela; Kaiser, Christoph J. O.; Jagtap, Pravinkumar; Kastenmüller, Andreas; Pischedda, Francesca; Marte, Antonella; von Zweydorf, Felix; Vogt, Andreas; Giesert, Florian; Pan, Lifeng; Antonucci, Flavia; Kiel, Christina; Zhang, Mingjie; Weinkauf, Sevil; Sattler, Michael; Sala, Carlo; Matteoli, Michela; Ueffing, Marius

2014-01-01

Mutations in the leucine-rich repeat kinase 2 gene (LRRK2) are associated with familial and sporadic Parkinson's disease (PD). LRRK2 is a complex protein that consists of multiple domains, including predicted C-terminal WD40 repeats. In this study, we analyzed functional and molecular features conferred by the WD40 domain. Electron microscopic analysis of the purified LRRK2 C-terminal domain revealed doughnut-shaped particles, providing experimental evidence for its WD40 fold. We demonstrate that LRRK2 WD40 binds and sequesters synaptic vesicles via interaction with vesicle-associated proteins. In fact, a domain-based pulldown approach combined with mass spectrometric analysis identified LRRK2 as being part of a highly specific protein network involved in synaptic vesicle trafficking. In addition, we found that a C-terminal sequence variant associated with an increased risk of developing PD, G2385R, correlates with a reduced binding affinity of LRRK2 WD40 to synaptic vesicles. Our data demonstrate a critical role of the WD40 domain within LRRK2 function. PMID:24687852

Why Are Peculiar Type Ia Supernovae More Likely to Show the Signature of a Single-degenerate Model?

NASA Astrophysics Data System (ADS)

Meng, Xiang-Cun; Han, Zhan-Wen

2018-03-01

Although type Ia supernovae (SNe Ia) are very useful in many astrophysical fields, their exact progenitor nature is still unclear. A basic method to distinguish the different progenitor models is to search the signal from the single-degenerate (SD) model, e.g., the signal for the existence of a nondegenerate companion before or after supernova explosion. Observationally, some SNe Ia show such signals, while the others do not. Here, we propose a universal model to explain these observations based on the spin-up/spin-down model, in which a white dwarf (WD) will experience a spin-down phase before supernova explosion, and the spin-down timescale is determined by its initial mass, i.e., the more massive the initial WD, the shorter the spin-down timescale and then the more likely the SN Ia is to show the SD signature. Therefore, our model predicts that the SNe Ia from hybrid carbon–oxygen–neon WDs are more likely to show the SD signature observationally, as some peculiar SNe Ia showed.

Integrating retrogenesis theory to Alzheimer's disease pathology: insight from DTI-TBSS investigation of the white matter microstructural integrity.

PubMed

Alves, Gilberto Sousa; Oertel Knöchel, Viola; Knöchel, Christian; Carvalho, André Férrer; Pantel, Johannes; Engelhardt, Eliasz; Laks, Jerson

2015-01-01

Microstructural abnormalities in white matter (WM) are often reported in Alzheimer's disease (AD) and may reflect primary or secondary circuitry degeneration (i.e., due to cortical atrophy). The interpretation of diffusion tensor imaging (DTI) eigenvectors, known as multiple indices, may provide new insights into the main pathological models supporting primary or secondary patterns of WM disruption in AD, the retrogenesis, and Wallerian degeneration models, respectively. The aim of this review is to analyze the current literature on the contribution of DTI multiple indices to the understanding of AD neuropathology, taking the retrogenesis model as a reference for discussion. A systematic review using MEDLINE, EMBASE, and PUBMED was performed. Evidence suggests that AD evolves through distinct patterns of WM disruption, in which retrogenesis or, alternatively, the Wallerian degeneration may prevail. Distinct patterns of WM atrophy may be influenced by complex interactions which comprise disease status and progression, fiber localization, concurrent risk factors (i.e., vascular disease, gender), and cognitive reserve. The use of DTI multiple indices in addition to other standard multimodal methods in dementia research may help to determine the contribution of retrogenesis hypothesis to the understanding of neuropathological hallmarks that lead to AD.

WD40 domain of Apc1 is critical for the coactivator-induced allosteric transition that stimulates APC/C catalytic activity.

PubMed

Li, Qiuhong; Chang, Leifu; Aibara, Shintaro; Yang, Jing; Zhang, Ziguo; Barford, David

2016-09-20

The anaphase-promoting complex/cyclosome (APC/C) is a large multimeric cullin-RING E3 ubiquitin ligase that orchestrates cell-cycle progression by targeting cell-cycle regulatory proteins for destruction via the ubiquitin proteasome system. The APC/C assembly comprises two scaffolding subcomplexes: the platform and the TPR lobe that together coordinate the juxtaposition of the catalytic and substrate-recognition modules. The platform comprises APC/C subunits Apc1, Apc4, Apc5, and Apc15. Although the role of Apc1 as an APC/C scaffolding subunit has been characterized, its specific functions in contributing toward APC/C catalytic activity are not fully understood. Here, we report the crystal structure of the N-terminal domain of human Apc1 (Apc1N) determined at 2.2-Å resolution and provide an atomic-resolution description of the architecture of its WD40 (WD40 repeat) domain (Apc1(WD40)). To understand how Apc1(WD40) contributes to APC/C activity, a mutant form of the APC/C with Apc1(WD40) deleted was generated and evaluated biochemically and structurally. We found that the deletion of Apc1(WD40) abolished the UbcH10-dependent ubiquitination of APC/C substrates without impairing the Ube2S-dependent ubiquitin chain elongation activity. A cryo-EM structure of an APC/C-Cdh1 complex with Apc1(WD40) deleted showed that the mutant APC/C is locked into an inactive conformation in which the UbcH10-binding site of the catalytic module is inaccessible. Additionally, an EM density for Apc15 is not visible. Our data show that Apc1(WD40) is required to mediate the coactivator-induced conformational change of the APC/C that is responsible for stimulating APC/C catalytic activity by promoting UbcH10 binding. In contrast, Ube2S activity toward APC/C substrates is not dependent on the initiation-competent conformation of the APC/C.

WD40 domain of Apc1 is critical for the coactivator-induced allosteric transition that stimulates APC/C catalytic activity

PubMed Central

Li, Qiuhong; Chang, Leifu; Aibara, Shintaro; Yang, Jing; Zhang, Ziguo; Barford, David

2016-01-01

The anaphase-promoting complex/cyclosome (APC/C) is a large multimeric cullin–RING E3 ubiquitin ligase that orchestrates cell-cycle progression by targeting cell-cycle regulatory proteins for destruction via the ubiquitin proteasome system. The APC/C assembly comprises two scaffolding subcomplexes: the platform and the TPR lobe that together coordinate the juxtaposition of the catalytic and substrate-recognition modules. The platform comprises APC/C subunits Apc1, Apc4, Apc5, and Apc15. Although the role of Apc1 as an APC/C scaffolding subunit has been characterized, its specific functions in contributing toward APC/C catalytic activity are not fully understood. Here, we report the crystal structure of the N-terminal domain of human Apc1 (Apc1N) determined at 2.2-Å resolution and provide an atomic-resolution description of the architecture of its WD40 (WD40 repeat) domain (Apc1WD40). To understand how Apc1WD40 contributes to APC/C activity, a mutant form of the APC/C with Apc1WD40 deleted was generated and evaluated biochemically and structurally. We found that the deletion of Apc1WD40 abolished the UbcH10-dependent ubiquitination of APC/C substrates without impairing the Ube2S-dependent ubiquitin chain elongation activity. A cryo-EM structure of an APC/C–Cdh1 complex with Apc1WD40 deleted showed that the mutant APC/C is locked into an inactive conformation in which the UbcH10-binding site of the catalytic module is inaccessible. Additionally, an EM density for Apc15 is not visible. Our data show that Apc1WD40 is required to mediate the coactivator-induced conformational change of the APC/C that is responsible for stimulating APC/C catalytic activity by promoting UbcH10 binding. In contrast, Ube2S activity toward APC/C substrates is not dependent on the initiation-competent conformation of the APC/C. PMID:27601667

Secondary damage in the spinal cord after motor cortex injury in rats.

PubMed

Weishaupt, Nina; Silasi, Gergely; Colbourne, Frederick; Fouad, Karim

2010-08-01

When neurons within the motor cortex are fatally injured, their axons, many of which project into the spinal cord, undergo wallerian degeneration. Pathological processes occurring downstream of the cortical damage have not been extensively studied. We created a focal forelimb motor cortex injury in rats and found that axons from cell bodies located in the hindlimb motor cortex (spared by the cortical injury) become secondarily damaged in the spinal cord. To assess axonal degeneration in the spinal cord, we quantified silver staining in the corticospinal tract (CST) at 1 week and 4 weeks after the injury. We found a significant increase in silver deposition at the thoracic spinal cord level at 4 weeks compared to 1 week post-injury. At both time points, no degenerating neurons could be found in the hindlimb motor cortex. In a separate experiment, we showed that direct injury of neurons within the hindlimb motor cortex caused marked silver deposition in the thoracic CST at 1 week post-injury, and declined thereafter. Therefore, delayed axonal degeneration in the thoracic spinal cord after a focal forelimb motor cortex injury is indicative of secondary damage at the spinal cord level. Furthermore, immunolabeling of spinal cord sections showed that a local inflammatory response dominated by partially activated Iba-1-positive microglia is mounted in the CST, a viable mechanism to cause the observed secondary degeneration of fibers. In conclusion, we demonstrate that following motor cortex injury, wallerian degeneration of axons in the spinal cord leads to secondary damage, which is likely mediated by inflammatory processes.

WD 0158-160, a new pulsating DB white dwarf

NASA Astrophysics Data System (ADS)

Kilkenny, D.

2016-03-01

The DB star, WD 0158-160 (=EC 01585-1600) is shown to be a variable white dwarf with a rich pulsation spectrum, dominated by a strong variation with a frequency near 1637 μHz (amplitude ˜0.024 mag, period 598 s), though at least 10 frequencies are detected between about 1285 and 5747 μHz (780-173 s) in a relatively small data set. At ˜14.5 mag, the star is one of the brightest known DBV stars.

VizieR Online Data Catalog: WD+dMs from the SUPERBLINK proper motion survey (Skinner+, 2017)

NASA Astrophysics Data System (ADS)

Skinner, J. N.; Morgan, D. P.; West, A. A.; Lepine, S.; Thorstensen, J. R.

2018-06-01

To select for nearby WD+dMs, we used the SUPERBLINK proper motion survey (Lepine et al. 2002, J/AJ/124/1190; Lepine & Shara 2005, Cat. I/298), an ongoing all-sky survey that identifies and characterizes stars with proper motions μ>40 mas/yr. For this study, we used the 2011 July version of SUPERBLINK, which listed 2270481 stars, and was estimated to be >90% complete to V=19.0. We selected WD+dMs based on a combination of V magnitudes derived from the DSS plates (see Lepine & Shara 2005, Cat. I/298), near-UV magnitudes from GALEX, and Ks magnitudes from 2MASS. Using the UV-optical-IR color selection outlined in Skinner et al. (2014AJ....148..115S), we selected targets for spectroscopic follow-up (see bottom panel of Figure 1). We acquired optical spectroscopy of 178 newly identified WD+dM candidates, with the Boller and Chivens CCD spectrograph (CCDS), using both the Hiltner 2.4 m and McGraw-Hill 1.3 m telescopes located at the MDM Observatory. (3 data files).

WD 1145+017: optical activity during 2016-2017 and limits on the X-ray flux

NASA Astrophysics Data System (ADS)

Rappaport, S.; Gary, B. L.; Vanderburg, A.; Xu, S.; Pooley, D.; Mukai, K.

2018-02-01

WD 1145+017 was observed from 2016 November through 2017 June for the purpose of further characterizing the transit behaviour of the dusty debris clouds orbiting this white dwarf. The optical observations were carried out with a small ground-based telescope run by an amateur astronomer, and covered 53 different nights over the 8-month interval. We have found that the optical activity has increased to the highest level observed since its discovery with Kepler K2, with approximately 17 per cent of the optical flux extinguished per orbit. The source exhibits some transits with depths of up to 55 per cent and durations as long as 2 h. The dominant period of the orbiting dust clouds during 2016-2017 is 4.49126 h. We present `waterfall' images for the entire 2016-2017 and 2015-2016 observing seasons. In addition, the white dwarf was observed with the Chandra X-ray Observatory for 10-ks on each of four different occasions, separated by about a month each. The upper limit on the average X-ray flux from WD 1145+017 is ≃ 5 × 10-15 erg cm-2 s-1 (unabsorbed over the range 0.1-100 keV), which translates to an upper limit on the X-ray luminosity, Lx, of ≃ 2 × 1028 erg s-1. If L_x ˜eq G M_wd \\dot{M}_acc/R_wd, where Mwd and Rwd are the mass and radius of the white dwarf, and \\dot{M}_acc is the accretion rate, then \\dot{M}_acc ≲ 2 × 10^{11} g s-1. This is just consistent with the value of \\dot{M} that is inferred from the level of dust activity.

Mass-accreting white dwarfs and type Ia supernovae

NASA Astrophysics Data System (ADS)

Wang, Bo

2018-05-01

Type Ia supernovae (SNe Ia) play a prominent role in understanding the evolution of the Universe. They are thought to be thermonuclear explosions of mass-accreting carbon-oxygen white dwarfs (CO WDs) in binaries, although the mass donors of the accreting WDs are still not well determined. In this article, I review recent studies on mass-accreting WDs, including H- and He-accreting WDs. I also review currently most studied progenitor models of SNe Ia, i.e., the single-degenerate model (including the WD+MS channel, the WD+RG channel and the WD+He star channel), the double-degenerate model (including the violent merger scenario) and the sub-Chandrasekhar mass model. Recent progress on these progenitor models is discussed, including the initial parameter space for producing SNe Ia, the binary evolutionary paths to SNe Ia, the progenitor candidates for SNe Ia, the possible surviving companion stars of SNe Ia, some observational constraints, etc. Some other potential progenitor models of SNe Ia are also summarized, including the hybrid CONe WD model, the core-degenerate model, the double WD collision model, the spin-up/spin-down model and the model of WDs near black holes. To date, it seems that two or more progenitor models are needed to explain the observed diversity among SNe Ia.

A dearth of small particles in the transiting material around the white dwarf WD 1145+017

NASA Astrophysics Data System (ADS)

Xu, S.; Rappaport, S.; van Lieshout, R.; Vanderburg, A.; Gary, B.; Hallakoun, N.; Ivanov, V. D.; Wyatt, M. C.; DeVore, J.; Bayliss, D.; Bento, J.; Bieryla, A.; Cameron, A.; Cann, J. M.; Croll, B.; Collins, K. A.; Dalba, P. A.; Debes, J.; Doyle, D.; Dufour, P.; Ely, J.; Espinoza, N.; Joner, M. D.; Jura, M.; Kaye, T.; McClain, J. L.; Muirhead, P.; Palle, E.; Panka, P. A.; Provencal, J.; Randall, S.; Rodriguez, J. E.; Scarborough, J.; Sefako, R.; Shporer, A.; Strickland, W.; Zhou, G.; Zuckerman, B.

2018-03-01

White dwarf WD 1145+017 is orbited by several clouds of dust, possibly emanating from actively disintegrating bodies. These dust clouds reveal themselves through deep, broad, and evolving transits in the star's light curve. Here, we report two epochs of multiwavelength photometric observations of WD 1145+017, including several filters in the optical, Ks and 4.5 μm bands in 2016 and 2017. The observed transit depths are different at these wavelengths. However, after correcting for excess dust emission at Ks and 4.5 μm, we find the transit depths for the white dwarf itself are the same at all wavelengths, at least to within the observational uncertainties of ˜5-10 per cent. From this surprising result, and under the assumption of low optical depth dust clouds, we conclude that there is a deficit of small particles (with radii s ≲ 1.5 μm) in the transiting material. We propose a model wherein only large particles can survive the high equilibrium temperature environment corresponding to 4.5 h orbital periods around WD 1145+017, while small particles sublimate rapidly. In addition, we evaluate dust models that are permitted by our measurements of infrared emission.

WD60/FAP163 is a dynein intermediate chain required for retrograde intraflagellar transport in cilia

PubMed Central

Patel-King, Ramila S.; Gilberti, Renée M.; Hom, Erik F. Y.; King, Stephen M.

2013-01-01

Retrograde intraflagellar transport (IFT) is required for assembly of cilia. We identify a Chlamydomonas flagellar protein (flagellar-associated protein 163 [FAP163]) as being closely related to the D1bIC(FAP133) intermediate chain (IC) of the dynein that powers this movement. Biochemical analysis revealed that FAP163 is present in the flagellar matrix and is actively trafficked by IFT. Furthermore, FAP163 copurified with D1bIC(FAP133) and the LC8 dynein light chain, indicating that it is an integral component of the retrograde IFT dynein. To assess the functional role of FAP163, we generated an RNA interference knockdown of the orthologous protein (WD60) in planaria. The Smed-wd60(RNAi) animals had a severe ciliary assembly defect that dramatically compromised whole-organism motility. Most cilia were present as short stubs that had accumulated large quantities of IFT particle–like material between the doublet microtubules and the membrane. The few remaining approximately full-length cilia had a chaotic beat with a frequency reduced from 24 to ∼10 Hz. Thus WD60/FAP163 is a dynein IC that is absolutely required for retrograde IFT and ciliary assembly. PMID:23864713

A NEW TIMESCALE FOR PERIOD CHANGE IN THE PULSATING DA WHITE DWARF WD 0111+0018

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hermes, J. J.; Montgomery, M. H.; Winget, D. E.

2013-03-20

We report the most rapid rate of period change measured to date for a pulsating DA (hydrogen atmosphere) white dwarf (WD), observed in the 292.9 s mode of WD 0111+0018. The observed period change, faster than 10{sup -12} s s{sup -1}, exceeds by more than two orders of magnitude the expected rate from cooling alone for this class of slow and simply evolving pulsating WDs. This result indicates the presence of an additional timescale for period evolution in these pulsating objects. We also measure the rates of period change of nonlinear combination frequencies and show that they share the evolutionarymore » characteristics of their parent modes, confirming that these combination frequencies are not independent modes but rather artifacts of some nonlinear distortion in the outer layers of the star.« less

Accretion onto CO White Dwarfs using MESA

NASA Astrophysics Data System (ADS)

Feng, Wanda; Starrfield, Sumner

2018-06-01

The nature of type Ia Supernovae (SNe Ia) progenitor systems and their underlying mechanism are not well understood. There are two competing progenitor scenarios: the single-degenerate scenario wherein a white dwarf (WD) star accretes material from a companion star, reaching the Chandrasekhar mass limit; and, the double-degenerate scenario wherein two WDs merge. In this study, we investigate the single-degenerate scenario by accretion onto carbon-oxygen (CO) WDs using the Modules for Experiments in Stellar Astrophysics (MESA). We vary the WD mass, composition of the accreting material, and accretion rate in our models. Mixing between the accreted material and the WD core is informed by multidimensional studies that suggest occurance after thermonuclear runaway (TNR) ensues. We compare the accretion of solar composition material onto CO WDs with the accretion of mixed solar and core material after TNR. As many of our models eject less material than accreted, our study supports that accretion onto CO WDs is a feasible channel for SNe I progenitors.

Analysis of heterogeneous gallstones using laser-induced breakdown spectroscopy (LIBS) and wavelength dispersive X-ray fluorescence (WD-XRF).

PubMed

Jaswal, Brij Bir S; Kumar, Vinay; Sharma, Jitendra; Rai, Pradeep K; Gondal, Mohammed A; Gondal, Bilal; Singh, Vivek K

2016-04-01

Laser-induced breakdown spectroscopy (LIBS) is an emerging analytical technique with numerous advantages such as rapidity, multi-elemental analysis, no specific sample preparation requirements, non-destructiveness, and versatility. It has been proven to be a robust elemental analysis tool attracting interest because of being applied to a wide range of materials including biomaterials. In this paper, we have performed spectroscopic studies on gallstones which are heterogeneous in nature using LIBS and wavelength dispersive X-ray fluorescence (WD-XRF) techniques. It has been observed that the presence and relative concentrations of trace elements in different kind of gallstones (cholesterol and pigment gallstones) can easily be determined using LIBS technique. From the experiments carried out on gallstones for trace elemental mapping and detection, it was found that LIBS is a robust tool for such biomedical applications. The stone samples studied in the present paper were classified using the Fourier transform infrared (FTIR) spectroscopy. WD-XRF spectroscopy has been applied for the qualitative and quantitative analysis of major and trace elements present in the gallstone which was compared with the LIBS data. The results obtained in the present paper show interesting prospects for LIBS and WD-XRF to study cholelithiasis better.

Bleeding score in type 1 von Willebrand disease patients using the condensed MCMDM-1 vWD validated questionnaire.

PubMed

Pathare, A; Al Hajri, F; Al Omrani, S; Al Obaidani, N; Al Balushi, B; Al Falahi, K

2018-05-13

Assessment of the severity of bleeding symptom has led to the evolution of bleeding assessment tools which are now validated. To administer the condensed molecular and clinical markers for the diagnosis and management of type 1 von Willebrand disease VWD (MCMDM-1 vWD) questionnaire to the Omani type 1 vWD patients and correlate it with the laboratory parameters. Patients and controls were personally interviewed and the condensed MCMDM-1 vWD questionnaire administered by a single investigator. Bleeding score (BS) was calculated, based on the presence or absence of the bleeding symptoms according to a standard validated questionnaire in both the patients and the controls. The median age of the patient cohort was 27 (range, 7-49) years with 60.87% of females. The median time to administer condensed MCMDM-1 BS questionnaire was 11 minutes (interquartile range-IQR;7,16). Overall, bleeding from the oral cavity was the most predominant symptom (63%). The median BS was 5 (IQR;1,8) although individual scores ranged between 0 and 29. However, there was no statistically significant difference in BS between genders (males: median 4; IQR 1,6 and females: median 5, IQR 1,10) (P > .05, Kruskal-Wallis test) The Spearman's correlation value of BS was weak with FVIII:C levels and von Willebrand Ristocetin co-factor activity; very weak with von Willebrand Antigen level, and moderate with vonWillebrand Collagen Binding activity being -0.29, -0.28, -0.14 and -0.43, respectively. The BS reflects the severity of bleeding among the vWD patients. Although the BS was abnormal, it did not correlate significantly with the surrogate laboratory parameters [P > .05]. © 2018 John Wiley & Sons Ltd.

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 ...

The WD40 domain of ATG16L1 is required for its non-canonical role in lipidation of LC3 at single membranes.

PubMed

Fletcher, Katherine; Ulferts, Rachel; Jacquin, Elise; Veith, Talitha; Gammoh, Noor; Arasteh, Julia M; Mayer, Ulrike; Carding, Simon R; Wileman, Thomas; Beale, Rupert; Florey, Oliver

2018-02-15

A hallmark of macroautophagy is the covalent lipidation of LC3 and insertion into the double-membrane phagophore, which is driven by the ATG16L1/ATG5-ATG12 complex. In contrast, non-canonical autophagy is a pathway through which LC3 is lipidated and inserted into single membranes, particularly endolysosomal vacuoles during cell engulfment events such as LC3-associated phagocytosis. Factors controlling the targeting of ATG16L1 to phagophores are dispensable for non-canonical autophagy, for which the mechanism of ATG16L1 recruitment is unknown. Here we show that the WD repeat-containing C-terminal domain (WD40 CTD) of ATG16L1 is essential for LC3 recruitment to endolysosomal membranes during non-canonical autophagy, but dispensable for canonical autophagy. Using this strategy to inhibit non-canonical autophagy specifically, we show a reduction of MHC class II antigen presentation in dendritic cells from mice lacking the WD40 CTD Further, we demonstrate activation of non-canonical autophagy dependent on the WD40 CTD during influenza A virus infection. This suggests dependence on WD40 CTD distinguishes between macroautophagy and non-canonical use of autophagy machinery. © 2018 The Authors. Published under the terms of the CC BY 4.0 license.

A pomegranate (Punica granatum L.) WD40-repeat gene is a functional homologue of Arabidopsis TTG1 and is involved in the regulation of anthocyanin biosynthesis during pomegranate fruit development.

PubMed

Ben-Simhon, Zohar; Judeinstein, Sylvie; Nadler-Hassar, Talia; Trainin, Taly; Bar-Ya'akov, Irit; Borochov-Neori, Hamutal; Holland, Doron

2011-11-01

Anthocyanins are the major pigments responsible for the pomegranate (Punica granatum L.) fruit skin color. The high variability in fruit external color in pomegranate cultivars reflects variations in anthocyanin composition. To identify genes involved in the regulation of anthocyanin biosynthesis pathway in the pomegranate fruit skin we have isolated, expressed and characterized the pomegranate homologue of the Arabidopsis thaliana TRANSPARENT TESTA GLABRA1 (TTG1), encoding a WD40-repeat protein. The TTG1 protein is a regulator of anthocyanins and proanthocyanidins (PAs) biosynthesis in Arabidopsis, and acts by the formation of a transcriptional regulatory complex with two other regulatory proteins: bHLH and MYB. Our results reveal that the pomegranate gene, designated PgWD40, recovered the anthocyanin, PAs, trichome and seed coat mucilage phenotype in Arabidopsis ttg1 mutant. PgWD40 expression and anthocyanin composition in the skin were analyzed during pomegranate fruit development, in two accessions that differ in skin color intensity and timing of appearance. The results indicate high positive correlation between the total cyanidin derivatives quantity (red pigments) and the expression level of PgWD40. Furthermore, strong correlation was found between the steady state levels of PgWD40 transcripts and the transcripts of pomegranate homologues of the structural genes PgDFR and PgLDOX. PgWD40, PgDFR and PgLDOX expression also correlated with the expression of pomegranate homologues of the regulatory genes PgAn1 (bHLH) and PgAn2 (MYB). On the basis of our results we propose that PgWD40 is involved in the regulation of anthocyanin biosynthesis during pomegranate fruit development and that expression of PgWD40, PgAn1 and PgAn2 in the pomegranate fruit skin is required to regulate the expression of downstream structural genes involved in the anthocyanin biosynthesis.

Changes of statistical structural fluctuations unveils an early compacted degraded stage of PNS myelin

NASA Astrophysics Data System (ADS)

Poccia, Nicola; Campi, Gaetano; Ricci, Alessandro; Caporale, Alessandra S.; di Cola, Emanuela; Hawkins, Thomas A.; Bianconi, Antonio

2014-06-01

Degradation of the myelin sheath is a common pathology underlying demyelinating neurological diseases from Multiple Sclerosis to Leukodistrophies. Although large malformations of myelin ultrastructure in the advanced stages of Wallerian degradation is known, its subtle structural variations at early stages of demyelination remains poorly characterized. This is partly due to the lack of suitable and non-invasive experimental probes possessing sufficient resolution to detect the degradation. Here we report the feasibility of the application of an innovative non-invasive local structure experimental approach for imaging the changes of statistical structural fluctuations in the first stage of myelin degeneration. Scanning micro X-ray diffraction, using advances in synchrotron x-ray beam focusing, fast data collection, paired with spatial statistical analysis, has been used to unveil temporal changes in the myelin structure of dissected nerves following extraction of the Xenopus laevis sciatic nerve. The early myelin degeneration is a specific ordered compacted phase preceding the swollen myelin phase of Wallerian degradation. Our demonstration of the feasibility of the statistical analysis of SµXRD measurements using biological tissue paves the way for further structural investigations of degradation and death of neurons and other cells and tissues in diverse pathological states where nanoscale structural changes may be uncovered.

Macular degeneration

MedlinePlus Videos and Cool Tools

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

Far-ultraviolet spectroscopy of the hot DA white dwarf WD 2218+706 (DeHt5) with STIS

NASA Astrophysics Data System (ADS)

Barstow, M. A.; Bannister, N. P.; Holberg, J. B.; Hubeny, I.; Bruhweiler, F. C.; Napiwotzki, R.

2001-08-01

We report a study of the photospheric composition of the hot DAQ3 white dwarf WD 2218+706, which is also the central star of the old planetary nebula DeHt5. Helium is detected in the far-UV spectrumQ4. In addition, the star clearly contains significant quantities of elements heavier than He at abundances generally a factor of 2 to 10 higher than those found in the archetypal heavy element-rich DA G191-B2B. This is the first detection of trace He using the Heii λ1640 line in an isolated DA white dwarf, but the low surface gravity is more indicative of a binary evolution route from the red giant branch rather than a path along the asymptotic giant branch (AGB) as a single star. However, the absence of any evidence for a companion star and the uncertainty in the measured mass for WD 2218+706 still allow the possibility of an origin along an AGB evolutionary track. We reanalyse the existing optical spectra of WD 2218+706 using our latest pure H and heavy element-rich model atmospheres, obtaining a good match between the observed and synthetic spectra with either set of models. We find little evidence of any inconsistency in the temperature required to fit individual Balmer lines, as reported elsewhere for this star. Any discrepancies we see are confined to the Hα line and the core of Hβ but they do not compromise our analysis.

Sub-Chandrasekhar-mass White Dwarf Detonations Revisited

NASA Astrophysics Data System (ADS)

Shen, Ken J.; Kasen, Daniel; Miles, Broxton J.; Townsley, Dean M.

2018-02-01

The detonation of a sub-Chandrasekhar-mass white dwarf (WD) has emerged as one of the most promising Type Ia supernova (SN Ia) progenitor scenarios. Recent studies have suggested that the rapid transfer of a very small amount of helium from one WD to another is sufficient to ignite a helium shell detonation that subsequently triggers a carbon core detonation, yielding a “dynamically driven double-degenerate double-detonation” SN Ia. Because the helium shell that surrounds the core explosion is so minimal, this scenario approaches the limiting case of a bare C/O WD detonation. Motivated by discrepancies in previous literature and by a recent need for detailed nucleosynthetic data, we revisit simulations of naked C/O WD detonations in this paper. We disagree to some extent with the nucleosynthetic results of previous work on sub-Chandrasekhar-mass bare C/O WD detonations; for example, we find that a median-brightness SN Ia is produced by the detonation of a 1.0 {M}ȯ WD instead of a more massive and rarer 1.1 {M}ȯ WD. The neutron-rich nucleosynthesis in our simulations agrees broadly with some observational constraints, although tensions remain with others. There are also discrepancies related to the velocities of the outer ejecta and light curve shapes, but overall our synthetic light curves and spectra are roughly consistent with observations. We are hopeful that future multidimensional simulations will resolve these issues and further bolster the dynamically driven double-degenerate double-detonation scenario’s potential to explain most SNe Ia.

NIDO, AMOP and vWD domains of MUC4 play synergic role in MUC4 mediated signaling

PubMed Central

Liu, Xian; Xie, Kun-Ling; Tang, Jie; Jiang, Kui-Rong; Gao, Wen-Tao; Tian, Lei; Zhang, Kai; Xu, Ze-Kuan; Miao, Yi

2017-01-01

MUC4 mucin is well known as an important potential target to overcome pancreatic cancer. Three unique domains (NIDO, AMOP, and vWD) with unclear roles only present in MUC4 but are not found in other membrane-bound mucins. Our previous studies first reported that its splice variant, MUC4/Y can be a model of MUC4 (MUC4 gene fragment is more than 30KB, too huge to clone and eukaryotic express) in pancreatic cancer. More importantly, based on MUC4/Y with the appropriate length of gene sequence, it is easy to construct the unique domain-lacking models of MUC4/Y (MUC4) for research. The present study focuses on investigation of the respective role of the unique NIDO, AMOP, and vWD domain or their synergistic effect on MUC4(MUC4/Y)-mediated functions and mechanisms by series of in vitro assays, sequence-based transcriptome analysis, validation of qRT-PCR & Western blot, and systematic comparative analysis. Our results demonstrate: 1) NIDO, AMOP, and vWD domain or their synergy play significant roles on MUC4/Y-mediated malignant function of pancreatic cancer, downstream of molecule mechanisms, particularly MUC4/Y-triggered malignancy-related positive feedback loops, respectively. 2) The synergistic roles of three unique domains on MUC4/Y-mediated functions and mechanisms are more prominent than the respective domain because the synergy of three domain plays the more remarkable effects on MUC4/Y-mediated signaling hub. Thus, to improve reversed effects of domain-lacking and break the synergism of domains will contribute to block MUC4/Y(MUC4) triggering various oncogenic signaling pathways. PMID:28060749

NIDO, AMOP and vWD domains of MUC4 play synergic role in MUC4 mediated signaling.

PubMed

Zhu, Yi; Zhang, Jing-Jing; Peng, Yun-Peng; Liu, Xian; Xie, Kun-Ling; Tang, Jie; Jiang, Kui-Rong; Gao, Wen-Tao; Tian, Lei; Zhang, Kai; Xu, Ze-Kuan; Miao, Yi

2017-02-07

MUC4 mucin is well known as an important potential target to overcome pancreatic cancer. Three unique domains (NIDO, AMOP, and vWD) with unclear roles only present in MUC4 but are not found in other membrane-bound mucins. Our previous studies first reported that its splice variant, MUC4/Y can be a model of MUC4 (MUC4 gene fragment is more than 30KB, too huge to clone and eukaryotic express) in pancreatic cancer. More importantly, based on MUC4/Y with the appropriate length of gene sequence, it is easy to construct the unique domain-lacking models of MUC4/Y (MUC4) for research. The present study focuses on investigation of the respective role of the unique NIDO, AMOP, and vWD domain or their synergistic effect on MUC4(MUC4/Y)-mediated functions and mechanisms by series of in vitro assays, sequence-based transcriptome analysis, validation of qRT-PCR & Western blot, and systematic comparative analysis. Our results demonstrate: 1) NIDO, AMOP, and vWD domain or their synergy play significant roles on MUC4/Y-mediated malignant function of pancreatic cancer, downstream of molecule mechanisms, particularly MUC4/Y-triggered malignancy-related positive feedback loops, respectively. 2) The synergistic roles of three unique domains on MUC4/Y-mediated functions and mechanisms are more prominent than the respective domain because the synergy of three domain plays the more remarkable effects on MUC4/Y-mediated signaling hub. Thus, to improve reversed effects of domain-lacking and break the synergism of domains will contribute to block MUC4/Y(MUC4) triggering various oncogenic signaling pathways.

Effects of disrupting the polyketide synthase gene WdPKS1 in Wangiella [Exophiala] dermatitidis on melanin production and resistance to killing by antifungal compounds, enzymatic degradation, and extremes in temperature

PubMed Central

Paolo, William F; Dadachova, Ekaterina; Mandal, Piyali; Casadevall, Arturo; Szaniszlo, Paul J; Nosanchuk, Joshua D

2006-01-01

Background Wangiella dermatitidis is a human pathogenic fungus that is an etiologic agent of phaeohyphomycosis. W. dermatitidis produces a black pigment that has been identified as a dihydroxynaphthalene melanin and the production of this pigment is associated with its virulence. Cell wall pigmentation in W. dermatitidis depends on the WdPKS1 gene, which encodes a polyketide synthase required for generating the key precursor for dihydroxynaphthalene melanin biosynthesis. Results We analyzed the effects of disrupting WdPKS1 on dihydroxynaphthalene melanin production and resistance to antifungal compounds. Transmission electron microscopy revealed that wdpks1Δ-1 yeast had thinner cell walls that lacked an electron-opaque layer compared to wild-type cells. However, digestion of the wdpks1Δ-1 yeast revealed small black particles that were consistent with a melanin-like compound, because they were acid-resistant, reacted with melanin-binding antibody, and demonstrated a free radical signature by electron spin resonance analysis. Despite lacking the WdPKS1 gene, the mutant yeast were capable of catalyzing the formation of melanin from L-3,4-dihyroxyphenylalanine. The wdpks1Δ-1 cells were significantly more susceptible to killing by voriconazole, amphotericin B, NP-1 [a microbicidal peptide], heat and cold, and lysing enzymes than the heavily melanized parental or complemented strains. Conclusion In summary, W. dermatitidis makes WdPKS-dependent and -independent melanins, and the WdPKS1-dependent deposition of melanin in the cell wall confers protection against antifungal agents and environmental stresses. The biological role of the WdPKS-independent melanin remains unclear. PMID:16784529

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.…

Dry Macular Degeneration

MedlinePlus

... developing macular degeneration. Include fish in your diet. Omega-3 fatty acids, which are found in fish, may ... macular degeneration. Nuts, such as walnuts, also contain omega-3 fatty acids. By Mayo Clinic Staff . Mayo Clinic ...

Finale of a Quartet: Hints on Supernova Formation

NASA Astrophysics Data System (ADS)

Fang, Xiao; Thompson, Todd A.; Hirata, Christopher M.

2018-01-01

The origin of Type Ia Supernovae (SNe) is not well understood. Two most popular hypotheses are the single-degenerate scenario, where one white dwarf (WD) accretes matter from its giant companion until the Chandrasekhar limit is reached, and the double-degenerate scenario, where two WDs merge and explode. We focus on the second scenario. It has long been realized that binary WD systems normally take extremely long time to merge via gravitational waves and it is still unclear whether WD mergers can fully account for the observed SN Ia rate. Recent effort has been devoted to the effects of introducing a distant tertiary to the binary system. The standard “Kozai-Lidov” mechanism can lead to high eccentricities of the binary WDs, which could lead to direct collisions or much efficient energy dissipation. Alternatively, we investigate the long-term evolution of the hierarchical quadruple systems, i.e. WD binary with a binary companion, which are basically unexplored, yet they should be numerous. We explore their interesting dynamics and find that the fraction of reaching high eccentricities is largely enhanced, which hints on a higher WD merger rate than predicted from triple systems with the same set of secular and non-secular effects considered. Considering the population of quadruple stellar systems, the quadruple scenario might contribute significantly to the overall rate of Ia SNe.

Degenerate pressure driven modified nucleus-acoustic waves in degenerate plasmas

NASA Astrophysics Data System (ADS)

Mamun, A. A.

2018-02-01

The existence of degenerate pressure driven modified nucleus-acoustic (DPDMNA) waves propagating in a cold degenerate quantum plasma (DQP) system [containing cold inertialess degenerate electron species (DES), cold inertial non-degenerate light nucleus species (LNS), and stationary heavy nucleus species (HNS)] is predicted for the first time. The DPDMNA waves (in which the mass density of the cold LNS provides the inertia and the cold inertialess DES gives rise to the restoring force) are new since they completely disappear if the degenerate pressure of the cold DES is neglected. It is found that the phase speed (Vp) of the DPDMNA waves decreases with the rise of the charge number density of the stationary HNS for both non-relativistic and ultra-relativistic DES, and that the ultra-relativistic DES does not have any effect on Vp when β = 1, where β = Λc/Λe with Λ e = ne 0 - 1 / 3 being the average inter-electron distance in the DQP system and Λc being the constant (˜10-10 cm) for the DES. However, the ultra-relativistic DES does have quite a significant effect on Vp for β ≫ 1 and β ≪ 1, and the ultra-relativistic effect significantly enhances (reduces) Vp for β ≫ 1 (β ≪ 1). The DPDMNA waves and their dispersion properties are expected to be useful in understanding the basic features of the electrostatic perturbation mode in space and laboratory DQP systems.

Evaluating the Effects of Restraint Systems on 4WD Testing Methodologies: A Collaborative Effort between the NVFEL and ANL

EPA Science Inventory

Testing vehicles for emissions and fuel economy has traditionally been conducted with a single-axle chassis dynamometer. The 2006 SAE All Wheel Drive Symposium cited four wheel drive (4WD) and all wheel drive (AWD) sales as climbing from 20% toward 30% of a motor vehicle mar...

X-82 to Treat Age-related Macular Degeneration

ClinicalTrials.gov

2018-05-30

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

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

Function of multiple Lis-Homology domain/WD-40 repeat-containing proteins in feed-forward transcriptional repression by silencing mediator for retinoic and thyroid receptor/nuclear receptor corepressor complexes.

PubMed

Choi, Hyo-Kyoung; Choi, Kyung-Chul; Kang, Hee-Bum; Kim, Han-Cheon; Lee, Yoo-Hyun; Haam, Seungjoo; Park, Hyoung-Gi; Yoon, Ho-Geun

2008-05-01

Lis-homology (LisH) motifs are involved in protein dimerization, and the discovery of the conserved N-terminal LisH domain in transducin beta-like protein 1 and its receptor (TBL1 and TBLR1) led us to examine the role of this domain in transcriptional repression. Here we show that multiple beta-transducin (WD-40) repeat-containing proteins interact to form oligomers in solution and that oligomerization depends on the presence of the LisH domain in each protein. Repression of transcription, as assayed using Gal4 fusion proteins, also depended on the presence of the LisH domain, suggesting that oligomerization is a prerequisite for efficient transcriptional repression. Furthermore, we show that the LisH domain is responsible for the binding to the hypoacetylated histone H4 tail and for stable chromatin targeting by the nuclear receptor corepressor complex. Mutations in conserved residues in the LisH motif of TBL1 and TBLR1 block histone binding, oligomerization, and transcriptional repression, supporting the functional importance of the LisH motif in transcriptional repression. Our results indicate that another WD-40 protein, TBL3, also preferentially binds to the N-terminal domain of TBL1 and TBLR1, and forms oligomers with other WD-40 proteins. Finally, we observed that the WD-40 proteins RbAp46 and RbAp48 of the sin3A corepressor complex failed to dimerize. We also found the specific interaction UbcH/E2 with TBL1, but not RbAp46/48. Altogether, our results thus indicate that the presence of multiple LisH/WD-40 repeat containing proteins is exclusive to nuclear receptor corepressor/ silencing mediator for retinoic and thyroid receptor complexes compared with other class 1 histone deacetylase-containing corepessor complexes.

Expression of inducible heat shock proteins Hsp27 and Hsp70 in the visual pathway of rats subjected to various models of retinal ganglion cell injury.

PubMed

Chidlow, Glyn; Wood, John P M; Casson, Robert J

2014-01-01

Inducible heat shock proteins (Hsps) are upregulated in the central nervous system in response to a wide variety of injuries. Surprisingly, however, no coherent picture has emerged regarding the magnitude, duration and cellular distribution of inducible Hsps in the visual system following injury to retinal ganglion cells (RGCs). The current study sought, therefore, to achieve the following two objectives. The first aim of this study was to systematically characterise the patterns of Hsp27 and -70 expression in the retina and optic nerve in four discrete models of retinal ganglion cell (RGC) degeneration: axonal injury (ON crush), somato-dendritic injury (NMDA-induced excitotoxicity), chronic hypoperfusion (bilateral occlusion of the carotid arteris) and experimental glaucoma. The second aim was to document Hsp27 and -70 expression in the optic tract, the subcortical retinorecipient areas of the brain, and the visual cortex during Wallerian degeneration of RGC axons. Hsp27 was robustly upregulated in the retina in each injury paradigm, with the chronic models, 2VO and experimental glaucoma, displaying a more persistent Hsp27 transcriptional response than the acute models. Hsp27 expression was always associated with astrocytes and with a subset of RGCs in each of the models excluding NMDA. Hsp27 was present within astrocytes of the optic nerve/optic tract in control rats. During Wallerian degeneration, Hsp27 was upregulated in the optic nerve/optic tract and expressed de novo by astrocytes in the lateral geniculate nucleus and the stratum opticum of the superior colliculus. Conversely, the results of our study indicate Hsp70 was minimally induced in any of the models of injury, either in the retina, or in the optic nerve/optic tract, or in the subcortical, retinorecipient areas of the brain. The findings of the present study augment our understanding of the involvement of Hsp27 and Hsp70 in the response of the visual system to RGC degeneration.

Expression of Inducible Heat Shock Proteins Hsp27 and Hsp70 in the Visual Pathway of Rats Subjected to Various Models of Retinal Ganglion Cell Injury

PubMed Central

Chidlow, Glyn; Wood, John P. M.; Casson, Robert J.

2014-01-01

Inducible heat shock proteins (Hsps) are upregulated in the central nervous system in response to a wide variety of injuries. Surprisingly, however, no coherent picture has emerged regarding the magnitude, duration and cellular distribution of inducible Hsps in the visual system following injury to retinal ganglion cells (RGCs). The current study sought, therefore, to achieve the following two objectives. The first aim of this study was to systematically characterise the patterns of Hsp27 and −70 expression in the retina and optic nerve in four discrete models of retinal ganglion cell (RGC) degeneration: axonal injury (ON crush), somato-dendritic injury (NMDA-induced excitotoxicity), chronic hypoperfusion (bilateral occlusion of the carotid arteris) and experimental glaucoma. The second aim was to document Hsp27 and −70 expression in the optic tract, the subcortical retinorecipient areas of the brain, and the visual cortex during Wallerian degeneration of RGC axons. Hsp27 was robustly upregulated in the retina in each injury paradigm, with the chronic models, 2VO and experimental glaucoma, displaying a more persistent Hsp27 transcriptional response than the acute models. Hsp27 expression was always associated with astrocytes and with a subset of RGCs in each of the models excluding NMDA. Hsp27 was present within astrocytes of the optic nerve/optic tract in control rats. During Wallerian degeneration, Hsp27 was upregulated in the optic nerve/optic tract and expressed de novo by astrocytes in the lateral geniculate nucleus and the stratum opticum of the superior colliculus. Conversely, the results of our study indicate Hsp70 was minimally induced in any of the models of injury, either in the retina, or in the optic nerve/optic tract, or in the subcortical, retinorecipient areas of the brain. The findings of the present study augment our understanding of the involvement of Hsp27 and Hsp70 in the response of the visual system to RGC degeneration. PMID:25535743

Acute myelopathy selectively involving lumbar anterior horns following intranasal insufflation of ecstasy and heroin

PubMed Central

Riva, Nilo; Riva, Nilo; Morana, Paolo; Cerri, Federica; Gerevini, Simonetta; Amadio, Stefano; Formaglio, Fabio; Comi, Giancarlo; Comola, Mauro; Del Carro, Ubaldo

2009-01-01

We report a patient who developed acute myelopathy after intranasal insufflation of amphetamines and heroin. The functional prognosis was very poor; after 4 months, she remained paraplegic. MRI imaging showed selective T2 hyperintensity and intense enhancement confined to the spinal anterior horns and lumbar nerve roots and plexus. This unique MRI pattern, together with neurophysiological data, suggests that the pathological process at the first primary affected spinal anterior horns (SAH), conditioning motoneuron cell death, and then nerve roots and lumbar plexus as a consequence of wallerian degeneration PMID:21686691

Mismanagement of Wilson's disease as psychotic disorder.

PubMed

Bidaki, Reza; Zarei, Mina; Mirhosseini, S M Mahdy; Moghadami, Samar; Hejrati, Maral; Kohnavard, Marjan; Shariati, Behnam

2012-01-01

Wilson's disease (WD) or hepatolenticular degeneration is an inherited neurodegenerative disorder of copper metabolism (autosomal recessive, chromosome13). Psychiatric disorders in WD include dementia, characterized by mental slowness, poor concentration, and memory impairment. Symptoms may progress rapidly, especially in younger patients, but are more often gradual in development with periods of remission and exacerbation. Delusional disorder and schizophrenia-like psychosis are rare forms of psychiatric presentation. In this report, the patient with WD presented by psychosis symptoms and treated mistaken as schizophrenia for almost ten years. Although he has treated with antipsychotics, he had periods of remissions and relapses and never was symptoms free. Since psychosis can be the manifestation of medical diseases such as WD, overall view of these patients is necessary and medical diseases should be considered as a differential diagnosis.

Near-infrared Detection of WD 0806-661 B with the Hubble Space Telescope

NASA Astrophysics Data System (ADS)

Luhman, K. L.; Morley, C. V.; Burgasser, A. J.; Esplin, T. L.; Bochanski, J. J.

2014-10-01

WD 0806-661 B is one of the coldest known brown dwarfs (T eff = 300-345 K) based on previous mid-infrared photometry from the Spitzer Space Telescope. In addition, it is a benchmark for testing theoretical models of brown dwarfs because its age and distance are well constrained via its primary star (2 ± 0.5 Gyr, 19.2 ± 0.6 pc). We present the first near-infrared detection of this object, which has been achieved through F110W imaging (~Y + J) with the Wide Field Camera 3 on board the Hubble Space Telescope. We measure a Vega magnitude of m 110 = 25.70 ± 0.08, which implies J ~ 25.0. When combined with the Spitzer photometry, our estimate of J helps to better define the empirical sequence of the coldest brown dwarfs in M 4.5 versus J - [4.5]. The positions of WD 0806-661 B and other Y dwarfs in that diagram are best matched by the cloudy models of Burrows et al. and the cloudless models of Saumon et al., both of which employ chemical equilibrium. The calculations by Morley et al. for 50% cloud coverage differ only modestly from the data. Spectroscopy would enable a more stringent test of the models, but based on our F110W measurement, such observations are currently possible only with Hubble, and would require at least ~10 orbits to reach a signal-to-noise ratio of ~5. Based on observations made with the NASA/ESA Hubble Space Telescope through program 12815, obtained at the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., under NASA contract NAS 5-26555, and observations with the ESO Telescopes at Paranal Observatory under programs ID 089.C-0428 and ID 089.C-0597.

Indian hedgehog contributes to human cartilage endplate degeneration.

PubMed

Wang, Shaowei; Yang, Kun; Chen, Shuai; Wang, Jiying; Du, Guoqing; Fan, Shunwu; Wei, Lei

2015-08-01

To determine the role of Indian hedgehog (Ihh) signaling in human cartilage endplate (CEP) degeneration. CEP-degenerated tissues from patients with Modic I or II changes (n = 9 and 45, respectively) and normal tissues from vertebral burst fracture patients (n = 17) were collected. Specimens were either cut into slices for organ culture ex vivo or digested to isolate chondrocytes for cell culture in vitro. Ihh expression and the effect of Ihh on cartilage degeneration were determined by investigating degeneration markers in this study. Ihh expression and cartilage degeneration markers significantly increased in the Modic I and II groups. The expression of cartilage degeneration markers was positively correlated with degeneration severity. Gain-of-function for Ihh promoted expression of cartilage degeneration markers in vitro, while loss-of-function for Ihh inhibited their expression both in vitro and ex vivo. These findings demonstrated that Ihh promotes CEP degeneration. Blocking Ihh pathway has potential clinical usage for attenuating CEP degeneration.

Spectral thresholds in macular degeneration.

PubMed Central

Alvarez, S L; King-Smith, P E; Bhargava, S K

1983-01-01

Spectral sensitivities were measured in 18 normal eyes, 9 eyes in patients with senile macular degeneration, 4 patients with Stargardt's juvenile macular degeneration (JMD), and 2 patients without conclusive signs--that is, genetic or morphological abnormalities--to indicate the cause of loss of central vision. Spectral sensitivity, testing for which included measurements on white, yellow, purple, and blue backgrounds, is here used as an aid in differential diagnosis for cases of macular degeneration. PMID:6871142

Supernovae Ia in 2017: a long time delay from merger/accretion to explosion

NASA Astrophysics Data System (ADS)

Soker, Noam

2018-04-01

I use recent observational and theoretical studies of type Ia supernovae (SNe Ia) to further constrain the viable SN Ia scenarios and to argue that there must be a substantial time delay between the end of the merger of the white dwarf (WD) with a companion or the end of mass accretion on to the WD and its terminal explosion. This merger/accretion to explosion delay (MED) is required to allow the binary system to lead to a more or less spherical explosion and to prevent a pre-explosion ionizing radiation. Considering these recent results and the required MED, I conclude that the core degenerate scenario is somewhat more favorable over the other scenarios, followed by the double degenerate scenario. Although the single degenerate scenario is viable as well, it is less likely to account for common (normal) SN Ia. As all scenarios require substantial MED, the MED has turned from a disadvantage of the core degenerate scenario to a challenge that theory should overcome. I hope that the requirement for a MED will stimulate the discussion of the different SN Ia scenarios and the comparison of the scenarios to each other.

Counting Patterns in Degenerated Sequences

NASA Astrophysics Data System (ADS)

Nuel, Grégory

Biological sequences like DNA or proteins, are always obtained through a sequencing process which might produce some uncertainty. As a result, such sequences are usually written in a degenerated alphabet where some symbols may correspond to several possible letters (ex: IUPAC DNA alphabet). When counting patterns in such degenerated sequences, the question that naturally arises is: how to deal with degenerated positions ? Since most (usually 99%) of the positions are not degenerated, it is considered harmless to discard the degenerated positions in order to get an observation, but the exact consequences of such a practice are unclear. In this paper, we introduce a rigorous method to take into account the uncertainty of sequencing for biological sequences (DNA, Proteins). We first introduce a Forward-Backward approach to compute the marginal distribution of the constrained sequence and use it both to perform a Expectation-Maximization estimation of parameters, as well as deriving a heterogeneous Markov distribution for the constrained sequence. This distribution is hence used along with known DFA-based pattern approaches to obtain the exact distribution of the pattern count under the constraints. As an illustration, we consider a EST dataset from the EMBL database. Despite the fact that only 1% of the positions in this dataset are degenerated, we show that not taking into account these positions might lead to erroneous observations, further proving the interest of our approach.

Degenerate Cauchy numbers of the third kind.

PubMed

Pyo, Sung-Soo; Kim, Taekyun; Rim, Seog-Hoon

2018-01-01

Since Cauchy numbers were introduced, various types of Cauchy numbers have been presented. In this paper, we define degenerate Cauchy numbers of the third kind and give some identities for the degenerate Cauchy numbers of the third kind. In addition, we give some relations between four kinds of the degenerate Cauchy numbers, the Daehee numbers and the degenerate Bernoulli numbers.

Abnormal turning behaviour, GABAergic inhibition and the degeneration of astrocytes in ovine Tribulus terrestris motor neuron disease.

PubMed

Bourke, C A

2006-01-01

To observe the clinical signs of sheep affected by Tribulus terrestris motor neuron disease, to ascertain their response to striatal dopamine reducing drugs, and to examine their brains and spinal cords for microscopic changes. Twenty-eight sheep displaying well developed clinical signs of the disorder were observed. Twenty-two of these and 22 normal sheep were then randomly allocated to three groups and treated with diazepam, chlorpromazine, or xylazine. The time that it took an animal to return to a standing position following drug administration was recorded. The brain and complete spinal cord were removed from each of the other six affected sheep and fixed in formalin. Brains were sectioned throughout at 5 mm intervals and spinal cords at 10 mm intervals. All tissues were paraffin embedded and examined by light microscopy. A few samples were examined by electron microscopy. Clinical signs included postural asymmetry with a right:left body-side dominance within the group of 50:50, unequal flaccid paresis in the pelvic limbs, extensor muscle atrophy and adduction of the weaker pelvic limb, and concurrent abduction of the stronger. Forward motion followed either a fixed left or right hand curved trajectory, the sheep no longer being able to choose which. Twelve animals intermittently displayed rotational behaviour that involved loss of postural balance without locomotor activation. The administration of diazepam, chlorpromazine, or xylazine caused limb paresis and sedation, with affected sheep being slower than normal sheep by factors of 8, 3 and 2 respectively, to return to a standing position. There were scattered areas of mild Wallerian degeneration throughout the spinal cord, and in both the brain and the cord there were small numbers of degenerate astrocytes containing novel cytoplasmic pigment granules. Affected sheep had a dysfunction in the control of directional change and this provides a new insight into the normal mechanism for 'turning' in quadrupeds

Evolution of Degenerate Space-Time from Non-Degenerate Initial Value in Ashtekar's Formalism

NASA Astrophysics Data System (ADS)

Ma, Yongge; Liang, Canbin

1998-09-01

The possibility of evolving a degenerate space-time from non-degenerate initial value in Ashtekar's formalism is considered in a constructed example. It is found that this possibility could be realized in the time evolution given by Ashtekar's equations, but the topology change of space makes it fail to be a Cauchy evolution.

An adaptive actuator failure compensation scheme for two linked 2WD mobile robots

NASA Astrophysics Data System (ADS)

Ma, Yajie; Al-Dujaili, Ayad; Cocquempot, Vincent; El Badaoui El Najjar, Maan

2017-01-01

This paper develops a new adaptive compensation control scheme for two linked mobile robots with actuator failurs. A configuration with two linked two-wheel drive (2WD) mobile robots is proposed, and the modelling of its kinematics and dynamics are given. An adaptive failure compensation scheme is developed to compensate actuator failures, consisting of a kinematic controller and a multi-design integration based dynamic controller. The kinematic controller is a virtual one, and based on which, multiple adaptive dynamic control signals are designed which covers all possible failure cases. By combing these dynamic control signals, the dynamic controller is designed, which ensures system stability and asymptotic tracking properties. Simulation results verify the effectiveness of the proposed adaptive failure compensation scheme.

The Mr 140,000 Intermediate Chain of Chlamydomonas Flagellar Inner Arm Dynein Is a WD-Repeat Protein Implicated in Dynein Arm Anchoring

PubMed Central

Yang, Pinfen; Sale, Winfield S.

1998-01-01

Previous structural and biochemical studies have revealed that the inner arm dynein I1 is targeted and anchored to a unique site located proximal to the first radial spoke in each 96-nm axoneme repeat on flagellar doublet microtubules. To determine whether intermediate chains mediate the positioning and docking of dynein complexes, we cloned and characterized the 140-kDa intermediate chain (IC140) of the I1 complex. Sequence and secondary structural analysis, with particular emphasis on β-sheet organization, predicted that IC140 contains seven WD repeats. Reexamination of other members of the dynein intermediate chain family of WD proteins indicated that these polypeptides also bear seven WD/β-sheet repeats arranged in the same pattern along each intermediate chain protein. A polyclonal antibody was raised against a 53-kDa fusion protein derived from the C-terminal third of IC140. The antibody is highly specific for IC140 and does not bind to other dynein intermediate chains or proteins in Chlamydomonas flagella. Immunofluorescent microscopy of Chlamydomonas cells confirmed that IC140 is distributed along the length of both flagellar axonemes. In vitro reconstitution experiments demonstrated that the 53-kDa C-terminal fusion protein binds specifically to axonemes lacking the I1 complex. Chemical cross-linking indicated that IC140 is closely associated with a second intermediate chain in the I1 complex. These data suggest that IC140 contains domains responsible for the assembly and docking of the I1 complex to the doublet microtubule cargo. PMID:9843573

Diffusion tensor imaging of early changes in corpus callosum after acute cerebral hemisphere lesions in newborns.

PubMed

Righini, Andrea; Doneda, Chiara; Parazzini, Cecilia; Arrigoni, Filippo; Matta, Ursula; Triulzi, Fabio

2010-11-01

The main purpose was to investigate any early diffusion tensor imaging (DTI) changes in corpus callosum (CC) associated with acute cerebral hemisphere lesions in term newborns. We retrospectively analysed 19 cases of term newborns acutely affected by focal or multi-focal lesions: hypoxic-ischemic encephalopathy, hypoglycaemic encephalopathy, focal ischemic stroke and deep medullary vein associated lesions. DTI was acquired at 1.5 Tesla with dedicated neonatal coil. DTI metrics (apparent diffusion coefficient (ADC), fractional anisotropy (FA), axial λ(∐) and radial λ(⟂) diffusivity) were measured in the hemisphere lesions and in the CC. The control group included seven normal newborns. The following significant differences were found between patients and normal controls in the CC: mean ADC was lower in patients (0.88 SD 0.23 versus 1.18 SD 0.07 μm(2)/s) and so was mean FA (0.50 SD 0.1 versus 0.67 SD 0.05) and mean λ(∐) value (1.61 SD 0.52 versus 2.36 SD 0.14 μm(2)/s). In CC the percentage of ADC always diminished independently of lesion age (with one exception), whereas in hemisphere lesions, it was negative in earlier lesions, but exceeded normal values in the older lesions. CC may undergo early DTI changes in newborns with acute focal or multi-focal hemisphere lesions of different aetiology. Although a direct insult to CC cannot be totally ruled out, DTI changes in CC (in particular λ(∐)) may also be compatible with very early Wallerian degeneration or pre-Wallerian degeneration.

Are ovine fenugreek (Trigonella foenum-graecum) staggers and kangaroo gait of lactating ewes two clinically and pathologically similar nervous disorders?

PubMed

Bourke, Ca

2009-03-01

Fenugreek staggers has occurred in sheep in Victoria, as both an acute and a chronic syndrome. Signs included quadraparesis, a high stepping fore limb gait and a 'bunny-hopping' hind limb gait. Changes consistent with acute oedema were found in the brain and spinal cord of acute cases, and Wallerian degeneration in the peripheral nerves of chronic cases. Kangaroo gait occurred in ewes in New South Wales, and the clinical signs and microscopic changes were remarkably similar to those of fenugreek staggers. Although the diet associated with each is different the causal agent may be the same.

Caught in the Act: UV spectroscopy of the ejecta-companion collision from a type Ia supernova

NASA Astrophysics Data System (ADS)

Kulkarni, Shrinivas

2017-08-01

There is now significant observational evidence for both of the leading models proposed to explain the origin of type Ia supernovae (SNe). While the majority of SNe Ia likely come from the merger of two white dwarf (WD) stars (known as the double degenerate model), a significant fraction are the result of a WD accreting mass from the hydrogen envelope of a binary companion (known as the single degenerate model). Eventually, as the accreting WD approaches the Chandrasekhar limit, the onset of unstable burning occurs ultimately leading to a thermonuclear explosion. With observational evidence for both channels firmly in place, future efforts to better understand the progenitors of SNe Ia will require detailed studies of individual systems.A fundamental expectation of the single degenerate model is that the collision of the blast wave with the donor star will produce a unique signature - a bright and rapidly declining UV pulse. This UV signal has only been previously observed in a single SN. Here, we propose to undertake STIS UV spectroscopy of one infant type Ia SN with similarly strong UV emission. The spectra will provide unique and detailed insight into the ejecta-companion interaction while also probing the chemical abundance of the outermost layers of the SN ejecta. The ejecta-companion signature is only visible UV, and HST/STIS is the only instrument capable of obtaining the spectra that are needed as a detailed probe of the interaction physics.

The Solar Neighborhood. XXXIX. Parallax Results from the CTIOPI and NOFS Programs: 50 New Members of the 25 parsec White Dwarf Sample

NASA Astrophysics Data System (ADS)

Subasavage, John P.; Jao, Wei-Chun; Henry, Todd J.; Harris, Hugh C.; Dahn, Conard C.; Bergeron, P.; Dufour, P.; Dunlap, Bart H.; Barlow, Brad N.; Ianna, Philip A.; Lépine, Sébastien; Margheim, Steven J.

2017-07-01

We present 114 trigonometric parallaxes for 107 nearby white dwarf (WD) systems from both the Cerro Tololo Inter-American Observatory Parallax Investigation (CTIOPI) and the U. S. Naval Observatory Flagstaff Station (NOFS) parallax programs. Of these, 76 parallaxes for 69 systems were measured by the CTIOPI program and 38 parallaxes for as many systems were measured by the NOFS program. A total of 50 systems are confirmed to be within the 25-pc horizon of interest. Coupled with a spectroscopic confirmation of a common proper-motion companion to a Hipparcos star within 25 pc as well as confirmation parallax determinations for two WD systems included in the recently released Tycho Gaia Astrometric Solution catalog, we add 53 new systems to the 25-pc WD sample—a 42% increase. Our sample presented here includes four strong candidate halo systems, a new metal-rich DAZ WD, a confirmation of a recently discovered nearby short-period (P = 2.85 hr) double degenerate, a WD with a new astrometric perturbation (long period, unconstrained with our data), and a new triple system where the WD companion main-sequence star has an astrometric perturbation (P ˜ 1.6 year).

Kraepelin and degeneration theory.

PubMed

Hoff, Paul

2008-06-01

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

Reprogramming the metabolome rescues retinal degeneration.

PubMed

Park, Karen Sophia; Xu, Christine L; Cui, Xuan; Tsang, Stephen H

2018-05-01

Metabolomics studies in the context of ophthalmology have largely focused on identifying metabolite concentrations that characterize specific retinal diseases. Studies involving mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy have shown that individuals suffering from retinal diseases exhibit metabolic profiles that markedly differ from those of control individuals, supporting the notion that metabolites may serve as easily identifiable biomarkers for specific conditions. An emerging branch of metabolomics resulting from biomarker studies, however, involves the study of retinal metabolic dysfunction as causes of degeneration. Recent publications have identified a number of metabolic processes-including but not limited to glucose and oxygen metabolism-that, when perturbed, play a role in the degeneration of photoreceptor cells. As a result, such studies have led to further research elucidating methods for prolonging photoreceptor survival in an effort to halt degeneration in its early stages. This review will explore the ways in which metabolomics has deepened our understanding of the causes of retinal degeneration and discuss how metabolomics can be used to prevent retinal degeneration from progressing to its later disease stages.

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.

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

PubMed Central

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

2012-01-01

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

Cortical-basal ganglionic degeneration.

PubMed

Riley, D E; Lang, A E; Lewis, A; Resch, L; Ashby, P; Hornykiewicz, O; Black, S

1990-08-01

We report our experience with 15 patients believed to have cortical-basal ganglionic degeneration. The clinical picture is distinctive, comprising features referable to both cortical and basal ganglionic dysfunction. Characteristic manifestations include cortical sensory loss, focal reflex myoclonus, "alien limb" phenomena, apraxia, rigidity and akinesia, a postural-action tremor, limb dystonia, hyperreflexia, and postural instability. The asymmetry of symptoms and signs is often striking. Brain imaging may demonstrate greater abnormalities contralateral to the more affected side. Postmortem studies in 2 patients revealed the characteristic pathologic features of swollen, poorly staining (achromatic) neurons and degeneration of cerebral cortex and substantia nigra. Biochemical analysis of 1 brain showed a severe, diffuse loss of dopamine in the striatum. This condition is more frequent than previously believed, and the diagnosis can be predicted during life on the basis of clinical findings. However, as with other "degenerative" diseases of the nervous system, a definitive diagnosis of cortical-basal ganglionic degeneration requires confirmation by autopsy.

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

Histopathology of cryoballoon ablation-induced phrenic nerve injury.

PubMed

Andrade, Jason G; Dubuc, Marc; Ferreira, Jose; Guerra, Peter G; Landry, Evelyn; Coulombe, Nicolas; Rivard, Lena; Macle, Laurent; Thibault, Bernard; Talajic, Mario; Roy, Denis; Khairy, Paul

2014-02-01

Hemi-diaphragmatic paralysis is the most common complication associated with cryoballoon ablation for atrial fibrillation, yet the histopathology of phrenic nerve injury has not been well described. A preclinical randomized study was conducted to characterize the histopathology of phrenic nerve injury induced by cryoballoon ablation and assess the potential for electromyographic (EMG) monitoring to limit phrenic nerve damage. Thirty-two dogs underwent cryoballoon ablation of the right superior pulmonary vein with the objective of inducing phrenic nerve injury. Animals were randomized 1:1 to standard monitoring (i.e., interruption of ablation upon reduction in diaphragmatic motion) versus EMG guidance (i.e., cessation of ablation upon a 30% reduction in the diaphragmatic compound motor action potential [CMAP] amplitude). The acute procedural endpoint was achieved in all dogs. Phrenic nerve injury was characterized by Wallerian degeneration, with subperineural injury to large myelinated axons and evidence of axonal regeneration. The degree of phrenic nerve injury paralleled the reduction in CMAP amplitude (P = 0.007). Animals randomized to EMG guidance had a lower incidence of acute hemi-diaphragmatic paralysis (50% vs 100%; P = 0.001), persistent paralysis at 30 days (21% vs 75%; multivariate odds ratio 0.12, 95% confidence interval [0.02, 0.69], P = 0.017), and a lesser severity of histologic injury (P = 0.001). Mature pulmonary vein ablation lesion characteristics, including circumferentiality and transmurality, were similar in both groups. Phrenic nerve injury induced by cryoballoon ablation is axonal in nature and characterized by Wallerian degeneration, with potential for recovery. An EMG-guided approach is superior to standard monitoring in limiting phrenic nerve damage. © 2013 Wiley Periodicals, Inc.

The curious ability of PEG-fusion technologies to restore lost behaviors after nerve severance

PubMed Central

Bittner, G.D.; Sengelaub, D.R.; Trevino, R.C.; Peduzzi, J.D.; Mikesh, M.; Ghergherehchi, C.L.; Schallert, T.; Thayer, W.P.

2016-01-01

Traumatic injuries to PNS and CNS axons are not uncommon. Restoration of lost behaviors following severance of mammalian peripheral nerve axons (PNAs) relies on regeneration by slow outgrowths and is typically poor or nonexistent if after ablation or injuries close to the soma. Behavioral recovery after severing spinal tract axons (STAs) is poor because STAs do not naturally regenerate. Current techniques to enhance PNA and/or STA regeneration have had limited success and do not prevent the onset of Wallerian degeneration of severed distal segments. This review describes the use of a recently-developed polyethylene glycol (PEG)-fusion technology combining concepts in biochemical engineering, cell biology and clinical microsurgery. Within minutes after micro-suturing carefully-trimmed cut ends and applying a well-specified sequence of solutions, PEG-fused axons exhibit morphological continuity (assessed by intra-axonal dye diffusion) and electrophysiological continuity (assessed by conduction of action potentials) across the lesion site. Wallerian degeneration of PEG-fused PNAs is greatly reduced as measured by counts of sensory and/or motor axons, and maintenance of axonal diameters and neuromuscular synapses. After PEG-fusion repair, cut- or crush-severed or ablated PNAs or crush-severed STAs rapidly (within days to weeks), more completely, and permanently restore PNA- or STA-mediated behaviors compared to non-treated or conventionally-treated animals. PEG-fusion success is enhanced or decreased by applying anti-oxidants or oxidants, trimming cut ends or stretching axons, exposure to Ca2+-free or - containing solutions, respectively. PEG-fusion technology employs surgical techniques and chemicals already used by clinicians and has the potential to produce a paradigm-shift in the treatment of traumatic injuries to PNAs and STAs. PMID:26525605

The WIRED Survey. 2; Infrared Excesses in the SDSS DR7 White Dwarf Catalog

NASA Technical Reports Server (NTRS)

Debes, John H.; Hoard, D. W.; Wachter, Stefanie; Leisawitz, David T.; Cohen, Martin

2011-01-01

With the launch of the Wide-field Infrar.ed Survey Explorer (WISE), a new era of detecting planetary debris and brown dwarfs (BDs) around white dwarfs (WDs) has begun with the WISE InfraRed Excesses around Degenerates (WIRED) Survey. The WIRED Survey is sensitive to substellar objects and dusty debris around WDs out to distances exceeding 100 pc, well beyond the completeness level of local WDs. In this paper, we present a cross-correlation of the preliminary Sloan Digital Sky Survey (SDSS) Data Release 7 (DR7) WD catalog between the WISE, Two-Micron All Sky Survey (2MASS), UKIRT Infrared Deep Sky Survey (UKIDSS), and SDSS DR7 photometric catalogs. From -18,000 input targets, there are WISE detections comprising 344 "naked" WDs (detection of the WD photosphere only), 1020 candidate WD+M dwarf binaries, 42 candidate WD+BD systems, 52 candidate WD+dust disk systems, and 69 targets with indeterminate infrared excess. We classified all of the detected targets through spectral energy distribution model fitting of the merged optical, near-IR, and WISE photometry. Some of these detections could be the result of contaminating sources within the large (approx. 6") WISE point-spread function; we make a preliminary estimate for the rates of contamination for our WD+BD and WD+disk candidates and provide notes for each target of interest. Each candidate presented here should be confirmed with higher angular resolution infrared imaging or infrared spectroscopy. We also present an overview of the observational characteristics of the detected WDs in the WISE photometric bands, including the relative frequencies of candidate WD+M, WD+BD, and WD+disk systems.

The Solar Neighborhood. XXXIX. Parallax Results from the CTIOPI and NOFS Programs: 50 New Members of the 25 parsec White Dwarf Sample

DOE Office of Scientific and Technical Information (OSTI.GOV)

Subasavage, John P.; Harris, Hugh C.; Dahn, Conard C.

We present 114 trigonometric parallaxes for 107 nearby white dwarf (WD) systems from both the Cerro Tololo Inter-American Observatory Parallax Investigation (CTIOPI) and the U. S. Naval Observatory Flagstaff Station (NOFS) parallax programs. Of these, 76 parallaxes for 69 systems were measured by the CTIOPI program and 38 parallaxes for as many systems were measured by the NOFS program. A total of 50 systems are confirmed to be within the 25-pc horizon of interest. Coupled with a spectroscopic confirmation of a common proper-motion companion to a Hipparcos star within 25 pc as well as confirmation parallax determinations for two WD systems included inmore » the recently released Tycho Gaia Astrometric Solution catalog, we add 53 new systems to the 25-pc WD sample—a 42% increase. Our sample presented here includes four strong candidate halo systems, a new metal-rich DAZ WD, a confirmation of a recently discovered nearby short-period ( P  = 2.85 hr) double degenerate, a WD with a new astrometric perturbation (long period, unconstrained with our data), and a new triple system where the WD companion main-sequence star has an astrometric perturbation ( P  ∼ 1.6 year).« less

Macular Degeneration

MedlinePlus

... 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 causes vision loss. Treatment can ...

Formation of Degenerate Band Gaps in Layered Systems

PubMed Central

Ignatov, Anton I.; Merzlikin, Alexander M.; Levy, Miguel; Vinogradov, Alexey P.

2012-01-01

In the review, peculiarities of spectra of one-dimensional photonic crystals made of anisotropic and/or magnetooptic materials are considered. The attention is focused on band gaps of a special type—the so called degenerate band gaps which are degenerate with respect to polarization. Mechanisms of formation and properties of these band gaps are analyzed. Peculiarities of spectra of photonic crystals that arise due to the linkage between band gaps are discussed. Particularly, it is shown that formation of a frozen mode is caused by linkage between Brillouin and degenerate band gaps. Also, existence of the optical Borrmann effect at the boundaries of degenerate band gaps and optical Tamm states at the frequencies of degenerate band gaps are analyzed. PMID:28817024

Signatures of progenitors of Type Ia supernovae

NASA Astrophysics Data System (ADS)

Hoeflich, P.; Chakraborty, S.; Comaskey, W.; Fisher, A.; Hristov, B.; Collins, D.; Diamond, T. R.; Dragulin, P.; Hsiao, E. Y.; Sadler, B.

Thermonuclear Supernovae (SNe Ia) are one of the building blocks of modern cosmology and laboratories for the explosion physics of White Dwarf star/s (WD) in close binary systems. The second star may be a WD (double degenerate systems, DD), or a non-degenerated star (SD) with a main sequence star, red giant or a helium star as companion \\citep{branch95,nomoto03,wang2012}. Light curves and spectra of the explosion look similar because a 'stellar amnesia' \\citep{h06}. Basic nuclear physics determines the progenitor structure and the explosion physics, breaking the link between progenitor evolution, and the explosion, resulting in three main classes of explosion scenarios: a) dynamical merging of two WD and a heating on time scales of seconds \\citep{webbink84,isern11}, b) surface helium detonations on top of a WD which ignite the central C/O by a detonation wave traveling inwards \\citep{n82,hk96,Kromer2010}; c) compressional heating in an accreting WD approaching the Chandrasekar mass on time of up to 108 years which may originated from SD and DD systems \\citep{WI73,Piersanti2004}. Simulations of the explosions depend on the inital conditions at the onset of the explosions, namely the mass and angular momentum of the WD(s). For all scenarios, diversity in SNe Ia must be expected because the WD originates from a range of Main Sequence masses (MMS < 8 M_⊙) and metallicities Z. Moreover, there is growing evidence that magnetic fields B may have to be added to the 'mix'. Only with recent advances in observations ranging from X-ray to radio, high precision spectroscopy, polarimetry and photometry and in the time-domain astronomy we obtain constraints for progenitor, on the explosion scenarios and links emerge between the progenitors and their environment with LCs and spectral signatures needed for high precision cosmology. It is too early to give final answers but we present our personal view. We will give some examples from the theory point of view and discuss

Does corticobasal degeneration exist? A clinicopathological re-evaluation.

PubMed

Ling, Helen; O'Sullivan, Sean S; Holton, Janice L; Revesz, Tamas; Massey, Luke A; Williams, David R; Paviour, Dominic C; Lees, Andrew J

2010-07-01

The pathological findings of corticobasal degeneration are associated with several distinct clinical syndromes, and the corticobasal syndrome has been linked with a number of diverse pathologies. We have reviewed all the archival cases in the Queen Square Brain Bank for Neurological Disorders over a 20-year period with either a clinical diagnosis of corticobasal syndrome or pathological diagnosis of corticobasal degeneration in an attempt to identify the main diagnostic pitfalls. Of 19 pathologically confirmed corticobasal degeneration cases, only five had been diagnosed correctly in life (sensitivity=26.3%) and four of these had received an alternative earlier diagnosis. All five of these had a unilateral presentation, clumsy useless limb, limb apraxia and myoclonus, four had cortical sensory impairment and focal limb dystonia and three had an alien limb. Eight cases of corticobasal degeneration had been clinically diagnosed as progressive supranuclear palsy, all of whom had vertical supranuclear palsy and seven had falls within the first 2 years. On the other hand, of 21 cases with a clinical diagnosis of corticobasal syndrome, only five had corticobasal degeneration pathology, giving a positive predictive value of 23.8%; six others had progressive supranuclear palsy pathology, five had Alzheimer's disease and the remaining five had other non-tau pathologies. Corticobasal degeneration can present very commonly with a clinical picture closely resembling classical progressive supranuclear palsy or Richardson's syndrome, and we propose the term corticobasal degeneration-Richardson's syndrome for this subgroup. Cases of corticobasal degeneration-Richardson's syndrome have delayed onset of vertical supranuclear gaze palsy (>3 years after onset of first symptom) and the infrequent occurrence of predominant downgaze abnormalities, both of which can be helpful pointers to their underlying corticobasal degeneration pathology. Fourty-two per cent of corticobasal

Degenerate r-Stirling Numbers and r-Bell Polynomials

NASA Astrophysics Data System (ADS)

Kim, T.; Yao, Y.; Kim, D. S.; Jang, G.-W.

2018-01-01

The purpose of this paper is to exploit umbral calculus in order to derive some properties, recurrence relations, and identities related to the degenerate r-Stirling numbers of the second kind and the degenerate r-Bell polynomials. Especially, we will express the degenerate r-Bell polynomials as linear combinations of many well-known families of special polynomials.

VizieR Online Data Catalog: The ELM survey. VI. 11 new ELM WD binaries (Gianninas+, 2015)

NASA Astrophysics Data System (ADS)

Gianninas, A.; Kilic, M.; Brown, W. R.; Canton, P.; Kenyon, S. J.

2016-02-01

We used the 6.5m MMT telescope equipped with the Blue Channel spectrograph, the 200 inch Hale telescope equipped with the Double spectrograph, the Kitt Peak National Observatory 4m telescope equipped with the R-C spectrograph, and more recently with Kitt Peak Ohio State Multi-Object Spectrograph (KOSMOS), to obtain spectroscopy of our 11 targets in several observing runs. We have also been obtaining radial-velocity measurements for candidates from other sources including the Large Sky Area Multi-Object Spectroscopy Telescope (LAMOST). Those 11 new Extremely low-mass white dwarf (ELM WD) binaries bring the total of ELM WDs identified by the ELM Survey up to 73. (4 data files).

Phagocyte dysfunction, tissue aging and degeneration

PubMed Central

2013-01-01

Immunologically-silent phagocytosis of apoptotic cells is critical to maintaining tissue homeostasis and innate immune balance. Aged phagocytes reduce their functional activity, leading to accumulation of unphagocytosed debris, chronic sterile inflammation and exacerbation of tissue aging and damage. Macrophage dysfunction plays an important role in immunosenescence. Microglial dysfunction has been linked to age-dependent neurodegenerations. Retinal pigment epithelial (RPE) cell dysfunction has been implicated in the pathogenesis of age-related macular degeneration (AMD). Despite several reports on the characterization of aged phagocytes, the role of phagocyte dysfunction in tissue aging and degeneration is yet to be fully appreciated. Lack of knowledge of molecular mechanisms by which aging reduces phagocyte function has hindered our capability to exploit the therapeutic potentials of phagocytosis for prevention or delay of tissue degeneration. This review summarizes our current knowledge of phagocyte dysfunction in aged tissues and discusses possible links to age-related diseases. We highlight the challenges to decipher the molecular mechanisms, present new research approaches and envisage future strategies to prevent phagocyte dysfunction, tissue aging and degeneration. PMID:23748186

Phagocyte dysfunction, tissue aging and degeneration.

PubMed

Li, Wei

2013-09-01

Immunologically-silent phagocytosis of apoptotic cells is critical to maintaining tissue homeostasis and innate immune balance. Aged phagocytes reduce their functional activity, leading to accumulation of unphagocytosed debris, chronic sterile inflammation and exacerbation of tissue aging and damage. Macrophage dysfunction plays an important role in immunosenescence. Microglial dysfunction has been linked to age-dependent neurodegenerations. Retinal pigment epithelial (RPE) cell dysfunction has been implicated in the pathogenesis of age-related macular degeneration (AMD). Despite several reports on the characterization of aged phagocytes, the role of phagocyte dysfunction in tissue aging and degeneration is yet to be fully appreciated. Lack of knowledge of molecular mechanisms by which aging reduces phagocyte function has hindered our capability to exploit the therapeutic potentials of phagocytosis for prevention or delay of tissue degeneration. This review summarizes our current knowledge of phagocyte dysfunction in aged tissues and discusses possible links to age-related diseases. We highlight the challenges to decipher the molecular mechanisms, present new research approaches and envisage future strategies to prevent phagocyte dysfunction, tissue aging and degeneration. Copyright © 2013 Elsevier B.V. All rights reserved.

Degenerate pressure driven self-gravito-acoustic solitary waves in a self-gravitating degenerate quantum plasma system

NASA Astrophysics Data System (ADS)

Mamun, A. A.

2018-02-01

A general (but realistic) self-gravitating degenerate quantum plasma system (SG-DQPS) containing inertialess degenerate electron species, inertial degenerate light, and heavy ion/nucleus species is considered to examine the possibility for the existence of degenerate pressure driven self-gravito-acoustic (DPD-SGA) solitary waves (SWs) formed in such a SG-DQPS. The pseudo-potential approach, which is valid for the arbitrary amplitude DPD-SGA SWs, is employed. It is found that depending on the value of the number density of heavy ion/nucleus species, the SG-DQPS under consideration supports the existence of positive or the coexistence of positive and negative DPD-SGA SWs. The basic features (polarity, amplitude, and width) of both positive and negative DPD-SGA SWs are found to be significantly modified by the dynamics of heavy ion/nucleus species. The theoretical investigation presented here is so general that it can be applied not only in astrophysical SG-DQPSs (such as white dwarf and neutron star SG-DQPSs), but also in laboratory SG-DQPSs (viz., solid density and laser-produced SG-DQPSs) to identify the salient features of the DPD-SGA SWs formed in them.

Human disc degeneration is associated with increased MMP 7 expression.

PubMed

Le Maitre, C L; Freemont, A J; Hoyland, J A

2006-01-01

During intervertebral disc (IVD) degeneration, normal matrix synthesis decreases and degradation of disc matrix increases. A number of proteases that are increased during disc degeneration are thought to be involved in its pathogenesis. Matrix metalloproteinase 7 (MMP 7) (Matrilysin, PUMP-1) is known to cleave the major matrix molecules found within the IVD, i.e., the proteoglycan aggrecan and collagen type II. To date, however, it is not known how its expression changes with degeneration or its exact location. We investigated the localization of MMP 7 in human, histologically graded, nondegenerate, degenerated and prolapsed discs to ascertain whether MMP 7 is up-regulated during disc degeneration. Samples of human IVD tissue were fixed in neutral buffered formalin, embedded in paraffin, and sections stained with hematoxylin and eosin to score the degree of morphological degeneration. Immunohistochemistry was performed to localize MMP 7 in 41 human IVDs with varying degrees of degeneration. We found that the chondrocyte-like cells of the nucleus pulposus and inner annulus fibrosus were MMP 7 immunopositive; little immunopositivity was observed in the outer annulus. Nondegenerate discs showed few immunopositive cells. A significant increase in the proportion of MMP 7 immunopositive cells was seen in the nucleus pulposus of discs classified as showing intermediate levels of degeneration and a further increase was seen in discs with severe degeneration. Prolapsed discs showed more MMP 7 immunopositive cells compared to nondegenerated discs, but fewer than those seen in cases of severe degeneration.

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

Arbitrary electron acoustic waves in degenerate dense plasmas

NASA Astrophysics Data System (ADS)

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

2017-05-01

A theoretical investigation is carried out of the nonlinear dynamics of electron-acoustic waves in a collisionless and unmagnetized plasma whose constituents are non-degenerate cold electrons, ultra-relativistic degenerate electrons, and stationary ions. A dispersion relation is derived for linear EAWs. An energy integral equation involving the Sagdeev potential is derived, and basic properties of the large amplitude solitary structures are investigated in such a degenerate dense plasma. It is shown that only negative large amplitude EA solitary waves can exist in such a plasma system. The present analysis may be important to understand the collective interactions in degenerate dense plasmas, occurring in dense astrophysical environments as well as in laser-solid density plasma interaction experiments.

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

Wet Macular Degeneration

MedlinePlus

... has a hereditary component. Researchers have identified several genes related to developing the condition. Smoking. Smoking cigarettes or being regularly exposed to smoke significantly increases your risk of macular degeneration. Obesity. Research indicates that being obese increases the chance ...

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

Polyethylene glycol treated allografts not tissue matched nor immunosuppressed rapidly repair sciatic nerve gaps, maintain neuromuscular functions, and restore voluntary behaviors in female rats.

PubMed

Mikesh, Michelle; Ghergherehchi, Cameron L; Rahesh, Sina; Jagannath, Karthik; Ali, Amir; Sengelaub, Dale R; Trevino, Richard C; Jackson, David M; Tucker, Haley O; Bittner, George D

2018-07-01

Many publications report that ablations of segments of peripheral nerves produce the following unfortunate results: (1) Immediate loss of sensory signaling and motor control; (2) rapid Wallerian degeneration of severed distal axons within days; (3) muscle atrophy within weeks; (4) poor behavioral (functional) recovery after many months, if ever, by slowly-regenerating (∼1mm/d) axon outgrowths from surviving proximal nerve stumps; and (5) Nerve allografts to repair gap injuries are rejected, often even if tissue matched and immunosuppressed. In contrast, using a female rat sciatic nerve model system, we report that neurorrhaphy of allografts plus a well-specified-sequence of solutions (one containing polyethylene glycol: PEG) successfully addresses each of these problems by: (a) Reestablishing axonal continuity/signaling within minutes by nonspecific ally PEG-fusing (connecting) severed motor and sensory axons across each anastomosis; (b) preventing Wallerian degeneration by maintaining many distal segments of inappropriately-reconnected, PEG-fused axons that continuously activate nerve-muscle junctions; (c) maintaining innervation of muscle fibers that undergo much less atrophy than otherwise-denervated muscle fibers; (d) inducing remarkable behavioral recovery to near-unoperated levels within days to weeks, almost certainly by CNS and PNS plasticities well-beyond what most neuroscientists currently imagine; and (e) preventing rejection of PEG-fused donor nerve allografts with no tissue matching or immunosuppression. Similar behavioral results are produced by PEG-fused autografts. All results for Negative Control allografts agree with current neuroscience data 1-5 given above. Hence, PEG-fusion of allografts for repair of ablated peripheral nerve segments expand on previous observations in single-cut injuries, provoke reconsideration of some current neuroscience dogma, and further extend the potential of PEG-fusion in clinical practice. © 2018 Wiley Periodicals

Spinal cord compression in two related Ursus arctos horribilis.

PubMed

Thomovsky, Stephanie A; Chen, Annie V; Roberts, Greg R; Schmidt, Carrie E; Layton, Arthur W

2012-09-01

Two 15-yr-old grizzly bear littermates were evaluated within 9 mo of each other with the symptom of acute onset of progressive paraparesis and proprioceptive ataxia. The most significant clinical examination finding was pelvic limb paresis in both bears. Magnetic resonance examinations of both bears showed cranial thoracic spinal cord compression. The first bear had left-sided extradural, dorsolateral spinal cord compression at T3-T4. Vertebral canal stenosis was also observed at T2-T3. Images of the second bear showed lateral spinal cord compression from T2-T3 to T4-T5. Intervertebral disk disease and associated spinal cord compression was also observed at T2-T3 and T3-T4. One grizzly bear continued to deteriorate despite reduced exercise, steroid, and antibiotic therapy. The bear was euthanized, and a necropsy was performed. The postmortem showed a spinal ganglion cyst that caused spinal cord compression at the level of T3-T4. Wallerian-like degeneration was observed from C3-T6. The second bear was prescribed treatment that consisted of a combination of reduced exercise and steroid therapy. He continued to deteriorate with these medical therapies and was euthanized 4 mo after diagnosis. A necropsy showed hypertrophy and protrusion of the dorsal longitudinal ligament at T2-T3 and T3-T4, with resulting spinal cord compression in this region. Wallerian-like degeneration was observed from C2-L1. This is one of few case reports that describes paresis in bears. It is the only case report, to the authors' knowledge, that describes spinal magnetic resonance imaging findings in a grizzly bear and also the only report that describes a cranial thoracic myelopathy in two related grizzly bears with neurologic signs.

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.

Mutations in ABCR (ABCA4) in patients with Stargardt macular degeneration or cone-rod degeneration.

PubMed

Briggs, C E; Rucinski, D; Rosenfeld, P J; Hirose, T; Berson, E L; Dryja, T P

2001-09-01

To determine the spectrum of ABCR mutations associated with Stargardt macular degeneration and cone-rod degeneration (CRD). One hundred eighteen unrelated patients with recessive Stargardt macular degeneration and eight with recessive CRD were screened for mutations in ABCR (ABCA4) by single-strand conformation polymorphism analysis. Variants were characterized by direct genomic sequencing. Segregation analysis was performed on the families of 20 patients in whom at least two or more likely pathogenic sequence changes were identified. The authors found 77 sequence changes likely to be pathogenic: 21 null mutations (15 novel), 55 missense changes (26 novel), and one deletion of a consensus glycosylation site (also novel). Fifty-two patients with Stargardt macular degeneration (44% of those screened) and five with CRD each had two of these sequence changes or were homozygous for one of them. Segregation analyses in the families of 19 of these patients were informative and revealed that the index cases and all available affected siblings were compound heterozygotes or homozygotes. The authors found one instance of an apparently de novo mutation, Ile824Thr, in a patient. Thirty-seven (31%) of the 118 patients with Stargardt disease and one with CRD had only one likely pathogenic sequence change. Twenty-nine patients with Stargardt disease (25%) and two with CRD had no identified sequence changes. This report of 42 novel mutations brings the growing number of identified likely pathogenic sequence changes in ABCR to approximately 250.

Spectroscopic Evolution of Disintegrating Planetesimals: Minute to Month Variability in the Circumstellar Gas Associated with WD 1145+017

DOE Office of Scientific and Technical Information (OSTI.GOV)

Redfield, Seth; Cauley, P. Wilson; Duvvuri, Girish M.

With the recent discovery of transiting planetary material around WD 1145+017, a critical target has been identified that links the evolution of planetary systems with debris disks and their accretion onto the star. We present a series of observations, five epochs over a year, taken with Keck and the VLT, which for the first time show variability of circumstellar absorption in the gas disk surrounding WD 1145+017 on timescales of minutes to months. Circumstellar absorption is measured in more than 250 lines of 14 ions among 10 different elements associated with planetary composition, e.g., O, Mg, Ca, Ti, Cr, Mn,more » Fe, and Ni. Broad circumstellar gas absorption with a velocity spread of 225 km s{sup −1} is detected, but over the course of a year blueshifted absorption disappears, while redshifted absorption systematically increases. A correlation of equivalent width and oscillator strength indicates that the gas is not highly optically thick (median τ ≈ 2). We discuss simple models of an eccentric disk coupled with magnetospheric accretion to explain the basic observed characteristics of these high-resolution and high signal-to-noise observations. Variability is detected on timescales of minutes in the two most recent observations, showing a loss of redshifted absorption for tens of minutes, coincident with major transit events and consistent with gas hidden behind opaque transiting material. This system currently presents a unique opportunity to learn how the gas causing the spectroscopic, circumstellar absorption is associated with the ongoing accretion evidenced by photospheric contamination, as well as the transiting planetary material detected in photometric observations.« less

Once in a blue moon: detection of `bluing' during debris transits in the white dwarf WD 1145+017

NASA Astrophysics Data System (ADS)

Hallakoun, N.; Xu, S.; Maoz, D.; Marsh, T. R.; Ivanov, V. D.; Dhillon, V. S.; Bours, M. C. P.; Parsons, S. G.; Kerry, P.; Sharma, S.; Su, K.; Rengaswamy, S.; Pravec, P.; Kušnirák, P.; Kučáková, H.; Armstrong, J. D.; Arnold, C.; Gerard, N.; Vanzi, L.

2017-08-01

The first transiting planetesimal orbiting a white dwarf was recently detected in K2 data of WD 1145+017 and has been followed up intensively. The multiple, long and variable transits suggest the transiting objects are dust clouds, probably produced by a disintegrating asteroid. In addition, the system contains circumstellar gas, evident by broad absorption lines, mostly in the u΄ band, and a dust disc, indicated by an infrared excess. Here we present the first detection of a change in colour of WD 1145+017 during transits, using simultaneous multiband fast-photometry ULTRACAM measurements over the u΄g΄r΄I΄ bands. The observations reveal what appears to be 'bluing' during transits; transits are deeper in the redder bands, with a u΄ - r΄ colour difference of up to ˜-0.05 mag. We explore various possible explanations for the bluing, including limb darkening or peculiar dust properties. 'Spectral' photometry obtained by integrating over bandpasses in the spectroscopic data in and out of transit, compared to the photometric data, shows that the observed colour difference is most likely the result of reduced circumstellar absorption in the spectrum during transits. This indicates that the transiting objects and the gas share the same line of sight and that the gas covers the white dwarf only partially, as would be expected if the gas, the transiting debris and the dust emitting the infrared excess are part of the same general disc structure (although possibly at different radii). In addition, we present the results of a week-long monitoring campaign of the system using a global network of telescopes.

Corticobasal degeneration.

PubMed

Stover, N P; Watts, R L

2001-01-01

Corticobasal degeneration (CBG) is an increasingly recognized neurodegenerative disease with both motor and cognitive dysfunction. The diagnosis is probably underestimated because of the heterogeneity of clinical features, overlap with symptoms, and pathologic findings of other neurodegenerative diseases. The most characteristic initial motor symptoms are akinesia, rigidity, and apraxia. Dystonia and alien limb phenomena are frequently observed. There is often a parkinsonian picture with failure or lack of efficacy of dopaminergic medical therapy. Cognitive decline, prompting the diagnosis of dementia, may be the most common presentation of CBD that is misdiagnosed. Pathology is characterized by an asymmetric frontoparietal neuronal loss and gliosis with ballooned, achromatic cortical neurons, nigral degeneration, and variable subcortical involvement. Neuroimaging and electrophysiologic studies may help with the diagnosis but are not specific. Treatment is primarily symptomatic and minimally effective, especially after the first several years of symptoms. CBD should be considered in the differential diagnosis of patients with motor and cognitive dysfunction presenting with cortical and subcortical features. Further studies to elucidate molecular abnormalities and biological markers associated with CBD are needed to improve clinical diagnosis and treatment of patients with this disorder.

[Tauopathy and Alzheimer disease: a full degenerating process].

PubMed

Buée, Luc; Delacourte, André

2006-12-01

Neurofibrillary degeneration is well correlated to the clinical signs of Alzheimer disease. However, the amyloid cascade is so well established in the scientific and medical community that the role of neurofibrillary degeneration in Alzheimer's disease etiopathogenesis is often underestimated. However, neuronal vulnerability is clearly a key factor for facilitating the amyloid pathology which allows the propagation of the degenerating process. In the present work, the role of tau pathology as both diagnostic marker and therapeutic target is highlighted in Alzheimer disease and related disorders.

Oxygen-induced retinopathy in mice with retinal photoreceptor cell degeneration.

PubMed

Zhang, Qian; Zhang, Zuo-Ming

2014-04-25

It is reported that retinal neovascularization seems to rarely co-exist with retinitis pigmentosa in patients and in some mouse models; however, it is not widely acknowledged as a universal phenomenon in all strains of all animal species. We aimed to further explore this phenomenon with an oxygen-induced retinopathy model in mice with retinal photoreceptor cell degeneration. Oxygen-induced retinopathy of colored and albino mice with rapid retinal degeneration were compared to homologous wild-type mice. The retinas were analyzed using high-molecular-weight FITC-dextran stained flat-mount preparation, hematoxylin and eosin (H&E) stained cross-sections, an immunohistochemical test for vascular endothelial growth factor (VEGF) distribution and Western blotting for VEGF expression after exposure to hyperoxia between postnatal days 17 (P17) and 21. Leakage and areas of non-perfusion of the retinal blood vessels were alleviated in the retinal degeneration mice. The number of preretinal vascular endothelial cell nuclei in the retinal degeneration mice was smaller than that in the homologous wild-type mice after exposure to hyperoxia (P<0.01). The degree of oxygen-induced retinopathy was positively correlated with the VEGF expression level. However, the VEGF expression level was lower in the retinal degeneration mice. Proliferative retinopathy occurred in mice with rapid retinal degeneration, but retinal photoreceptor cell degeneration could partially restrain the retinal neovascularization in this rapid retinal degeneration mouse model. Copyright © 2014 Elsevier Inc. All rights reserved.

The prevalence of sacroiliac joint degeneration in asymptomatic adults.

PubMed

Eno, Jonathan-James T; Boone, Christopher R; Bellino, Michael J; Bishop, Julius A

2015-06-03

Degenerative changes of the sacroiliac joint have been implicated as a cause of lower back pain in adults. The purpose of this study was to determine the prevalence of sacroiliac joint degeneration in asymptomatic patients. Five hundred consecutive pelvic computed tomography (CT) scans, made at a tertiary-care medical center, of patients with no history of pain in the lower back or pelvic girdle were retrospectively reviewed and analyzed for degenerative changes of the sacroiliac joint. After exclusion criteria were applied, 373 CT scans (746 sacroiliac joints) were evaluated for degenerative changes. Regression analysis was used to determine the association between age and the degree of sacroiliac joint degeneration. The prevalence of sacroiliac joint degeneration was 65.1%, with substantial degeneration occurring in 30.5% of asymptomatic subjects. The prevalence steadily increased with age, with 91% of subjects in the ninth decade of life displaying degenerative changes. Radiographic evidence of sacroiliac joint degeneration is highly prevalent in the asymptomatic population and is associated with age. Caution must be exercised when attributing lower back or pelvic girdle pain to sacroiliac joint degeneration seen on imaging. Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence. Copyright © 2015 by The Journal of Bone and Joint Surgery, Incorporated.

[Pharmacological therapy of age-related macular degeneration based on etiopathogenesis].

PubMed

Fischer, Tamás

2015-11-15

It is of great therapeutic significance that disordered function of the vascular endothelium which supply the affected ocular structures plays a major role in the pathogenesis and development of age-related macular degeneration. Chronic inflammation is closely linked to diseases associated with endothelial dysfunction, and age-related macular degeneration is accompanied by a general inflammatory response. According to current concept, age-related macular degeneration is a local manifestation of systemic vascular disease. This recognition could have therapeutic implications because restoration of endothelial dysfunction can restabilize the condition of chronic vascular disease including age-related macular degeneration as well. Restoration of endothelial dysfunction by pharmaacological or non pharmacological interventions may prevent the development or improve endothelial dysfunction, which result in prevention or improvement of age related macular degeneration as well. Medicines including inhibitors of the renin-angiotensin system (converting enzyme inhibitors, angiotensin-receptor blockers and renin inhibitors), statins, acetylsalicylic acid, trimetazidin, third generation beta-blockers, peroxisome proliferator-activated receptor gamma agonists, folate, vitamin D, melatonin, advanced glycation end-product crosslink breaker alagebrium, endothelin-receptor antagonist bosentan, coenzyme Q10; "causal" antioxidant vitamins, N-acetyl-cysteine, resveratrol, L-arginine, serotonin receptor agonists, tumor necrosis factor-alpha blockers, specific inhibitor of the complement alternative pathway, curcumin and doxycyclin all have beneficial effects on endothelial dysfunction. Restoration of endothelial dysfunction can restabilize chronic vascular disease including age-related macular degeneration as well. Considering that the human vascular system is consubstantial, medicines listed above should be given to patients (1) who have no macular degeneration but have risk factors

Bilateral aniridia lenticular coloboma and snowflake retinal degeneration.

PubMed

Doganay, Selim; Emre, Sinan; Firat, Penpegül

2009-01-01

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

The burden of age-related macular degeneration: a value-based analysis.

PubMed

Brown, Melissa M; Brown, Gary C; Sharma, Sanjay; Stein, Joshua D; Roth, Zachary; Campanella, Joseph; Beauchamp, George R

2006-06-01

The quality-of-life loss and the financial consequences associated with age-related macular degeneration are assessed. The quality-of-life loss associated with macular degeneration is markedly underestimated by the general public, nonophthalmic physicians, and ophthalmologists who treat patients with this condition. Mild age-related macular degeneration causes a 17% decrement in the quality of life of the average patient, similar to that encountered with moderate cardiac angina or symptomatic human immunodeficiency virus syndrome. Moderate age-related macular degeneration causes a 40% decrease in the average patient's quality of life, similar to that associated with severe cardiac angina or renal dialysis. Very severe age-related macular degeneration causes a large 63% decrease in the average patient's quality of life, similar to that encountered with end-stage prostatic cancer or a catastrophic stroke that leaves a person bedridden, incontinent and requiring constant nursing care. The return on investment is high for both treatment with current age-related macular degeneration therapies and the research costs invested in the development of age-related macular degeneration treatment modalities. Age-related macular degeneration is a major public health problem that has a devastating effect upon patients and marked adverse financial consequences for the economy.

Coupled modes in magnetized dense plasma with relativistic-degenerate electrons

NASA Astrophysics Data System (ADS)

Khan, S. A.

2012-01-01

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

Anomalous skin effects in a weakly magnetized degenerate electron plasma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abbas, G., E-mail: gohar.abbas@gcu.edu.pk; 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 themore » 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].« less

The degenerate parametric oscillator and Ince's equation

NASA Astrophysics Data System (ADS)

Cordero-Soto, Ricardo; Suslov, Sergei K.

2011-01-01

We construct Green's function for the quantum degenerate parametric oscillator in the coordinate representation in terms of standard solutions of Ince's equation in a framework of a general approach to variable quadratic Hamiltonians. Exact time-dependent wavefunctions and their connections with dynamical invariants and SU(1, 1) group are also discussed. An extension to the degenerate parametric oscillator with time-dependent amplitude and phase is also mentioned.

Iron homeostasis and toxicity in retinal degeneration.

PubMed

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

2007-11-01

Iron is essential for many metabolic processes but can also cause damage. As a potent generator of hydroxyl radical, the most reactive of the free radicals, iron can cause considerable oxidative stress. Since iron is absorbed through diet but not excreted except through menstruation, total body iron levels buildup with age. Macular iron levels increase with age, in both men and women. This iron has the potential to contribute to retinal degeneration. Here we present an overview of the evidence suggesting that iron may contribute to retinal degenerations. Intraocular iron foreign bodies cause retinal degeneration. Retinal iron buildup resulting from hereditary iron homeostasis disorders aceruloplasminemia, Friedreich's ataxia, and panthothenate kinase-associated neurodegeneration cause retinal degeneration. Mice with targeted mutation of the iron exporter ceruloplasmin have age-dependent retinal iron overload and a resulting retinal degeneration with features of age-related macular degeneration (AMD). Post mortem retinas from patients with AMD have more iron and the iron carrier transferrin than age-matched controls. Over the past 10 years much has been learned about the intricate network of proteins involved in iron handling. Many of these, including transferrin, transferrin receptor, divalent metal transporter-1, ferritin, ferroportin, ceruloplasmin, hephaestin, iron-regulatory protein, and histocompatibility leukocyte antigen class I-like protein involved in iron homeostasis (HFE) have been found in the retina. Some of these proteins have been found in the cornea and lens as well. Levels of the iron carrier transferrin are high in the aqueous and vitreous humors. The functions of these proteins in other tissues, combined with studies on cultured ocular tissues, genetically engineered mice, and eye exams on patients with hereditary iron diseases provide clues regarding their ocular functions. Iron may play a role in a broad range of ocular diseases, including

Iron homeostasis and toxicity in retinal degeneration

PubMed Central

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

2007-01-01

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

Progress toward the maintenance and repair of degenerating retinal circuitry.

PubMed

Vugler, Anthony A

2010-01-01

Retinal diseases such as age-related macular degeneration and retinitis pigmentosa remain major causes of severe vision loss in humans. Clinical trials for treatment of retinal degenerations are underway and advancements in our understanding of retinal biology in health/disease have implications for novel therapies. A review of retinal biology is used to inform a discussion of current strategies to maintain/repair neural circuitry in age-related macular degeneration, retinitis pigmentosa, and Type 2 Leber congenital amaurosis. In age-related macular degeneration/retinitis pigmentosa, a progressive loss of rods/cones results in corruption of bipolar cell circuitry, although retinal output neurons/photoreceptive melanopsin cells survive. Visual function can be stabilized/enhanced after treatment in age-related macular degeneration, but in advanced degenerations, reorganization of retinal circuitry may preclude attempts to restore cone function. In Type 2 Leber congenital amaurosis, useful vision can be restored by gene therapy where central cones survive. Remarkable progress has been made in restoring vision to rodents using light-responsive ion channels inserted into bipolar cells/retinal ganglion cells. Advances in genetic, cellular, and prosthetic therapies show varying degrees of promise for treating retinal degenerations. While functional benefits can be obtained after early therapeutic interventions, efforts should be made to minimize circuitry changes as soon as possible after rod/cone loss. Advances in retinal anatomy/physiology and genetic technologies should allow refinement of future reparative strategies.

Subretinal transplantation of bone marrow mesenchymal stem cells delays retinal degeneration in the RCS rat model of retinal degeneration.

PubMed

Inoue, Yuji; Iriyama, Aya; Ueno, Shuji; Takahashi, Hidenori; Kondo, Mineo; Tamaki, Yasuhiro; Araie, Makoto; Yanagi, Yasuo

2007-08-01

Because there is no effective treatment for this retinal degeneration, potential application of cell-based therapy has attracted considerable attention. Several investigations support that bone marrow mesenchymal stem cells (MSCs) can be used for a broad spectrum of indications. Bone marrow MSCs exert their therapeutic effect in part by secreting trophic factors to promote cell survival. The current study investigates whether bone marrow MSCs secrete factor(s) to promote photoreceptor cell survival and whether subretinal transplantation of bone marrow MSCs promotes photoreceptor survival in a retinal degeneration model using Royal College of Surgeons (RCS) rats. In vitro, using mouse retinal cell culture, it was demonstrated that the conditioned medium of the MSCs delays photoreceptor cell apoptosis, suggesting that the secreted factor(s) from the MSCs promote photoreceptor cell survival. In vivo, the MSCs were injected into the subretinal space of the RCS rats and histological analysis, real-time RT-PCR and electrophysiological analysis demonstrated that the subretinal transplantation of MSCs delays retinal degeneration and preserves retinal function in the RCS rats. These results suggest that MSC is a useful cell source for cell-replacement therapy for some forms of retinal degeneration.

[CORRELATION OF LUMBAR FACET JOINT DEGENERATION AND SPINE-PELVIC SAGITTAL BALANCE].

PubMed

Lo, Xin; Zhang, Bin; Liu, Yuan; Dai, Min

2015-08-01

To investigate the relationship between lumbar facet joint degeneration of each segment and spine-pelvic sagittal balance parameters. A retrospective analysis was made the clinical data of 120 patients with lumbar degenerative disease, who accorded with the inclusion criteria between June and November 2014. There were 58 males and 62 females with an average age of 53 years (range, 24-77 years). The disease duration ranged from 3 to 96 months (mean, 6.6 months). Affected segments included L3,4 in 32 cases, L4,5 in 47 cases, and L5, S1 in 52 cases. The CT and X-ray films of the lumbar vertebrae were taken. The facet joint degeneration was graded based on the grading system of Pathria. The spine-pelvic sagittal balance parameters were measured, including lumbar lordosis (LL), upper lumbar lordosis (ULL), lower lumbar lordosis (LLL), pelvic incidence (PI), pelvic tilt (PT), and sacral slope (SS). According to normal range of PI, the patients were divided into 3 groups: group A (PI was less than normal range), group B (PI was within normal range), and group C (PI was more than normal range). The facet joint degeneration was compared; according to the facet joint degeneration degree, the patients were divided into group N (mild degeneration group) and group M (serious degeneration group) to observe the relationship of lumbar facet joint degeneration of each segment and spine-pelvic sagittal balance parameters. At L4,5 and L5, S1, facet joint degeneration showed significant difference among groups A, B, and C (P < 0.05), more serious facet joint degeneration was observed in group C; no significant difference was found in facet joint degeneration at L3,4 (P > 0.05). There was no significant difference in the other spine-pelvic sagittal balance parameters between groups N and M at each segment (P > 0.05) except for PT (P < 0.05). PI of more than normal range may lead to or aggravate lumbar facet joint degeneration at L4,5 and L5, Si; PT and PI are significantly associated

Relationship of Tear Size and Location to Fatty Degeneration of the Rotator Cuff

PubMed Central

Kim, H. Mike; Dahiya, Nirvikar; Teefey, Sharlene A.; Keener, Jay D.; Galatz, Leesa M.; Yamaguchi, Ken

2010-01-01

Background: Fatty degeneration of the rotator cuff muscles may have detrimental effects on both anatomical and functional outcomes following shoulder surgery. The purpose of this study was to investigate the relationship between tear geometry and muscle fatty degeneration in shoulders with a deficient rotator cuff. Methods: Ultrasonograms of both shoulders of 262 patients were reviewed to assess the type of rotator cuff tear and fatty degeneration in the supraspinatus and infraspinatus muscles. The 251 shoulders with a full-thickness tear underwent further evaluation for tear size and location. The relationship of tear size and location to fatty degeneration of the supraspinatus and infraspinatus muscles was investigated with use of statistical comparisons and regression models. Results: Fatty degeneration was found almost exclusively in shoulders with a full-thickness rotator cuff tear. Of the 251 shoulders with a full-thickness tear, eighty-seven (34.7%) had fatty degeneration in either the supraspinatus or infraspinatus, or both. Eighty-two (32.7%) of the 251 full-thickness tears had a distance of 0 mm between the biceps tendon and anterior margin of the tear. Ninety percent of the full-thickness tears with fatty degeneration in both muscles had a distance of 0 mm posterior from the biceps, whereas only 9% of those without fatty degeneration had a distance of 0 mm. Tears with fatty degeneration had significantly greater width and length than those without fatty degeneration (p < 0.0001). Tears with fatty degeneration had a significantly shorter distance posterior from the biceps than those without fatty degeneration (p < 0.0001). The distance posterior from the biceps was found to be the most important predictor for supraspinatus fatty degeneration, whereas tear width and length were found to be the most important predictors for infraspinatus fatty degeneration. Conclusions: Fatty degeneration of the rotator cuff muscles is closely associated with tear size and

A disease-specific metabolic brain network associated with corticobasal degeneration

PubMed Central

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

2014-01-01

Corticobasal degeneration is an uncommon parkinsonian variant condition that is diagnosed mainly on clinical examination. To facilitate the differential diagnosis of this disorder, we used metabolic brain imaging to characterize a specific network that can be used to discriminate corticobasal degeneration from other atypical parkinsonian syndromes. Ten non-demented patients (eight females/two males; age 73.9 ± 5.7 years) underwent metabolic brain imaging with 18F-fluorodeoxyglucose positron emission tomography for atypical parkinsonism. These individuals were diagnosed clinically with probable corticobasal degeneration. This diagnosis was confirmed in the three subjects who additionally underwent post-mortem examination. Ten age-matched healthy subjects (five females/five males; age 71.7 ± 6.7 years) served as controls for the imaging studies. Spatial covariance analysis was applied to scan data from the combined group to identify a significant corticobasal degeneration-related metabolic pattern that discriminated (P < 0.001) the patients from the healthy control group. This pattern was characterized by bilateral, asymmetric metabolic reductions involving frontal and parietal cortex, thalamus, and caudate nucleus. These pattern-related changes were greater in magnitude in the cerebral hemisphere opposite the more clinically affected body side. The presence of this corticobasal degeneration-related metabolic topography was confirmed in two independent testing sets of patient and control scans, with elevated pattern expression (P < 0.001) in both disease groups relative to corresponding normal values. We next determined whether prospectively computed expression values for this pattern accurately discriminated corticobasal degeneration from multiple system atrophy and progressive supranuclear palsy (the two most common atypical parkinsonian syndromes) on a single case basis. Based upon this measure, corticobasal degeneration was successfully distinguished from

Thermonuclear Explosions from Hybrid C/O/Ne White Dwarf Progenitors Ignited Centrally After Interior Mixing

NASA Astrophysics Data System (ADS)

Augustine, Carlyn

2018-01-01

Type Ia Supernovae are thermonuclear explosions of white dwarf (WD) stars. Past studies predict the existence of "hybrid" white dwarfs, made of a C/O/Ne core with a O/Ne shell, and that these are viable progenitors for supernovae. More recent work found that the C/O core is mixed with the surrounding O/Ne while the WD cools. Inspired by this scenario, we performed simulations of thermonuclear supernovae in the single degenerate paradigm from these hybrid progenitors. Our investigation began by constructing a hybrid white dwarf model with the one-dimensional stellar evolution code MESA. The model was allowed to go through unstable interior mixing ignite carbon burning centrally. The MESA model was then mapped to a two-dimensional initial condition and an explosion simulated from that with FLASH. For comparison, a similar simulation of an explosion was performed from a traditional C/O progenitor WD. Comparing the yields produced by explosion simulations allows us to determine which model produces more 56Ni, and therefore brighter events, and how explosions from these models differ from explosions from previous models without the mixing during the WD cooling.

[Current concepts in pathogenesis of age-related macular degeneration].

PubMed

Kubicka-Trząska, Agnieszka; Karska-Basta, Izabella; Romanowska-Dixon, Bożena

2014-01-01

Age-related macular degeneration is the leading cause of central blindness in elderly population of the western world. The pathogenesis of this disease, likely multifactorial, is not well known, although a number of theories have been put forward, including oxidative stress, genetic interactions, hemodynamic imbalance, immune and inflammatory processes. The understanding of age-related macular degeneration pathogenesis will give rise to new approaches in prevention and treatment of the early and late stages of both atrophic and neovascular age-related macular degeneration.

MRI evaluation of spontaneous intervertebral disc degeneration in the alpaca cervical spine.

PubMed

Stolworthy, Dean K; Bowden, Anton E; Roeder, Beverly L; Robinson, Todd F; Holland, Jacob G; Christensen, S Loyd; Beatty, Amanda M; Bridgewater, Laura C; Eggett, Dennis L; Wendel, John D; Stieger-Vanegas, Susanne M; Taylor, Meredith D

2015-12-01

Animal models have historically provided an appropriate benchmark for understanding human pathology, treatment, and healing, but few animals are known to naturally develop intervertebral disc degeneration. The study of degenerative disc disease and its treatment would greatly benefit from a more comprehensive, and comparable animal model. Alpacas have recently been presented as a potential large animal model of intervertebral disc degeneration due to similarities in spinal posture, disc size, biomechanical flexibility, and natural disc pathology. This research further investigated alpacas by determining the prevalence of intervertebral disc degeneration among an aging alpaca population. Twenty healthy female alpacas comprised two age subgroups (5 young: 2-6 years; and 15 older: 10+ years) and were rated according to the Pfirrmann-grade for degeneration of the cervical intervertebral discs. Incidence rates of degeneration showed strong correlations with age and spinal level: younger alpacas were nearly immune to developing disc degeneration, and in older animals, disc degeneration had an increased incidence rate and severity at lower cervical levels. Advanced disc degeneration was present in at least one of the cervical intervertebral discs of 47% of the older alpacas, and it was most common at the two lowest cervical intervertebral discs. The prevalence of intervertebral disc degeneration encourages further investigation and application of the lower cervical spine of alpacas and similar camelids as a large animal model of intervertebral disc degeneration. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Deuterium Abundance Toward WD2211-495: Results from the Far Ultraviolet Spectroscopic Explorer (FUSE) Mission

NASA Technical Reports Server (NTRS)

Hebrard, G.; Lemoine, M.; Vidal-Madjar, A.; Desert, J. M.; LecavelierdesEtangs, A.; Ferlet, R.; Wood, B. E.; Linsky, J. L.; Kruk, J. W.; Chayer, P.;

Simultaneous infrared and optical observations of the transiting debris cloud around WD 1145+017

NASA Astrophysics Data System (ADS)

Zhou, G.; Kedziora-Chudczer, L.; Bailey, J.; Marshall, J. P.; Bayliss, D. D. R.; Stockdale, C.; Nelson, P.; Tan, T. G.; Rodriguez, J. E.; Tinney, C. G.; Dragomir, D.; Colon, K.; Shporer, A.; Bento, J.; Sefako, R.; Horne, K.; Cochran, W.

2016-12-01

We present multiwavelength photometric monitoring of WD 1145+017, a white dwarf exhibiting periodic dimming events interpreted to be the transits of orbiting, disintegrating planetesimals. Our observations include the first set of near-infrared light curves for the object, obtained on multiple nights over the span of 1 month, and recorded multiple transit events with depths varying between ˜20 and 50 per cent. Simultaneous near-infrared and optical observations of the deepest and longest duration transit event were obtained on two epochs with the Anglo-Australian Telescope and three optical facilities, over the wavelength range of 0.5-1.2 μm. These observations revealed no measurable difference in transit depths for multiple photometric pass bands, allowing us to place a 2σ lower limit of 0.8 μm on the grain size in the putative transiting debris cloud. This conclusion is consistent with the spectral energy distribution of the system, which can be fit with an optically thin debris disc with minimum particle sizes of 10^{+5}_{-3} μm.

LONGITUDINAL STRUCTURAL CHANGES IN LATE-ONSET RETINAL DEGENERATION.

PubMed

Cukras, Catherine; Flamendorf, Jason; Wong, Wai T; Ayyagari, Radha; Cunningham, Denise; Sieving, Paul A

2016-12-01

To characterize longitudinal structural changes in early stages of late-onset retinal degeneration to investigate pathogenic mechanisms. Two affected siblings, both with a S163R missense mutation in the causative gene C1QTNF5, were followed for 8+ years. Color fundus photos, fundus autofluorescence images, near-infrared reflectance fundus images, and spectral domain optical coherence tomography scans were acquired during follow-up. Both patients, aged 45 and 50 years, had good visual acuities (>20/20) in the context of prolonged dark adaptation. Baseline color fundus photography demonstrated yellow-white, punctate lesions in the temporal macula that correlated with a reticular pattern on fundus autofluorescence and near-infrared reflectance imaging. Baseline spectral domain optical coherence tomography imaging revealed subretinal deposits that resemble reticular pseudodrusen described in age-related macular degeneration. During follow-up, these affected areas developed confluent thickening of the retinal pigment epithelial layer and disruption of the ellipsoid zone of photoreceptors before progressing to overt retinal pigment epithelium and outer retinal atrophy. Structural changes in early stages of late-onset retinal degeneration, revealed by multimodal imaging, resemble those of reticular pseudodrusen observed in age-related macular degeneration and other retinal diseases. Longitudinal follow-up of these lesions helps elucidate their progression to frank atrophy and may lend insight into the pathogenic mechanisms underlying diverse retinal degenerations.

Ethanol Exposure Causes Muscle Degeneration in Zebrafish

PubMed Central

Coffey, Elizabeth C.; Pasquarella, Maggie E.; Goody, Michelle F.

2018-01-01

Alcoholic myopathies are characterized by neuromusculoskeletal symptoms such as compromised movement and weakness. Although these symptoms have been attributed to neurological damage, EtOH may also target skeletal muscle. EtOH exposure during zebrafish primary muscle development or adulthood results in smaller muscle fibers. However, the effects of EtOH exposure on skeletal muscle during the growth period that follows primary muscle development are not well understood. We determined the effects of EtOH exposure on muscle during this phase of development. Strikingly, muscle fibers at this stage are acutely sensitive to EtOH treatment: EtOH induces muscle degeneration. The severity of EtOH-induced muscle damage varies but muscle becomes more refractory to EtOH as muscle develops. NF-kB induction in muscle indicates that EtOH triggers a pro-inflammatory response. EtOH-induced muscle damage is p53-independent. Uptake of Evans blue dye shows that EtOH treatment causes sarcolemmal instability before muscle fiber detachment. Dystrophin-null sapje mutant zebrafish also exhibit sarcolemmal instability. We tested whether Trichostatin A (TSA), which reduces muscle degeneration in sapje mutants, would affect EtOH-treated zebrafish. We found that TSA and EtOH are a lethal combination. EtOH does, however, exacerbate muscle degeneration in sapje mutants. EtOH also disrupts adhesion of muscle fibers to their extracellular matrix at the myotendinous junction: some detached muscle fibers retain beta-Dystroglycan indicating failure of muscle end attachments. Overexpression of Paxillin, which reduces muscle degeneration in zebrafish deficient for beta-Dystroglycan, is not sufficient to rescue degeneration. Taken together, our results suggest that EtOH exposure has pleiotropic deleterious effects on skeletal muscle. PMID:29615556

The nature of apraxia in corticobasal degeneration.

PubMed

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

1994-04-01

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

The nature of apraxia in corticobasal degeneration.

PubMed Central

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

1994-01-01

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

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.

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

PubMed

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

2014-11-01

Corticobasal degeneration is an uncommon parkinsonian variant condition that is diagnosed mainly on clinical examination. To facilitate the differential diagnosis of this disorder, we used metabolic brain imaging to characterize a specific network that can be used to discriminate corticobasal degeneration from other atypical parkinsonian syndromes. Ten non-demented patients (eight females/two males; age 73.9 ± 5.7 years) underwent metabolic brain imaging with (18)F-fluorodeoxyglucose positron emission tomography for atypical parkinsonism. These individuals were diagnosed clinically with probable corticobasal degeneration. This diagnosis was confirmed in the three subjects who additionally underwent post-mortem examination. Ten age-matched healthy subjects (five females/five males; age 71.7 ± 6.7 years) served as controls for the imaging studies. Spatial covariance analysis was applied to scan data from the combined group to identify a significant corticobasal degeneration-related metabolic pattern that discriminated (P < 0.001) the patients from the healthy control group. This pattern was characterized by bilateral, asymmetric metabolic reductions involving frontal and parietal cortex, thalamus, and caudate nucleus. These pattern-related changes were greater in magnitude in the cerebral hemisphere opposite the more clinically affected body side. The presence of this corticobasal degeneration-related metabolic topography was confirmed in two independent testing sets of patient and control scans, with elevated pattern expression (P < 0.001) in both disease groups relative to corresponding normal values. We next determined whether prospectively computed expression values for this pattern accurately discriminated corticobasal degeneration from multiple system atrophy and progressive supranuclear palsy (the two most common atypical parkinsonian syndromes) on a single case basis. Based upon this measure, corticobasal degeneration was successfully distinguished from

Human cells derived from degenerate intervertebral discs respond differently to those derived from non-degenerate intervertebral discs following application of dynamic hydrostatic pressure.

PubMed

Le Maitre, Christine Lyn; Frain, Jennie; Fotheringham, Andrew P; Freemont, Anthony J; Hoyland, Judith Alison

2008-01-01

The intervertebral disc (IVD) is one of the body's most important load-bearing structures with the major mechanical force experienced in the nucleus pulposus (NP) being hydrostatic pressure (HP). Physiological levels of HP have an anabolic effect on IVD matrix metabolism in cells derived from non-degenerate animal and herniated IVD while excessive HP has a catabolic effect. However, no studies have investigated the response of non-degenerate and degenerate human disc cells derived from non-herniated discs to HP. Here we investigate the effect of physiological HP on such cells using a novel loading rig. Human IVD cells (both NP and AF) cultured in alginate were subjected to dynamic HP (0.8-1.7 MPa 0.5 Hz) for 2 h. Cell viability was assessed, RNA extracted and qRT-PCR for 18 s, c-fos, Sox-9, collagen type II, aggrecan and MMP-3 performed. Cell viability was unaffected by the loading regime. In non-degenerate NP cells, HP increased c-fos, aggrecan, Sox-9 and collagen type II (significantly so in the case of c-fos and aggrecan), but not MMP-3 gene expression. In contrast, application of HP to AF or degenerate NP cells had no effect on target gene expression. Our data shows that cells obtained from the healthy NP respond to dynamic HP by up-regulating genes indicative of healthy matrix homeostasis. However, responses differed in degenerate NP cells suggesting that an altered mechanotransduction pathway may be operational.

The Changing Nature of QU Carinae: SN Ia Progenitor or a Hoax?

NASA Astrophysics Data System (ADS)

Kafka, Stella

2013-01-01

The race to the elusive Type Ia supernovae (SNe Ia) progenitors is at its zenith, with numerous clues from SNe Ia ejecta and a dearth of observational candidates. Still, the single degenerate channel is a viable route of mass accumulation onto a white dwarf to the Chandrasekhar limit. I present long-term high resolution spectroscopy of QU Carinae, one of the most promising single degenerate SNe Ia progenitors. I discuss its highly variable nature and compare it to current scenarios for mass accumulation onto high-mass white dwarfs, eventually leading to WD detonation and to a supernova explosion.

Axonal Degeneration Is Mediated by the Mitochondrial Permeability Transition Pore

PubMed Central

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

2011-01-01

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

Fibrotic-like changes in degenerate human intervertebral discs revealed by quantitative proteomic analysis.

PubMed

Yee, A; Lam, M P Y; Tam, V; Chan, W C W; Chu, I K; Cheah, K S E; Cheung, K M C; Chan, D

2016-03-01

Intervertebral disc degeneration (IDD) can lead to symptomatic conditions including sciatica and back pain. The purpose of this study is to understand the extracellular matrix (ECM) changes in disc biology through comparative proteomic analysis of degenerated and non-degenerated human intervertebral disc (IVD) tissues of different ages. Seven non-degenerated (11-46 years of age) and seven degenerated (16-53 years of age) annulus fibrosus (AF) and nucleus pulposus (NP) samples were used. Proteins were extracted using guanidine hydrochloride, separated from large proteoglycans (PGs) by caesium chloride (CsCl) density gradient ultracentrifugation, and identified using liquid chromatography (LC) coupled with tandem mass spectrometry (MS/MS). For quantitative comparison, proteins were labeled with iTRAQ reagents. Collagen fibrils in the NP were assessed using scanning electron microscopy (SEM). In the AF, quantitative analysis revealed increased levels of HTRA1, COMP and CILP in degeneration when compared with samples from older individuals. Fibronectin showed increment with age and degeneration. In the NP, more CILP and CILP2 were present in degenerated samples of younger individuals. Reduced protein solubility was observed in degenerated and older non-degenerated samples correlated with an accumulation of type I collagen in the insoluble fibers. Characterization of collagen fibrils in the NP revealed smaller mean fibril diameters and decreased porosity in the degenerated samples. Our study identified distinct matrix changes associated with aging and degeneration in the intervertebral discs (IVDs). The nature of the ECM changes, together with observed decreased in solubility and changes in fibril diameter is consistent with a fibrotic-like environment. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Essential role of the NH2-terminal WD/EPF motif in the phosphorylation-activated protective function of mammalian Hsp27.

PubMed

Thériault, Jimmy R; Lambert, Herman; Chávez-Zobel, Aura T; Charest, Gabriel; Lavigne, Pierre; Landry, Jacques

2004-05-28

Hsp27 is expressed at high levels after mild heat shock and contributes to making cells extremely resistant to subsequent treatments. The activity of the protein is regulated at the transcriptional level, but also by phosphorylation, which occurs rapidly during stress and is responsible for causing the dissociation of large 700-kDa Hsp27 oligomers into dimers. We investigated the mechanism by which phosphorylation and oligomerization modulate the protective activity of Chinese hamster Hsp27. In contrast to oligomer dissociation, which only required Ser90 phosphorylation, activation of Hsp27 thermoprotective activity required the phosphorylation of both Ser90 and Ser15. Replacement of Ser90 by Ala90, which prevented the dissociation of the oligomer upon stress, did cause a severe defect in the protective activity. Dissociation was, however, not a sufficient condition to activate the protein because replacement of Ser15 by Ala15, which caused little effect in the oligomeric organization of the protein, also yielded an inactive protein. Analyzes of mutants with short deletions in the NH2 terminus identified the Hsp27 WD/EPF or PF-rich domain as essential for protection, maintenance of the oligomeric structure, and in vitro chaperone activity of the protein. In light of a three-dimensional model of Hsp27 based on the crystallographic structure of wheat Hsp16.9, we propose that the conserved WD/EPF motif of mammalian Hsp27 mediates important intramolecular interactions with hydrophic surfaces of the alpha-crystallin domain of the protein. These interactions are destabilized by Ser90 phosphorylation, making the motif free to interact with heterologous molecular targets upon the additional phosphorylation of the nearby Ser15.

Application of MRIL-WD (Magnetic Resonance Imaging Logging While Drilling) for irreducible water saturation, total reservoir, free-fluid, bound-fluid porosity measurements and its value for the petrophysical analysis of RT/RM data from the Shah Deniz well

NASA Astrophysics Data System (ADS)

Amirov, Elnur

2016-04-01

Sperry-Sun (Sperry Drilling Services) is the leader in MWD/LWD reliability, has developed the industry's first LWD NMR/MRIL-WD (nuclear magnetic resonance) tool. The MRIL-WD (magnetic resonance imaging logging-while-drilling) service directly measures the T1 component of hydrogen in subsurface rock units while drilling to obtain total reservoir porosity and to dissect the observed total porosity into its respective components of free fluid and bound fluid porosity. These T1 data are used to secure accurate total, free-fluid, capillary-bound water, and clay-bound water porosity of the reservoir sections which can be drilled in the several Runs. Over the last decade, results from Magnetic Resonance Imaging logs (NMR) have added significant value to petrophysical analysis and understanding by providing total, free-fluid and bound-fluid porosities, combined with fluid typing capabilities. With MRIL-WD very valuable Real-Time or Recorded Memory data/information is now available during or shortly after the drilling operation (formation properties measurement can be taken right after a drill bit penetration), while trip in and trip out as well. A key point in utilizing MRIL in an LWD environment is motion-tolerant measurements. Recent MRIL-WD logging runs from the Shah Deniz wells located in the Khazarian-Caspian Sea of the Azerbaijan Republic helped to delineate and assess hydrocarbon bearing zones. Acquired results demonstrate how MRIL data can be acquired while-drilling and provide reliable/high quality measurements. Magnetic Resonance Imaging logs at some developments wells have become a cornerstone in formation evaluation and petrophysical understanding. By providing total, free-fluid, and bound-fluid porosities together with fluid typing, MRIL results have significantly added to the assessment of reservoirs. In order to reduce NPT (Non-Productive Time) and save the rig operations time, there is always the desire to obtain logging results as soon as possible

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

PubMed Central

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

2005-01-01

In this study, we investigated the hypotheses that in human intervertebral disc (IVD) degeneration there is local production of the cytokine IL-1, and that this locally produced cytokine can induce the cellular and matrix changes of IVD degeneration. Immunohistochemistry was used to localize five members of the IL-1 family (IL-1α, IL-1β, IL-1Ra (IL-1 receptor antagonist), IL-1RI (IL-1 receptor, type I), and ICE (IL-1β-converting enzyme)) in non-degenerate and degenerate human IVDs. In addition, cells derived from non-degenerate and degenerate human IVDs were challenged with IL-1 agonists and the response was investigated using real-time PCR for a number of matrix-degrading enzymes, matrix proteins, and members of the IL-1 family. This study has shown that native disc cells from non-degenerate and degenerate discs produced the IL-1 agonists, antagonist, the active receptor, and IL-1β-converting enzyme. In addition, immunopositivity for these proteins, with the exception of IL-1Ra, increased with severity of degeneration. We have also shown that IL-1 treatment of human IVD cells resulted in increased gene expression for the matrix-degrading enzymes (MMP 3 (matrix metalloproteinase 3), MMP 13 (matrix metalloproteinase 13), and ADAMTS-4 (a disintegrin and metalloproteinase with thrombospondin motifs)) and a decrease in the gene expression for matrix genes (aggrecan, collagen II, collagen I, and SOX6). In conclusion we have shown that IL-1 is produced in the degenerate IVD. It is synthesized by native disc cells, and treatment of human disc cells with IL-1 induces an imbalance between catabolic and anabolic events, responses that represent the changes seen during disc degeneration. Therefore, inhibiting IL-1 could be an important therapeutic target for preventing and reversing disc degeneration. PMID:15987475

Cystic adventitial degeneration: ectopic ganglia from adjacent joint capsules.

PubMed

Ortmann, J; Widmer, M K; Gretener, S; Do, D D; Willenberg, T; Daliri, A; Baumgartner, I

2009-11-01

Cystic adventitial degeneration is a rare non-atherosclerotic cause of peripheral arterial occlusive disease, mainly seen in young men without other evidence of vascular disease. Diagnosis will be established by clinical findings and by ultrasound or angiography and can be treated by excision or enucleation of the affected arterial segment or by percutaneous ultrasound-guided aspiration. However, the etiology of adventitial cysts remains unknown. We report a case of cystic adventitial degeneration showing a connection between the joint capsule and the adventitial cyst, supporting the theory that cystic adventitial degeneration may represent ectopic ganglia from adjacent joint capsules.

Probing the degenerate states of V-point singularities.

PubMed

Ram, B S Bhargava; Sharma, Anurag; Senthilkumaran, Paramasivam

2017-09-15

V-points are polarization singularities in spatially varying linearly polarized optical fields and are characterized by the Poincare-Hopf index η. Each V-point singularity is a superposition of two oppositely signed orbital angular momentum states in two orthogonal spin angular momentum states. Hence, a V-point singularity has zero net angular momentum. V-points with given |η| have the same (amplitude) intensity distribution but have four degenerate polarization distributions. Each of these four degenerate states also produce identical diffraction patterns. Hence to distinguish these degenerate states experimentally, we present in this Letter a method involving a combination of polarization transformation and diffraction. This method also shows the possibility of using polarization singularities in place of phase singularities in optical communication and quantum information processing.

Ecological transition predictably associated with gene degeneration.

PubMed

Wessinger, Carolyn A; Rausher, Mark D

2015-02-01

Gene degeneration or loss can significantly contribute to phenotypic diversification, but may generate genetic constraints on future evolutionary trajectories, potentially restricting phenotypic reversal. Such constraints may manifest as directional evolutionary trends when parallel phenotypic shifts consistently involve gene degeneration or loss. Here, we demonstrate that widespread parallel evolution in Penstemon from blue to red flowers predictably involves the functional inactivation and degeneration of the enzyme flavonoid 3',5'-hydroxylase (F3'5'H), an anthocyanin pathway enzyme required for the production of blue floral pigments. Other types of genetic mutations do not consistently accompany this phenotypic shift. This pattern may be driven by the relatively large mutational target size of degenerative mutations to this locus and the apparent lack of associated pleiotropic effects. The consistent degeneration of F3'5'H may provide a mechanistic explanation for the observed asymmetry in the direction of flower color evolution in Penstemon: Blue to red transitions are common, but reverse transitions have not been observed. Although phenotypic shifts in this system are likely driven by natural selection, internal constraints may generate predictable genetic outcomes and may restrict future evolutionary trajectories. © The Author 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

NUTRITIONAL SUPPLEMENTATION IN AGE-RELATED MACULAR DEGENERATION.

PubMed

Parodi, Maurizio Battaglia; Zucchiatti, Ilaria; Cicinelli, Maria Vittoria; Cascavilla, Maria Lucia; Bandello, Francesco

2016-06-01

To evaluate the rate of adherence to prescribed nutritional supplementation in patients affected by age-related macular degeneration, in an Italian tertiary referral tertiary center. Patients with age-related macular degeneration, age-related eye disease study Categories 3 and 4, were recruited and underwent an 11-item questionnaire. The study included a total of 193 patients meeting the age-related eye disease study nutritional supplementation criteria (174 patients with age-related eye disease study Category 4 and 19 with Category 3). Seventy-seven (40%) were taking oral supplementation, 70 of whom (90%) 1 tablet/day. Oral supplementation was recommended by the personal ophthalmologist in 85 patients (44%), including all those currently receiving it. Eight patients of 85 (9.4%) rejected supplementation despite it being recommended, mostly because they were already taking other medicines. Ninety-four patients (48%) claimed they had not received any information from their ophthalmologist. Our data reveal that Italian patients with age-related eye disease study Categories 3 and 4 have a low adherence to nutritional supplementation. In 65% of cases, patients were not adequately informed by their ophthalmologist of the potential benefits of oral supplementation for age-related macular degeneration; indeed, 108 patients (56%) were not even aware such nutritional treatments are available. Ophthalmologists should be aware of the importance of giving advice to persons with age-related macular degeneration regarding the benefits of oral supplements.

Tamoxifen Provides Structural and Functional Rescue in Murine Models of Photoreceptor Degeneration

PubMed Central

Wang, Xu; Ma, Wenxin; Gonzalez, Shaimar R.; Kretschmer, Friedrich; Badea, Tudor C.

2017-01-01

Photoreceptor degeneration is a cause of irreversible vision loss in incurable blinding retinal diseases including retinitis pigmentosa (RP) and atrophic age-related macular degeneration. We found in two separate mouse models of photoreceptor degeneration that tamoxifen, a selective estrogen receptor modulator and a drug previously linked with retinal toxicity, paradoxically provided potent neuroprotective effects. In a light-induced degeneration model, tamoxifen prevented onset of photoreceptor apoptosis and atrophy and maintained near-normal levels of electroretinographic responses. Rescue effects were correlated with decreased microglial activation and inflammatory cytokine production in the retina in vivo and a reduction of microglia-mediated toxicity to photoreceptors in vitro, indicating a microglia-mediated mechanism of rescue. Tamoxifen also rescued degeneration in a genetic (Pde6brd10) model of RP, significantly improving retinal structure, electrophysiological responses, and visual behavior. These prominent neuroprotective effects warrant the consideration of tamoxifen as a drug suitable for being repurposed to treat photoreceptor degenerative disease. SIGNIFICANCE STATEMENT Photoreceptor degeneration is a cause of irreversible blindness in a number of retinal diseases such as retinitis pigmentosa (RP) and atrophic age-related macular degeneration. Tamoxifen, a selective estrogen receptor modulator approved for the treatment of breast cancer and previously linked to a low incidence of retinal toxicity, was unexpectedly found to exert marked protective effects against photoreceptor degeneration. Structural and functional protective effects were found for an acute model of light-induced photoreceptor injury and for a genetic model for RP. The mechanism of protection involved the modulation of microglial activation and the production of inflammatory cytokines, highlighting the role of inflammatory mechanisms in photoreceptor degeneration. Tamoxifen may be

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 found...

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 found...

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 found...

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 found...

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 found...

Qualitative and quantitative assessment of degeneration of cervical intervertebral discs and facet joints.

PubMed

Walraevens, Joris; Liu, Baoge; Meersschaert, Joke; Demaerel, Philippe; Delye, Hans; Depreitere, Bart; Vander Sloten, Jos; Goffin, Jan

2009-03-01

Degeneration of intervertebral discs and facet joints is one of the most frequently encountered spinal disorders. In order to describe and quantify degeneration and evaluate a possible relationship between degeneration and biomechanical parameters, e.g., the intervertebral range of motion and intradiscal pressure, a scoring system for degeneration is mandatory. However, few scoring systems for the assessment of degeneration of the cervical spine exist. Therefore, two separate objective scoring systems to qualitatively and quantitatively assess the degree of cervical intervertebral disc and facet joint degeneration were developed and validated. The scoring system for cervical disc degeneration consists of three variables which are individually scored on neutral lateral radiographs: "height loss" (0-4 points), "anterior osteophytes" (0-3 points) and "endplate sclerosis" (0-2 points). The scoring system for facet joint degeneration consists of four variables which are individually scored on neutral computed tomography scans: "hypertrophy" (0-2 points), "osteophytes" (0-1 point), "irregularity" on the articular surface (0-1 point) and "joint space narrowing" (0-1 point). Each variable contributes with varying importance to the overall degeneration score (max 9 points for the scoring system of cervical disc degeneration and max 5 points for facet joint degeneration). Degeneration of 20 discs and facet joints of 20 patients was blindly assessed by four raters: two neurosurgeons (one senior and one junior) and two radiologists (one senior and one junior), firstly based on first subjective impression and secondly using the scoring systems. Measurement errors and inter- and intra-rater agreement were determined. The measurement error of the scoring system for cervical disc degeneration was 11.1 versus 17.9% of the subjective impression results. This scoring system showed excellent intra-rater agreement (ICC = 0.86, 0.75-0.93) and excellent inter-rater agreement (ICC = 0

Self-reported optometric practise patterns in age-related macular degeneration.

PubMed

Ly, Angelica; Nivison-Smith, Lisa; Zangerl, Barbara; Assaad, Nagi; Kalloniatis, Michael

2017-11-01

The use of advanced imaging in clinical practice is emerging and the use of this technology by optometrists in assessing patients with age-related macular degeneration is of interest. Therefore, this study explored contemporary, self-reported patterns of practice regarding age-related macular degeneration diagnosis and management using a cross-sectional survey of optometrists in Australia and New Zealand. Practising optometrists were surveyed on four key areas, namely, demographics, clinical skills and experience, assessment and management of age-related macular degeneration. Questions pertaining to self-rated competency, knowledge and attitudes used a five-point Likert scale. Completed responses were received from 127 and 87 practising optometrists in Australia and New Zealand, respectively. Advanced imaging showed greater variation in service delivery than traditional techniques (such as slitlamp funduscopy) and trended toward optical coherence tomography, which was routinely performed in age-related macular degeneration by 49 per cent of respondents. Optical coherence tomography was also associated with higher self-rated competency, knowledge and perceived relevance to practice than other modalities. Most respondents (93 per cent) indicated that they regularly applied patient symptoms, case history, visual function results and signs from traditional testing, when queried about their management of patients with age-related macular degeneration. Over half (63 per cent) also considered advanced imaging, while 31 per cent additionally considered all of these as well as the disease stage and clinical guidelines. Contrary to the evidence base, 68 and 34 per cent rated nutritional supplements as highly relevant or relevant in early age-related macular degeneration and normal aging changes, respectively. These results highlight the emergence of multimodal and advanced imaging (especially optical coherence tomography) in the assessment of age-related macular degeneration

[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. Copyright © 2012 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Degenerated uterine fibroid mimicking hydrometra: fallacy in CT

PubMed Central

Tok, CH; Bux, SI; Mohamed, SI; Lim, BK

2006-01-01

Fibroids are the commonest uterine neoplasms, occurring in 20% - 30% of women of reproductive age. In women who have pelvic masses of unknown cause, unusual manifestations of fibroids such as necrosis or degeneration may simulate a carcinoma or hydrometra resulting in problems with image interpretation. We report a case of an unsuspected large degenerated uterine fibroid in a lady mistakenly diagnosed as hydrometra on computed tomography scanning. PMID:21614328

Age-Related Macular Degeneration.

PubMed

Mehta, Sonia

2015-09-01

Age-related macular degeneration (AMD) is the leading cause of vision loss in the elderly. AMD is diagnosed based on characteristic retinal findings in individuals older than 50. Early detection and treatment are critical in increasing the likelihood of retaining good and functional vision. Copyright © 2015 Elsevier Inc. All rights reserved.

A Chandrasekhar mass progenitor for the Type Ia supernova remnant 3C 397 from the enhanced abundances of nickel and manganese

DOE PAGES

Yamaguchi, Hiroya; Badenes, Carles; Foster, Adam R.; ...

2015-03-12

Despite decades of intense efforts, many fundamental aspects of Type Ia supernovae (SNe Ia) remain elusive. One of the major open questions is whether the mass of an exploding white dwarf (WD) is close to the Chandrasekhar limit. Here, we report the detection of strong K-shell emission from stable Fe-peak elements in the Suzaku X-ray spectrum of the Type Ia supernova remnant (SNR) 3C 397. The high Ni/Fe and Mn/Fe mass ratios (0.11–0.24 and 0.018–0.033, respectively) in the hot plasma component that dominates the K-shell emission lines indicate a degree of neutronization in the supernova ejecta that can only bemore » achieved by electron capture in the dense cores of exploding WDs with a near-Chandrasekhar mass. This suggests a single-degenerate origin for 3C 397, since Chandrasekhar mass progenitors are expected naturally if the WD accretes mass slowly from a companion. Altogether with other results supporting the double-degenerate scenario, our work adds to the mounting evidence that both progenitor channels make a significant contribution to the SN Ia rate in star-forming galaxies.« less

A Chandrasekhar Mass Progenitor for the Type Ia Supernova Remnant 3C 397 from the Enhanced Abundances of Nickel and Manganese

NASA Technical Reports Server (NTRS)

Yamaguchi, Hiroya; Badenes, Carles; Foster, Adam R.; Bravo, Eduardo; Williams, Brian J.; Maeda, Keiichi; Nobukawa, Masayoshi; Eriksen, Kristoffer A.; Brickhouse, Nancy S.; Petre, Robert;

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yamaguchi, Hiroya; Badenes, Carles; Foster, Adam R.

Despite decades of intense efforts, many fundamental aspects of Type Ia supernovae (SNe Ia) remain elusive. One of the major open questions is whether the mass of an exploding white dwarf (WD) is close to the Chandrasekhar limit. Here, we report the detection of strong K-shell emission from stable Fe-peak elements in the Suzaku X-ray spectrum of the Type Ia supernova remnant (SNR) 3C 397. The high Ni/Fe and Mn/Fe mass ratios (0.11–0.24 and 0.018–0.033, respectively) in the hot plasma component that dominates the K-shell emission lines indicate a degree of neutronization in the supernova ejecta that can only bemore » achieved by electron capture in the dense cores of exploding WDs with a near-Chandrasekhar mass. This suggests a single-degenerate origin for 3C 397, since Chandrasekhar mass progenitors are expected naturally if the WD accretes mass slowly from a companion. Altogether with other results supporting the double-degenerate scenario, our work adds to the mounting evidence that both progenitor channels make a significant contribution to the SN Ia rate in star-forming galaxies.« less

Degeneration of Bethe subalgebras in the Yangian of gl_n

NASA Astrophysics Data System (ADS)

Ilin, Aleksei; Rybnikov, Leonid

2018-04-01

We study degenerations of Bethe subalgebras B( C) in the Yangian Y(gl_n), where C is a regular diagonal matrix. We show that closure of the parameter space of the family of Bethe subalgebras, which parameterizes all possible degenerations, is the Deligne-Mumford moduli space of stable rational curves \\overline{M_{0,n+2}}. All subalgebras corresponding to the points of \\overline{M_{0,n+2}} are free and maximal commutative. We describe explicitly the "simplest" degenerations and show that every degeneration is the composition of the simplest ones. The Deligne-Mumford space \\overline{M_{0,n+2}} generalizes to other root systems as some De Concini-Procesi resolution of some toric variety. We state a conjecture generalizing our results to Bethe subalgebras in the Yangian of arbitrary simple Lie algebra in terms of this De Concini-Procesi resolution.

Enhanced Expression of WD Repeat-Containing Protein 35 via Nuclear Factor-Kappa B Activation in Bupivacaine-Treated Neuro2a Cells

PubMed Central

Huang, Lei; Kondo, Fumio; Harato, Misako; Feng, Guo-Gang; Ishikawa, Naoshisa; Fujiwara, Yoshihiro; Okada, Shoshiro

2014-01-01

The family of WD repeat proteins comprises a large number of proteins and is involved in a wide variety of cellular processes such as signal transduction, cell growth, proliferation, and apoptosis. Bupivacaine is a sodium channel blocker administered for local infiltration, nerve block, epidural, and intrathecal anesthesia. Recently, we reported that bupivacaine induces reactive oxygen species (ROS) generation and p38 mitogen-activated protein kinase (MAPK) activation, resulting in an increase in the expression of WD repeat-containing protein 35 (WDR35) in mouse neuroblastoma Neuro2a cells. It has been shown that ROS activate MAPK through phosphorylation, followed by activation of nuclear factor-kappa B (NF-κB) and activator protein 1 (AP-1). The present study was undertaken to test whether NF-κB and c-Jun/AP-1 are involved in bupivacaine-induced WDR35 expression in Neuro2a cells. Bupivacaine activated both NF-κB and c-Jun in Neuro2a cells. APDC, an NF-κB inhibitor, attenuated the increase in NF-κB activity and WDR35 protein expression in bupivacaine-treated Neuro2a cells. GW9662, a selective peroxisome proliferator-activated receptor-γ antagonist, enhanced the increase in NF-κB activity and WDR35 protein expression in bupivacaine-treated Neuro2a cells. In contrast, c-Jun siRNA did not inhibit the bupivacaine-induced increase in WDR35 mRNA expression. These results indicate that bupivacaine induces the activation of transcription factors NF-κB and c-Jun/AP-1 in Neuro2a cells, while activation of NF-κB is involved in bupivacaine-induced increases in WDR35 expression. PMID:24466034

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. © Society for Leukocyte Biology.

PATTERNS OF FUNDUS AUTOFLUORESCENCE DEFECTS IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION SUBTYPES.

PubMed

Ozkok, Ahmet; Sigford, Douglas K; Tezel, Tongalp H

2016-11-01

To test define characteristic fundus autofluorescence patterns of different exudative age-related macular degeneration subtypes. Cross-sectional study. Fifty-two patients with choroidal neovascularization because of three different neovascular age-related macular degeneration subtypes were included in the study. Macular and peripheral fundus autofluorescence patterns of study subjects were compared in a masked fashion. Fundus autofluorescence patterns of all three neovascular age-related macular degeneration subtypes revealed similar patterns. However, peripapillary hypo-autofluorescence was more common among patients with polypoidal choroidal vasculopathy (88.2%) compared with patients with retinal angiomatous proliferation (12.5%) and patients without retinal angiomatous proliferation and polypoidal choroidal vasculopathy (21.1%) (P < 0.0001). Presence of peripapillary fundus autofluorescence defects in neovascular age-related macular degeneration maybe suggestive of polypoidal choroidal vasculopathy as a variant of neovascular age-related macular degeneration.

Mechanisms of motor recovery after subtotal spinal cord injury: insights from the study of mice carrying a mutation (WldS) that delays cellular responses to injury.

PubMed

Zhang, Z; Guth, L; Steward, O

1998-01-01

Partial lesions of the mammalian spinal cord result in an immediate motor impairment that recovers gradually over time; however, the cellular mechanisms responsible for the transient nature of this paralysis have not been defined. A unique opportunity to identify those injury-induced cellular responses that mediate the recovery of function has arisen from the discovery of a unique mutant strain of mice in which the onset of Wallerian degeneration is dramatically delayed. In this strain of mice (designated WldS for Wallerian degeneration, slow), many of the cellular responses to spinal cord injury are also delayed. We have used this experimental animal model to evaluate possible causal relationships between these delayed cellular responses and the onset of functional recovery. For this purpose, we have compared the time course of locomotor recovery in C57BL/6 (control) mice and in WldS (mutant) mice by hemisecting the spinal cord at T8 and evaluating locomotor function at daily postoperative intervals. The time course of locomotor recovery (as determined by the Tarlov open-field walking procedure) was substantially delayed in mice carrying the WldS mutation: C57BL/6 control mice began to stand and walk within 6 days (mean Tarlov score of 4), whereas mutant mice did not exhibit comparable locomotor function until 16 days postoperatively. (a) The rapid return of locomotor function in the C57BL/6 mice suggests that the recovery resulted from processes of functional plasticity rather than from regeneration or collateral sprouting of nerve fibers. (b) The marked delay in the return of locomotor function in WldS mice indicates that the processes of neuroplasticity are induced by degenerative changes in the damaged neurons. (c) These strains of mice can be effectively used in future studies to elucidate the specific biochemical and physiological alterations responsible for inducing functional plasticity and restoring locomotor function after spinal cord injury.

Biological treatment strategies for disc degeneration: potentials and shortcomings

PubMed Central

Nerlich, Andreas G.; Boos, Norbert

2006-01-01

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

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

Quantization with maximally degenerate Poisson brackets: the harmonic oscillator!

NASA Astrophysics Data System (ADS)

Nutku, Yavuz

2003-07-01

Nambu's construction of multi-linear brackets for super-integrable systems can be thought of as degenerate Poisson brackets with a maximal set of Casimirs in their kernel. By introducing privileged coordinates in phase space these degenerate Poisson brackets are brought to the form of Heisenberg's equations. We propose a definition for constructing quantum operators for classical functions, which enables us to turn the maximally degenerate Poisson brackets into operators. They pose a set of eigenvalue problems for a new state vector. The requirement of the single-valuedness of this eigenfunction leads to quantization. The example of the harmonic oscillator is used to illustrate this general procedure for quantizing a class of maximally super-integrable systems.

Subretinally transplanted embryonic stem cells rescue photoreceptor cells from degeneration in the RCS rats.

PubMed

Schraermeyer, U; Thumann, G; Luther, T; Kociok, N; Armhold, S; Kruttwig, K; Andressen, C; Addicks, K; Bartz-Schmidt, K U

2001-01-01

The Royal College of Surgeons (RCS) rat is an animal model for retinal degeneration such as the age-related macular degeneration. The RCS rat undergoes a progressive retinal degeneration during the early postnatal period. A potential treatment to prevent this retinal degeneration is the transplantation into the subretinal space of cells that would replace functions of the degenerating retinal pigment epithelium (RPE) cells or may form neurotrophic factors. In this study we have investigated the potential of subretinally transplanted embryonic stem cells to prevent the genetically determined photoreceptor cell degeneration in the RCS rat. Embryonic stem cells from the inner cell mass of the mouse blastocyst were allowed to differentiate to neural precursor cells in vitro and were then transplanted into the subretinal space of 20-day-old RCS rats. Transplanted and sham-operated rats were sacrificed 2 months following cell transplantation. The eyes were enucleated and photoreceptor degeneration was quantified by analyzing and determining the thickness of the outer nuclear layer by light and electron microscopy. In the eyes transplanted with embryonic cells up to 8 rows of photoreceptor cell nuclei were observed, whereas in nontreated control eyes the outer nuclear layer had degenerated completely. Transplantation of embryonic stem cells appears to delay photoreceptor cell degeneration in RCS rats.

Expression and regulation of neurotrophins in the nondegenerate and degenerate human intervertebral disc

PubMed Central

Purmessur, Devina; Freemont, Anthony J; Hoyland, Judith A

2008-01-01

Introduction The neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) have been identified in the human intervertebral disc (IVD) and have been implicated in the mechanisms associated with nerve ingrowth and nociception in degeneration of the IVD. The aim of the current study was to investigate an association between neurotrophin expression in the IVD and the severity of disc degeneration, including the effect of disc-related proinflammatory cytokines on neurotrophin and neuropeptide expression in cells derived from the human IVD. Methods Immunohistochemical analysis was performed to examine the expression of NGF, BDNF and their high-affinity receptors Trk-A and Trk-B in human IVD samples, divided into three categories: non-degenerate, moderate degeneration and severe degeneration. In order to study the effect of disc-related cytokines on neurotrophin/neuropeptide gene expression, nucleus pulposus cells derived from non-degenerate and degenerate IVD samples were seeded in alginate and were stimulated with either IL-1β or TNFα for 48 hours. RNA was extracted, cDNA was synthesised and quantitative real-time PCR was performed to examine the expression of NGF, BDNF and substance P. Results Immunohistochemistry showed expression of NGF and BDNF in the native chondrocyte-like cells in all regions of the IVD and in all grades of degeneration. Interestingly only BDNF significantly increased with the severity of degeneration (P < 0.05). Similar expression was observed for Trk-A and Trk-B, although no association with disease severity was demonstrated. In cultured human nucleus pulposus cells, stimulation with IL-1β led to significant increases in NGF and BDNF gene expression (P < 0.05). Treatment with TNFα was associated with an upregulation of substance P expression only. Conclusion Our findings show that both the annulus fibrosus and nucleus pulposus cells of the IVD express the neurotrophins NGF and BDNF, factors that may influence and

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

NASA Astrophysics Data System (ADS)

Bengtsson, Ingemar

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

The role of microglia in synaptic stripping and synaptic degeneration: a revised perspective

PubMed Central

Hugh Perry, V; O'Connor, Vincent

2010-01-01

Chronic neurodegenerative diseases of the CNS (central nervous system) are characterized by the loss of neurons. There is, however, growing evidence to show that an early stage of this process involves degeneration of presynaptic terminals prior to the loss of the cell body. Synaptic plasticity in CNS pathology has been associated with microglia and the phenomenon of synaptic stripping. We review here the evidence for the involvement of microglia in synaptic stripping and synapse degeneration and we conclude that this is a case of guilt by association. In disease models of chronic neurodegeneration, there is no evidence that microglia play an active role in either synaptic stripping or synapse degeneration, but the degeneration of the synapse and the envelopment of a degenerating terminal appears to be a neuron autonomous event. We highlight here some of the gaps in our understanding of synapse degeneration in chronic neurodegenerative disease. PMID:20967131

Rapid Y degeneration and dosage compensation in plant sex chromosomes

PubMed Central

Papadopulos, Alexander S. T.; Chester, Michael; Ridout, Kate; Filatov, Dmitry A.

2015-01-01

The nonrecombining regions of animal Y chromosomes are known to undergo genetic degeneration, but previous work has failed to reveal large-scale gene degeneration on plant Y chromosomes. Here, we uncover rapid and extensive degeneration of Y-linked genes in a plant species, Silene latifolia, that evolved sex chromosomes de novo in the last 10 million years. Previous transcriptome-based studies of this species missed unexpressed, degenerate Y-linked genes. To identify sex-linked genes, regardless of their expression, we sequenced male and female genomes of S. latifolia and integrated the genomic contigs with a high-density genetic map. This revealed that 45% of Y-linked genes are not expressed, and 23% are interrupted by premature stop codons. This contrasts with X-linked genes, in which only 1.3% of genes contained stop codons and 4.3% of genes were not expressed in males. Loss of functional Y-linked genes is partly compensated for by gene-specific up-regulation of X-linked genes. Our results demonstrate that the rate of genetic degeneration of Y-linked genes in S. latifolia is as fast as in animals, and that the evolutionary trajectories of sex chromosomes are similar in the two kingdoms. PMID:26438872

MRI histogram analysis enables objective and continuous classification of intervertebral disc degeneration.

PubMed

Waldenberg, Christian; Hebelka, Hanna; Brisby, Helena; Lagerstrand, Kerstin Magdalena

2018-05-01

Magnetic resonance imaging (MRI) is the best diagnostic imaging method for low back pain. However, the technique is currently not utilized in its full capacity, often failing to depict painful intervertebral discs (IVDs), potentially due to the rough degeneration classification system used clinically today. MR image histograms, which reflect the IVD heterogeneity, may offer sensitive imaging biomarkers for IVD degeneration classification. This study investigates the feasibility of using histogram analysis as means of objective and continuous grading of IVD degeneration. Forty-nine IVDs in ten low back pain patients (six males, 25-69 years) were examined with MRI (T2-weighted images and T2-maps). Each IVD was semi-automatically segmented on three mid-sagittal slices. Histogram features of the IVD were extracted from the defined regions of interest and correlated to Pfirrmann grade. Both T2-weighted images and T2-maps displayed similar histogram features. Histograms of well-hydrated IVDs displayed two separate peaks, representing annulus fibrosus and nucleus pulposus. Degenerated IVDs displayed decreased peak separation, where the separation was shown to correlate strongly with Pfirrmann grade (P < 0.05). In addition, some degenerated IVDs within the same Pfirrmann grade displayed diametrically different histogram appearances. Histogram features correlated well with IVD degeneration, suggesting that IVD histogram analysis is a suitable tool for objective and continuous IVD degeneration classification. As histogram analysis revealed IVD heterogeneity, it may be a clinical tool for characterization of regional IVD degeneration effects. To elucidate the usefulness of histogram analysis in patient management, IVD histogram features between asymptomatic and symptomatic individuals needs to be compared.

Associations between Rs4244285 and Rs762551 gene polymorphisms and age-related macular degeneration.

PubMed

Stasiukonyte, Neringa; Liutkeviciene, Rasa; Vilkeviciute, Alvita; Banevicius, Mantas; Kriauciuniene, Loresa

2017-01-01

Age-related macular degeneration is the leading cause of blindness in elderly individuals in developed countries. The etiology and pathophysiology of age-related macular degeneration have not been elucidated yet. Knowing that the main pathological change of age-related macular degeneration is formation of drusen containing about 40% of lipids, there have been attempts to find associations between age-related macular degeneration and genes controlling lipid metabolism. To determine the frequency of CYP2C19 (G681A) Rs4244285 and CYP1A2 (-163C>A) Rs762551 genotypes in patients with age-related macular degeneration. The study enrolled 150 patients with early age-related macular degeneration and 296 age- and gender-matched healthy controls. The genotyping of Rs4244285 and Rs762551 was carried out by using the real-time polymerase chain reaction method. The CYP1A2 (-163C>A) Rs762551 C/C genotype was more frequently detected in patients with age-related macular degeneration than in the control group (32.7% vs. 21.6%, p = 0.011) and was associated with an increased risk of developing early age-related macular degeneration (OR = 1.759, 95% CI: 1.133-2.729; p = 0.012). The CYP1A2 (-163C>A) Rs762551 C/A genotype was more frequently documented in the control group compared with patients with age-related macular degeneration (46.3% vs. 30.7%, p = 0.002) and was associated with a decreased risk of having age-related macular degeneration (OR = 0.580. 95% CI: 0.362-0.929, p = 0.023) in the co-dominant model. The study showed that the CYP1A2 (-163C>A) Rs762551 C/C genotype was associated with an increased risk of age-related macular degeneration.

Relativistic many-body XMCD theory including core degenerate effects

NASA Astrophysics Data System (ADS)

Fujikawa, Takashi

2009-11-01

A many-body relativistic theory to analyze X-ray Magnetic Circular Dichroism (XMCD) spectra has been developed on the basis of relativistic quantum electrodynamic (QED) Keldysh Green's function approach. This theoretical framework enables us to handle relativistic many-body effects in terms of correlated nonrelativistic Green's function and relativistic correction operator Q, which naturally incorporates radiation field screening and other optical field effects in addition to electron-electron interactions. The former can describe the intensity ratio of L2/L3 which deviates from the statistical weight (branching ratio) 1/2. In addition to these effects, we consider the degenerate or nearly degenerate effects of core levels from which photoelectrons are excited. In XPS spectra, for example in Rh 3d sub level excitations, their peak shapes are quite different: This interesting behavior is explained by core-hole moving after the core excitation. We discuss similar problems in X-ray absorption spectra in particular excitation from deep 2p sub levels which are degenerate in each sub levels and nearly degenerate to each other in light elements: The hole left behind is not frozen there. We derive practical multiple scattering formulas which incorporate all those effects.

Identification of Age-Related Macular Degeneration Using OCT Images

NASA Astrophysics Data System (ADS)

Arabi, Punal M., Dr; Krishna, Nanditha; Ashwini, V.; Prathibha, H. M.

2018-02-01

Age-related Macular Degeneration is the most leading retinal disease in the recent years. Macular degeneration occurs when the central portion of the retina, called macula deteriorates. As the deterioration occurs with the age, it is commonly referred as Age-related Macular Degeneration. This disease can be visualized by several imaging modalities such as Fundus imaging technique, Optical Coherence Tomography (OCT) technique and many other. Optical Coherence Tomography is the widely used technique for screening the Age-related Macular Degeneration disease, because it has an ability to detect the very minute changes in the retina. The Healthy and AMD affected OCT images are classified by extracting the Retinal Pigmented Epithelium (RPE) layer of the images using the image processing technique. The extracted layer is sampled, the no. of white pixels in each of the sample is counted and the mean value of the no. of pixels is calculated. The average mean value is calculated for both the Healthy and the AMD affected images and a threshold value is fixed and a decision rule is framed to classify the images of interest. The proposed method showed an accuracy of 75%.

RING finger and WD repeat domain 3 (RFWD3) associates with replication protein A (RPA) and facilitates RPA-mediated DNA damage response.

PubMed

Liu, Shangfeng; Chu, Jessica; Yucer, Nur; Leng, Mei; Wang, Shih-Ya; Chen, Benjamin P C; Hittelman, Walter N; Wang, Yi

2011-06-24

DNA damage response is crucial for maintaining genomic integrity and preventing cancer by coordinating the activation of checkpoints and the repair of damaged DNA. Central to DNA damage response are the two checkpoint kinases ATM and ATR that phosphorylate a wide range of substrates. RING finger and WD repeat domain 3 (RFWD3) was initially identified as a substrate of ATM/ATR from a proteomic screen. Subsequent studies showed that RFWD3 is an E3 ubiquitin ligase that ubiquitinates p53 in vitro and positively regulates p53 levels in response to DNA damage. We report here that RFWD3 associates with replication protein A (RPA), a single-stranded DNA-binding protein that plays essential roles in DNA replication, recombination, and repair. Binding of RPA to single-stranded DNA (ssDNA), which is generated by DNA damage and repair, is essential for the recruitment of DNA repair factors to damaged sites and the activation of checkpoint signaling. We show that RFWD3 is physically associated with RPA and rapidly localizes to sites of DNA damage in a RPA-dependent manner. In vitro experiments suggest that the C terminus of RFWD3, which encompass the coiled-coil domain and the WD40 domain, is necessary for binding to RPA. Furthermore, DNA damage-induced phosphorylation of RPA and RFWD3 is dependent upon each other. Consequently, loss of RFWD3 results in the persistent foci of DNA damage marker γH2AX and the repair protein Rad51 in damaged cells. These findings suggest that RFWD3 is recruited to sites of DNA damage and facilitates RPA-mediated DNA damage signaling and repair.

Comparative and quantitative proteomic analysis of normal and degenerated human annulus fibrosus cells.

PubMed

Ye, Dongping; Liang, Weiguo; Dai, Libing; Zhou, Longqiang; Yao, Yicun; Zhong, Xin; Chen, Honghui; Xu, Jiake

2015-05-01

Degeneration of the intervertebral disc (IVD) is a major chronic medical condition associated with back pain. To better understand the pathogenesis of IVD degeneration, we performed comparative and quantitative proteomic analyses of normal and degenerated human annulus fibrosus (AF) cells and identified proteins that are differentially expressed between them. Annulus fibrosus cells were isolated and cultured from patients with lumbar disc herniation (the experimental group, degenerated AF cells) and scoliosis patients who underwent orthopaedic surgery (the control group, normal AF cells). Comparative proteomic analyses of normal and degenerated cultured AF cells were carried out using 2-D electrophoresis, mass spectrometric analyses, and database searching. Quantitative analyses of silver-stained 2-D electrophoresis gels of normal and degenerated cultured AF cells identified 10 protein spots that showed the most altered differential expression levels between the two groups. Among these, three proteins were decreased, including heat shock cognate 71-kDa protein, glucose-6-phosphate 1-dehydrogenase, and protocadherin-23, whereas seven proteins were increased, including guanine nucleotide-binding protein G(i) subunit α-2, superoxide dismutase, transmembrane protein 51, adenosine receptor A3, 26S protease regulatory subunit 8, lipid phosphate phosphatase-related protein, and fatty acyl-crotonic acid reductase 1. These differentially expressed proteins might be involved in the pathophysiological process of IVD degeneration and have potential values as biomarkers of the degeneration of IVD. © 2015 Wiley Publishing Asia Pty Ltd.

Degree of tendon degeneration and stage of rotator cuff disease.

PubMed

Jo, Chris Hyunchul; Shin, Won Hyoung; Park, Ji Wan; Shin, Ji Sun; Kim, Ji Eun

2017-07-01

While tendon degeneration has been known to be an important cause of rotator cuff disease, few studies have objectively proven the association of tendon degeneration and rotator cuff disease. The purpose of this study was to investigate changes of tendon degeneration with respect to the stage of rotator cuff disease. A total of 48 patients were included in the study: 12 with tendinopathy, 12 with a partial-thickness tear (pRCT), 12 with a full-thickness tear (fRCT), and 12 as the control. A full-thickness supraspinatus tendon sample was harvested en bloc from the middle portion between the lateral edge and the musculotendinous junction of the tendon using a biopsy punch with a diameter of 3 mm. Harvested samples were evaluated using a semi-quantitative grading scale with 7 parameters after haematoxylin and eosin staining. There was no significant difference in age, gender, symptom duration, and Kellgren-Lawrence grade between the groups except for the global fatty degeneration index. All of the seven parameters were significantly different between the groups and could be categorized as follows: early responders (fibre structure and arrangement), gradual responder (rounding of the nuclei), after-tear responders (cellularity, vascularity, and stainability), and late responder (hyalinization). The total degeneration scores were not significantly different between the control (6.08 ± 1.16) and tendinopathy (6.67 ± 1.83) (n.s.). However, the score of pRCT group (10.42 ± 1.31) was greater than that of tendinopathy (P < 0.001), and so was the score of fRCT (12.33 ± 1.15) than that of pRCT (p = 0.009). This study showed that the degeneration of supraspinatus tendon increases as the stage of rotator cuff disease progresses from tendinopathy to pRCT, and then to fRCT. The degree of degeneration of tendinopathy was not different from that of normal but aged tendons, and significant tendon degeneration began from the stage of pRCT. The clinical relevance of

On the existence of solutions to a one-dimensional degenerate nonlinear wave equation

NASA Astrophysics Data System (ADS)

Hu, Yanbo

2018-07-01

This paper is concerned with the degenerate initial-boundary value problem to the one-dimensional nonlinear wave equation utt =((1 + u) aux) x which arises in a number of various physical contexts. The global existence of smooth solutions to the degenerate problem was established under relaxed conditions on the initial-boundary data by the characteristic decomposition method. Moreover, we show that the solution is uniformly C 1 , α continuous up to the degenerate boundary and the degenerate curve is C 1 , α continuous for α ∈ (0 , min ⁡ a/1+a, 1/1+a).

Sequential involvement of the nervous system in subacute combined degeneration.

PubMed

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

2012-03-01

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

Sequential Involvement of the Nervous System in Subacute Combined Degeneration

PubMed Central

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

2012-01-01

Purpose Subacute combined degeneration (SCD) involves progressive degeneration of the spinal cord, optic nerve, and peripheral nerves. Vitamin B12 (VB12) is a co-factor in myelin synthesis. Because each cell that constitutes the myelin component in the central nervous system and peripheral nervous system is different, it is improbable that these cells undergo simultaneous degeneration. However, the sequence of degeneration in SCD has not been established. Materials and Methods In this study, we analysed medical records and electrophysiological data of patients who showed neurological symptoms and whose serum VB12 levels were lower than 200 pg/mL. Results We enrolled 49 patients in this study. Their mean VB12 level was 68.3 pg/mL. Somatosensory evoked potential (SEP) study showed abnormal findings in 38 patients. Of the 40 patients who underwent visual evoked potential (VEP) study, 14 showed abnormal responses. Eighteen patients showed abnormal findings on a nerve conduction study (NCS). In this study, abnormal posterior tibial nerve SEPs only were seen in 16 patients, median nerve SEPs only were seen in 3 patients, abnormal VEPs only in two, and abnormal NCS responses in one patient. No patient complained of cognitive symptoms. Conclusion In SCD, degeneration appears to progress in the following order: lower spinal cord, cervical spinal cord, peripheral nerve/optic nerve, and finally, the brain. PMID:22318813

Magnetic resonance imaging of hypertrophic olivary degeneration.

PubMed

Blanco Ulla, M; López Carballeira, A; Pumar Cebreiro, J M

2015-01-01

To review the pathophysiologic mechanisms involved in hypertrophic olivary degeneration, with attention to epidemiologic and clinical aspects and especially to imaging findings. We reviewed 5 patients diagnosed with hypertrophic olivary degeneration at our center from 2010 through 2013, analyzing relevant clinical, epidemiologic, and radiologic findings. In all cases, a hyperintensity was seen in the inferior olivary nuclei in FLAIR and T2-weighted sequences. No signal alterations were seen on T1-weighted sequences, and no enhancement was seen after intravenous injection of contrast material. In the cases studied by diffusion-weighted imaging, no significant alterations were seen in these sequences. Olivary hypertrophy was seen in all patients except in one, in whom presumably not enough time had elapsed for hypertrophy to occur. The alterations were bilateral in two of the five cases. Only one case exhibited the typical clinical manifestations. Given that patients may not present clinical manifestations that can be attributed to hypertrophic olivary degeneration, it is important to recognize the characteristic radiologic signs of this entity. Copyright © 2014 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

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.

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.

Managing abnormal eating behaviours in frontotemporal lobar degeneration patients with topiramate.

PubMed

Shinagawa, Shunichiro; Tsuno, Norifumi; Nakayama, Kazuhiko

2013-03-01

Abnormal eating behaviours are specific to frontotemporal lobar degeneration and increase caregiver burden. Topiramate, an anticonvulsant, suppresses cravings for alcohol and other substances and is a potential treatment for binge eating. However, there are few reports on topiramate efficacy for abnormal eating behaviours in frontotemporal lobar degeneration patients. We present three Japanese frontotemporal lobar degeneration patients with abnormal eating behaviours. Topiramate was effective, especially for compulsive eating, in cases with distinct lobar atrophy, but not for all abnormal eating behaviours. © 2013 The Authors. Psychogeriatrics © 2013 Japanese Psychogeriatric Society.

New GABA modulators protect photoreceptor cells from light-induced degeneration in mouse models.

PubMed

Schur, Rebecca M; Gao, Songqi; Yu, Guanping; Chen, Yu; Maeda, Akiko; Palczewski, Krzysztof; Lu, Zheng-Rong

2018-01-24

No clinically approved therapies are currently available that prevent the onset of photoreceptor death in retinal degeneration. Signaling between retinal neurons is regulated by the release and uptake of neurotransmitters, wherein GABA is the main inhibitory neurotransmitter. In this work, novel 3-chloropropiophenone derivatives and the clinical anticonvulsants tiagabine and vigabatrin were tested to modulate GABA signaling and protect against light-induced retinal degeneration. Abca4 -/- Rdh8 -/- mice, an accelerated model of retinal degeneration, were exposed to intense light after prophylactic injections of one of these compounds. Imaging and functional assessments of the retina indicated that these compounds successfully protected photoreceptor cells from degeneration to maintain a full-visual-field response. Furthermore, these compounds demonstrated a strong safety profile in wild-type mice and did not compromise visual function or damage the retina, despite repeated administration. These results indicate that modulating inhibitory GABA signaling can offer prophylactic protection against light-induced retinal degeneration.-Schur, R. M., Gao, S., Yu, G., Chen, Y., Maeda, A., Palczewski, K., Lu, Z.-R. New GABA modulators protect photoreceptor cells from light-induced degeneration in mouse models.

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

NASA Astrophysics Data System (ADS)

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

2016-04-01

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

WldS but not Nmnat1 protects dopaminergic neurites from MPP+ neurotoxicity.

PubMed

Antenor-Dorsey, Jo Ann V; O'Malley, Karen L

2012-02-08

The WldS mouse mutant ("Wallerian degeneration-slow") delays axonal degeneration in a variety of disorders including in vivo models of Parkinson's disease. The mechanisms underlying WldS -mediated axonal protection are unclear, although many studies have attributed WldS neuroprotection to the NAD+-synthesizing Nmnat1 portion of the fusion protein. Here, we used dissociated dopaminergic cultures to test the hypothesis that catalytically active Nmnat1 protects dopaminergic neurons from toxin-mediated axonal injury. Using mutant mice and lentiviral transduction of dopaminergic neurons, the present findings demonstrate that WldS but not Nmnat1, Nmnat3, or cytoplasmically-targeted Nmnat1 protects dopamine axons from the parkinsonian mimetic N-methyl-4-phenylpyridinium (MPP+). Moreover, NAD+ synthesis is not required since enzymatically-inactive WldS still protects. In addition, NAD+ by itself is axonally protective and together with WldS is additive in the MPP+ model. Our data suggest that NAD+ and WldS act through separate and possibly parallel mechanisms to protect dopamine axons. As MPP+ is thought to impair mitochondrial function, these results suggest that WldS might be involved in preserving mitochondrial health or maintaining cellular metabolism.

Articular cartilage degeneration classification by means of high-frequency ultrasound.

PubMed

Männicke, N; Schöne, M; Oelze, M; Raum, K

2014-10-01

To date only single ultrasound parameters were regarded in statistical analyses to characterize osteoarthritic changes in articular cartilage and the potential benefit of using parameter combinations for characterization remains unclear. Therefore, the aim of this work was to utilize feature selection and classification of a Mankin subset score (i.e., cartilage surface and cell sub-scores) using ultrasound-based parameter pairs and investigate both classification accuracy and the sensitivity towards different degeneration stages. 40 punch biopsies of human cartilage were previously scanned ex vivo with a 40-MHz transducer. Ultrasound-based surface parameters, as well as backscatter and envelope statistics parameters were available. Logistic regression was performed with each unique US parameter pair as predictor and different degeneration stages as response variables. The best ultrasound-based parameter pair for each Mankin subset score value was assessed by highest classification accuracy and utilized in receiver operating characteristics (ROC) analysis. The classifications discriminating between early degenerations yielded area under the ROC curve (AUC) values of 0.94-0.99 (mean ± SD: 0.97 ± 0.03). In contrast, classifications among higher Mankin subset scores resulted in lower AUC values: 0.75-0.91 (mean ± SD: 0.84 ± 0.08). Variable sensitivities of the different ultrasound features were observed with respect to different degeneration stages. Our results strongly suggest that combinations of high-frequency ultrasound-based parameters exhibit potential to characterize different, particularly very early, degeneration stages of hyaline cartilage. Variable sensitivities towards different degeneration stages suggest that a concurrent estimation of multiple ultrasound-based parameters is diagnostically valuable. In-vivo application of the present findings is conceivable in both minimally invasive arthroscopic ultrasound and high-frequency transcutaneous ultrasound

[In situ analysis of pathomechanisms of human intervertebral disc degeneration].

PubMed

Weiler, C

2013-11-01

Low back pain is one of the major causes of pain and disability in the western world, with a constantly rising life-time prevalence of approximately 60-85 %. Degeneration of the intervertebral disc is believed to be a major cause of low back pain. Semiquantitative macroscopic and microscopic changes of the intervertebral disc were assessed and classified. Furthermore additional methods, such as immunohistochemistry, in situ hybridization and in situ zymography were used to analyze phenotypic cellular and matrix changes. We have developed and tested a practicable, valid and reliable histological classification system for lumbar discs which can serve as a morphological reference framework to allow more sophisticated molecular biological studies on the pathogenesis of ageing and degeneration of discs. Secondly, we were able to demonstrate that intrinsic (genetic) and extrinsic (e.g. overweight) factors have a profound effect on the process of disc degeneration. Cells with a notochord-like phenotype are present in a considerable fraction of adult lumbar intervertebral discs. The presence of these cells is associated with distinct features of (early) age-related disc degeneration. During the process of disc degeneration, the intervertebral disc shows a progressive and significant reduction in height due to tissue resorption. This matrix loss is related to an imbalance between matrix synthesis and degradation. During this process an inflammatory reaction takes place and resident disc cells are causatively involved. In summary, disc degeneration is a multifactorial disease with a strong intrinsic (hereditary) and extrinsic (e.g. mechanical factors) background. The process starts as early as in the second decade of life and shows high interindividual differences. The loss of regenerative capacity in the intervertebral disc is probably related to the loss of stem cells, e.g. notochord-like cells. Resident disc cells are involved in the inflammatory reaction with increased

T1ρ MRI Quantification of Arthroscopically-Confirmed Cartilage Degeneration

PubMed Central

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

2010-01-01

9 asymptomatic subjects and 6 patients underwent T1ρ MRI to determine whether Outerbridge grade 1 or 2 cartilage degeneration observed during arthroscopy could be detected noninvasively. MRI was performed 2–3 months post-arthroscopy using sagittal T1-weighted and axial and coronal T1ρ MRI from which spatial T1ρ relaxation maps were calculated from segmented T1-weighted images. Median T1ρ relaxation times of patients with arthroscopically documented cartilage degeneration and asymptomatic subjects were significantly different (p < 0.001) and median T1ρ exceeded asymptomatic articular cartilage median T1ρ by 2.5 to 9.2 ms. In 8 observations of mild cartilage degeneration at arthroscopy (Outerbridge grades 1 and 2), mean compartment T1ρ was elevated in 5, but in all observations, large foci of increased T1ρ were observed. It was determined that T1ρ could detect some, but not all, Outerbridge grade 1 and 2 cartilage degeneration but that a larger patient population is needed to determine the sensitivity to these changes. PMID:20432308

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

PubMed Central

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

2014-01-01

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

Isomonodromy for the Degenerate Fifth Painlevé Equation

NASA Astrophysics Data System (ADS)

Acosta-Humánez, Primitivo B.; van der Put, Marius; Top, Jaap

2017-05-01

This is a sequel to papers by the last two authors making the Riemann-Hilbert correspondence and isomonodromy explicit. For the degenerate fifth Painlevé equation, the moduli spaces for connections and for monodromy are explicitly computed. It is proven that the extended Riemann-Hilbert morphism is an isomorphism. As a consequence these equations have the Painlevé property and the Okamoto-Painlevé space is identified with a moduli space of connections. Using MAPLE computations, one obtains formulas for the degenerate fifth Painlevé equation, for the Bäcklund transformations.

The Rate of Vitamin A Dimerization in Lipofuscinogenesis, Fundus Autofluorescence, Retinal Senescence and Degeneration.

PubMed

Washington, Ilyas; Saad, Leonide

2016-01-01

One of the earliest events preceding several forms of retinal degeneration is the formation and accumulation of vitamin A dimers in the retinal pigment epithelium (RPE) and underlying Bruch's membrane (BM). Such degenerations include Stargardt disease, Best disease, forms of retinitis pigmentosa, and age-related macular degeneration (AMD). Since their discovery in the 1990's, dimers of vitamin A, have been postulated as chemical triggers driving retinal senescence and degeneration. There is evidence to suggest that the rate at which vitamin A dimerizes and the eye's response to the dimerization products may dictate the retina's lifespan. Here, we present outstanding questions, finding the answers to which may help to elucidate the role of vitamin A dimerization in retinal degeneration.

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

PubMed Central

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

2014-01-01

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

Association of age-related macular degeneration and reticular macular disease with cardiovascular disease.

PubMed

Rastogi, Neelesh; Smith, R Theodore

2016-01-01

Age-related macular degeneration is the leading cause of adult blindness in the developed world. Thus, major endeavors to understand the risk factors and pathogenesis of this disease have been undertaken. Reticular macular disease is a proposed subtype of age-related macular degeneration correlating histologically with subretinal drusenoid deposits located between the retinal pigment epithelium and the inner segment ellipsoid zone. Reticular lesions are more prevalent in females and in older age groups and are associated with a higher mortality rate. Risk factors for developing age-related macular degeneration include hypertension, smoking, and angina. Several genes related to increased risk for age-related macular degeneration and reticular macular disease are also associated with cardiovascular disease. Better understanding of the clinical and genetic risk factors for age-related macular degeneration and reticular macular disease has led to the hypothesis that these eye diseases are systemic. A systemic origin may help to explain why reticular disease is diagnosed more frequently in females as males suffer cardiovascular mortality at an earlier age, before the age of diagnosis of reticular macular disease and age-related macular degeneration. Copyright © 2015 Elsevier Inc. All rights reserved.

Catabolic cytokine expression in degenerate and herniated human intervertebral discs: IL-1β and TNFα expression profile

PubMed Central

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

2007-01-01

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

Strategies to Improve Efficiency and Specificity of Degenerate Primers in PCR.

PubMed

Campos, Maria Jorge; Quesada, Alberto

2017-01-01

PCR with degenerate primers can be used to identify the coding sequence of an unknown protein or to detect a genetic variant within a gene family. These primers, which are complex mixtures of slightly different oligonucleotide sequences, can be optimized to increase the efficiency and/or specificity of PCR in the amplification of a sequence of interest by the introduction of mismatches with the target sequence and balancing their position toward the primers 5'- or 3'-ends. In this work, we explain in detail examples of rational design of primers in two different applications, including the use of specific determinants at the 3'-end, to: (1) improve PCR efficiency with coding sequences for members of a protein family by fully degeneration at a core box of conserved genetic information, with the reduction of degeneration at the 5'-end, and (2) optimize specificity of allelic discrimination of closely related orthologous by 5'-end degenerate primers.

Quantitative OCT and MRI biomarkers for the differentiation of cartilage degeneration.

PubMed

Nebelung, Sven; Brill, Nicolai; Tingart, Markus; Pufe, Thomas; Kuhl, Christiane; Jahr, Holger; Truhn, Daniel

2016-04-01

To evaluate the usefulness of quantitative parameters obtained by optical coherence tomography (OCT) and magnetic resonance imaging (MRI) in the comprehensive assessment of human articular cartilage degeneration. Human osteochondral samples of variable degeneration (n = 45) were obtained from total knee replacements and assessed by MRI sequences measuring T1, T1ρ, T2 and T2* relaxivity and by OCT-based quantification of irregularity (OII, optical irregularity index), homogeneity (OHI, optical homogeneity index]) and attenuation (OAI, optical attenuation index]). Samples were also assessed macroscopically (Outerbridge classification) and histologically (Mankin classification) as grade-0 (Mankin scores 0-4)/grade-I (scores 5-8)/grade-II (scores 9-10)/grade-III (score 11-14). After data normalisation, differences between Mankin grades and correlations between imaging parameters were assessed using ANOVA and Tukey's post-hoc test and Spearman's correlation coefficients, respectively. Sensitivities and specificities in the detection of Mankin grade-0 were calculated. Significant degeneration-related increases were found for T2 and OII and decreases for OAI, while T1, T1ρ, T2* or OHI did not reveal significant changes in relation to degeneration. A number of significant correlations between imaging parameters and histological (sub)scores were found, in particular for T2 and OII. Sensitivities and specificities in the detection of Mankin grade-0 were highest for OHI/T1 and OII/T1ρ, respectively. Quantitative OCT and MRI techniques seem to complement each other in the comprehensive assessment of cartilage degeneration. Sufficiently large structural and compositional changes in the extracellular matrix may thus be parameterized and quantified, while the detection of early degeneration remains challenging.

The surviving companions in type Ia supernova remnants

NASA Astrophysics Data System (ADS)

Chen, Li-Qing; Meng, Xiang-Cun; Han, Zhan-Wen

2017-08-01

The single-degenerate (SD) model is one of the most popular progenitor models of type Ia supernovae (SNe Ia), in which the companion star can survive after an SN Ia explosion and show peculiar properties. Therefore, searching for the surviving companion in type Ia supernova remnants (SNRs) is a potential method to verify the SD model. In the SN 1604 remnant (Kepler’s SNR), although Chandra X-ray observation suggests that the progenitor is most likely a WD+AGB system, a the surviving companion has not been found. One possible reason is rapid rotation of the white dwarf (WD), causing explosion of the WD to be delayed for a spin-down timescale, and then the companion evolved into a WD before the supernova explosion, so the companion is too dim to be detected. We aim to verify this possible explanation by carrying out binary evolution calculations. In this paper, we use Eggleton’s stellar evolution code to calculate the evolution of binaries consisting of a WD+red giant (RG). We assume that the rapidly rotating WD can continuously increase its mass when its mass exceeds the Chandrasekhar mass limit ({M}{{Ch}}=1.378 {M}⊙ ) until the mass-transfer rate decreases to be lower than a critical value. Eventually, we obtain the final masses of a WD in the range 1.378 M ⊙ to 2.707 M ⊙. We also show that if the spin-down time is less than 106 yr, the companion star will be very bright and easily observed; but if the spin-down time is as long as ˜ 107 yr, the luminosities of the surviving companion would be lower than the detection limit. Our simulation provides guidance in hunting for the surviving companion stars in SNRs, and the fact that no surviving companion has been found in Kepler’s SNR may not be definite evidence disfavoring the SD origin of Kepler’s SN.

Degeneration of serotonergic neurons in amyotrophic lateral sclerosis: a link to spasticity.

PubMed

Dentel, Christel; Palamiuc, Lavinia; Henriques, Alexandre; Lannes, Béatrice; Spreux-Varoquaux, Odile; Gutknecht, Lise; René, Frédérique; Echaniz-Laguna, Andoni; Gonzalez de Aguilar, Jose-Luis; Lesch, Klaus Peter; Meininger, Vincent; Loeffler, Jean-Philippe; Dupuis, Luc

2013-02-01

Spasticity is a common and disabling symptom observed in patients with central nervous system diseases, including amyotrophic lateral sclerosis, a disease affecting both upper and lower motor neurons. In amyotrophic lateral sclerosis, spasticity is traditionally thought to be the result of degeneration of the upper motor neurons in the cerebral cortex, although degeneration of other neuronal types, in particular serotonergic neurons, might also represent a cause of spasticity. We performed a pathology study in seven patients with amyotrophic lateral sclerosis and six control subjects and observed that central serotonergic neurons suffer from a degenerative process with prominent neuritic degeneration, and sometimes loss of cell bodies in patients with amyotrophic lateral sclerosis. Moreover, distal serotonergic projections to spinal cord motor neurons and hippocampus systematically degenerated in patients with amyotrophic lateral sclerosis. In SOD1 (G86R) mice, a transgenic model of amyotrophic lateral sclerosis, serotonin levels were decreased in brainstem and spinal cord before onset of motor symptoms. Furthermore, there was noticeable atrophy of serotonin neuronal cell bodies along with neuritic degeneration at disease onset. We hypothesized that degeneration of serotonergic neurons could underlie spasticity in amyotrophic lateral sclerosis and investigated this hypothesis in vivo using tail muscle spastic-like contractions in response to mechanical stimulation as a measure of spasticity. In SOD1 (G86R) mice, tail muscle spastic-like contractions were observed at end-stage. Importantly, they were abolished by 5-hydroxytryptamine-2b/c receptors inverse agonists. In line with this, 5-hydroxytryptamine-2b receptor expression was strongly increased at disease onset. In all, we show that serotonergic neurons degenerate during amyotrophic lateral sclerosis, and that this might underlie spasticity in mice. Further research is needed to determine whether inverse

Glial degeneration with oxidative damage drives neuronal demise in MPSII disease

PubMed Central

Zalfa, Cristina; Verpelli, Chiara; D'Avanzo, Francesca; Tomanin, Rosella; Vicidomini, Cinzia; Cajola, Laura; Manara, Renzo; Sala, Carlo; Scarpa, Maurizio; Vescovi, Angelo Luigi; De Filippis, Lidia

2016-01-01

Mucopolysaccharidosis type II (MPSII) is a lysosomal storage disorder due to the deficit of the iduronate 2-sulfatase (IDS) enzyme, causing progressive neurodegeneration in patients. Neural stem cells (NSCs) derived from the IDS-ko mouse can recapitulate MPSII pathogenesis in vitro. In differentiating IDS-ko NSCs and in the aging IDS-ko mouse brain, glial degeneration precedes neuronal degeneration. Here we show that pure IDS-ko NSC-derived astrocytes are selectively able to drive neuronal degeneration when cocultured with healthy neurons. This phenotype suggests concurrent oxidative damage with metabolic dysfunction. Similar patterns were observed in murine IDS-ko animals and in human MPSII brains. Most importantly, the mutant phenotype of IDS-ko astrocytes was reversed by low oxygen conditions and treatment with vitamin E, which also reversed the toxic effect on cocultured neurons. Moreover, at very early stages of disease we detected in vivo the development of a neuroinflammatory background that precedes astroglial degeneration, thus suggesting a novel model of MPSII pathogenesis, with neuroinflammation preceding glial degeneration, which is finally followed by neuronal death. This hypothesis is also consistent with the progression of white matter abnormalities in MPSII patients. Our study represents a novel breakthrough in the elucidation of MPSII brain pathogenesis and suggests the antioxidant molecules as potential therapeutic tools to delay MPSII onset and progression. PMID:27512952

Glial degeneration with oxidative damage drives neuronal demise in MPSII disease.

PubMed

Zalfa, Cristina; Verpelli, Chiara; D'Avanzo, Francesca; Tomanin, Rosella; Vicidomini, Cinzia; Cajola, Laura; Manara, Renzo; Sala, Carlo; Scarpa, Maurizio; Vescovi, Angelo Luigi; De Filippis, Lidia

2016-08-11

Mucopolysaccharidosis type II (MPSII) is a lysosomal storage disorder due to the deficit of the iduronate 2-sulfatase (IDS) enzyme, causing progressive neurodegeneration in patients. Neural stem cells (NSCs) derived from the IDS-ko mouse can recapitulate MPSII pathogenesis in vitro. In differentiating IDS-ko NSCs and in the aging IDS-ko mouse brain, glial degeneration precedes neuronal degeneration. Here we show that pure IDS-ko NSC-derived astrocytes are selectively able to drive neuronal degeneration when cocultured with healthy neurons. This phenotype suggests concurrent oxidative damage with metabolic dysfunction. Similar patterns were observed in murine IDS-ko animals and in human MPSII brains. Most importantly, the mutant phenotype of IDS-ko astrocytes was reversed by low oxygen conditions and treatment with vitamin E, which also reversed the toxic effect on cocultured neurons. Moreover, at very early stages of disease we detected in vivo the development of a neuroinflammatory background that precedes astroglial degeneration, thus suggesting a novel model of MPSII pathogenesis, with neuroinflammation preceding glial degeneration, which is finally followed by neuronal death. This hypothesis is also consistent with the progression of white matter abnormalities in MPSII patients. Our study represents a novel breakthrough in the elucidation of MPSII brain pathogenesis and suggests the antioxidant molecules as potential therapeutic tools to delay MPSII onset and progression.

Automated design of degenerate codon libraries.

PubMed

Mena, Marco A; Daugherty, Patrick S

2005-12-01

Degenerate codon libraries are frequently used in protein engineering and evolution studies but are often limited to targeting a small number of positions to adequately limit the search space. To mitigate this, codon degeneracy can be limited using heuristics or previous knowledge of the targeted positions. To automate design of libraries given a set of amino acid sequences, an algorithm (LibDesign) was developed that generates a set of possible degenerate codon libraries, their resulting size, and their score relative to a user-defined scoring function. A gene library of a specified size can then be constructed that is representative of the given amino acid distribution or that includes specific sequences or combinations thereof. LibDesign provides a new tool for automated design of high-quality protein libraries that more effectively harness existing sequence-structure information derived from multiple sequence alignment or computational protein design data.

Trp-Asp (WD) Repeat Domain 1 Is Essential for Mouse Peri-implantation Development and Regulates Cofilin Phosphorylation.

PubMed

Xiao, Yi; Ma, Haixia; Wan, Ping; Qin, Dandan; Wang, Xiaoxiao; Zhang, Xiaoxin; Xiang, Yunlong; Liu, Wenbo; Chen, Jiong; Yi, Zhaohong; Li, Lei

2017-01-27

Trp-Asp (WD) repeat domain 1 (WDR1) is a highly conserved actin-binding protein across all eukaryotes and is involved in numerous actin-based processes by accelerating Cofilin severing actin filament. However, the function and the mechanism of WDR1 in mammalian early development are still largely unclear. We now report that WDR1 is essential for mouse peri-implantation development and regulates Cofilin phosphorylation in mouse cells. The disruption of maternal WDR1 does not obviously affect ovulation and female fertility. However, depletion of zygotic WDR1 results in embryonic lethality at the peri-implantation stage. In WDR1 knock-out cells, we found that WDR1 regulates Cofilin phosphorylation. Interestingly, WDR1 is overdosed to regulate Cofilin phosphorylation in mouse cells. Furthermore, we showed that WDR1 interacts with Lim domain kinase 1 (LIMK1), a well known phosphorylation kinase of Cofilin. Altogether, our results provide new insights into the role and mechanism of WDR1 in physiological conditions. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Observation of a Degenerate Fermi Gas Trapped by a Bose-Einstein Condensate

NASA Astrophysics Data System (ADS)

DeSalvo, B. J.; Patel, Krutik; Johansen, Jacob; Chin, Cheng

2017-12-01

We report on the formation of a stable quantum degenerate mixture of fermionic 6Li and bosonic 133Cs in an optical trap by sympathetic cooling near an interspecies Feshbach resonance. New regimes of quantum degenerate Bose-Fermi mixtures are identified. With moderate attractive interspecies interactions, we show that a degenerate Fermi gas of Li can be fully confined in a Cs Bose-Einstein condensate without external potentials. For stronger attraction where mean-field collapse is expected, no such instability is observed. Potential mechanisms to explain this phenomenon are discussed.

Juvenile Macular Degenerations

PubMed Central

Altschwager, Pablo; Ambrosio, Lucia; Swanson, Emily A.; Moskowitz, Anne; Fulton, Anne B.

2017-01-01

In this paper we review three common juvenile macular degenerations: Stargardt disease, X-linked retinoschisis, and Best vitelliform macular dystrophy. These are inherited disorders that typically present during childhood, when vision is still developing. They are sufficiently common that they should be included in the differential diagnosis of visual loss in pediatric patients. Diagnosis is secured by a combination of clinical findings, optical coherence tomography (OCT) imaging, and genetic testing. Early diagnosis promotes optimal management. While there is currently no definitive cure for these conditions, therapeutic modalities under investigation include pharmacologic treatment, gene therapy, and stem cell transplantation. PMID:28941524

The white dwarf binary pathways survey - II. Radial velocities of 1453 FGK stars with white dwarf companions from LAMOST DR 4

NASA Astrophysics Data System (ADS)

Rebassa-Mansergas, A.; Ren, J. J.; Irawati, P.; García-Berro, E.; Parsons, S. G.; Schreiber, M. R.; Gänsicke, B. T.; Rodríguez-Gil, P.; Liu, X.; Manser, C.; Nevado, S. P.; Jiménez-Ibarra, F.; Costero, R.; Echevarría, J.; Michel, R.; Zorotovic, M.; Hollands, M.; Han, Z.; Luo, A.; Villaver, E.; Kong, X.

2017-12-01

We present the second paper of a series of publications aiming at obtaining a better understanding regarding the nature of type Ia supernovae (SN Ia) progenitors by studying a large sample of detached F, G and K main-sequence stars in close orbits with white dwarf companions (i.e. WD+FGK binaries). We employ the Large Sky Area Multi-Object Fibre Spectroscopic Telescope (LAMOST) data release 4 spectroscopic data base together with Galaxy Evolution Explorer (GALEX) ultraviolet fluxes to identify 1549 WD+FGK binary candidates (1057 of which are new), thus doubling the number of known sources. We measure the radial velocities of 1453 of these binaries from the available LAMOST spectra and/or from spectra obtained by us at a wide variety of different telescopes around the globe. The analysis of the radial velocity data allows us to identify 24 systems displaying more than 3σ radial velocity variation that we classify as close binaries. We also discuss the fraction of close binaries among WD+FGK systems, which we find to be ∼10 per cent, and demonstrate that high-resolution spectroscopy is required to efficiently identify double-degenerate SN Ia progenitor candidates.

Planar and non-planar nucleus-acoustic shock structures in self-gravitating degenerate quantum plasma systems

NASA Astrophysics Data System (ADS)

Zaman, D. M. S.; Amina, M.; Dip, P. R.; Mamun, A. A.

2017-11-01

The basic properties of planar and non-planar (spherical and cylindrical) nucleus-acoustic (NA) shock structures (SSs) in a strongly coupled self-gravitating degenerate quantum plasma system (containing strongly coupled non-relativistically degenerate heavy nuclear species, weakly coupled non-relativistically degenerate light nuclear species, and inertialess non-/ultra-relativistically degenerate electrons) have been investigated. The generalized quantum hydrodynamic model and the reductive perturbation method have been used to derive the modified Burgers equation. It is shown that the strong correlation among heavy nuclear species acts as the source of dissipation and is responsible for the formation of the NA SSs with positive (negative) electrostatic (self-gravitational) potential. It is also observed that the effects of non-/ultra-relativistically degenerate electron pressure, dynamics of non-relativistically degenerate light nuclear species, spherical geometry, etc., significantly modify the basic features of the NA SSs. The applications of our results in astrophysical compact objects like white dwarfs and neutron stars are briefly discussed.

FOXP2 Expression in Frontotemporal Lobar Degeneration-Tau.

PubMed

López-González, Irene; Palmeira, Andre; Aso, Ester; Carmona, Margarita; Fernandez, Liana; Ferrer, Isidro

2016-09-06

FOXP2 is altered in a variety of language disorders. We found reduced mRNA and protein expression of FOXP2 in frontal cortex area 8 in Pick's disease, and frontotemporal lobar degeneration-tau linked to P301L mutation presenting with language impairment in comparison with age-matched controls and cases with parkinsonian variant progressive supranuclear palsy. Foxp2 mRNA and protein are also reduced with disease progression in the somatosensory cortex in transgenic mice bearing the P301S mutation in MAPT when compared with wild-type littermates. Our findings support the presence of FOXP2 expression abnormalities in sporadic and familial frontotemporal degeneration tauopathies.

The macular degeneration and aging study: Design and research protocol of a randomized trial for a psychosocial intervention with macular degeneration patients.

PubMed

Sörensen, Silvia; White, Katherine; Mak, Wingyun; Zanibbi, Katherine; Tang, Wan; O'Hearn, Amanda; Hegel, Mark T

2015-05-01

Age-related Macular Degeneration (AMD) is the leading cause of irreversible and predictable blindness among older adults with serious physical and mental health consequences. Visual impairment is associated with negative future outlook and depression and has serious consequences for older adults' quality of life and, by way of depression, on long-term survival. Psychosocial interventions have the potential to alleviate and prevent depression symptoms among older AMD patients. We describe the protocol of the Macular Degeneration and Aging Study, a randomized clinical trial of a psychosocial Preventive Problem-Solving Intervention. The intervention is aimed at enhancing well-being and future planning among older adults with macular degeneration by increasing preparation for future care. Adequate randomization and therapeutic fidelity were achieved. Current retention rates were acceptable, given the vulnerability of the population. Acceptability (adherence and satisfaction) was high. Given the high public health significance and impact on quality of life among older adults with vision loss, this protocol contributes a valid test of a promising intervention for maintaining mental and physical health in this population. Copyright © 2015 Elsevier Inc. All rights reserved.

A mouse model for degeneration of the spiral ligament.

PubMed

Kada, Shinpei; Nakagawa, Takayuki; Ito, Juichi

2009-06-01

Previous studies have indicated the importance of the spiral ligament (SL) in the pathogenesis of sensorineural hearing loss. The aim of this study was to establish a mouse model for SL degeneration as the basis for the development of new strategies for SL regeneration. We injected 3-nitropropionic acid (3-NP), an inhibitor of succinate dehydrogenase, at various concentrations into the posterior semicircular canal of adult C57BL/6 mice. Saline-injected animals were used as controls. Auditory function was monitored by measurements of auditory brain stem responses (ABRs). On postoperative day 14, cochlear specimens were obtained after the measurement of the endocochlear potential (EP). Animals that were injected with 5 or 10 mM 3-NP showed a massive elevation of ABR thresholds along with extensive degeneration of the cochleae. Cochleae injected with 1 mM 3-NP exhibited selective degeneration of the SL fibrocytes but alterations in EP levels and ABR thresholds were not of sufficient magnitude to allow for testing functional recovery after therapeutic interventions. Animals injected with 3 mM 3-NP showed a reduction of around 50% in the EP along with a significant loss of SL fibrocytes, although degeneration of spiral ganglion neurons and hair cells was still present in certain regions. These findings indicate that cochleae injected with 3 mM 3-NP may be useful in investigations designed to test the feasibility of new therapeutic manipulations for functional SL regeneration.

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

PubMed

Tan, Lee T; Shuttleworth, Garry N

2008-01-01

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

Exploring Nonconvex, Crossed and Degenerate Polygons

ERIC Educational Resources Information Center

Contreras, Jose N.

2004-01-01

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

[Disease perception in patients with wet age-related macular degeneration].

PubMed

Kostadinov, F; Valmaggia, C

2015-04-01

The disease perception of the patients treated with intravitreal injections of anti-vascular endothelial growth factor due to wet age-related macular degeneration was investigated. 177 questionnaires focusing on the development of the perceived visual acuity and the quality of life were evaluated. The subgroup 1 included 125 patients (70.6%) with a unilateral wet age-related macular degeneration. The subgroup 2 included 52 patients (29.4%) with a bilateral wet age-related macular degeneration. Patients would almost always recommend the therapy to a friend (97.2%). The critical remarks are related to the uncertain course of the disease (22.8%) and the uncertain duration of the treatment (19%). There was a discrepancy between the measured visual outcome and the perceived one in 5.6% in the subgroup 1, and in 38.5% in the subgroup 2. This difference was statistically significant (chi-square test with p<0.01). The treatment of wet age-related macular degeneration with intravitreal injections of anti-vascular endothelial growth factor is judged positively. Binocular affected patients have a higher disease perception and therefore a poorer self-assessment of their visual acuity and their quality of life compared with monocular affected patients. Georg Thieme Verlag KG Stuttgart · New York.

A Transcriptional Program for Arbuscule Degeneration during AM Symbiosis Is Regulated by MYB1.

PubMed

Floss, Daniela S; Gomez, S Karen; Park, Hee-Jin; MacLean, Allyson M; Müller, Lena M; Bhattarai, Kishor K; Lévesque-Tremblay, Veronique; Maldonado-Mendoza, Ignacio E; Harrison, Maria J

2017-04-24

During the endosymbiosis formed between plants and arbuscular mycorrhizal (AM) fungi, the root cortical cells are colonized by branched hyphae called arbuscules, which function in nutrient exchange with the plant [1]. Despite their positive function, arbuscules are ephemeral structures, and their development is followed by a degeneration phase, in which the arbuscule and surrounding periarbuscular membrane and matrix gradually disappear from the root cell [2, 3]. Currently, the root cell's role in this process and the underlying regulatory mechanisms are unknown. Here, by using a Medicago truncatula pt4 mutant in which arbuscules degenerate prematurely [4], we identified arbuscule degeneration-associated genes, of which 38% are predicted to encode secreted hydrolases, suggesting a role in disassembly of the arbuscule and interface. Through RNAi and analysis of an insertion mutant, we identified a symbiosis-specific MYB-like transcription factor (MYB1) that suppresses arbuscule degeneration in mtpt4. In myb1, expression of several degeneration-associated genes is reduced. Conversely, in roots constitutively overexpressing MYB1, expression of degeneration-associated genes is increased and subsequent development of symbiosis is impaired. MYB1-regulated gene expression is enhanced by DELLA proteins and is dependent on NSP1 [5], but not NSP2 [6]. Furthermore, MYB1 interacts with DELLA and NSP1. Our data identify a transcriptional program for arbuscule degeneration and reveal that its regulators include MYB1 in association with two transcriptional regulators, NSP1 and DELLA, both of which function in preceding phases of the symbiosis. We propose that the combinatorial use of transcription factors enables the sequential expression of transcriptional programs for arbuscule development and degeneration. Copyright © 2017 Elsevier Ltd. All rights reserved.

Degenerate band edge laser

NASA Astrophysics Data System (ADS)

Veysi, Mehdi; Othman, Mohamed A. K.; Figotin, Alexander; Capolino, Filippo

2018-05-01

We propose a class of lasers based on a fourth-order exceptional point of degeneracy (EPD) referred to as the degenerate band edge (DBE). EPDs have been found in parity-time-symmetric photonic structures that require loss and/or gain; here we show that the DBE is a different kind of EPD since it occurs in periodic structures that are lossless and gainless. Because of this property, a small level of gain is sufficient to induce single-frequency lasing based on a synchronous operation of four degenerate Floquet-Bloch eigenwaves. This lasing scheme constitutes a light-matter interaction mechanism that leads also to a unique scaling law of the laser threshold with the inverse of the fifth power of the laser-cavity length. The DBE laser has the lowest lasing threshold in comparison to a regular band edge laser and to a conventional laser in cavities with the same loaded quality (Q ) factor and length. In particular, even without mirror reflectors the DBE laser exhibits a lasing threshold which is an order of magnitude lower than that of a uniform cavity laser of the same length and with very high mirror reflectivity. Importantly, this novel DBE lasing regime enforces mode selectivity and coherent single-frequency operation even for pumping rates well beyond the lasing threshold, in contrast to the multifrequency nature of conventional uniform cavity lasers.

Degenerate higher derivative theories beyond Horndeski: evading the Ostrogradski instability

DOE Office of Scientific and Technical Information (OSTI.GOV)

Langlois, David; Noui, Karim, E-mail: langlois@apc.univ-paris7.fr, E-mail: karim.noui@lmpt.univ-tours.fr

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 degeneratemore » 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.« less

Acquired hepatocerebral degeneration: A case report

PubMed Central

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

2005-01-01

AIM: Acquired hepatocerebral degeneration (AHD) is an exceptional type of hepatic encephalopathies (HE). It is characterized by neuropsychiatric and extrapyramidal symptomathology similar to that seen in hepatolenticular degeneration (Wilson’s disease). In this paper, we report a case of AHD with unusual presenting features. METHODS: A 28-year-old man with AHD was described and the literature was reviewed. RESULTS: The man had a history of HBV-related liver cirrhosis. He was admitted to our hospital with apathy, dysarthria, mild consciousness impairment and extrapyramidal symptoms after hematemesis. By review of the literature, cases with AHD often did not present consciousness impairment. So our case was once diagnosed incorrectly as Wilson’s disease. CONCLUSION: AHD is a rare syndrome and its variable clinical manifestations make it difficult to be diagnosed. But we believe that extensive examination and thorough understanding of the disease are beneficial to a correct diagnosis. Moreover, biocoene is effective in treating the case. PMID:15655841

Adolescent disc degeneration--no headache association.

PubMed

Laimi, K; Erkintalo, M; Metsähonkala, L; Vahlberg, T; Mikkelsson, M; Sonninen, P; Parkkola, R; Aromaa, M; Sillanpäa, M; Rautava, P; Anttila, P; Salminen, J

2007-01-01

The objective of the study was to determine whether adolescents with headache have more disc degeneration in the cervical spine than headache-free controls. This study is part of a population-based follow-up study of adolescents with and without headache. At the age of 17 years, adolescents with headache at least three times a month (N = 47) and adolescents with no headache (N = 22) participated in a magnetic resonance imaging (MRI) study of the cervical spine. Of the 47 headache sufferers, 17 also had weekly neck pain and 30 had neck pain less than once a month. MRI scans were interpreted independently by three neuroradiologists. Disc degeneration was found in 67% of participants, with no difference between adolescents with and without headache. Most of the degenerative changes were located in the lower cervical spine. In adolescence, mild degenerative changes of the cervical spine are surprisingly common but do not contribute to headache.

Atomic rate coefficients in a degenerate plasma

NASA Astrophysics Data System (ADS)

Aslanyan, Valentin; Tallents, Greg

2015-11-01

The electrons in a dense, degenerate plasma follow Fermi-Dirac statistics, which deviate significantly in this regime from the usual Maxwell-Boltzmann approach used by many models. We present methods to calculate the atomic rate coefficients for the Fermi-Dirac distribution and present a comparison of the ionization fraction of carbon calculated using both models. We have found that for densities close to solid, although the discrepancy is small for LTE conditions, there is a large divergence from the ionization fraction by using classical rate coefficients in the presence of strong photoionizing radiation. We have found that using these modified rates and the degenerate heat capacity may affect the time evolution of a plasma subject to extreme ultraviolet and x-ray radiation such as produced in free electron laser irradiation of solid targets.

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. Copyright © 2016 Elsevier Ltd. All rights reserved.

Human Cartilage Endplate Permeability Varies with Degeneration and Intervertebral Disc Site

PubMed Central

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

2016-01-01

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

[Vitreomacular adhesion in HD-OCT images in the age-related macular degeneration].

PubMed

Latalska, Małgorzata; Swiech-Zubilewicz, Anna; Mackiewicz, Jerzy

2013-01-01

The aim of this study was to evaluate an incidence of the vitreomacular adhesion in patients with age-related macular degeneration. We examined 472 eyes in 241 patients (136 W/ 105 M) in age of 54-92 years (mean 62.6 years +/- 8.5) with dry or wet age-related macular degeneration using Cirrus HD-OCT (Zeiss) macular cube 512x128 program or 5-line pro-gram. Vitreomacular adhesion was observed in 139 eyes with dry age-related macular degeneration (29.4%, p=0.000*), in 101 eyes with drusen (21.4%, p=0.000*), in 38 eyes with retinal pigment epithelium alterations (8%, p=0.202), in 278 eyes with wet age-related macular degeneration (58.9%, p=0.001*), in 21 eyes with pigment epithelial detachment (4.4%, p=0.303), in 161 eyes with choroidal neovascularzation (34. 1%, p=0.031*/ and in 96 eyes with scar (20.4%, p=0.040*). Probably, vitreomacular adhesion alone is not able to induce age-related macular degeneration, but it may be associated with choroidal neovascularization development, it can contribute to exudate formation and choroidal neovascularization, it may induces or sustains a chronic low-grade inflammation in the macula region.

Impact of age-related macular degeneration in patients with glaucoma: understanding the patients' perspective.

PubMed

Skalicky, Simon E; Fenwick, Eva; Martin, Keith R; Crowston, Jonathan; Goldberg, Ivan; McCluskey, Peter

2016-07-01

The aim of the study is to measure the impact of age-related macular degeneration on vision-related activity limitation and preference-based status for glaucoma patients. This was a cross-sectional study. Two-hundred glaucoma patients of whom 73 had age-related macular degeneration were included in the research. Sociodemographic information, visual field parameters and visual acuity were collected. Age-related macular degeneration was scored using the Age-Related Eye Disease Study system. The Rasch-analysed Glaucoma Activity Limitation-9 and the Visual Function Questionnaire Utility Index measured vision-related activity limitation and preference-based status, respectively. Regression models determined factors predictive of vision-related activity limitation and preference-based status. Differential item functioning compared Glaucoma Activity Limitation-9 item difficulty for those with and without age-related macular degeneration. Mean age was 73.7 (±10.1) years. Lower better eye mean deviation (β: 1.42, 95% confidence interval: 1.24-1.63, P < 0.001) and age-related macular degeneration (β: 1.26 95% confidence interval: 1.10-1.44, P = 0.001) were independently associated with worse vision-related activity limitation. Worse eye visual acuity (β: 0.978, 95% confidence interval: 0.961-0.996, P = 0.018), high risk age-related macular degeneration (β: 0.981, 95% confidence interval: 0.965-0.998, P = 0.028) and severe glaucoma (β: 0.982, 95% confidence interval: 0.966-0.998, P = 0.032) were independently associated with worse preference-based status. Glaucoma patients with age-related macular degeneration found using stairs, walking on uneven ground and judging distances of foot to step/curb significantly more difficult than those without age-related macular degeneration. Vision-related activity limitation and preference-based status are negatively impacted by severe glaucoma and age-related macular degeneration. Patients with both conditions

Degeneration modulates retinal response to transient exogenous oxidative injury.

PubMed

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

2014-01-01

Oxidative injury is involved in retinal and macular degeneration. We aim to assess if retinal degeneration associated with genetic defect modulates the retinal threshold for encountering additional oxidative challenges. Retinal oxidative injury was induced in degenerating retinas (rd10) and in control mice (WT) by intravitreal injections of paraquat (PQ). Retinal function and structure was evaluated by electroretinogram (ERG) and histology, respectively. Oxidative injury was assessed by immunohistochemistry for 4-Hydroxy-2-nonenal (HNE), and by Thiobarbituric Acid Reactive Substances (TBARS) and protein carbonyl content (PCC) assays. Anti-oxidant mechanism was assessed by quantitative real time PCR (QPCR) for mRNA of antioxidant genes and genes related to iron metabolism, and by catalase activity assay. Three days following PQ injections (1 µl of 0.25, 0.75, and 2 mM) the average ERG amplitudes decreased more in the WT mice compared with the rd10 mice. For example, following 2 mM PQ injection, ERG amplitudes reduced 1.84-fold more in WT compared with rd10 mice (p = 0.02). Injection of 4 mM PQ resulted in retinal destruction. Altered retina morphology associated with PQ was substantially more severe in WT eyes compared with rd10 eyes. Oxidative injury according to HNE staining and TBARS assay increased 1.3-fold and 2.1-fold more, respectively, in WT compared with rd10 mice. At baseline, prior to PQ injection, mRNA levels of antioxidant genes (Superoxide Dismutase1, Glutathione Peroxidase1, Catalase) and of Transferrin measured by quantitative PCR were 2.1-7.8-fold higher in rd10 compared with WT mice (p<0.01 each), and catalase activity was 1.7-fold higher in rd10 (p = 0.0006). This data suggests that degenerating rd10 retinas encounter a relatively lower degree of damage in response to oxidative injury compared with normal retinas. Constitutive up-regulation of the oxidative defense mechanism in degenerating retinas may confer such relative protection from

Degeneration Modulates Retinal Response to Transient Exogenous Oxidative Injury

PubMed Central

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

2014-01-01

Purpose Oxidative injury is involved in retinal and macular degeneration. We aim to assess if retinal degeneration associated with genetic defect modulates the retinal threshold for encountering additional oxidative challenges. Methods Retinal oxidative injury was induced in degenerating retinas (rd10) and in control mice (WT) by intravitreal injections of paraquat (PQ). Retinal function and structure was evaluated by electroretinogram (ERG) and histology, respectively. Oxidative injury was assessed by immunohistochemistry for 4-Hydroxy-2-nonenal (HNE), and by Thiobarbituric Acid Reactive Substances (TBARS) and protein carbonyl content (PCC) assays. Anti-oxidant mechanism was assessed by quantitative real time PCR (QPCR) for mRNA of antioxidant genes and genes related to iron metabolism, and by catalase activity assay. Results Three days following PQ injections (1 µl of 0.25, 0.75, and 2 mM) the average ERG amplitudes decreased more in the WT mice compared with the rd10 mice. For example, following 2 mM PQ injection, ERG amplitudes reduced 1.84-fold more in WT compared with rd10 mice (p = 0.02). Injection of 4 mM PQ resulted in retinal destruction. Altered retina morphology associated with PQ was substantially more severe in WT eyes compared with rd10 eyes. Oxidative injury according to HNE staining and TBARS assay increased 1.3-fold and 2.1-fold more, respectively, in WT compared with rd10 mice. At baseline, prior to PQ injection, mRNA levels of antioxidant genes (Superoxide Dismutase1, Glutathione Peroxidase1, Catalase) and of Transferrin measured by quantitative PCR were 2.1–7.8-fold higher in rd10 compared with WT mice (p<0.01 each), and catalase activity was 1.7-fold higher in rd10 (p = 0.0006). Conclusions This data suggests that degenerating rd10 retinas encounter a relatively lower degree of damage in response to oxidative injury compared with normal retinas. Constitutive up-regulation of the oxidative defense mechanism in degenerating retinas

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

PubMed Central

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

2013-01-01

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

Treatment of Macular Degeneration with Sildenafil: Results of a Two-Year Trial.

PubMed

Coleman, D Jackson; Lee, Winston; Chang, Stanley; Silverman, Ronald H; Lloyd, Harriet O; Daly, Suzanne; Tsang, Stephen H

2018-04-25

To evaluate PDE5/6 inhibition with sildenafil to reduce choroidal ischemia and treat age-related macular degeneration. Sildenafil was prescribed to treat participants with macular degenerations or macular dystrophies measured by spectral-domain optical coherence tomography, color fundus photography, enhanced depth imaging, and best-corrected visual acuity. No change in calcified drusen was noted. Vitelliform-type soft drusen were not substantially changed. A participant with Best vitelliform macular dystrophy had a significant improvement in vision as well as in photoreceptor and ellipsoid layers. Our research supports sildenafil as a safe treatment for age-related and vitelliform macular degenerations. Thickened Bruch's membrane reduces the beneficial effect of perfusion increase, but all eyes appear to benefit from PDE6. Notably, maintenance or improvement in the photoreceptor layer may be the most significant result of sildenafil and is consistent with PDE6 inhibition. Thus, sil-denafil treatment of macular degeneration offers significant potential for vision retention and recovery. © 2018 S. Karger AG, Basel.

Effect of pharmacologically induced retinal degeneration on retinal autofluorescence lifetimes in mice.

PubMed

Dysli, Chantal; Dysli, Muriel; Zinkernagel, Martin S; Enzmann, Volker

2016-12-01

Fluorescence lifetime imaging ophthalmoscopy (FLIO) was used to investigate retinal autofluorescence lifetimes in mouse models of pharmacologically induced retinal degeneration over time. Sodium iodate (NaIO 3 , 35 mg/kg intravenously) was used to induce retinal pigment epithelium (RPE) degeneration with subsequent loss of photoreceptors (PR) whereas N-methyl-N-nitrosourea (MNU, 45 mg/kg intraperitoneally) was employed for degeneration of the photoreceptor cell layer alone. All mice were measured at day 3, 7, 14, and 28 after the respective injection of NaIO 3 , MNU or NaCl (control). Fluorescence lifetime imaging was performed using a fluorescence lifetime imaging ophthalmoscope (Heidelberg Engineering, Heidelberg, Germany). Fluorescence was excited at 473 nm and fluorescence lifetimes were measured in a short and a long spectral channel (498-560 nm and 560-720 nm). Corresponding optical coherence tomography (OCT) images were consecutively acquired and histology was performed at the end of the experiments. Segmentation of OCT images and histology verified the cell type-specific degeneration process over time. Retinal autofluorescence lifetimes increased from day 3 to day 28 in mice after NaIO 3 treatment. Finally, at day 28, fluorescence lifetimes were prolonged by 8% in the short and 61% in the long spectral channel compared to control animals (p = 0.21 and p = 0.004, respectively). In mice after MNU treatment, the mean retinal autofluorescence lifetimes were already decreased at day 3 and retinal lifetimes were finally shortened by 27% in the short and 51% in the long spectral channel at day 28 (p = 0.0028). In conclusion, degeneration of the RPE with subsequent photoreceptor degeneration by NaIO 3 lead to longer mean fluorescence lifetimes of the retina compared to control mice, whereas during specific degeneration of the photoreceptor layer induced by MNU shorter lifetimes were measured. Therefore, short retinal fluorescence lifetimes may originate

An Unconventional Approach to Reducing Retinal Degeneration After Traumatic Ocular Injury

DTIC Science & Technology

2017-09-01

AWARD NUMBER: W81XWH-15-1-0138 TITLE: An Unconventional Approach to Reducing Retinal Degeneration After Traumatic Ocular Injury PRINCIPAL...2015 - 30 Jun 2017 4. TITLE AND SUBTITLE An Unconventional Approach to Reducing Retinal Degeneration After Traumatic Ocular Injury 5 a . CONTRACT...optic confocal microscope system , test it, and establish protocols for the first successful in vivo retinal microvessel and pericyte advanced

Asymptotic coincidence of the statistics for degenerate and non-degenerate correlated real Wishart ensembles

NASA Astrophysics Data System (ADS)

Wirtz, Tim; Kieburg, Mario; Guhr, Thomas

2017-06-01

The correlated Wishart model provides the standard benchmark when analyzing time series of any kind. Unfortunately, the real case, which is the most relevant one in applications, poses serious challenges for analytical calculations. Often these challenges are due to square root singularities which cannot be handled using common random matrix techniques. We present a new way to tackle this issue. Using supersymmetry, we carry out an anlaytical study which we support by numerical simulations. For large but finite matrix dimensions, we show that statistical properties of the fully correlated real Wishart model generically approach those of a correlated real Wishart model with doubled matrix dimensions and doubly degenerate empirical eigenvalues. This holds for the local and global spectral statistics. With Monte Carlo simulations we show that this is even approximately true for small matrix dimensions. We explicitly investigate the k-point correlation function as well as the distribution of the largest eigenvalue for which we find a surprisingly compact formula in the doubly degenerate case. Moreover we show that on the local scale the k-point correlation function exhibits the sine and the Airy kernel in the bulk and at the soft edges, respectively. We also address the positions and the fluctuations of the possible outliers in the data.

Ernest Borgnine Lays it on the Line Hollywood Hero Focuses on Macular Degeneration

MedlinePlus

... it on the Line Hollywood Hero Focuses on Macular Degeneration Past Issues / Summer 2008 Table of Contents For ... going strong at 91, and speaking out on macular degeneration for the National Eye Institute. Photo courtesy of ...

Juvenile Macular Degenerations.

PubMed

Altschwager, Pablo; Ambrosio, Lucia; Swanson, Emily A; Moskowitz, Anne; Fulton, Anne B

2017-05-01

In this article, we review the following 3 common juvenile macular degenerations: Stargardt disease, X-linked retinoschisis, and Best vitelliform macular dystrophy. These are inherited disorders that typically present during childhood, when vision is still developing. They are sufficiently common that they should be included in the differential diagnosis of visual loss in pediatric patients. Diagnosis is secured by a combination of clinical findings, optical coherence tomography imaging, and genetic testing. Early diagnosis promotes optimal management. Although there is currently no definitive cure for these conditions, therapeutic modalities under investigation include pharmacologic treatment, gene therapy, and stem cell transplantation. Copyright © 2017 Elsevier Inc. All rights reserved.

Correlations between the feature of sagittal spinopelvic alignment and facet joint degeneration: a retrospective study.

PubMed

Lv, Xin; Liu, Yuan; Zhou, Song; Wang, Qiang; Gu, Houyun; Fu, Xiaoxing; Ding, Yi; Zhang, Bin; Dai, Min

2016-08-15

Sagittal spinopelvic alignment changes associated with degenerative facet joint arthritis have been assessed in a few studies. It has been documented that patients with facet joint degeneration have higher pelvic incidence, but the relationship between facet joint degeneration and other sagittal spinopelvic alignment parameters is still disputed. Our purpose was to evaluate the correlation between the features of sagittal spinopelvic alignment and facet joint degeneration. Imaging data of 140 individuals were retrospectively analysed. Lumbar lordosis, pelvic tilt (PT), pelvic incidence (PI), sacral slope, and height of the lumbar intervertebral disc were measured on lumbar X-ray plates. Grades of facet joint degeneration were evaluated from the L2 to S1 on CT scans. Spearman's rank correlation coefficient and Student's t-test were used for statistical analyses, and a P-value <0.05 was considered statistically significant. PI was positively associated with degeneration of the facet joint at lower lumbar levels (p < 0.001 r = 0.50 at L5/S1 and P = 0.002 r = 0.25 at L4/5). A significant increase of PT was found in the severe degeneration group compared with the mild degeneration group: 22.0° vs 15.7°, P = 0.034 at L2/3;21.4°vs 15.1°, P = 0.006 at L3/4; 21.0° vs 13.5°, P = 0.000 at L4/5; 20.8° vs 12.1°, P = 0.000 at L5/S1. Our results indicate that a high PI is a predisposing factor for facet joint degeneration at the lower lumbar spine, and that severe facet joint degeneration may accompany with greater PT at lumbar spine.

CODEHOP (COnsensus-DEgenerate Hybrid Oligonucleotide Primer) PCR primer design

PubMed Central

Rose, Timothy M.; Henikoff, Jorja G.; Henikoff, Steven

2003-01-01

We have developed a new primer design strategy for PCR amplification of distantly related gene sequences based on consensus-degenerate hybrid oligonucleotide primers (CODEHOPs). An interactive program has been written to design CODEHOP PCR primers from conserved blocks of amino acids within multiply-aligned protein sequences. Each CODEHOP consists of a pool of related primers containing all possible nucleotide sequences encoding 3–4 highly conserved amino acids within a 3′ degenerate core. A longer 5′ non-degenerate clamp region contains the most probable nucleotide predicted for each flanking codon. CODEHOPs are used in PCR amplification to isolate distantly related sequences encoding the conserved amino acid sequence. The primer design software and the CODEHOP PCR strategy have been utilized for the identification and characterization of new gene orthologs and paralogs in different plant, animal and bacterial species. In addition, this approach has been successful in identifying new pathogen species. The CODEHOP designer (http://blocks.fhcrc.org/codehop.html) is linked to BlockMaker and the Multiple Alignment Processor within the Blocks Database World Wide Web (http://blocks.fhcrc.org). PMID:12824413

Characterization of an Early-Onset, Autosomal Recessive, Progressive Retinal Degeneration in Bengal Cats.

PubMed

Ofri, Ron; Reilly, Christopher M; Maggs, David J; Fitzgerald, Paul G; Shilo-Benjamini, Yael; Good, Kathryn L; Grahn, Robert A; Splawski, Danielle D; Lyons, Leslie A

2015-08-01

A form of retinal degeneration suspected to be hereditary was discovered in a family of Bengal cats. A breeding colony was established to characterize disease progression clinically, electrophysiologically, and morphologically, and to investigate the mode of inheritance. Affected and related cats were donated by owners for breeding trials and pedigree analysis. Kittens from test and complementation breedings underwent ophthalmic and neuro-ophthalmic examinations and ERG, and globes were evaluated using light microscopy. Pedigree analysis, along with test and complementation breedings, indicated autosomal recessive inheritance and suggested that this disease is nonallelic to a retinal degeneration found in Persian cats. Mutation analysis confirmed the disease is not caused by CEP290 or CRX variants found predominantly in Abyssinian and Siamese cats. Ophthalmoscopic signs of retinal degeneration were noted at 9 weeks of age and became more noticeable over the next 4 months. Visual deficits were behaviorally evident by 1 year of age. Electroretinogram demonstrated reduced rod and cone function at 7 and 9 weeks of age, respectively. Rod responses were mostly extinguished at 14 weeks of age; cone responses were minimal by 26 weeks. Histologic degeneration was first observed at 8 weeks, evidenced by reduced photoreceptor numbers, then rapid deterioration of the photoreceptor layer and, subsequently, severe outer retinal degeneration. A recessively inherited primary photoreceptor degeneration was characterized in the Bengal cat. The disease is characterized by early onset, with histologic, ophthalmoscopic, and electrophysiological signs evident by 2 months of age, and rapid progression to blindness.

White Dwarf WD-1145+17 "Zombie Star" Consumes Asteroid

NASA Astrophysics Data System (ADS)

Kaye, Thomas G.; Gary, Bruce L.; Rappaport, Saul A.; Foote, Jerry, Benni, Paul

2016-05-01

It has long been suspected that white dwarfs accrete asteroid debris as evidenced by heavy metals in many white dwarf spectra. WD1145 was initially detected in Kepler data as an exoplanet candidate with a repeating 1.3% dip over the course of the Jul-Sep 2014 observing season. Follow-up ground based observations were conducted with professional telescopes during March through May of 2015, and these showed that the Kepler dip must likely consist of deeper and shorter dips which come and go with an uncertain pattern. It was hypothesized that the observations were due to an asteroid in a 4.5 hour orbit. In anticipation of its return to nighttime visibility, major observatories scheduled time starting in 2016 Feb. A pro/am collaboration was formed in late 2015 for amateur observations prior to the 2016 Feb professional observations in order to determine an ephemeris for fade activity for the purpose of scheduling relatively short observations with professional telescopes. The amateur observations began in 2015 Nov, sooner than requested, and they showed that the fade activity level had exploded, becoming 20 times the level measured by Kepler. As many as 13 different fades per 4.5-hour orbit were measured, and these varied in depth from night to night. The amateur project turned into a full assault on the star with as many as 4 amateur telescopes observing on the same night. Continuous monitoring mysteriously showed that the clouds drifted in phase with respect to the dominant period i.e., they have a shorter period than measured by Kepler; this would imply that the orbiting dust clouds were located inside the orbit of the parent planetesimal. The best model indicated that the parent planetesimal was releasing fragments from inside its Hill sphere at the L1 Lagrange point, causing them to fall into an inner orbit. New astrophysics was described for the first time when the team used the diameter of the planetesimal orbit, and the diameter of the drift fragment orbit, to

A Layered Approach to Raising Public Awareness of Macular Degeneration in Australia

PubMed Central

Heraghty, Julie; Cummins, Robert

2012-01-01

Between 2007 and 2011, the Australian Macular Degeneration Foundation conducted a multifaceted campaign to increase public awareness of macular degeneration. Regular national polls conducted by an independent social research company have shown that awareness of macular degeneration increased from 47% to 80% in Australians aged 16 years or older and from 58% to 92% in those aged 50 years or older. The percentage of people aged 50 years or older who reported having had their macula checked in the 2 years prior to the survey increased from 33% to 70% from 2007 to 2011. Other measures, including analysis of Medicare data, have confirmed the success of the campaign. PMID:22813341

Age-related macular degeneration

PubMed Central

Querques, Giuseppe; Avellis, Fernando Onofrio; Querques, Lea; Bandello, Francesco; Souied, Eric H

2011-01-01

Clinical question: Is there any new knowledge about the pathogenesis and treatment of age-related macular degeneration (AMD)? Results: We now understand better the biochemical and pathological pathways involved in the genesis of AMD. Treatment of exudative AMD is based on intravitreal injection of new antivascular endothelial growth factor drugs for which there does not yet exist a unique recognized strategy of administration. No therapies are actually available for atrophic AMD, despite some experimental new pharmacological approaches. Implementation: strategy of administration, safety of intravitreal injection PMID:21654887

SARM1-specific motifs in the TIR domain enable NAD+ loss and regulate injury-induced SARM1 activation.

PubMed

Summers, Daniel W; Gibson, Daniel A; DiAntonio, Aaron; Milbrandt, Jeffrey

2016-10-11

Axon injury in response to trauma or disease stimulates a self-destruction program that promotes the localized clearance of damaged axon segments. Sterile alpha and Toll/interleukin receptor (TIR) motif-containing protein 1 (SARM1) is an evolutionarily conserved executioner of this degeneration cascade, also known as Wallerian degeneration; however, the mechanism of SARM1-dependent neuronal destruction is still obscure. SARM1 possesses a TIR domain that is necessary for SARM1 activity. In other proteins, dimerized TIR domains serve as scaffolds for innate immune signaling. In contrast, dimerization of the SARM1 TIR domain promotes consumption of the essential metabolite NAD + and induces neuronal destruction. This activity is unique to the SARM1 TIR domain, yet the structural elements that enable this activity are unknown. In this study, we identify fundamental properties of the SARM1 TIR domain that promote NAD + loss and axon degeneration. Dimerization of the TIR domain from the Caenorhabditis elegans SARM1 ortholog TIR-1 leads to NAD + loss and neuronal death, indicating these activities are an evolutionarily conserved feature of SARM1 function. Detailed analysis of sequence homology identifies canonical TIR motifs as well as a SARM1-specific (SS) loop that are required for NAD + loss and axon degeneration. Furthermore, we identify a residue in the SARM1 BB loop that is dispensable for TIR activity yet required for injury-induced activation of full-length SARM1, suggesting that SARM1 function requires multidomain interactions. Indeed, we identify a physical interaction between the autoinhibitory N terminus and the TIR domain of SARM1, revealing a previously unrecognized direct connection between these domains that we propose mediates autoinhibition and activation upon injury.

Acidic pH promotes intervertebral disc degeneration: Acid-sensing ion channel -3 as a potential therapeutic target.

PubMed

Gilbert, Hamish T J; Hodson, Nathan; Baird, Pauline; Richardson, Stephen M; Hoyland, Judith A

2016-11-17

The aetiology of intervertebral disc (IVD) degeneration remains poorly understood. Painful IVD degeneration is associated with an acidic intradiscal pH but the response of NP cells to this aberrant microenvironmental factor remains to be fully characterised. The aim here was to address the hypothesis that acidic pH, similar to that found in degenerate IVDs, leads to the altered cell/functional phenotype observed during IVD degeneration, and to investigate the involvement of acid-sensing ion channel (ASIC) -3 in the response. Human NP cells were treated with a range of pH, from that of a non-degenerate (pH 7.4 and 7.1) through to mildly degenerate (pH 6.8) and severely degenerate IVD (pH 6.5 and 6.2). Increasing acidity of pH caused a decrease in cell proliferation and viability, a shift towards matrix catabolism and increased expression of proinflammatory cytokines and pain-related factors. Acidic pH resulted in an increase in ASIC-3 expression. Importantly, inhibition of ASIC-3 prevented the acidic pH induced proinflammatory and pain-related phenotype in NP cells. Acidic pH causes a catabolic and degenerate phenotype in NP cells which is inhibited by blocking ASIC-3 activity, suggesting that this may be a useful therapeutic target for treatment of IVD degeneration.

Congenital Head Nodding and Nystagmus with Cerebrocerebellar Degeneration

ERIC Educational Resources Information Center

Kalyanaraman, K.; And Others

1973-01-01

Reported are three case histories of children with congenital head nodding and nystagmus (rhytmic oscillation of the eyeballs) associated with brain degeneration and motor and mental retardation. (DB)

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,…

WD-repeat instability and diversification of the Podospora anserina hnwd non-self recognition gene family.

PubMed

Chevanne, Damien; Saupe, Sven J; Clavé, Corinne; Paoletti, Mathieu

2010-05-06

Genes involved in non-self recognition and host defence are typically capable of rapid diversification and exploit specialized genetic mechanism to that end. Fungi display a non-self recognition phenomenon termed heterokaryon incompatibility that operates when cells of unlike genotype fuse and leads to the cell death of the fusion cell. In the fungus Podospora anserina, three genes controlling this allorecognition process het-d, het-e and het-r are paralogs belonging to the same hnwd gene family. HNWD proteins are STAND proteins (signal transduction NTPase with multiple domains) that display a WD-repeat domain controlling recognition specificity. Based on genomic sequence analysis of different P. anserina isolates, it was established that repeat regions of all members of the gene family are extremely polymorphic and undergoing concerted evolution arguing for frequent recombination within and between family members. Herein, we directly analyzed the genetic instability and diversification of this allorecognition gene family. We have constituted a collection of 143 spontaneous mutants of the het-R (HNWD2) and het-E (hnwd5) genes with altered recognition specificities. The vast majority of the mutants present rearrangements in the repeat arrays with deletions, duplications and other modifications as well as creation of novel repeat unit variants. We investigate the extreme genetic instability of these genes and provide a direct illustration of the diversification strategy of this eukaryotic allorecognition gene family.

Advances in repairing the degenerate retina by rod photoreceptor transplantation☆

PubMed Central

Pearson, Rachael A.

2014-01-01

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

Novel regulation of Skp1 by the Dictyostelium AgtA α-galactosyltransferase involves the Skp1-binding activity of its WD40 repeat domain.

PubMed

Schafer, Christopher M; Sheikh, M Osman; Zhang, Dongmei; West, Christopher M

2014-03-28

The role of Skp1 as an adaptor protein that links Cullin-1 to F-box proteins in E3 Skp1/Cullin-1/F-box protein (SCF) ubiquitin ligases is well characterized. In the social amoeba Dictyostelium and probably many other unicellular eukaryotes, Skp1 is modified by a pentasaccharide attached to a hydroxyproline near its C terminus. This modification is important for oxygen-sensing during Dictyostelium development and is mediated by a HIF-α type prolyl 4-hydroxylase and five sequentially acting cytoplasmic glycosyltransferase activities. Gene disruption studies show that AgtA, the enzyme responsible for addition of the final two galactose residues, in α-linkages to the Skp1 core trisaccharide, is unexpectedly critical for oxygen-dependent terminal development. AgtA possesses a WD40 repeat domain C-terminal to its single catalytic domain and, by use of domain deletions, binding studies, and enzyme assays, we find that the WD40 repeats confer a salt-sensitive second-site binding interaction with Skp1 that mediates novel catalytic activation in addition to simple substrate recognition. In addition, AgtA binds similarly well to precursor isoforms of Skp1 by a salt-sensitive mechanism that competes with binding to an F-box protein and recognition by early modification enzymes, and the effect of binding is diminished when AgtA modifies Skp1. Genetic studies show that loss of AgtA is more severe when an earlier glycosylation step is blocked, and overexpressed AgtA is deleterious if catalytically inactivated. Together, the findings suggest that AgtA mediates non-enzymatic control of unmodified and substrate precursor forms of Skp1 by a binding mechanism that is normally relieved by switch-like activation of its glycosylation function.

Novel Regulation of Skp1 by the Dictyostelium AgtA α-Galactosyltransferase Involves the Skp1-binding Activity of Its WD40 Repeat Domain*

PubMed Central

Schafer, Christopher M.; Sheikh, M. Osman; Zhang, Dongmei; West, Christopher M.

2014-01-01

The role of Skp1 as an adaptor protein that links Cullin-1 to F-box proteins in E3 Skp1/Cullin-1/F-box protein (SCF) ubiquitin ligases is well characterized. In the social amoeba Dictyostelium and probably many other unicellular eukaryotes, Skp1 is modified by a pentasaccharide attached to a hydroxyproline near its C terminus. This modification is important for oxygen-sensing during Dictyostelium development and is mediated by a HIF-α type prolyl 4-hydroxylase and five sequentially acting cytoplasmic glycosyltransferase activities. Gene disruption studies show that AgtA, the enzyme responsible for addition of the final two galactose residues, in α-linkages to the Skp1 core trisaccharide, is unexpectedly critical for oxygen-dependent terminal development. AgtA possesses a WD40 repeat domain C-terminal to its single catalytic domain and, by use of domain deletions, binding studies, and enzyme assays, we find that the WD40 repeats confer a salt-sensitive second-site binding interaction with Skp1 that mediates novel catalytic activation in addition to simple substrate recognition. In addition, AgtA binds similarly well to precursor isoforms of Skp1 by a salt-sensitive mechanism that competes with binding to an F-box protein and recognition by early modification enzymes, and the effect of binding is diminished when AgtA modifies Skp1. Genetic studies show that loss of AgtA is more severe when an earlier glycosylation step is blocked, and overexpressed AgtA is deleterious if catalytically inactivated. Together, the findings suggest that AgtA mediates non-enzymatic control of unmodified and substrate precursor forms of Skp1 by a binding mechanism that is normally relieved by switch-like activation of its glycosylation function. PMID:24550398

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

PubMed

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

2013-02-05

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

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

PubMed Central

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

2009-01-01

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

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

PubMed

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

2009-01-01

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

STUDIES UPON CALCAREOUS DEGENERATION

PubMed Central

Klotz, Oskar

1905-01-01

It will be seen from the above that we have studied the conditions associated with the deposit of calcareous salts: (I) in connection with normal and pathological ossification, and (2) in pathological calcification as exhibited in (a) atheroma of the vessels; (b) calcification of caseating tubercular lesions; (c) calcification of inflammatory new growth, and (d) degenerating tumors; and we have induced experimentally deposits of calcareous salts in the lower animals: (a) within celloidin capsules containing fats and soaps; (b) in the kidney, and (c) in connection with fat necrosis. I. We have found that bone formation and pathological calcareous infiltration are wholly distinct processes. In the former there is no evidence of associated fatty change, and the cells associated with the process of deposition of calcium are functionally active. In the latter there is an antecedent fatty change in the affected areas, and the cells involved present constant evidences of degeneration. The view that would seem to account best for the changes observed in the latter case is that with lowered vitality the cells are unable to utilize the products brought to them by the blood, or which they continue to absorb, so that the normal series of decompositions associated with their metabolism fails to take place and hence they interact among themselves in the cytoplasm with the result that insoluble compounds replace soluble ones. II. Besides the fact that calcification is always preceded by fatty change within the cells, another fact should be emphasized. namely: that combination of the fats present with calcium salts to form calcium soaps tends to occur. The stages immediately preceding these are difficult to follow with anything approaching certainty, perhaps because the earlier stages vary under different conditions. In fat necrosis, for instance, the cells affected are normally storehouses for neutral fats, and as long as they remain healthy neutral fats alone are present in them

[Age-related macular degeneration as a local manifestation of atherosclerosis - a novel insight into pathogenesis].

PubMed

Machalińska, Anna

2013-01-01

Age-related macular degeneration is the leading cause of irreversible visual impairment and disability among the elderly in developed countries. There is compelling evidence that atherosclerosis and age-related macular degeneration share a similar pathogenic process. The association between atherosclerosis and age-related macular degeneration has been inferred from histological, biochemical and epidemiological studies. Many published data indicate that drusen are similar in molecular composition to plaques in atherosclerosis. Furthermore, a great body of evidence has emerged over the past decade that implicates the chronic inflammatory processes in the pathogenesis and progression of both disorders. We speculate that vascular atherosclerosis and age-related macular degeneration may represent different manifestations of the same disease induced by a pathologic tissue response to the damage caused by oxidative stress and local ischemia. In this review, we characterise in detail a strong association between age-related macular degeneration and atherosclerosis development, and we postulate the hypothesis that age-related macular degeneration is a local manifestation of a systemic disease. This provides a new approach for understanding the aspects of pathogenesis and might improve the prevention and treatment of both diseases which both result from ageing of the human body.

Fully nonlinear heavy ion-acoustic solitary waves in astrophysical degenerate relativistic quantum plasmas

NASA Astrophysics Data System (ADS)

Sultana, S.; Schlickeiser, R.

2018-05-01

Fully nonlinear features of heavy ion-acoustic solitary waves (HIASWs) have been investigated in an astrophysical degenerate relativistic quantum plasma (ADRQP) containing relativistically degenerate electrons and non-relativistically degenerate light ion species, and non-degenerate heavy ion species. The pseudo-energy balance equation is derived from the fluid dynamical equations by adopting the well-known Sagdeev-potential approach, and the properties of arbitrary amplitude HIASWs are examined. The small amplitude limit for the propagation of HIASWs is also recovered. The basic features (width, amplitude, polarity, critical Mach number, speed, etc.) of HIASWs are found to be significantly modified by the relativistic effect of the electron species, and also by the variation of the number density of electron, light ion, and heavy ion species. The basic properties of HIASWs, that may propagated in some realistic astrophysical plasma systems (e.g., in white dwarfs), are briefly discussed.

Mutant WDR36 directly affects axon growth of retinal ganglion cells leading to progressive retinal degeneration in mice

PubMed Central

Chi, Zai-Long; Yasumoto, Fumie; Sergeev, Yuri; Minami, Masayoshi; Obazawa, Minoru; Kimura, Itaru; Takada, Yuichiro; Iwata, Takeshi

2010-01-01

Primary open-angle glaucoma (POAG) is one of the three principal subtypes of glaucoma and among the leading cause of blindness worldwide. POAG is defined by cell death of the retinal ganglion cells (RGCs) and surrounding neuronal cells at higher or normal intraocular pressure (IOP). Coded by one of the three genes responsible for POAG, WD repeat-containing protein 36 (WDR36) has two domains with a similar folding. To address whether WDR36 is functionally important in the retina, we developed four transgenic mice strains overexpressing a wild-type (Wt) and three mutant variants of D606G, deletion of amino acids at positions 605–607 (Del605–607) and at 601–640 (Del601–640) equivalent to the location of the D658G mutation observed in POAG patients. A triple amino acid deletion of mouse Wdr36 at positions 605–607 corresponding to the deletion at positions 657–659 in humans developed progressive retinal degeneration at the peripheral retina with normal IOP. RGCs and connecting amacrine cell synapses were affected at the peripheral retina. Axon outgrowth rate of cultured RGC directly isolated from transgenic animal was significantly reduced by the Wdr36 mutation compared with Wt. Molecular modeling of wild and mutant mouse Wdr36 revealed that deletion at positions 605–607 removed three residues and a hydrogen bond, required to stabilize anti-parallel β-sheet of the 6th β-propeller in the second domain. We concluded that WDR36 plays an important functional role in the retina homeostasis and mutation to this gene can cause devastating retinal damage. These data will improve understanding of the functional property of WDR36 in the retina and provide a new animal model for glaucoma therapeutics. PMID:20631153

AlphaB-crystallin regulates remyelination after peripheral nerve injury

PubMed Central

Lim, Erin-Mai F.; Nakanishi, Stan T.; Hoghooghi, Vahid; Eaton, Shane E. A.; Palmer, Alexandra L.; Frederick, Ariana; Stratton, Jo A.; Stykel, Morgan G.; Zochodne, Douglas W.; Biernaskie, Jeffrey; Ousman, Shalina S.

2017-01-01

AlphaB-crystallin (αBC) is a small heat shock protein that is constitutively expressed by peripheral nervous system (PNS) axons and Schwann cells. To determine what role this crystallin plays after peripheral nerve damage, we found that loss of αBC impaired remyelination, which correlated with a reduced presence of myelinating Schwann cells and increased numbers of nonmyelinating Schwann cells. The heat shock protein also seems to regulate the cross-talk between Schwann cells and axons, because expected changes in neuregulin levels and ErbB2 receptor expression after PNS injury were disrupted in the absence of αBC. Such dysregulations led to defects in conduction velocity and motor and sensory functions that could be rescued with therapeutic application of the heat shock protein in vivo. Altogether, these findings show that αBC plays an important role in regulating Wallerian degeneration and remyelination after PNS injury. PMID:28137843

Characterization of an Early-Onset, Autosomal Recessive, Progressive Retinal Degeneration in Bengal Cats

PubMed Central

Ofri, Ron; Reilly, Christopher M.; Maggs, David J.; Fitzgerald, Paul G.; Shilo-Benjamini, Yael; Good, Kathryn L.; Grahn, Robert A.; Splawski, Danielle D.; Lyons, Leslie A.

2015-01-01

Purpose A form of retinal degeneration suspected to be hereditary was discovered in a family of Bengal cats. A breeding colony was established to characterize disease progression clinically, electrophysiologically, and morphologically, and to investigate the mode of inheritance. Methods Affected and related cats were donated by owners for breeding trials and pedigree analysis. Kittens from test and complementation breedings underwent ophthalmic and neuro-ophthalmic examinations and ERG, and globes were evaluated using light microscopy. Results Pedigree analysis, along with test and complementation breedings, indicated autosomal recessive inheritance and suggested that this disease is nonallelic to a retinal degeneration found in Persian cats. Mutation analysis confirmed the disease is not caused by CEP290 or CRX variants found predominantly in Abyssinian and Siamese cats. Ophthalmoscopic signs of retinal degeneration were noted at 9 weeks of age and became more noticeable over the next 4 months. Visual deficits were behaviorally evident by 1 year of age. Electroretinogram demonstrated reduced rod and cone function at 7 and 9 weeks of age, respectively. Rod responses were mostly extinguished at 14 weeks of age; cone responses were minimal by 26 weeks. Histologic degeneration was first observed at 8 weeks, evidenced by reduced photoreceptor numbers, then rapid deterioration of the photoreceptor layer and, subsequently, severe outer retinal degeneration. Conclusions A recessively inherited primary photoreceptor degeneration was characterized in the Bengal cat. The disease is characterized by early onset, with histologic, ophthalmoscopic, and electrophysiological signs evident by 2 months of age, and rapid progression to blindness. PMID:26258614

Spinogenesis in spinal cord motor neurons following pharmacological lesions to the rat motor cortex.

PubMed

Martínez-Torres, N I; González-Tapia, D; Flores-Soto, M; Vázquez-Hernández, N; Salgado-Ceballos, H; González-Burgos, I

2018-03-16

Motor function is impaired in multiple neurological diseases associated with corticospinal tract degeneration. Motor impairment has been linked to plastic changes at both the presynaptic and postsynaptic levels. However, there is no evidence of changes in information transmission from the cortex to spinal motor neurons. We used kainic acid to induce stereotactic lesions to the primary motor cortex of female adult rats. Fifteen days later, we evaluated motor function with the BBB scale and the rotarod and determined the density of thin, stubby, and mushroom spines of motor neurons from a thoracolumbar segment of the spinal cord. Spinophilin, synaptophysin, and β iii-tubulin expression was also measured. Pharmacological lesions resulted in poor motor performance. Spine density and the proportion of thin and stubby spines were greater. We also observed increased expression of the 3 proteins analysed. The clinical symptoms of neurological damage secondary to Wallerian degeneration of the corticospinal tract are associated with spontaneous, compensatory plastic changes at the synaptic level. Based on these findings, spontaneous plasticity is a factor to consider when designing more efficient strategies in the early phase of rehabilitation. Copyright © 2018 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Degenerative myelopathy and vitamin A deficiency in a young black-maned lion (Panthera leo).

PubMed

Maratea, Kimberly A; Hooser, Stephen B; Ramos-Vara, José A

2006-11-01

Degenerative myelopathy and vitamin A deficiency were diagnosed in a 1-year-old, female, black-maned lion (Panthera leo). Diffuse white matter degeneration characterized by dilated myelin sheaths, Wallerian degeneration, and reactive astrocytosis was present at all levels of the spinal cord. With luxol fast blue-resyl echt violet stain, bilaterally symmetrical demyelination was observed in the fasciculus cuneatus of the cervical spinal cord and in peripheral white matter of cervical, thoracic, and lumbar segments. Additionally, the ventral gray columns and brain stem nuclei contained rare chromatolytic neurons with abnormal neurofilament accumulation. Leptomeninges of the cervical spinal cord were focally adhered to the dura and thickened by fibrosis and osseous metaplasia. Vitamin A deficiency was diagnosed based on hepatic vitamin A concentration of 1.71 microg/g dry weight. Adequate hepatic vitamin A concentration for yearling to adult domestic animals ranges between 150 and 1000 microg/g dry weight. Lesions were distinct from those previously described in young captive lions with vitamin A deficiency, which had thickened skull bones and cerebellar herniation. The pathogenesis of vitamin A-associated myelopathy in this lion may be similar to that described in adult cattle, which is believed to result from spinal cord compression secondary to elevated pressure of cerebrospinal fluid.

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

PubMed Central

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

2013-01-01

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

The human first carpometacarpal joint: osteoarthritic degeneration and 3-dimensional modeling.

PubMed

Kovler, Maksim; Lundon, Katie; McKee, Nancy; Agur, Anne

2004-01-01

The purpose of this study was to gain insight into potential mechanical factors contributing to osteoarthritis of the human first carpometacarpal joint (CMC). This was accomplished by creating three-dimensional (3-D) computer models of the articular surfaces of CMC joints of older humans and by determining their locus of cartilage degeneration. The research questions of this study were: 1) What is the articular wear pattern of cartilage degeneration in CMC osteoarthritis?, (2) Are there significant topographic differences in joint area and contour between the joints of males and females?, and 3) Are there measurable bony joint recesses consistently found within the joint? The articular surfaces of 25 embalmed cadaveric joints (from 13 cadavers) were graded for degree of osteoarthritis, and the location of degeneration was mapped using a dissection microscope. The surfaces of 14 mildly degenerated joints were digitized and reconstructed as 3-D computer models using the Microscribe 3D-X Digitizer and the Rhinoceros 2.0 NURBS Modeling Software. This technology provided accurate and reproducible information on joint area and topography. The dorsoradial trapezial region was found to be significantly more degenerated than other quadrants in both males and females. Mean trapezial articular surface area was 197 mm 2 in males and 160 mm(2) in females; the respective mean areas for the metacarpal were 239 mm(2) in males and 184 mm(2) in females. Joints of females were found to be significantly more concave in radioulnar profile than those of males. Three bony joint recesses were consistently found, two in the radial and ulnar aspects of the trapezium and the third in the palmar surface of the metacarpal.

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…

Multi-Disciplinary, Multi-Fidelity Discrete Data Transfer Using Degenerate Geometry Forms

NASA Technical Reports Server (NTRS)

Olson, Erik D.

2016-01-01

In a typical multi-fidelity design process, different levels of geometric abstraction are used for different analysis methods, and transitioning from one phase of design to the next often requires a complete re-creation of the geometry. To maintain consistency between lower-order and higher-order analysis results, Vehicle Sketch Pad (OpenVSP) recently introduced the ability to generate and export several degenerate forms of the geometry, representing the type of abstraction required to perform low- to medium-order analysis for a range of aeronautical disciplines. In this research, the functionality of these degenerate models was extended, so that in addition to serving as repositories for the geometric information that is required as input to an analysis, the degenerate models can also store the results of that analysis mapped back onto the geometric nodes. At the same time, the results are also mapped indirectly onto the nodes of lower-order degenerate models using a process called aggregation, and onto higher-order models using a process called disaggregation. The mapped analysis results are available for use by any subsequent analysis in an integrated design and analysis process. A simple multi-fidelity analysis process for a single-aisle subsonic transport aircraft is used as an example case to demonstrate the value of the approach.

Mitofusin2 mutations disrupt axonal mitochondrial positioning and promote axon degeneration

PubMed Central

Misko, Albert; Sasaki, Yo; Tuck, Elizabeth; Milbrandt, Jeffrey; Baloh, Robert H.

2012-01-01

Summary Alterations in mitochondrial dynamics (fission, fusion and movement) are implicated in many neurodegenerative diseases, from rare genetic disorders such as Charcot-Marie-Tooth disease, to common conditions including Alzheimer’s disease. However, the relationship between altered mitochondrial dynamics and neurodegeneration is incompletely understood. Here we show that disease associated MFN2 proteins suppressed both mitochondrial fusion and transport, and produced classic features of segmental axonal degeneration without cell body death, including neurofilament filled swellings, loss of calcium homeostasis, and accumulation of reactive oxygen species. By contrast, depletion of Opa1 suppressed mitochondrial fusion while sparing transport, and did not induce axonal degeneration. Axon degeneration induced by mutant MFN2 proteins correlated with the disruption of the proper mitochondrial positioning within axons, rather than loss of overall mitochondrial movement, or global mitochondrial dysfunction. We also found that augmenting expression of MFN1 rescued the axonal degeneration caused by MFN2 mutants, suggesting a possible therapeutic strategy for Charcot-Marie-Tooth disease. These experiments provide evidence that the ability of mitochondria to sense energy requirements and localize properly within axons is key to maintaining axonal integrity, and may be a common pathway by which disruptions in axonal transport contribute to neurodegeneration. PMID:22442078

Degeneration of the Y chromosome in evolutionary aging models

NASA Astrophysics Data System (ADS)

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

2005-06-01

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

High-Resolution Laser Spectroscopy of Free Radicals in Nearly Degenerate Electronic States

NASA Astrophysics Data System (ADS)

Liu, Jinjun

2017-06-01

Rovibronic structure of molecules in orbitally degenerate electronic states including Renner-Teller (RT) and Jahn-Teller (JT) active molecules has been extensively studied. Less is known about rotational structure of polyatomic molecules in nearly degenerate states, especially those with low (e.g., C_s) symmetry that are subject to the pseudo-Jahn-Teller (pJT) effect. In the case of free radicals, the unpaired electron further complicates energy levels by inducing spin-orbit (SO) and spin-rotation (SR) splittings. Asymmetric deuteration or methyl substitution of C_{3v} free radicals such as CH_3O, CaCH_3, and CaOCH_3 lowers the molecular symmetry, lifts the vibronic degeneracy, and reduces the JT effect to the pJT effect. New spectroscopic models are required to reproduce the rovibronic structure and simulate the experimentally obtained spectra of pJT-active free radicals. It has been found that rotational and fine-structure analysis of spectra involving nearly degenerate states may aid in vibronic analysis and interpretation of effective molecular constants. Especially, SO and Coriolis interactions that couple the two states can be determined accurately from fitting the experimental spectra. Coupling between the two electronic states also affects the intensities of rotational and vibronic transitions. The study on free radicals in nearly degenerate states provides a promising avenue of research which may bridge the gap between symmetry-induced degenerate states and the Born-Oppenheimer (BO) limit of unperturbed electronic states.

Ubiquitin–Synaptobrevin Fusion Protein Causes Degeneration of Presynaptic Motor Terminals in Mice

PubMed Central

Liu, Yun; Li, Hongqiao; Sugiura, Yoshie; Han, Weiping; Gallardo, Gilbert; Khvotchev, Mikhail; Zhang, Yinan; Kavalali, Ege T.; Südhof, Thomas C.

2015-01-01

Protein aggregates containing ubiquitin (Ub) are commonly observed in neurodegenerative disorders, implicating the involvement of the ubiquitin proteasome system (UPS) in their pathogenesis. Here, we aimed to generate a mouse model for monitoring UPS function using a green fluorescent protein (GFP)-based substrate that carries a “noncleavable” N-terminal ubiquitin moiety (UbG76V). We engineered transgenic mice expressing a fusion protein, consisting of the following: (1) UbG76V, GFP, and a synaptic vesicle protein synaptobrevin-2 (UbG76V-GFP-Syb2); (2) GFP-Syb2; or (3) UbG76V-GFP-Syntaxin1, all under the control of a neuron-specific Thy-1 promoter. As expected, UbG76V-GFP-Syb2, GFP-Syb2, and UbG76V-GFP-Sytaxin1 were highly expressed in neurons, such as motoneurons and motor nerve terminals of the neuromuscular junction (NMJ). Surprisingly, UbG76V-GFP-Syb2 mice developed progressive adult-onset degeneration of motor nerve terminals, whereas GFP-Syb2 and UbG76V-GFP-Syntaxin1 mice were normal. The degeneration of nerve terminals in UbG76V-GFP-Syb2 mice was preceded by a progressive impairment of synaptic transmission at the NMJs. Biochemical analyses demonstrated that UbG76V-GFP-Syb2 interacted with SNAP-25 and Syntaxin1, the SNARE partners of synaptobrevin. Ultrastructural analyses revealed a marked reduction in synaptic vesicle density, accompanying an accumulation of tubulovesicular structures at presynaptic nerve terminals. These morphological defects were largely restricted to motor nerve terminals, as the ultrastructure of motoneuron somata appeared to be normal at the stages when synaptic nerve terminals degenerated. Furthermore, synaptic vesicle endocytosis and membrane trafficking were impaired in UbG76V-GFP-Syb2 mice. These findings indicate that UbG76V-GFP-Syb2 may compete with endogenous synaptobrevin, acting as a gain-of-function mutation that impedes SNARE function, resulting in the depletion of synaptic vesicles and degeneration of the nerve

Radiative and Auger recombination of degenerate carriers in InN

NASA Astrophysics Data System (ADS)

McAllister, Andrew; Bayerl, Dylan; Kioupakis, Emmanouil

Group-III nitrides find applications in many fields - energy conversion, sensors, and solid-state lighting. The band gaps of InN, GaN and AlN alloys span the infrared to ultraviolet spectral range. However, nitride optoelectronic devices suffer from a drop in efficiency as carrier density increases. A major component of this decrease is Auger recombination, but its influence is not fully understood, particularly for degenerate carriers. For nondegenerate carriers the radiative rate scales as the carrier density squared, while the Auger rate scales as the density cubed. However, it is unclear how these power laws decrease as carriers become degenerate. Using first-principles calculations we studied the dependence of the radiative and Auger recombination rates on carrier density in InN. We found a more complex dependence on the Auger rate than expected. The power law of the Auger rate changes at different densities depending on the type of Auger process involved and the type of carriers that have become degenerate. In contrast, the power law of the radiative rate changes when either carrier type becomes degenerate. This creates problems in designing devices, as Auger remains a major contributor to carrier recombination at densities for which radiative recombination is suppressed by phase-space filling. This work was supported by NSF (GRFP DGE 1256260 and CAREER DMR-1254314). Computational resources provided by the DOE NERSC facility (DE-AC02-05CH11231).

Longitudinal Structural changes in Late-onset Retinal Degeneration

PubMed Central

Cukras, Catherine; Flamendorf, Jason; Wong, Wai T; Ayyagari, Radha; Cunningham, Denise; Sieving, Paul A.

2016-01-01

Purpose To characterize longitudinal structural changes in early stages of late-onset retinal degeneration (L-ORD) to investigate pathogenic mechanisms. Methods Two affected siblings, both with a S163R missense mutation in the causative gene C1QTNF5, were followed for 8+ years. Color fundus photos, fundus autofluorescence (FAF) images, near infrared reflectance (NIR-R) fundus images, and spectral domain optical coherence tomography (SD-OCT) scans were acquired during follow-up. Results Both patients, aged 45 and 50 years, had good visual acuities (> 20/20 OU) in the context of prolonged dark adaptation. Baseline color fundus photography demonstrated yellow-white, punctate lesions in the temporal macula that correlated with a reticular pattern on FAF and NIR-R imaging. Baseline SD-OCT imaging revealed subretinal deposits that resemble reticular pseudodrusen (RPD) described in age-related macular degeneration (AMD). During follow-up, these affected areas developed confluent thickening of the retinal pigment epithelial (RPE) layer and disruption of the ellipsoid zone of photoreceptors before progressing to overt RPE and outer retinal atrophy. Conclusions Structural changes in early stage L-ORD revealed by multimodal imaging resemble those of RPD observed in AMD and other retinal diseases. Longitudinal follow-up of these lesions helps elucidate their progression to frank atrophy and may lend insight into the pathogenic mechanisms underlying diverse retinal degenerations. PMID:27388725

Morphological Asymmetry of the Superior Cervical Facets from C3 through C7 due to Degeneration.

PubMed

Van Vlasselaer, Nicolas; Van Roy, Peter; Cattrysse, Erik

2017-01-01

Knowledge about facet morphology has already been discussed extensively in literature but is limited regarding asymmetry and its relation to facet degeneration. Facet dimensions, surface area, curvature, and degeneration of the superior facets were measured in 85 dried human vertebrae from the anatomical collection of the Vrije Universiteit Brussel. The vertebrae were analysed using the Microscribe G2X digitizer (Immersion Co., San Jose, CA) and a grading system for the evaluation of cervical facet degeneration. Coordinates were processed mathematically to evaluate articular tropism. The statistical analysis includes the paired t -test and the Pearson correlation. On average, no systematic differences between the left and right facets were found concerning morphology and degeneration. However, there were significant differences regardless of the side-occurrence. There was a significant correlation between the dimensions of the total facet surface and the degree of degeneration but not for the recognizable joint surface. Facet tropism of the upper joint facets occurred often in the cervical spine but without side preference. A bigger difference in degeneration asymmetry was associated with a bigger difference in facet joint dimension asymmetry.

Nonexistence of degenerate horizons in static vacua and black hole uniqueness

NASA Astrophysics Data System (ADS)

Khuri, Marcus; Woolgar, Eric

2018-02-01

We show that in any spacetime dimension D ≥ 4, degenerate components of the event horizon do not exist in static vacuum configurations with positive cosmological constant. We also show that without a cosmological constant asymptotically flat solutions cannot possess a degenerate horizon component. Several independent proofs are presented. One proof follows easily from differential geometry in the near-horizon limit, while others use Bakry-Émery-Ricci bounds for static Einstein manifolds.

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

NASA Astrophysics Data System (ADS)

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

2016-10-01

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

Role of Mitochondrial Oxidative Stress in Spaceflight-Induced Tissue Degeneration

NASA Technical Reports Server (NTRS)

Torres, Samantha M.; Schreurs, Ann-Sofie; Truong, Tiffany A.; Tahimic, Candice; Globus, Ruth

2017-01-01

Microgravity and ionizing radiation in the spaceflight environment poses multiple challenges to homeostasis and may contribute to cellular stress. Effects may include increased generation of reactive oxygen species (ROS), DNA damage and repair error, cell cycle arrest, cell senescence or death. Our central hypothesis is that prolonged exposure to the spaceflight environment leads to the excess production of ROS and oxidative damage, culminating in accelerated tissue degeneration. The main goal of this project is to determine the importance of cellular redox defense for physiological adaptations and tissue degeneration in the space environment.

Time course of organ of Corti degeneration after noise exposure.

PubMed

Bohne, Barbara A; Kimlinger, Melissa; Harding, Gary W

2017-02-01

From our permanent collection of plastic-embedded flat preparations of chinchilla cochleae, 22 controls and 199 ears from noise-exposed animals were used to determine when, postexposure, hair cell (HC) and supporting cell (SC) degeneration were completed. The exposed ears were divided into four groups based on exposure parameters: 0.5- or 4-kHz octave band of noise at moderate (M) or high (H) intensities. Postexposure survival ranged from <1 h to 2.5 y. Ears fixed ≤ 0-12 h postexposure were called 'acute'. For 'chronic' ears, postexposure survival was ≥7 d for groups 0.5M and 4M, ≥ 1 mo for the 4H group and ≥7 mo for the 0.5H group. The time course of inner-ear degeneration after noise exposure was determined from data in the 0.5H and 4H groups because these groups contained ears with intermediate survival times. Outer hair cells (OHCs) began dying during the exposure. OHC loss slowed down beyond 1 mo but was still present. Conversely, much inner hair cell loss was delayed until 1-3 wk postexposure. Outer pillar and inner pillar losses were present at a low level in acute ears but increased exponentially thereafter. These results are the first to demonstrate quantitatively that hair cells (HCs) and supporting cells (SCs) may continue to degenerate for months postexposure. With short postexposure survivals, the remaining SCs often had pathological changes, including: buckled pillar bodies, shifted Deiters' cell (DC) nuclei, detachment of DCs from the basilar membrane and/or splitting of the reticular lamina. These pathological changes appeared to allow endolymph and perilymph to intermix in the fluid spaces of the organ of Corti, damaging additional HCs, SCs and nerve fibers. This mechanism may account for some postexposure degeneration. In ears exposed to moderate noise, some of these SC changes appeared to be reversible. In ears exposed to high-level noise, these changes appeared to indicate impending degeneration. Copyright © 2016 Elsevier B

Quantitative muscle ultrasound is useful for evaluating secondary axonal degeneration in chronic inflammatory demyelinating polyneuropathy.

PubMed

Hokkoku, Keiichi; Matsukura, Kiyoshi; Uchida, Yudai; Kuwabara, Midori; Furukawa, Yuichi; Tsukamoto, Hiroshi; Hatanaka, Yuki; Sonoo, Masahiro

2017-10-01

In chronic inflammatory demyelinating polyneuropathy (CIDP), exclusion of secondary axonal degeneration is challenging with conventional methods such as nerve conduction study (NCS), needle electromyography, and nerve biopsy. Increased echo intensity (EI) and decreased muscle thickness (MT) identified on muscle ultrasound (MUS) examination represent muscle denervation due to axonal degeneration in neurogenic disorders, suggesting MUS as a new tool to detect secondary axonal degeneration in patients with CIDP. EI and MT of abductor pollicis brevis, abductor digiti minimi, and first dorsal interosseous muscles were measured in 16 CIDP patients. Raw values were converted into z -scores using data from 60 normal controls (NCs). Six of 45 muscles showed abnormally high EI and low MT, suggesting denervation following secondary axonal degeneration. These six muscles belonged to two patients with long disease history, unresponsiveness to treatment, and long interval from onset to initial therapy. There were no significant differences in EI and MT ( p  = .23 and .67, respectively) between the CIDP and NC groups, although NCS results revealed obvious demyelinating abnormalities in all CIDP patients, suggesting the fact that muscle structures will be preserved, and EI and MT will not change unless secondary axonal degeneration occurs in CIDP. MUS is a promising tool for evaluating secondary axonal degeneration in patients with CIDP.

Cartilage Degeneration, Subchondral Mineral and Meniscal Mineral Densities in Hartley and Strain 13 Guinea Pigs

PubMed Central

Sun, Yubo; Scannell, Brian P; Honeycutt, Patrick R; Mauerhan, David R; H, James Norton; Hanley Jr, Edward N

2015-01-01

Osteoarthritis is a joint disease involved in articular cartilage, subchondral bone, meniscus and synovial membrane. This study sought to examine cartilage degeneration, subchondral bone mineral density (BMD) and meniscal mineral density (MD) in male Hartley, female Hartley and female strain 13 guinea pigs to determine the association of cartilage degeneration with subchondral BMD and meniscal MD. Cartilage degeneration, subchondral BMD and meniscal MD in 12 months old guinea pigs were examined with histochemistry, X-ray densitometry and calcium analysis. We found that male Hartley guinea pigs had more severe cartilage degeneration, subchondral BMD and meniscal MD than female Hartley guinea pigs, but not female strain 13 guinea pigs. Female strain 13 guinea pigs had more severe cartilage degeneration and higher subchondral BMD, but not meniscal MD, than female Hartley guinea pigs. These findings indicate that higher subchondral BMD, not meniscal MD, is associated with more severe cartilage degeneration in the guinea pigs and suggest that abnormal subchondral BMD may be a therapeutic target for OA treatment. These findings also indicate that the pathogenesis of OA in the male guinea pigs and female guinea pigs are different. Female strain 13 guinea pig may be used to study female gender-specific pathogenesis of OA. PMID:26401159

Retinal degeneration increases susceptibility to myopia in mice

PubMed Central

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

2013-01-01

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

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

PubMed Central

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

2012-01-01

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

Age-dependent Changes of Cerebral Copper Metabolism in Atp7b−/− Knockout Mouse Model of Wilson’s Disease by [64Cu]CuCl2-PET/CT

PubMed Central

Xie, Fang; Xi, Yin; Pascual, Juan M.; Muzik, Otto; Peng, Fangyu

2017-01-01

Copper is a nutritional metal required for brain development and function. Wilson’s disease (WD), or hepatolenticular degeneration, is an inherited human copper metabolism disorder caused by mutation of ATP7B gene. Many WD patients present with variable neurological and psychiatric symptoms, which may be related to neurodegeneration secondary to copper metabolism imbalance. The objective of this study is to explore feasibility and use of copper-64 chloride ([64C]CuCl2) as a tracer for noninvasive assessment of age-dependence changes of cerebral copper metabolism in WD using an Atp7b−/− knockout mouse model of WD and a positron emission tomography/computed tomography (PET/CT) scanner. Continuing from recent study of biodistribution and radiation dosimetry of [64C]CuCl2 in Atp7b−/− knockout mice, PET quantitative analysis revealed low 64Cu radioactivity in the brains of Atp7b−/− knockout mice at 7th week of age, compared with the 64Cu radioactivity in the brains of age and gender-matched wild type C57BL/6 mice, at 24 hour (h) post intravenous injection of [64C]CuCl2 as a tracer. Furthermore, age-dependent increase of 64Cu radioactivity was detected in the brains of Atp7b−/− knockout mice from 13th to 21th week of age, using the data derived from a longitudinal [64C]CuCl2-PET/CT study of Atp7b−/− knockout mice with orally administered [64Cu]CuCl2 as a tracer. The findings of this study support the use of [64Cu]CuCl2-PET/CT as a tool for noninvasive assessment of age-dependent changes of cerebral copper metabolism in WD patients presenting with variable neurological and psychiatric symptoms. PMID:28130615

Contribution of Va24Vb11 natural killer T cells in Wilsonian hepatitis.

PubMed

Kinebuchi, M; Matsuura, A; Ohya, K; Abo, W; Kitazawa, J

2005-01-01

Wilson disease (WD) is an autosomal recessive disorder of copper transport, resulting in copper accumulation and toxicity to the liver and brain. There is no evidence that the WD patient's immune system attacks copper accumulated hepatocytes. Here we describe that the frequency and absolute number of Valpha24+Vbeta11+ natural killer T (NKT) cells were significantly increased in 3 cases of WD, whereas those of CD3+CD161+ NKT cells were within the normal range. Patients no. 1 and 2 had a presymptomatic form of WD. Their tissue specimens showed pathological changes of mild degeneration of hepatocytes with a few infiltrating mononuclear cells and a low degree of fatty change. Patient no. 3 displayed fulminant hepatitis with Coombs-negative haemolytic anaemia. The tissue specimens of patient no. 3 showed macronodular cirrhosis with thick fibrosis, inflammatory infiltrates and spotty necrosis. Human Valpha24+Vbeta11+ NKT cells are almost equal to CD1d-restricted NKT cells. Therefore we investigated CD1d-restricted NKT cells in the LEC rat as an animal model of WD. In LEC rats before hepatitis onset, the number and phenotype of liver NKT cells were normal. At about 4 months of age all LEC rats developed acute hepatitis accompanied by acute jaundice, and CD161high NKT cells developed in their livers. CD161highalphabetaTCRbright NKT cells developed in some of them. Their hepatitis was severe. CD161highalphabetaTCRbright NKT cells expressed an invariant rat Valpha14-Jalpha281 chain, which is CD1d-restricted. Furthermore, liver lymphocytes in the acute jaundiced LEC rats with CD161highalphabetaTCRbright NKT cells had significant and CD1d-specific cytotoxic activity.

Age-dependent changes of cerebral copper metabolism in Atp7b -/- knockout mouse model of Wilson's disease by [64Cu]CuCl2-PET/CT.

PubMed

Xie, Fang; Xi, Yin; Pascual, Juan M; Muzik, Otto; Peng, Fangyu

2017-06-01

Copper is a nutritional metal required for brain development and function. Wilson's disease (WD), or hepatolenticular degeneration, is an inherited human copper metabolism disorder caused by a mutation of the ATP7B gene. Many WD patients present with variable neurological and psychiatric symptoms, which may be related to neurodegeneration secondary to copper metabolism imbalance. The objective of this study was to explore the feasibility and use of copper-64 chloride ([ 64 C]CuCl 2 ) as a tracer for noninvasive assessment of age-dependent changes of cerebral copper metabolism in WD using an Atp7b -/- knockout mouse model of WD and positron emission tomography/computed tomography (PET/CT) imaging. Continuing from our recent study of biodistribution and radiation dosimetry of [ 64 C]CuCl 2 in Atp7b -/- knockout mice, PET quantitative analysis revealed low 64 Cu radioactivity in the brains of Atp7b -/- knockout mice at 7th weeks of age, compared with 64 Cu radioactivity in the brains of age- and gender-matched wild type C57BL/6 mice, at 24 h (h) post intravenous injection of [ 64 C]CuCl 2 as a tracer. Furthermore, age-dependent increase of 64 Cu radioactivity was detected in the brains of Atp7b -/- knockout mice from the 13th to 21th weeks of age, based on the data derived from a longitudinal [ 64 C]CuCl 2 -PET/CT study of Atp7b -/- knockout mice with orally administered [ 64 Cu]CuCl 2 as a tracer. The findings of this study support clinical use of [ 64 Cu]CuCl 2 -PET/CT imaging as a tool for noninvasive assessment of age-dependent changes of cerebral copper metabolism in WD patients presenting with variable neurological and psychiatric symptoms.

Association of HTRA1 rs11200638 with age-related macular degeneration (AMD) in Brazilian patients.

PubMed

Lana, Tamires Prates; da Silva Costa, Sueli Matilde; Ananina, Galina; Hirata, Fábio Endo; Rim, Priscila Hae Hyun; Medina, Flávio MacCord; de Vasconcellos, José Paulo Cabral; de Melo, Mônica Barbosa

2018-01-01

Age-related macular degeneration is a multifactorial disease that can lead to vision impairment in older individuals. Although the etiology of age-related macular degeneration remains unknown, risk factors include age, ethnicity, smoking, hypertension, obesity, and genetic factors. Two main loci have been identified through genome-wide association studies, on chromosomes 1 and 10. Among the variants located at the 10q26 region, rs11200638, located at the HTRA1 gene promoter, has been associated with age-related macular degeneration in several populations and is considered the main polymorphism. We conducted a replication case-control study to analyze the frequency and participation of rs11200638 in the etiology of age-related macular degeneration in a sample of patients and controls from the State of São Paulo, Brazil, through polymerase chain reaction and enzymatic digestion. The frequency of the A allele was 57.60% in patients with age-related macular degeneration and 36.45% in controls (p value < 1e-07), representing a 2.369-fold higher risk factor for the disease. Both the AA and AG genotypes were observed more frequently in the age-related macular degeneration group compared to the control group (p = 1.21 e-07 and 0.0357, respectively). No statistically significant results were observed after stratification in dry versus wet types or advanced versus non-advanced forms. To our knowledge, this is the first time the association between rs11200638 and overall age-related macular degeneration has been reported in South America.

Advances in repairing the degenerate retina by rod photoreceptor transplantation.

PubMed

Pearson, Rachael A

2014-01-01

Despite very different aetiologies, age-related macular degeneration (AMD) and most inherited retinal disorders culminate in the same final common pathway, loss of the light-sensitive photoreceptors. There are few clinical treatments and none can reverse the loss of vision. Photoreceptor replacement by transplantation is proposed as a broad treatment strategy applicable to all degenerations. The past decade has seen a number of landmark achievements in this field, which together provide strong justification for continuing investigation into photoreceptor replacement strategies. These include proof of principle for restoring vision by rod-photoreceptor transplantation in mice with congenital stationary night blindness and advances in stem cell biology, which have led to the generation of complete optic structures in vitro from embryonic stem cells. The latter represents enormous potential for generating suitable and renewable donor cells with which to achieve the former. However, there are still challenges presented by the degenerating recipient retinal environment that must be addressed as we move to translating these technologies towards clinical application. Copyright © 2014 The Author. Published by Elsevier Inc. All rights reserved.

Comparison of Spectral Linewidths for Quantum Degenerate Bosons and Fermions

NASA Astrophysics Data System (ADS)

Notermans, R. P. M. J. W.; Rengelink, R. J.; Vassen, W.

2016-11-01

We observe a dramatic difference in optical line shapes of a 4He Bose-Einstein condensate and a 3He degenerate Fermi gas by measuring the 1557-nm 2 3S -2 1S magnetic dipole transition (8 Hz natural linewidth) in an optical dipole trap. The 15 kHz FWHM condensate line shape is only broadened by mean field interactions, whereas the degenerate Fermi gas line shape is broadened to 75 kHz FWHM due to the effect of Pauli exclusion on the spatial and momentum distributions. The asymmetric optical line shapes are observed in excellent agreement with line shape models for the quantum degenerate gases. For 4He a triplet-singlet s -wave scattering length a =+50 (10 )stat(43 )systa0 is extracted. The high spectral resolution reveals a doublet in the absorption spectrum of the BEC, and this effect is understood by the presence of a weak optical lattice in which a degeneracy of the lattice recoil and the spectroscopy photon recoil leads to Bragg-like scattering.

Comparison of Spectral Linewidths for Quantum Degenerate Bosons and Fermions.

PubMed

Notermans, R P M J W; Rengelink, R J; Vassen, W

2016-11-18

We observe a dramatic difference in optical line shapes of a ^{4}He Bose-Einstein condensate and a ^{3}He degenerate Fermi gas by measuring the 1557-nm 2 ^{3}S-2 ^{1}S magnetic dipole transition (8 Hz natural linewidth) in an optical dipole trap. The 15 kHz FWHM condensate line shape is only broadened by mean field interactions, whereas the degenerate Fermi gas line shape is broadened to 75 kHz FWHM due to the effect of Pauli exclusion on the spatial and momentum distributions. The asymmetric optical line shapes are observed in excellent agreement with line shape models for the quantum degenerate gases. For ^{4}He a triplet-singlet s-wave scattering length a=+50(10)_{stat}(43)_{syst}a_{0} is extracted. The high spectral resolution reveals a doublet in the absorption spectrum of the BEC, and this effect is understood by the presence of a weak optical lattice in which a degeneracy of the lattice recoil and the spectroscopy photon recoil leads to Bragg-like scattering.

Are animal models useful for studying human disc disorders/degeneration?

PubMed Central

Eisenstein, Stephen M.; Ito, Keita; Little, Christopher; Kettler, A. Annette; Masuda, Koichi; Melrose, James; Ralphs, Jim; Stokes, Ian; Wilke, Hans Joachim

2007-01-01

Intervertebral disc (IVD) degeneration is an often investigated pathophysiological condition because of its implication in causing low back pain. As human material for such studies is difficult to obtain because of ethical and government regulatory restriction, animal tissue, organs and in vivo models have often been used for this purpose. However, there are many differences in cell population, tissue composition, disc and spine anatomy, development, physiology and mechanical properties, between animal species and human. Both naturally occurring and induced degenerative changes may differ significantly from those seen in humans. This paper reviews the many animal models developed for the study of IVD degeneration aetiopathogenesis and treatments thereof. In particular, the limitations and relevance of these models to the human condition are examined, and some general consensus guidelines are presented. Although animal models are invaluable to increase our understanding of disc biology, because of the differences between species, care must be taken when used to study human disc degeneration and much more effort is needed to facilitate research on human disc material. PMID:17632738

Dendrimer-based targeted intravitreal therapy for sustained attenuation of neuroinflammation in retinal degeneration.

PubMed

Iezzi, Raymond; Guru, Bharath R; Glybina, Inna V; Mishra, Manoj K; Kennedy, Alexander; Kannan, Rangaramanujam M

2012-01-01

Retinal neuroinflammation, mediated by activated microglia, plays a key role in the pathogenesis of photoreceptor and retinal pigment epithelial cell loss in age-related macular degeneration and retinitis pigmentosa. Targeted drug therapy for attenuation of neuroinflammation in the retina was explored using hydroxyl-terminated polyamidoamine (PAMAM) dendrimer-drug conjugate nanodevices. We show that, upon intravitreal administration, PAMAM dendrimers selectively localize within activated outer retinal microglia in two rat models of retinal degeneration, but not in the retina of healthy controls. This pathology-dependent biodistribution was exploited for drug delivery, by covalently conjugating fluocinolone acetonide to the dendrimer. The conjugate released the drug in a sustained manner over 90 days. In vivo efficacy was assessed using the Royal College of Surgeons (RCS) rat retinal degeneration model over a four-week period when peak retinal degeneration occurs. One intravitreal injection of 1 μg of FA conjugated to 7 μg of the dendrimer was able to arrest retinal degeneration, preserve photoreceptor outer nuclear cell counts, and attenuate activated microglia, for an entire month. These studies suggest that PAMAM dendrimers (with no targeting ligands) have an intrinsic ability to selectively localize in activated microglia, and can deliver drugs inside these cells for a sustained period for the treatment of retinal neuroinflammation. Copyright © 2011 Elsevier Ltd. All rights reserved.

Permissive role for mGlu1 metabotropic glutamate receptors in excitotoxic retinal degeneration.

PubMed

Liberatore, Francesca; Bucci, Domenico; Mascio, Giada; Madonna, Michele; Di Pietro, Paola; Beneventano, Martina; Puliti, Alda Maria; Battaglia, Giuseppe; Bruno, Valeria; Nicoletti, Ferdinando; Romano, Maria Rosaria

2017-11-05

Neuroprotection is an unmet need in eye disorders characterized by retinal ganglion cell (RGC) death, such as prematurity-induced retinal degeneration, glaucoma, and age-related macular degeneration. In all these disorders excitotoxicity is a prominent component of neuronal damage, but clinical data discourage the development of NMDA receptor antagonists as neuroprotectants. Here, we show that activation of mGlu1 metabotropic glutamate receptors largely contributes to excitotoxic degeneration of RGCs. Mice at postnatal day 9 were challenged with a toxic dose of monosodium glutamate (MSG, 3g/kg), which caused the death of >70% of Brn-3a + RGCs. Systemic administration of the mGlu1 receptor negative allosteric modulator (NAM), JNJ16259685 (2.5mg/kg, s.c.), was largely protective against MSG-induced RGC death. This treatment did not cause changes in motor behavior in the pups. We also injected MSG to crv4 mice, which lack mGlu1 receptors because of a recessive mutation of the gene encoding the mGlu1 receptor. MSG did not cause retinal degeneration in crv4 mice, whereas it retained its toxic activity in their wild-type littermates. These findings demonstrate that mGlu1 receptors play a key role in excitotoxic degeneration of RGCs, and encourage the study of mGlu1 receptor NAMs in models of retinal neurodegeneration. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Stimulation of nicotinamide adenine dinucleotide biosynthetic pathways delays axonal degeneration after axotomy.

PubMed

Sasaki, Yo; Araki, Toshiyuki; Milbrandt, Jeffrey

2006-08-16

Axonal degeneration occurs in many neurodegenerative diseases and after traumatic injury and is a self-destructive program independent from programmed cell death. Previous studies demonstrated that overexpression of nicotinamide mononucleotide adenylyltransferase 1 (Nmnat1) or exogenous application of nicotinamide adenine dinucleotide (NAD) can protect axons of cultured dorsal root ganglion (DRG) neurons from degeneration caused by mechanical or neurotoxic injury. In mammalian cells, NAD can be synthesized from multiple precursors, including tryptophan, nicotinic acid, nicotinamide, and nicotinamide riboside (NmR), via multiple enzymatic steps. To determine whether other components of these NAD biosynthetic pathways are capable of delaying axonal degeneration, we overexpressed each of the enzymes involved in each pathway and/or exogenously administered their respective substrates in DRG cultures and assessed their capacity to protect axons after axotomy. Among the enzymes tested, Nmnat1 had the strongest protective effects, whereas nicotinamide phosphoribosyl transferase and nicotinic acid phosphoribosyl transferase showed moderate protective activity in the presence of their substrates. Strong axonal protection was also provided by Nmnat3, which is predominantly located in mitochondria, and an Nmnat1 mutant localized to the cytoplasm, indicating that the subcellular location of NAD production is not crucial for protective activity. In addition, we showed that exogenous application of the NAD precursors that are the substrates of these enzymes, including nicotinic acid mononucleotide, nicotinamide mononucleotide, and NmR, can also delay axonal degeneration. These results indicate that stimulation of NAD biosynthetic pathways via a variety of interventions may be useful in preventing or delaying axonal degeneration.

Lumbar Disc Degenerative Disease: Disc Degeneration Symptoms and Magnetic Resonance Image Findings

PubMed Central

Saleem, Shafaq; Rehmani, Muhammad Asim Khan; Raees, Aisha; Alvi, Arsalan Ahmad; Ashraf, Junaid

2013-01-01

Study Design Cross sectional and observational. Purpose To evaluate the different aspects of lumbar disc degenerative disc disease and relate them with magnetic resonance image (MRI) findings and symptoms. Overview of Literature Lumbar disc degenerative disease has now been proven as the most common cause of low back pain throughout the world. It may present as disc herniation, lumbar spinal stenosis, facet joint arthropathy or any combination. Presenting symptoms of lumbar disc degeneration are lower back pain and sciatica which may be aggravated by standing, walking, bending, straining and coughing. Methods This study was conducted from January 2012 to June 2012. Study was conducted on the diagnosed patients of lumbar disc degeneration. Diagnostic criteria were based upon abnormal findings in MRI. Patients with prior back surgery, spine fractures, sacroiliac arthritis, metabolic bone disease, spinal infection, rheumatoid arthritis, active malignancy, and pregnancy were excluded. Results During the targeted months, 163 patients of lumbar disc degeneration with mean age of 43.92±11.76 years, came into Neurosurgery department. Disc degeneration was most commonly present at the level of L4/L5 105 (64.4%).Commonest types of disc degeneration were disc herniation 109 (66.9%) and lumbar spinal stenosis 37 (22.7%). Spondylolisthesis was commonly present at L5/S1 10 (6.1%) and associated mostly with lumbar spinal stenosis 7 (18.9%). Conclusions Results reported the frequent occurrence of lumbar disc degenerative disease in advance age. Research efforts should endeavor to reduce risk factors and improve the quality of life. PMID:24353850

Effect of Interbody Fusion on the Remaining Discs of the Lumbar Spine in Subjects with Disc Degeneration.

PubMed

Ryu, Robert; Techy, Fernando; Varadarajan, Ravikumar; Amirouche, Farid

2016-02-01

To study effects (stress loads) of lumbar fusion on the remaining segments (adjacent or not) of the lumbar spine in the setting of degenerated adjacent discs. A lumbar spine finite element model was built and validated. The full model of the lumbar spine was a parametric finite element model of segments L 1-5 . Numerous hypothetical combinations of one-level lumbar spine fusion and one-level disc degeneration were created. These models were subjected to 10 Nm flexion and extension moments and the stresses on the endplates and consequently on the intervertebral lumbar discs measured. These values were compared to the stresses on healthy lumbar spine discs under the same load and fusion scenarios. Increased stress at endplates was observed only in the settings of L4-5 fusion and L3-4 disc degeneration (8% stress elevation at L2,3 in flexion or extension, and 25% elevation at L3,4 in flexion only). All other combinations showed less endplate stress than did the control model. For fusion at L3-4 and degeneration at L4-5 , the stresses in the endplates at the adjacent level inferior to the fused disc decreased for both loading disc height reductions. Stresses in flexion decreased after fusion by 29.5% and 25.8% for degeneration I and II, respectively. Results for extension were similar. For fusion at L2-3 and degeneration at L4-5 , stresses in the endplates decreased more markedly at the degenerated (30%), than at the fused level (14%) in the presence of 25% disc height reduction and 10 Nm flexion, whereas in extension stresses decreased more at the fused (24.3%) than the degenerated level (5.86%). For fusion at L3-4 and degeneration at L2-3 , there were no increases in endplate stress in any scenario. For fusion at L4-5 and degeneration at L3-4 , progression of degeneration from I to II had a significant effect only in flexion. A dramatic increase in stress was noted in the endplates of the degenerated disc (L3-4 ) in flexion for degeneration II. Stresses are greater

Tocotrienol prevents AAPH-induced neurite degeneration in neuro2a cells.

PubMed

Fukui, Koji; Sekiguchi, Hidekazu; Takatsu, Hirokatsu; Koike, Taisuke; Koike, Tatsuro; Urano, Shiro

2013-01-01

Reactive oxygen species induce neurite degeneration before inducing cell death. However, the degenerative mechanisms have not yet been elucidated. While tocotrienols have a known neuroprotective function, the underlying mechanism remains unclear and may or may not involve antioxidant action. In this study, we hypothesize that free radical-derived membrane injury is one possible mechanism for inducing neurite degeneration. Therefore, we examined the potential neuroprotective effect of tocotrienols mediated through its antioxidant activity. Mouse neuroblastoma neuro2a cells were used to examine the effect of the water-soluble free radical generator 2,2'-azobis(2-methylpropionamide) dihydrochloride (AAPH) on neurite dynamics. After 24 hours of AAPH treatment, cell viability, neurite number, and the number of altered neurites were measured in the presence or absence of α-tocotrienol. Treatment of neuro2a cells with a low concentration of AAPH induces neurite degeneration, but not cell death. Treatment with 5 µM α-tocotrienol significantly inhibited neurite degeneration in AAPH-treated neuro2a cells. Furthermore, morphological changes in AAPH-treated neuro2a cells were similar to those observed with colchicine treatment. α-Tocotrienol may scavenge AAPH-derived free radicals and alkoxyl radicals that are generated from AAPH-derived peroxyl radicals on cell membranes. Therefore, α-tocotrienol may have a neuroprotective effect mediated by its antioxidant activity.

Degenerate mixing of plasma waves on cold, magnetized single-species plasmas

NASA Astrophysics Data System (ADS)

Anderson, M. W.; O'Neil, T. M.; Dubin, D. H. E.; Gould, R. W.

2011-10-01

In the cold-fluid dispersion relation ω =ωp/[1+(k⊥/kz)2]1/2 for Trivelpiece-Gould waves on an infinitely long magnetized plasma cylinder, the transverse and axial wavenumbers appear only in the combination k⊥/kz. As a result, for any frequency ω <ωp, there are infinitely many degenerate waves, all having the same value of k⊥/kz. On a cold finite-length plasma column, these degenerate waves reflect into one another at the ends; thus, each standing-wave normal mode of the bounded plasma is a mixture of many degenerate waves, not a single standing wave as is often assumed. A striking feature of the many-wave modes is that the short-wavelength waves often add constructively along resonance cones given by dz /dr=±(ωp2/ω2-1)1/2. Also, the presence of short wavelengths in the admixture for a predominantly long-wavelength mode enhances the viscous damping beyond what the single-wave approximation would predict. Here, numerical solutions are obtained for modes of a cylindrical plasma column with rounded ends. Exploiting the fact that the modes of a spheroidal plasma are known analytically (the Dubin modes), a perturbation analysis is used to investigate the mixing of low-order, nearly degenerate Dubin modes caused by small deformations of a plasma spheroid.

Development of Multistep and Degenerate Variational Integrators for Applications in Plasma Physics

NASA Astrophysics Data System (ADS)

Ellison, Charles Leland

Geometric integrators yield high-fidelity numerical results by retaining conservation laws in the time advance. A particularly powerful class of geometric integrators is symplectic integrators, which are widely used in orbital mechanics and accelerator physics. An important application presently lacking symplectic integrators is the guiding center motion of magnetized particles represented by non-canonical coordinates. Because guiding center trajectories are foundational to many simulations of magnetically confined plasmas, geometric guiding center algorithms have high potential for impact. The motivation is compounded by the need to simulate long-pulse fusion devices, including ITER, and opportunities in high performance computing, including the use of petascale resources and beyond. This dissertation uses a systematic procedure for constructing geometric integrators --- known as variational integration --- to deliver new algorithms for guiding center trajectories and other plasma-relevant dynamical systems. These variational integrators are non-trivial because the Lagrangians of interest are degenerate - the Euler-Lagrange equations are first-order differential equations and the Legendre transform is not invertible. The first contribution of this dissertation is that variational integrators for degenerate Lagrangian systems are typically multistep methods. Multistep methods admit parasitic mode instabilities that can ruin the numerical results. These instabilities motivate the second major contribution: degenerate variational integrators. By replicating the degeneracy of the continuous system, degenerate variational integrators avoid parasitic mode instabilities. The new methods are therefore robust geometric integrators for degenerate Lagrangian systems. These developments in variational integration theory culminate in one-step degenerate variational integrators for non-canonical magnetic field line flow and guiding center dynamics. The guiding center integrator

Morphological Asymmetry of the Superior Cervical Facets from C3 through C7 due to Degeneration

PubMed Central

Van Roy, Peter

2017-01-01

Introduction Knowledge about facet morphology has already been discussed extensively in literature but is limited regarding asymmetry and its relation to facet degeneration. Method Facet dimensions, surface area, curvature, and degeneration of the superior facets were measured in 85 dried human vertebrae from the anatomical collection of the Vrije Universiteit Brussel. The vertebrae were analysed using the Microscribe G2X digitizer (Immersion Co., San Jose, CA) and a grading system for the evaluation of cervical facet degeneration. Coordinates were processed mathematically to evaluate articular tropism. The statistical analysis includes the paired t-test and the Pearson correlation. Results On average, no systematic differences between the left and right facets were found concerning morphology and degeneration. However, there were significant differences regardless of the side-occurrence. There was a significant correlation between the dimensions of the total facet surface and the degree of degeneration but not for the recognizable joint surface. Conclusions Facet tropism of the upper joint facets occurred often in the cervical spine but without side preference. A bigger difference in degeneration asymmetry was associated with a bigger difference in facet joint dimension asymmetry. PMID:29359153

Assessment of Intervertebral Disc Degeneration Based on Quantitative MRI Analysis: an in vivo study

PubMed Central

Grunert, Peter; Hudson, Katherine D.; Macielak, Michael R.; Aronowitz, Eric; Borde, Brandon H.; Alimi, Marjan; Njoku, Innocent; Ballon, Douglas; Tsiouris, Apostolos John; Bonassar, Lawrence J.; Härtl, Roger

2015-01-01

Study design Animal experimental study Objective To evaluate a novel quantitative imaging technique for assessing disc degeneration. Summary of Background Data T2-relaxation time (T2-RT) measurements have been used to quantitatively assess disc degeneration. T2 values correlate with the water content of inter vertebral disc tissue and thereby allow for the indirect measurement of nucleus pulposus (NP) hydration. Methods We developed an algorithm to subtract out MRI voxels not representing NP tissue based on T2-RT values. Filtered NP voxels were used to measure nuclear size by their amount and nuclear hydration by their mean T2-RT. This technique was applied to 24 rat-tail intervertebral discs’ (IVDs), which had been punctured with an 18-gauge needle according to different techniques to induce varying degrees of degeneration. NP voxel count and average T2-RT were used as parameters to assess the degeneration process at 1 and 3 months post puncture. NP voxel counts were evaluated against X-ray disc height measurements and qualitative MRI studies based on the Pfirrmann grading system. Tails were collected for histology to correlate NP voxel counts to histological disc degeneration grades and to NP cross-sectional area measurements. Results NP voxel count measurements showed strong correlations to qualitative MRI analyses (R2=0.79, p<0.0001), histological degeneration grades (R2=0.902, p<0.0001) and histological NP cross-sectional area measurements (R2=0.887, p<0.0001). In contrast to NP voxel counts, the mean T2-RT for each punctured group remained constant between months 1 and 3. The mean T2-RTs for the punctured groups did not show a statistically significant difference from those of healthy IVDs (63.55ms ±5.88ms month 1 and 62.61ms ±5.02ms) at either time point. Conclusion The NP voxel count proved to be a valid parameter to quantitatively assess disc degeneration in a needle puncture model. The mean NP T2-RT does not change significantly in needle

N=2 gauge theories and degenerate fields of Toda theory

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kanno, Shoichi; Matsuo, Yutaka; Shiba, Shotaro

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

Humor and laughter in patients with cerebellar degeneration.

PubMed

Frank, B; Propson, B; Göricke, S; Jacobi, H; Wild, B; Timmann, D

2012-06-01

Humor is a complex behavior which includes cognitive, affective and motor responses. Based on observations of affective changes in patients with cerebellar lesions, the cerebellum may support cerebral and brainstem areas involved in understanding and appreciation of humorous stimuli and expression of laughter. The aim of the present study was to examine if humor appreciation, perception of humorous stimuli, and the succeeding facial reaction differ between patients with cerebellar degeneration and healthy controls. Twenty-three adults with pure cerebellar degeneration were compared with 23 age-, gender-, and education-matched healthy control subjects. No significant difference in humor appreciation and perception of humorous stimuli could be found between groups using the 3 Witz-Dimensionen Test, a validated test asking for funniness and aversiveness of jokes and cartoons. Furthermore, while observing jokes, humorous cartoons, and video sketches, facial expressions of subjects were videotaped and afterwards analysed using the Facial Action Coding System. Using depression as a covariate, the number, and to a lesser degree, the duration of facial expressions during laughter were reduced in cerebellar patients compared to healthy controls. In sum, appreciation of humor appears to be largely preserved in patients with chronic cerebellar degeneration. Cerebellar circuits may contribute to the expression of laughter. Findings add to the literature that non-motor disorders in patients with chronic cerebellar disease are generally mild, but do not exclude that more marked disorders may show up in acute cerebellar disease and/or in more specific tests of humor appreciation.

Degeneration of the long biceps tendon: comparison of MRI with gross anatomy and histology.

PubMed

Buck, Florian M; Grehn, Holger; Hilbe, Monika; Pfirrmann, Christian W A; Manzanell, Silvana; Hodler, Jürg

2009-11-01

The objective of our study was to relate alterations in biceps tendon diameter and signal on MR images to gross anatomy and histology. T1-weighted, T2-weighted fat-saturated, and proton density-weighted fat-saturated spin-echo sequences were acquired in 15 cadaveric shoulders. Biceps tendon diameter (normal, flattened, thickened, and partially or completely torn) and signal intensity (compared with bone, fat, muscle, and joint fluid) were graded by two readers independently and in a blinded fashion. The distance of tendon abnormalities from the attachment at the glenoid were noted in millimeters. MRI findings were related to gross anatomic and histologic findings. On the basis of gross anatomy, there were six normal, five flattened, two thickened, and two partially torn tendons. Reader 1 graded nine diameter changes correctly, missed two, and incorrectly graded four. The corresponding values for reader 2 were seven, one, and five, respectively, with kappa = 0.75. Histology showed mucoid degeneration (n = 13), lipoid degeneration (n = 7), and fatty infiltration (n = 6). At least one type of abnormality was found in each single tendon. Mucoid degeneration was hyperintense compared with fatty infiltration on T2-weighted fat-saturated images and hyperintense compared with magic-angle artifacts on proton density-weighted fat-saturated images. MRI-based localization of degeneration agreed well with histologic findings. Diameter changes are specific but not sensitive in diagnosing tendinopathy of the biceps tendon. Increased tendon signal is most typical for mucoid degeneration but should be used with care as a sign of tendon degeneration.

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

PubMed

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

2015-03-01

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

Nutritional modulation of age-related macular degeneration

USDA-ARS?s Scientific Manuscript database

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

MRI Quantification of Human Spine Cartilage Endplate Geometry: Comparison With Age, Degeneration, Level, and Disc Geometry

PubMed Central

DeLucca, John F.; Peloquin, John M.; Smith, Lachlan J.; Wright, Alexander C.; Vresilovic, Edward J.; Elliott, Dawn M.

2017-01-01

Geometry is an important indicator of disc mechanical function and degeneration. While the geometry and associated degenerative changes in the nucleus pulposus and the annulus fibrosus are well-defined, the geometry of the cartilage endplate (CEP) and its relationship to disc degeneration are unknown. The objectives of this study were to quantify CEP geometry in three dimensions using an MRI FLASH imaging sequence and evaluate relationships between CEP geometry and age, degeneration, spinal level, and overall disc geometry. To do so, we assessed the MRI-based measurements for accuracy and repeatability. Next, we measured CEP geometry across a larger sample set and correlated CEP geometric parameters to age, disc degeneration, level, and disc geometry. The MRI-based measures resulted in thicknesses (0.3–1 mm) that are comparable to prior measurements of CEP thickness. CEP thickness was greatest at the anterior/posterior (A/P) margins and smallest in the center. The CEP A/P thickness, axial area, and lateral width decreased with age but were not related to disc degeneration. Age-related, but not degeneration-related, changes in geometry suggest that the CEP may not follow the progression of disc degeneration. Ultimately, if the CEP undergoes significant geometric changes with aging and if these can be related to low back pain, a clinically feasible translation of the FLASH MRI-based measurement of CEP geometry presented in this study may prove a useful diagnostic tool. PMID:27232974

Qualitative assessment of online information about age-related macular degeneration available in Portuguese.

PubMed

Agi, Jorge; Kasahara, Niro; Lottenberg, Claudio Luiz

2018-06-07

To evaluate the quality of online information on age-related macular degeneration available in Portuguese. The search term "age-related macular degeneration" was used to browse the web using four different search engines. The first 40 websites appearing on match lists provided by each search engine were recorded and those listed in at least three tab pages selected. The Sandvik Severity Index was used as to assess website quality. Quality of information available on selected websites was rated average (mean Sandvik Score 7.08±2.23). Most websites disseminating information about age-related macular degeneration were of average quality. The need to readjust web-based information to target lay public and promote increased understanding was emphasized.

The Effect of Single-Level Disc Degeneration on Dynamic Response of the Whole Lumbar Spine to Vertical Vibration.

PubMed

Guo, Li-Xin; Fan, Wei

2017-09-01

The objective of this study was to investigate the effect of single-level disc degeneration on dynamic response of the whole lumbar spine to vertical whole body vibration that is typically present when driving vehicles. Ligamentous finite element models of the lumbar L1-S1 motion segment in different grades of degeneration (healthy, mild, and moderate) at the L4-L5 level were developed with consideration of changing disc height and material properties of the nucleus pulpous. All models were loaded with a compressive follower preload of 400 N and a sinusoidal vertical vibration load of ±40 N. After transient dynamic analyses, computational results for the 3 models in terms of disc bulge, von-Mises stress in annulus ground substance, and nucleus pressure were plotted as a function of time and compared. All the predicted results showed a cyclic response with time. At the degenerated L4-L5 disc level, as degeneration progressed, maximum value of the predicted response showed a decrease in disc bulge and von-Mises stress in annulus ground substance but a slight increase in nucleus pressure, and their vibration amplitudes were all decreased. At the adjacent levels of the degenerated disc, there was a slight decrease in maximum value and vibration amplitude of these predicted responses with the degeneration. The results indicated that single-level disc degeneration can alter vibration characteristics of the whole lumbar spine especially for the degenerated disc level, and increasing the degeneration did not deteriorate the effect of vertical vibration on the spine. Copyright © 2017 Elsevier Inc. All rights reserved.

Menopause is associated with articular cartilage degeneration: a clinical study of knee joint in 860 women.

PubMed

Lou, Chao; Xiang, Guangheng; Weng, Qiaoyou; Chen, Zhaojie; Chen, Deheng; Wang, Qingqing; Zhang, Di; Zhou, Bin; He, Dengwei; Chen, Hongliang

2016-11-01

The purpose of this study was to investigate the association between menopause and severity of knee joint cartilage degeneration using a magnetic resonance imaging-based six-level grading system, with six cartilage surfaces, the medial and lateral femoral condyle, the femoral trochlea, the medial and lateral tibia plateau, and the patella. The study cohort comprised 860 healthy women (age 36-83 y), and 5,160 cartilage surfaces were analyzed. Age, weight, height, age at natural menopause, and years since menopause (YSM) were obtained. Cartilage degeneration was assessed using a magnetic resonance imaging-based six-level grading system. After removing the age, height, and weight effects, postmenopausal women had more severe cartilage degeneration than pre- and perimenopausal women (P < 0.001). A positive trend was observed between YSM and severity of cartilage degeneration (P < 0.05). Postmenopausal women were divided into seven subgroups by every five YSM. When YSM was less than 25 years, the analysis of covariance indicated a significant difference in medial tibia plateau, medial femoral condyle, trochlea, patella, and total surfaces (P < 0.05 or 0.01) between every two groups. When YSM was more than 25 years, the significant difference, however, disappeared in these four surfaces (P > 0.05). No significant difference was observed in lateral tibia plateau and lateral femoral condyle in postmenopausal women. Menopause is associated with cartilage degeneration of knee joint. After menopause, cartilage showed progressive severe degeneration that occurred in the first 25 YSM, suggesting estrogen deficiency might be a risk factor of cartilage degeneration of the knee joint. Further studies are needed to investigate whether age or menopause plays a more important role in the progression of cartilage degeneration in the knee joint.

Age-dependent synapse withdrawal at axotomised neuromuscular junctions in Wlds mutant and Ube4b/Nmnat transgenic mice

PubMed Central

Gillingwater, Thomas H; Thomson, Derek; Mack, Till G A; Soffin, Ellen M; Mattison, Richard J; Coleman, Michael P; Ribchester, Richard R

2002-01-01

Axons in WldS mutant mice are protected from Wallerian degeneration by overexpression of a chimeric Ube4b/Nmnat (Wld) gene. Expression of Wld protein was independent of age in these mice. However we identified two distinct neuromuscular synaptic responses to axotomy. In young adult Wlds mice, axotomy induced progressive, asynchronous synapse withdrawal from motor endplates, strongly resembling neonatal synapse elimination. Thus, five days after axotomy, 50–90 % of endplates were still partially or fully occupied and expressed endplate potentials (EPPs). By 10 days, fewer than 20 % of endplates still showed evidence of synaptic activity. Recordings from partially occupied junctions indicated a progressive decrease in quantal content in inverse proportion to endplate occupancy. In Wlds mice aged > 7 months, axons were still protected from axotomy but synapses degenerated rapidly, in wild-type fashion: within three days less than 5 % of endplates contained vestiges of nerve terminals. The axotomy-induced synaptic withdrawal phenotype decayed with a time constant of ∼30 days. Regenerated synapses in mature Wlds mice recapitulated the juvenile phenotype. Within 4–6 days of axotomy 30–50 % of regenerated nerve terminals still occupied motor endplates. Age-dependent synapse withdrawal was also seen in transgenic mice expressing the Wld gene. Co-expression of Wld protein and cyan fluorescent protein (CFP) in axons and neuromuscular synapses did not interfere with the protection from axotomy conferred by the Wld gene. Thus, Wld expression unmasks age-dependent, compartmentally organised programmes of synapse withdrawal and degeneration. PMID:12231635

Progressive Retinal Degeneration and Accumulation of Autofluorescent Lipopigments in Progranulin Deficient Mice

PubMed Central

Hafler, Brian P.; Klein, Zoe A.; Zhou, Z. Jimmy; Strittmatter, Stephen M.

2014-01-01

Prior investigations have shown that patients with neuronal ceroid lipofuscinosis (NCL) develop neurodegeneration characterized by vision loss, motor dysfunction, seizures, and often early death. Neuropathological analysis of patients with NCL shows accumulation of intracellular autofluorescent storage material, lipopigment, throughout neurons in the central nervous system including in the retina. A recent study of a sibling pair with adult onset NCL and retinal degeneration showed linkage to the region of the progranulin (GRN) locus and a homozygous mutation was demonstrated in GRN. In particular, the sibling pair with a mutation in GRN developed retinal degeneration and optic atrophy. This locus for this form of adult onset neuronal ceroid lipofuscinosis was designated neuronal ceroid lipofuscinosis-11 (CLN11). Based on these clinical observations, we wished to determine whether Grn-null mice develop accumulation of autofluorescent particles and retinal degeneration. Retinas of both wild-type and Progranulin deficient mice were examined by immunostaining and autofluorescence. Accumulation of autofluorescent material was present in Progranulin deficient mice at 12 months. Degeneration of multiple classes of neurons including photoreceptors and retinal ganglion cells was noted in mice at 12 and 18 months. Our data shows that Grn−/− mice develop degenerative pathology similar to features of human CLN11. PMID:25234724

Bending response of cross-ply laminated composite plates with diagonally perturbed localized interfacial degeneration.

PubMed

Kam, Chee Zhou; Kueh, Ahmad Beng Hong

2013-01-01

A laminated composite plate element with an interface description is developed using the finite element approach to investigate the bending performance of two-layer cross-ply laminated composite plates in presence of a diagonally perturbed localized interfacial degeneration between laminae. The stiffness of the laminate is expressed through the assembly of the stiffnesses of lamina sub-elements and interface element, the latter of which is formulated adopting the well-defined virtually zero-thickness concept. To account for the extent of both shear and axial weak bonding, a degeneration ratio is introduced in the interface formulation. The model has the advantage of simulating a localized weak bonding at arbitrary locations, with various degeneration areas and intensities, under the influence of numerous boundary conditions since the interfacial description is expressed discretely. Numerical results show that the bending behavior of laminate is significantly affected by the aforementioned parameters, the greatest effect of which is experienced by those with a localized total interface degeneration, representing the case of local delamination.

Endomicroscopy and electromyography of neuromuscular junctions in situ

PubMed Central

Brown, Rosalind; Dissanayake, Kosala N; Skehel, Paul A; Ribchester, Richard R

2014-01-01

Objective Electromyography (EMG) is used routinely to diagnose neuromuscular dysfunction in a wide range of peripheral neuropathies, myopathies, and neuromuscular degenerative diseases including motor neuron diseases such as amyotrophic lateral sclerosis (ALS). Definitive neurological diagnosis may also be indicated by the analysis of pathological neuromuscular innervation in motor-point biopsies. Our objective in this study was to preempt motor-point biopsy by combining live imaging with electrophysiological analysis of slow degeneration of neuromuscular junctions (NMJs) in vivo. Methods We combined conventional needle electromyography with fiber-optic confocal endomicroscopy (CEM), using an integrated hand-held, 1.5-mm-diameter probe. We utilized as a test bed, various axotomized muscles in the hind limbs of anaesthetized, double-homozygous thy1.2YFP16: WldS mice, which coexpress the Wallerian-degeneration Slow (WldS) protein and yellow fluorescent protein (YFP) in motor neurons. We also tested exogenous vital stains, including Alexa488-α-bungarotoxin; the styryl pyridinium dye 4-Di-2-Asp; and a GFP conjugate of botulinum toxin Type A heavy chain (GFP-HcBoNT/A). Results We show that an integrated EMG/CEM probe is effective in longitudinal evaluation of functional and morphological changes that take place over a 7-day period during axotomy-induced, slow neuromuscular synaptic degeneration. EMG amplitude declined in parallel with overt degeneration of motor nerve terminals. EMG/CEM was safe and effective when nerve terminals and motor endplates were selectively stained with vital dyes. Interpretation Our findings constitute proof-of-concept, based on live imaging in an animal model, that combining EMG/CEM may be useful as a minimally invasive precursor or alternative to motor-point biopsy in neurological diagnosis and for monitoring local administration of potential therapeutics. PMID:25540801

On the Behavior of Eisenstein Series Through Elliptic Degeneration

NASA Astrophysics Data System (ADS)

Garbin, D.; Pippich, A.-M. V.

2009-12-01

Let Γ be a Fuchsian group of the first kind acting on the hyperbolic upper half plane {mathbb{H}}, and let {M = Γbackslash mathbb{H}} be the associated finite volume hyperbolic Riemann surface. If γ is a primitive parabolic, hyperbolic, resp. elliptic element of Γ, there is an associated parabolic, hyperbolic, resp. elliptic Eisenstein series. In this article, we study the limiting behavior of these Eisenstein series on an elliptically degenerating family of finite volume hyperbolic Riemann surfaces. In particular, we prove the following result. The elliptic Eisenstein series associated to a degenerating elliptic element converges up to a factor to the parabolic Eisenstein series associated to the parabolic element which fixes the newly developed cusp on the limit surface.

Relationship between meniscal integrity and risk factors for cartilage degeneration.

PubMed

Arno, Sally; Bell, Christopher P; Xia, Ding; Regatte, Ravinder R; Krasnokutsky, Svetlana; Samuels, Jonathan; Oh, Cheongeun; Abramson, Steven; Walker, Peter S

2016-08-01

The purpose of this study was to use MRI to determine if a loss of meniscal intra-substance integrity, as determined by T2* relaxation time, is associated with an increase of Kellgren-Lawrence (KL) grade, and if this was correlated with risk factors for cartilage degeneration, namely meniscal extrusion, contact area and anterior-posterior (AP) displacement. Eleven symptomatic knees with a KL 2 to 4 and 11 control knees with a KL 0 to 1 were studied. A 3 Tesla MRI scanner was used to scan all knees at 15° of flexion. With a 222N compression applied, a 3D SPACE sequence was obtained, followed by a spin echo 3D T2* mapping sequence. Next, an internal tibial torque of 5Nm was added and a second 3D SPACE sequence obtained. The MRI scans were post-processed to evaluate meniscal extrusion, contact area, AP displacement and T2* relaxation time. KL grade was correlated with T2* relaxation time for both the anterior medial meniscus (r=0.79, p<0.001) and the posterior lateral meniscus (r=0.55, p=0.009). In addition, T2* relaxation time was found to be correlated with risk factors for cartilage degeneration. The largest increases in meniscal extrusion and decreases in contact area were noted for those with meniscal tears (KL 3 to 4). All patients with KL 3 to 4 indicated evidence of meniscal tears. This suggests that a loss of meniscal integrity, in the form of intra-substance degeneration, is correlated with risk factors for cartilage degeneration. Copyright © 2015 Elsevier B.V. All rights reserved.

[Influence of patellofemoral joint degeneration on outcome of medial unicompartmental knee arthroplasty].

PubMed

Xu, B Y; Ji, B C; Guo, W T; Mu, W B; Cao, L

2017-06-01

Objective: To evaluate the influence of patellofemoral joint degeneration and pre-operative pain location on the outcome of medial Oxford unicompartmental knee arthroplasty (UKA). Methods: A total of 58 patients (58 knees) with medial Oxford UKA had been performed for medial osteoarthritis from March 2013 to July 2014 in Department of Orthopaedic Surgery at First Teaching Hospital of Xinjiang Medical University were retrospective reviewed. There were 24 males and 34 females, the age from 43 to 87 years with the mean age was 68.5 years. The mean body mass index was 25.2 kg/m(2) ranging from 19.7 to 31.5 kg/m(2). Patients were divided into anterior-medial pain group (35 knees), anterior knee pain group (17 knees) and general knee pain group (6 knees) according to pre-operative pain location. Pre-operative radiological statuses of the patellefemoral joint were defined by Ahlback system and divided into patellofemoral joint degeneration group (16 knees) and normal group (42 knees). Patients were also divided into medial patellofemoral degeneration group (20 knees), lateral patellofemoral degeneration group (12 knees) and normal group (26 knees) according to Altman scoring system. Outerbridge system was used intraoperatively and the patients were divided into patellofemoral joint degeneration group (21 knees) and normal group (37 knees). Pre- and post-operative outcomes were evaluated with Oxford Knee Score (OKS), Western Ontario and MacMaster (WOMAC) and patellofemoral score system of Lonner. T test and ANOVA were used to analyze the data. Results: The average duration of follow-up was 33 months (from 26 to 42 months). There were no patients had complications of infection, deep vein thrombosis, dislocation or loosing at the last follow-up. Compared to pre-operation, OKS (18.9±3.5 vs . 38.9±4.7, 19.3±4.2 vs . 39.6±4.6, 18.1±3.2 vs . 38.1±3.7)( t =5.64 to 7.08, all P <0.01) and WOMAC (10.9±2.3 vs .53.2±4.5, 10.4±2.1 vs .54.6±3.4, 11.7±1.8 vs .52.8±3.7)( t =14

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

PubMed Central

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

2014-01-01

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

HIF-1α stabilization reduces retinal degeneration in a mouse model of retinitis pigmentosa.

PubMed

Olivares-González, Lorena; Martínez-Fernández de la Cámara, Cristina; Hervás, David; Millán, José María; Rodrigo, Regina

2018-05-01

Retinitis pigmentosa (RP) is a group of inherited retinal dystrophies characterized by progressive and irreversible loss of vision due to rod and cone degeneration. Evidence suggests that an inappropriate oxygen level could contribute to its pathogenesis. Rod cell death could increase oxygen concentration, reduce hypoxia-inducible factor 1 (HIF-1α) and contribute to cone cell death. The purposes of this study were: 1) to analyze the temporal profile of HIF-1α, its downstream effectors VEGF, endothelin-1 (ET-1), iNOS, and glucose transporter 1 (GLUT1), and neuroinflammation in retinas of the murine model of rd10 ( retinal degeneration 10) mice with RP; 2) to study oxygen bioavailability in these retinas; and 3) to investigate how stabilizing HIF-1α proteins with dimethyloxaloglycine (DMOG), a prolyl hydroxylase inhibitor, affects retinal degeneration, neuroinflammation, and antioxidant response in rd10 mice. A generalized down-regulation of HIF-1α and its downstream targets was detected in parallel with reactive gliosis, suggesting high oxygen levels during retinal degeneration. At postnatal d 18, DMOG treatment reduced photoreceptor cell death and glial activation. In summary, retinas of rd10 mice seem to be exposed to a hyperoxic environment even at early stages of degeneration. HIF-1α stabilization could have a temporal neuroprotective effect on photoreceptor cell survival, glial activation, and antioxidant response at early stages of RP.-Olivares-González, L., Martínez-Fernández de la Cámara, C., Hervás, D., Millán, J. M., Rodrigo, R. HIF-1α stabilization reduces retinal degeneration in a mouse model of retinitis pigmentosa.

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…

Gene-diet interactions in age-related macular degeneration

USDA-ARS?s Scientific Manuscript database

Age-related macular degeneration (AMD) is a prevalent blinding disease, accounting for roughly 50% of blindness in developed nations. Very significant advances have been made in terms of discovering genetic susceptibilities to AMD as well as dietary risk factors. To date, nutritional supplementation...

Clinical Characteristics and Current Treatment of Age-Related Macular Degeneration

PubMed Central

Yonekawa, Yoshihiro; Kim, Ivana K.

2015-01-01

Age-related macular degeneration (AMD) is a multifactorial degeneration of photoreceptors and retinal pigment epithelium. The societal impact is significant, with more than 2 million individuals in the United States alone affected by advanced stages of AMD. Recent progress in our understanding of this complex disease and parallel developments in therapeutics and imaging have translated into new management paradigms in recent years. However, there are many unanswered questions, and diagnostic and prognostic precision and treatment outcomes can still be improved. In this article, we discuss the clinical features of AMD, provide correlations with modern imaging and histopathology, and present an overview of treatment strategies. PMID:25280900

Chronic nerve compression alters Schwann cell myelin architecture in a murine model

PubMed Central

Gupta, Ranjan; Nassiri, Nima; Hazel, Antony; Bathen, Mary; Mozaffar, Tahseen

2011-01-01

Introduction Myelinating Schwann cells compartmentalize their outermost layer to form actin-rich channels known as Cajal bands. Here, we investigate changes in Schwann cell architecture and cytoplasmic morphology in a novel mouse model of carpal tunnel syndrome. Methods Chronic nerve compression (CNC) injury was created in wild-type and slow-Wallerian degeneration (WldS) mice. Over 12 weeks, nerves were electrodiagnostically assessed, and Schwann cell morphology was thoroughly evaluated. Results A decline in nerve conduction velocity and increase in g-ratio is observed without early axonal damage. Schwann cells display shortened internodal lengths and severely disrupted Cajal bands. Quite surprisingly, the latter is reconstituted without improvements to nerve conduction velocity. Discussion Chronic entrapment injuries like carpal tunnel syndrome are primarily mediated by the Schwann cell response, wherein decreases in internodal length and myelin thickness disrupt the efficiency of impulse propagation. Restitution of Cajal bands is not sufficient for remyelination post-CNC injury. PMID:22246880

Coherent frequency division with a degenerate synchronously pumped optical parametric oscillator.

PubMed

Wan, Chenchen; Li, Peng; Ruehl, Axel; Hartl, Ingmar

2018-03-01

Synchronously pumped optical parametric oscillators (OPOs) are important tools for frequency comb (FC) generation in the mid-IR spectral range, where few suitable laser gain materials exist. For degenerate OPOs, self-phase-locking to the pump FC has been demonstrated. Here, we present a phase noise study of the carrier envelope offset frequency, revealing a -6  dB reduction compared to the pump FC over a wide Fourier frequency range. These results demonstrate that a degenerate OPO can be an ideal coherent frequency divider without any excess noise.

Polarization-sensitive optical coherence tomography-based imaging, parameterization, and quantification of human cartilage degeneration

NASA Astrophysics Data System (ADS)

Brill, Nicolai; Wirtz, Mathias; Merhof, Dorit; Tingart, Markus; Jahr, Holger; Truhn, Daniel; Schmitt, Robert; Nebelung, Sven

2016-07-01

Polarization-sensitive optical coherence tomography (PS-OCT) is a light-based, high-resolution, real-time, noninvasive, and nondestructive imaging modality yielding quasimicroscopic cross-sectional images of cartilage. As yet, comprehensive parameterization and quantification of birefringence and tissue properties have not been performed on human cartilage. PS-OCT and algorithm-based image analysis were used to objectively grade human cartilage degeneration in terms of surface irregularity, tissue homogeneity, signal attenuation, as well as birefringence coefficient and band width, height, depth, and number. Degeneration-dependent changes were noted for the former three parameters exclusively, thereby questioning the diagnostic value of PS-OCT in the assessment of human cartilage degeneration.

Inpatient rehabilitation performance of patients with paraneoplastic cerebellar degeneration.

PubMed

Fu, Jack B; Raj, Vishwa S; Asher, Arash; Lee, Jay; Guo, Ying; Konzen, Benedict S; Bruera, Eduardo

2014-12-01

To evaluate the functional improvement of rehabilitation inpatients with paraneoplastic cerebellar degeneration. Retrospective review. Referral-based hospitals. Cancer rehabilitation inpatients (N=7) admitted to 3 different cancer centers with a diagnosis of paraneoplastic cerebellar degeneration. Medical records were retrospectively analyzed for demographic, laboratory, medical, and functional data. FIM. All 7 patients were white women (median age, 62y). Primary cancers included ovarian carcinoma (n=2), small cell lung cancer (n=2), uterine carcinoma (n=2), and invasive ductal breast carcinoma (n=1). Mean admission total FIM score was 61±23.97. Mean discharge total FIM score was 73.6±29.35. The mean change in total FIM score was 12.6 (P=.0018). The mean length of rehabilitation stay was 17.1 days. The mean total FIM efficiency was .73. Of the 7 patients, 5 (71%) were discharged home, 1 (14%) was discharged to a nursing home, and 1 (14%) was transferred to the primary acute care service. To our knowledge, this is the first study to demonstrate the functional performance of a group of rehabilitation inpatients with paraneoplastic cerebellar degeneration. Despite the poor neurologic prognosis associated with this syndrome, these patients made significant functional improvements in inpatient rehabilitation. When appropriate, inpatient rehabilitation should be considered. Further studies with larger sample sizes are needed. Copyright © 2014 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Inpatient Rehabilitation Performance of Patients with Paraneoplastic Cerebellar Degeneration

PubMed Central

Fu, Jack B.; Raj, Vishwa S.; Asher, Arash; Lee, Jay; Guo, Ying; Konzen, Benedict S.; Bruera, Eduardo

2014-01-01

Objective To evaluate the functional improvement of rehabilitation inpatients with paraneoplastic cerebellar degeneration. Design Retrospective Review Setting Three tertiary referral based hospitals. Interventions Medical records were retrospectively analyzed for demographic, laboratory, medical and functional data. Main Outcome Measure Functional Independence Measure (FIM) Participants Cancer rehabilitation inpatients admitted to three different cancer centers with a diagnosis of paraneoplastic cerebellar degeneration (n=7). Results All 7 patients were white females. Median age was 62. Primary cancers included ovarian carcinoma (2), small cell lung cancer (2), uterine carcinoma (2), and invasive ductal breast carcinoma. Mean admission total FIM score was 61.0 (SD=23.97). Mean discharge total FIM score was 73.6 (SD=29.35). The mean change in total FIM score was 12.6 (p=.0018). The mean length of rehabilitation stay was 17.1 days. The mean total FIM efficiency was 0.73. 5/7 (71%) patients were discharged home. 1/7 (14%) was discharged to a nursing home. 1/7 (14%) transferred to the primary acute care service. Conclusions This is the first study to demonstrate the functional performance of a group of rehabilitation inpatients with paraneoplastic cerebellar degeneration. Despite the poor neurologic prognosis associated with this syndrome, these patients made significant functional improvements on inpatient rehabilitation. When appropriate, inpatient rehabilitation should be considered. Further studies with larger sample sizes are needed. PMID:25051460

Costs of newly diagnosed neovascular age-related macular degeneration among medicare beneficiaries, 2004-2008.

PubMed

Qualls, Laura G; Hammill, Bradley G; Wang, Fang; Lad, Eleonora M; Schulman, Kevin A; Cousins, Scott W; Curtis, Lesley H

2013-04-01

To examine associations between newly diagnosed neovascular age-related macular degeneration and direct medical costs. This retrospective observational study matched 23,133 Medicare beneficiaries diagnosed with neovascular age-related macular degeneration between 2004 and 2008 with a control group of 92,532 beneficiaries on the basis of age, sex, and race. The index date for each case-control set corresponded to the first diagnosis for the case. Main outcome measures were total costs per patient and age-related macular degeneration-related costs per case 1 year before and after the index date. Mean cost per case in the year after diagnosis was $12,422, $4,884 higher than the year before diagnosis. Postindex costs were 41% higher for cases than controls after adjustment for preindex costs and comorbid conditions. Age-related macular degeneration-related costs represented 27% of total costs among cases in the postindex period and were 50% higher for patients diagnosed in 2008 than in 2004. This increase was attributable primarily to the introduction of intravitreous injections of vascular endothelial growth factor antagonists. Intravitreous injections averaged $203 for patients diagnosed in 2004 and $2,749 for patients diagnosed in 2008. Newly diagnosed neovascular age-related macular degeneration was associated with a substantial increase in total medical costs. Costs increased over time, reflecting growing use of anti-vascular endothelial growth factor therapies.

Quantitative neurohistological features of frontotemporal degeneration.

PubMed

Arnold, S E; Han, L Y; Clark, C M; Grossman, M; Trojanowski, J Q

2000-01-01

Frontotemporal degeneration (FTD) is a neurodegenerative condition that has been principally associated with frontal lobe dementia. In this study, we compared neuropathological abnormalities in frontal, hippocampal, and calcarine cortices from patients assigned a diagnosis of FTD, normal elderly and Alzheimer's disease (AD). Densities of Nissl-stained neurons and lesions which were immunolabeled for tau, beta-amyloid (Abeta), alpha- and beta-synuclein, ubiquitin, glial fibrillary acidic protein (GFAP) and CD68 antigen were determined using computer-assisted, non-biased quantitative microscopy. We found that FTD frontal and hippocampal regions exhibited marked neuron loss, abundant ubiquitin-immunoreactive (ir) dystrophic neurites, GFAP-ir astrocytes, and CD68-ir microglia, while calcarine cortex was spared. No alpha- or beta-synuclein-ir lesions were observed, and neither the density of tau-ir neurofibrillary tangles nor that of Abeta-ir plaques in FTD exceeded normal controls. In addition, there were no neuropathological differences between FTD subjects who presented clinically with a frontal lobe dementia versus an AD-like dementia. These findings indicate that FTD is a category of neurodegnerative dementias with varying clinical presentations that is characterized by the progressive degeneration of select populations of cortical neurons. The molecular neurodegenerative mechanisms that lead to FTD remain to be elucidated.

Symmetrical infantile thalamic degeneration in two sibs

PubMed Central

Abuelo, Dianne N; Barsel-Bowers, Gail; Tutschka, Barbara G; Ambler, Mary; Singer, Don B

1981-01-01

This is the first observation of two cases of symmetrical infantile thalamic degeneration with cell mineralisation in a family. Although it cannot be established at present, autosomal recessive inheritance of a metabolic error causing or predisposing to damage to specific areas of the central nervous system is a possible aetiology for this condition. Images PMID:7334503

Early Microglia Activation Precedes Photoreceptor Degeneration in a Mouse Model of CNGB1-Linked Retinitis Pigmentosa.

PubMed

Blank, Thomas; Goldmann, Tobias; Koch, Mirja; Amann, Lukas; Schön, Christian; Bonin, Michael; Pang, Shengru; Prinz, Marco; Burnet, Michael; Wagner, Johanna E; Biel, Martin; Michalakis, Stylianos

2017-01-01

Retinitis pigmentosa (RP) denotes a family of inherited blinding eye diseases characterized by progressive degeneration of rod and cone photoreceptors in the retina. In most cases, a rod-specific genetic defect results in early functional loss and degeneration of rods, which is followed by degeneration of cones and loss of daylight vision at later stages. Microglial cells, the immune cells of the central nervous system, are activated in retinas of RP patients and in several RP mouse models. However, it is still a matter of debate whether activated microglial cells may be responsible for the amplification of the typical degenerative processes. Here, we used Cngb1 -/- mice, which represent a slow degenerative mouse model of RP, to investigate the extent of microglia activation in retinal degeneration. With a combination of FACS analysis, immunohistochemistry and gene expression analysis we established that microglia in the Cngb1 -/- retina were already activated in an early, predegenerative stage of the disease. The evidence available so far suggests that early retinal microglia activation represents a first step in RP, which might initiate or accelerate photoreceptor degeneration.

Superior cervical gangliectomy induces non-exudative age-related macular degeneration in mice.

PubMed

Dieguez, Hernán H; Romeo, Horacio E; González Fleitas, María F; Aranda, Marcos L; Milne, Georgia A; Rosenstein, Ruth E; Dorfman, Damián

2018-02-07

Non-exudative age-related macular degeneration, a prevalent cause of blindness, is a progressive and degenerative disease characterized by alterations in Bruch's membrane, retinal pigment epithelium, and photoreceptors exclusively localized in the macula. Although experimental murine models exist, the vast majority take a long time to develop retinal alterations and, in general, these alterations are ubiquitous, with many resulting from non-eye-specific genetic manipulations; additionally, most do not always reproduce the hallmarks of human age-related macular degeneration. Choroid vessels receive sympathetic innervation from the superior cervical ganglion, which, together with the parasympathetic system, regulates blood flow into the choroid. Choroid blood flow changes have been involved in age-related macular degeneration development and progression. At present, no experimental models take this factor into account. The aim of this work was to analyze the effect of superior cervical gangliectomy (also known as ganglionectomy) on the choroid, Bruch's membrane, retinal pigment epithelium and retina. Adult male C57BL/6J mice underwent unilateral superior cervical gangliectomy and a contralateral sham procedure. Although superior cervical gangliectomy induced ubiquitous choroid and choriocapillaris changes, it induced Bruch's membrane thickening, loss of retinal pigment epithelium melanin content and retinoid isomerohydrolase, the appearance of drusen-like deposits, and retinal pigment epithelium and photoreceptor atrophy, exclusively localized in the temporal side. Moreover, superior cervical gangliectomy provoked a localized increase in retinal pigment epithelium and photoreceptor apoptosis, and a decline in photoreceptor electroretinographic function. Therefore, superior cervical gangliectomy recapitulated the main features of human non-exudative age-related macular degeneration, and could become a new experimental model of dry age-related macular degeneration, and

Melatonin delays photoreceptor degeneration in a mouse model of autosomal recessive retinitis pigmentosa.

PubMed

Xu, Xiao-Jian; Wang, Shu-Min; Jin, Ying; Hu, Yun-Tao; Feng, Kang; Ma, Zhi-Zhong

2017-10-01

Retinitis pigmentosa (RP) comprises a group of incurable inherited retinal degenerations. Targeting common processes, instead of mutation-specific treatment, has proven to be an innovative strategy to combat debilitating retinal degeneration. Growing evidence indicates that melatonin possesses a potent activity against neurodegenerative disorders by mitigating cell damage associated with apoptosis and inflammation. Given the pleiotropic role of melatonin in central nervous system, the aim of the present study was to investigate whether melatonin would afford protection against retinal degeneration in autosomal recessive RP (arRP). Rd10, a well-characterized murine model of human arRP, received daily intraperitoneal injection of melatonin (15 mg/kg) between postnatal day (P) 13 and P30. Retinas treated with melatonin or vehicle were harvested for analysis at P30 and P45, respectively. The findings showed that melatonin could dampen the photoreceptors death and delay consequent retinal degeneration. We also observed that melatonin weakened the expression of glial fibrillary acidic protein (GFAP) in Müller cells. Additionally, melatonin could alleviate retinal inflammatory response visualized by IBA1 staining, which was further corroborated by downregulation of inflammation-related genes, such as tumor necrosis factor alpha (Tnf-α), chemokine (C-C motif) ligand 2 (Ccl2), and chemokine (C-X-C motif) ligand 10 (Cxcl10). These data revealed that melatonin could ameliorate retinal degeneration through potentially attenuating apoptosis, reactive gliosis, and microglial activation in rd10 mice. Moreover, these results suggest melatonin as a promising agent improving photoreceptors survival in human RP. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Small heat shock proteins mediate cell-autonomous and -nonautonomous protection in a Drosophila model for environmental-stress-induced degeneration.

PubMed

Kawasaki, Fumiko; Koonce, Noelle L; Guo, Linda; Fatima, Shahroz; Qiu, Catherine; Moon, Mackenzie T; Zheng, Yunzhen; Ordway, Richard W

2016-09-01

Cell and tissue degeneration, and the development of degenerative diseases, are influenced by genetic and environmental factors that affect protein misfolding and proteotoxicity. To better understand the role of the environment in degeneration, we developed a genetic model for heat shock (HS)-stress-induced degeneration in Drosophila This model exhibits a unique combination of features that enhance genetic analysis of degeneration and protection mechanisms involving environmental stress. These include cell-type-specific failure of proteostasis and degeneration in response to global stress, cell-nonautonomous interactions within a simple and accessible network of susceptible cell types, and precise temporal control over the induction of degeneration. In wild-type flies, HS stress causes selective loss of the flight ability and degeneration of three susceptible cell types comprising the flight motor: muscle, motor neurons and associated glia. Other motor behaviors persist and, accordingly, the corresponding cell types controlling leg motor function are resistant to degeneration. Flight motor degeneration was preceded by a failure of muscle proteostasis characterized by diffuse ubiquitinated protein aggregates. Moreover, muscle-specific overexpression of a small heat shock protein (HSP), HSP23, promoted proteostasis and protected muscle from HS stress. Notably, neurons and glia were protected as well, indicating that a small HSP can mediate cell-nonautonomous protection. Cell-autonomous protection of muscle was characterized by a distinct distribution of ubiquitinated proteins, including perinuclear localization and clearance of protein aggregates associated with the perinuclear microtubule network. This network was severely disrupted in wild-type preparations prior to degeneration, suggesting that it serves an important role in muscle proteostasis and protection. Finally, studies of resistant leg muscles revealed that they sustain proteostasis and the microtubule

Constitutive Overexpression of Human Erythropoietin Protects the Mouse Retina against Induced But Not Inherited Retinal Degeneration

PubMed Central

Grimm, Christian; Wenzel, Andreas; Stanescu, Dinu; Samardzija, Marijana; Hotop, Svenja; Groszer, Mathias; Naash, Muna; Gassmann, Max; Remé, Charlotte

2010-01-01

Elevation of erythropoietin (Epo) concentrations by hypoxic preconditioning or application of recombinant human Epo (huEpo) protects the mouse retina against light-induced degeneration by inhibiting photoreceptor cell apoptosis. Because photoreceptor apoptosis is also the common path to cell loss in retinal dystrophies such as retinitis pigmentosa (RP), we tested whether high levels of huEpo would reduce apoptotic cell death in two mouse models of human RP. We combined the two respective mutant mouse lines with a transgenic line (tg6) that constitutively overexpresses huEpo mainly in neural tissues. Transgenic expression of huEpo caused constitutively high levels of Epo in the retina and protected photoreceptors against light-induced degeneration; however, the presence of high levels of huEpo did not affect the course or the extent of retinal degeneration in a light-independent (rd1) and a light-accelerated (VPP) mouse model of RP. Similarly, repetitive intraperitoneal injections of recombinant huEpo did not protect the retina in the rd1 and the VPP mouse. Lack of neuroprotection by Epo in the two models of inherited retinal degeneration was not caused by adaptational downregulation of Epo receptor. Our results suggest that apoptotic mechanisms during acute, light-induced photoreceptor cell death differ from those in genetically based retinal degeneration. Therapeutic intervention with cell death in inherited retinal degeneration may therefore require different drugs and treatments. PMID:15215287

Nonlinear ion-acoustic cnoidal waves in a dense relativistic degenerate magnetoplasma.

PubMed

El-Shamy, E F

2015-03-01

The complex pattern and propagation characteristics of nonlinear periodic ion-acoustic waves, namely, ion-acoustic cnoidal waves, in a dense relativistic degenerate magnetoplasma consisting of relativistic degenerate electrons and nondegenerate cold ions are investigated. By means of the reductive perturbation method and appropriate boundary conditions for nonlinear periodic waves, a nonlinear modified Korteweg-de Vries (KdV) equation is derived and its cnoidal wave is analyzed. The various solutions of nonlinear ion-acoustic cnoidal and solitary waves are presented numerically with the Sagdeev potential approach. The analytical solution and numerical simulation of nonlinear ion-acoustic cnoidal waves of the nonlinear modified KdV equation are studied. Clearly, it is found that the features (amplitude and width) of nonlinear ion-acoustic cnoidal waves are proportional to plasma number density, ion cyclotron frequency, and direction cosines. The numerical results are applied to high density astrophysical situations, such as in superdense white dwarfs. This research will be helpful in understanding the properties of compact astrophysical objects containing cold ions with relativistic degenerate electrons.

Primary amines protect against retinal degeneration in mouse models of retinopathies

PubMed Central

Maeda, Akiko; Golczak, Marcin; Chen, Yu; Okano, Kiichiro; Kohno, Hideo; Shiose, Satomi; Ishikawa, Kaede; Harte, William; Palczewska, Grazyna; Maeda, Tadao; Palczewski, Krzysztof

2011-01-01

Vertebrate vision is initiated by photoisomerization of the visual pigment chromophore, 11-cis-retinal, and is maintained by continuous regeneration of this retinoid through a series of reactions termed the retinoid cycle. However, toxic side reaction products, especially those involving reactive aldehyde groups of the photoisomered product, all-trans-retinal, can cause severe retinal pathology. Here we lowered peak concentrations of free all-trans-retinal with primary amine-containing FDA-approved drugs that did not inhibit chromophore regeneration in mouse models of retinal degeneration. Schiff base adducts between all-trans-retinal and these amines were identified by mass spectrometry. Adducts were observed in mouse eyes only when an experimental drug protected the retina from degeneration in both short-term and long-term treatment experiments. This study demonstrates a molecular basis of all-trans-retinal-induced retinal pathology and identifies an assemblage of FDA-approved compounds with protective effects against this pathology in a mouse model that displays features of Stargardt’s and age-related retinal degeneration. PMID:22198730

Bilateral rhegmatogenous retinal detachment due to unusual retinal degeneration in Down syndrome: A case report.

PubMed

Yonemoto, Yumiko; Morishita, Seita; Fukumoto, Masanori; Mimura, Masashi; Sato, Takaki; Kida, Teruyo; Kojima, Shota; Oku, Hidehiro; Sugasawa, Jun; Ikeda, Tsunehiko

2018-06-01

The aim of this study was to report a case of Down syndrome (DS) complicated with bilateral retinal detachment (RD) due to unusual retinal degeneration. A 9-year-old girl complained of bilateral visual disturbance during a follow-up examination for myopia and strabismus. Slit-lamp examination revealed moderate posterior subcapsular cataract in both eyes. B-mode echography showed bilateral bullous RD; however, it was difficult to detect the causal retinal breaks due to poor mydriasis. For treatment, the patient underwent bilateral lensectomy, vitrectomy, and silicone oil tamponade. Intraoperative findings revealed symmetrical retinal breaks and unusual caterpillar-like retinal degeneration on the upper temporal side of both eyes. Three months later, the patient underwent bilateral silicone oil removal and intraocular lens implantation. In this case, the retinal degeneration was morphologically different from retinal lattice degeneration, thus suggesting that it might be involved in the onset of DS-related bilateral RD.

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.

Cartilage degeneration and not age influences the health-related quality of life outcome after partial meniscectomy.

PubMed

Liebensteiner, Michael C; Nogler, Michael; Giesinger, Johannes M; Lechner, Ricarda; Lenze, Florian; Thaler, Martin

2015-01-01

The purpose of this study is to investigate whether inconsistently reported factors influence the health-related quality of life (HRQOL) outcome of partial meniscectomy. Short Form 36 (SF-36) data on 216 patients were retrospectively analysed for the influence of the factors age, gender and degree of cartilage degeneration. Mixed linear models were applied for univariate and multivariate analyses. All SF-36 scales, including the psychosocial scales, showed a significant improvement from pre- to post-operative (p < 0.001). The factor 'degree of cartilage degeneration' was found to significantly influence post-surgical improvement of the SF-36 'physical component summary' score. Patients with mild cartilage degeneration benefited significantly more from surgery than did patients with advanced cartilage degeneration (p = 0.011). Older patients had significantly lower scores on each subscale, but showed no significant age-time interaction, that is, no association was seen between age and the degree of improvement. No effect was determined for the variable gender. The findings of the current study can be interpreted to show that arthroscopic partial meniscectomy significantly improves HRQOL, even in mental or psychosocial dimensions of HRQOL. Not age but the degree of cartilage degeneration influences the HRQOL gain that can be expected. The factor gender has no effect on HRQOL. The findings of our study influence our daily routine, in that we take the degree of cartilage degeneration and not age as predictive value for the success to be anticipated from the procedure. Concerning the preoperative consenting, it is important to mention that advanced cartilage degeneration is a predictor of a less favourable outcome. IV.

[Non-pharmacologic therapy of age-related macular degeneration, based on the etiopathogenesis of the disease].

PubMed

Fischer, Tamás

2015-07-12

It has a great therapeutic significance that the disorder of the vascular endothelium, which supplies the affected ocular structures, plays a major role in the development of age-related macular degeneration. Chronic inflammation is closely linked to diseases associated with endothelial dysfuncition and age-related macular degeneration is accompanied by a general inflammatory response. The vascular wall including those in chorioids may be activated by several repeated and/or prolonged mechanical, physical, chemical, microbiological, immunologic and genetic factors causing a protracted host defence response with a consequent vascular damage, which leads to age-related macular degeneration. Based on this concept, age-related macular degeneration is a local manifestation of the systemic vascular disease. This recognition should have therapeutic implications because restoration of endothelial dysfunction can stabilize the condition of chronic vascular disease including age-related macular degeneration, as well. Restoration of endothelial dysfunction by non-pharmacological or pharmacological interventions may prevent the development or improve endothelial dysfunction resulting in prevention or improvement of age-related macular degeneration. Non-pharmacological interventions which may have beneficial effect in endothelial dysfunction include (1) smoking cessation; (2) reduction of increased body weight; (3) adequate physical activity; (4) appropriate diet (a) proper dose of flavonoids, polyphenols and kurcumin; (b) omega-3 long-chain polyunsaturated fatty acids: docosahexaenoic acid and eicosapentaenoic acid; (c) carotenoids, lutein and zeaxanthins), (d) management of dietary glycemic index, (e) caloric restriction, and (5) elimination of stressful lifestyle. Non-pharmacological interventions should be preferable even if medicaments are also used for the treatment of endothelial dysfunction.

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

PubMed Central

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

1997-01-01

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

Existence and Stability of Traveling Waves for Degenerate Reaction-Diffusion Equation with Time Delay

NASA Astrophysics Data System (ADS)

Huang, Rui; Jin, Chunhua; Mei, Ming; Yin, Jingxue

2018-01-01

This paper deals with the existence and stability of traveling wave solutions for a degenerate reaction-diffusion equation with time delay. The degeneracy of spatial diffusion together with the effect of time delay causes us the essential difficulty for the existence of the traveling waves and their stabilities. In order to treat this case, we first show the existence of smooth- and sharp-type traveling wave solutions in the case of c≥c^* for the degenerate reaction-diffusion equation without delay, where c^*>0 is the critical wave speed of smooth traveling waves. Then, as a small perturbation, we obtain the existence of the smooth non-critical traveling waves for the degenerate diffusion equation with small time delay τ >0 . Furthermore, we prove the global existence and uniqueness of C^{α ,β } -solution to the time-delayed degenerate reaction-diffusion equation via compactness analysis. Finally, by the weighted energy method, we prove that the smooth non-critical traveling wave is globally stable in the weighted L^1 -space. The exponential convergence rate is also derived.

Existence and Stability of Traveling Waves for Degenerate Reaction-Diffusion Equation with Time Delay

NASA Astrophysics Data System (ADS)

Huang, Rui; Jin, Chunhua; Mei, Ming; Yin, Jingxue

2018-06-01

This paper deals with the existence and stability of traveling wave solutions for a degenerate reaction-diffusion equation with time delay. The degeneracy of spatial diffusion together with the effect of time delay causes us the essential difficulty for the existence of the traveling waves and their stabilities. In order to treat this case, we first show the existence of smooth- and sharp-type traveling wave solutions in the case of c≥c^* for the degenerate reaction-diffusion equation without delay, where c^*>0 is the critical wave speed of smooth traveling waves. Then, as a small perturbation, we obtain the existence of the smooth non-critical traveling waves for the degenerate diffusion equation with small time delay τ >0. Furthermore, we prove the global existence and uniqueness of C^{α ,β }-solution to the time-delayed degenerate reaction-diffusion equation via compactness analysis. Finally, by the weighted energy method, we prove that the smooth non-critical traveling wave is globally stable in the weighted L^1-space. The exponential convergence rate is also derived.

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…

Helicoid peripapillary chorioretinal degeneration complicated by choroidal neovascularization.

PubMed

Triantafylla, Magdalini; Panos, Georgios D; Dardabounis, Doukas; Nanos, Panagiotis; Konstantinidis, Aristeidis

2016-02-15

Helicoid peripapillary chorioretinal degeneration (HPCD) is a hereditary disease of the fundus that is characterized by atrophic chorioretinal areas that appear early in life and expand gradually from the optic disc towards the macula and the periphery. We describe the case of an elderly man with a known diagnosis of HPCD who developed choroidal neovascular membrane (CNV) in both eyes during the course of the disease. The patient was treated with intravitreal injection of ranibizumab, to which he had excellent response. The CNV subsided with 2 injections in the right eye and 1 in the left. Two years after the initial diagnosis of CNV in the right eye, visual acuity was 5/10 OD and 9/10 OS. Helicoid peripapillary chorioretinal degeneration is rarely complicated by CNV as the fundus lacks the trigger factors that would sustain this process. Although rare, HPCD complicated by CNV can be seen bilaterally, but responds well to few ranibizumab injections.

Cygnus X-2 - Neutron star or degenerate dwarf?

NASA Technical Reports Server (NTRS)

Mcclintock, J. E.; Remillard, R. A.; Petro, L. D.; Hammerschlag-Hensberge, G.; Proffitt, C. R.

1984-01-01

Some conflicting models have been proposed for Cyg X-2: a degenerate dwarf model which predicts a distance of 250 + or 50 pc; and a neutron star model which implies a distance of about 8000 pc. Based on a reddening study, it is found that the distance to Cyg X-2 is greater than 1100 pc, which rules strongly against the degenerate dwarf model. This conclusion is based on observations of the 2200 A feature in the spectrum of Cyg X-2 made with the International Ultraviolet Explorer (IUE), and UBV and spectroscopic observations of 38 field stars. For the reddening of Cyg X-2 values of E(B-V) = 0.40 + or - 0.07 (1 sigma) are found and are consistent with the reddening to infinity in that direction inferred from radio data. Consequently, Cyg X-2 may be located in the halo at about 8 kpc as proposed in 1979 by Cowley, Crampton, and Hutchings.

Diagnosis of non-exudative (DRY) age related macular degeneration by non-invasive photon-correlation spectroscopy.

PubMed

Fankhauser, Franz Ii; Ott, Maria; Munteanu, Mihnea

2016-01-01

Photon-correlation spectroscopy (PCS) (quasi-elastic light scattering spectroscopy, dynamic light scattering spectroscopy) allows the non-invasively reveal of local dynamics and local heterogeneities of macromolecular systems. The capability of this technique to diagnose the retinal pathologies by in-vivo investigations of spatial anomalies of retinas displaying non-exudative senile macular degeneration was evaluated. Further, the potential use of the technique for the diagnosis of the macular degeneration was analyzed and displayed by the Receiver Operating Curve (ROC). The maculae and the peripheral retina of 73 normal eyes and of 26 eyes afflicted by an early stage of non-exudative senile macular degeneration were characterized by time-correlation functions and analyzed in terms of characteristic decay times and apparent size distributions. The characteristics of the obtained time-correlation functions of the eyes afflicted with nonexudative macular degeneration and of normal eyes differed significantly, which could be referred to a significant change of the nano- and microstructure of the investigated pathologic maculas. Photon-correlation spectroscopy is able to assess the macromolecular and microstructural aberrations in the macula afflicted by non-exudative, senile macular degeneration. It has been demonstrated that macromolecules of this disease show a characteristic abnormal behavior in the macula.

Activation of Müller cells occurs during retinal degeneration in RCS rats.

PubMed

Zhao, Tong Tao; Tian, Chun Yu; Yin, Zheng Qin

2010-01-01

Müller cells can be activated and included in different functions under many kinds of pathological conditions, however, the status of Müller cells in retinitis pigmentosa are still unknown. Using immunohistochemisty, Western blots and co-culture, we found that Müller cells RCS rats, a classic model of RP, could be activated during the progression of retinal degeneration. After being activated at early stage, Müller cells began to proliferate and hypertrophy, while at later stages, they formed a local 'glial seal' in the subretinal space. As markers of Müller cells activation, the expression of GFAP and ERK increased significantly with progression of retinal degeneration. Co-cultures of normal rat Müller cells and mixed RCS rat retinal cells show that Müller cells significantly increase GFAP and ERK in response to diffusable factors from the degenerting retina, which implies that Müller cells activation is a secondary response to retinal degeneration.

A selective inhibition of c-Fos/activator protein-1 as a potential therapeutic target for intervertebral disc degeneration and associated pain.

PubMed

Makino, Hiroto; Seki, Shoji; Yahara, Yasuhito; Shiozawa, Shunichi; Aikawa, Yukihiko; Motomura, Hiraku; Nogami, Makiko; Watanabe, Kenta; Sainoh, Takeshi; Ito, Hisakatsu; Tsumaki, Noriyuki; Kawaguchi, Yoshiharu; Yamazaki, Mitsuaki; Kimura, Tomoatsu

2017-12-05

Intervertebral disc (IVD) degeneration is a major cause of low back pain. The transcription factor c-Fos/Activator Protein-1 (AP-1) controls the expression of inflammatory cytokines and matrix metalloproteinases (MMPs) that contribute to the pathogenesis IVD degeneration. We investigated the effects of inhibition of c-Fos/AP-1 on IVD degeneration and associated pain. A selective inhibitor, T-5224, significantly suppressed the interleukin-1β-induced up-regulation of Mmp-3, Mmp-13 and Adamts-5 transcription in human nucleus pulposus cells and in a mouse explant culture model of IVD degeneration. We used a tail disc percutaneous needle puncture method to further assess the effects of oral administration of T-5224 on IVD degeneration. Analysis of disc height, T2-magnetic resonance imaging (MRI) findings, and histology revealed that IVD degeneration was significantly mitigated by T-5224. Further, oral administration of T-5224 ameliorated pain as indicated by the extended tail-flick latency in response to heat stimulation of rats with needle-puncture-induced IVD degeneration. These findings suggest that the inhibition of c-Fos/AP-1 prevents disc degeneration and its associated pain and that T-5224 may serve as a drug for the prevention of IVD degeneration.

Temporal and spatial characteristics of cone degeneration in RCS rats.

PubMed

Huang, Yan Ming; Yin, Zheng Qin; Liu, Kang; Huo, Shu Jia

2011-03-01

The temporal and spatial characteristics of cone degeneration in the Royal College of Surgeons (RCS) rat were studied to provide information for treatment strategies of retinitis pigmentosa. Nonpigmented dystrophic RCS rats (RCS) and pigmented nondystrophic RCS rats (controls) were used. Cone processes were visualized with peanut agglutinin (PNA). Cone development appears to have been completed by postnatal day 21 (P21) in both the RCS and control rats. Signs of cone degeneration were obvious by P30, with shorter outer segments (OSs) and enlarged inner segments (ISs). At that time, 81.7% of the cones retained stained ISs. The rate of IS density decline was slower in the peripheral, nasal, and superior retina, and only 43.6% of the cones with ISs were present at P45. By P60, PNA-labeled cone ISs were distorted and restricted to the peripheral retina, and by P90, few cone pedicles were detected. Our findings indicate that therapeutic strategies aimed at rescuing cones in the degenerating retina should be applied before P21 and no later than P45 while substantial numbers of cones retain their ISs. Either the middle or peripheral regions of the nasal and superior retina are the best locations for transplantation strategies.

'From Man to Bacteria': W.D. Hamilton, the theory of inclusive fitness, and the post-war social order.

PubMed

Swenson, Sarah A

2015-02-01

W.D. Hamilton's theory of inclusive fitness aimed to define the evolved limits of altruism with mathematical precision. Although it was meant to apply universally, it has been almost irretrievably entwined with the particular case of social insects that featured in his famous 1964 papers. The assumption that social insects were central to Hamilton's early work contradicts material in his rich personal archive. In fact, careful study of Hamilton's notes, letters, diaries, and early essays indicates the extent to which he had humans in mind when he decided altruism was a topic worthy of biological inquiry. For this reason, this article reconsiders the role of extra-scientific factors in Hamilton's early theorizing. In doing so, it offers an alternative perspective as to why Hamilton saw self-sacrifice to be an important subject. Although the traditional narrative prioritizes his distaste for benefit-of-the-species explanations as a motivating factor behind his foundational work, I argue that greater attention ought to be given to Hamilton's hope that science could be used to address social ills. By reconsidering the meaning Hamilton intended inclusive fitness to have, we see that while he was no political ideologue, the socio-political relevance of his theory was nevertheless integral to its development. Copyright © 2015 Elsevier Ltd. All rights reserved.

Lycium Barbarum (Wolfberry) Reduces Secondary Degeneration and Oxidative Stress, and Inhibits JNK Pathway in Retina after Partial Optic Nerve Transection

PubMed Central

Li, Hongying; Liang, Yuxiang; Chiu, Kin; Yuan, Qiuju; Lin, Bin; Chang, Raymond Chuen-Chung; So, Kwok-Fai

2013-01-01

Our group has shown that the polysaccharides extracted from Lycium barbarum (LBP) are neuroprotective for retinal ganglion cells (RGCs) in different animal models. Protecting RGCs from secondary degeneration is a promising direction for therapy in glaucoma management. The complete optic nerve transection (CONT) model can be used to study primary degeneration of RGCs, while the partial optic nerve transection (PONT) model can be used to study secondary degeneration of RGCs because primary degeneration of RGCs and secondary degeneration can be separated in location in the same retina in this model; in other situations, these types of degeneration can be difficult to distinguish. In order to examine which kind of degeneration LBP could delay, both CONT and PONT models were used in this study. Rats were fed with LBP or vehicle daily from 7 days before surgery until sacrifice at different time-points and the surviving numbers of RGCs were evaluated. The expression of several proteins related to inflammation, oxidative stress, and the c-jun N-terminal kinase (JNK) pathways were detected with Western-blot analysis. LBP did not delay primary degeneration of RGCs after either CONT or PONT, but it did delay secondary degeneration of RGCs after PONT. We found that LBP appeared to exert these protective effects by inhibiting oxidative stress and the JNK/c-jun pathway and by transiently increasing production of insulin-like growth factor-1 (IGF-1). This study suggests that LBP can delay secondary degeneration of RGCs and this effect may be linked to inhibition of oxidative stress and the JNK/c-jun pathway in the retina. PMID:23894366

Abdominal adipose tissue thickness measured using magnetic resonance imaging is associated with lumbar disc degeneration in a Chinese patient population.

PubMed

Yang, Lili; Mu, Liangshan; Huang, Kaiyu; Zhang, Tianyi; Mei, Zihan; Zeng, Wenrong; He, Jiawei; Chen, Wei; Liu, Xiaozheng; Ye, Xinjian; Yan, Zhihan

2016-12-13

The relationship between abdominal adiposity and disc degeneration remains largely uninvestigated. Here, we investigated the association between abdominal adipose tissue thickness and lumbar disc degeneration in a cross-sectional study of 2415 participants from The Second Affiliated Hospital of Wenzhou Medical University. All subjects were scanned with a 3T Magnetic Resonance Imaging system to evaluate the degree of lumbar disc degeneration. Multiple logistic regression analysis revealed that men in the highest quartiles for abdominal diameter (AD), sagittal diameter (SAD), and ventral subcutaneous thickness (VST) were at higher odds ratio for severe lumbar disc degeneration than men in the lowest quartiles. The adjusted model revealed that women in the highest quartiles for AD and SAD were also at higher odds ratio for severe lumbar disc degeneration than women in the lowest quartiles. Our results suggest that abdominal obesity might be one of underlying mechanisms of lumbar disc degeneration, and preventive strategies including weight control could be useful to reduce the incidence of lumbar disc degeneration. Prospective studies are needed to this confirm these results and to identify more deeper underlying mechanisms.

Immunology of age-related macular degeneration.

PubMed

Ambati, Jayakrishna; Atkinson, John P; Gelfand, Bradley D

2013-06-01

Age-related macular degeneration (AMD) is a leading cause of blindness in aged individuals. Recent advances have highlighted the essential role of immune processes in the development, progression and treatment of AMD. In this Review we discuss recent discoveries related to the immunological aspects of AMD pathogenesis. We outline the diverse immune cell types, inflammatory activators and pathways that are involved. Finally, we discuss the future of inflammation-directed therapeutics to treat AMD in the growing aged population.

A Large Animal Model that Recapitulates the Spectrum of Human Intervertebral Disc Degeneration

PubMed Central

Gullbrand, Sarah E.; Malhotra, Neil R.; Schaer, Thomas P.; Zawacki, Zosia; Martin, John T.; Bendigo, Justin R.; Milby, Andrew H.; Dodge, George R.; Vresilovic, Edward J.; Elliott, Dawn M.; Mauck, Robert L.; Smith, Lachlan J.

2016-01-01

Objective The objective of this study was to establish a large animal model that recapitulates the spectrum of intervertebral disc degeneration that occurs in humans and which is suitable for pre-clinical evaluation of a wide range of experimental therapeutics. Design Degeneration was induced in the lumbar intervertebral discs of large frame goats by either intradiscal injection of chondroitinase ABC (ChABC) over a range of dosages (0.1U, 1U or 5U) or subtotal nucleotomy. Radiographs were used to assess disc height changes over 12 weeks. Degenerative changes to the discs and endplates were assessed via magnetic resonance imaging (MRI), semi-quantitative histological grading, micro-computed tomography (µCT), and measurement of disc biomechanical properties. Results Degenerative changes were observed for all interventions that ranged from mild (0.1U ChABC) to moderate (1U ChABC and nucleotomy) to severe (5U ChABC). All groups showed progressive reductions in disc height over 12 weeks. Histological scores were significantly increased in the 1U and 5U ChABC groups. Reductions in T2 and T1ρ, and increased Pfirrmann grade were observed on MRI. Resorption and remodeling of the cortical boney endplate adjacent to ChABC injected discs also occurred. Spine segment range of motion was greater and compressive modulus was lower in 1U ChABC and nucleotomy discs compared to intact. Conclusions A large animal model of disc degeneration was established that recapitulates the spectrum of structural, compositional and biomechanical features of human disc degeneration. This model may serve as a robust platform for evaluating the efficacy of therapeutics targeted towards varying degrees of disc degeneration. PMID:27568573

Pathophysiology, diagnosis and treatment of intermittent claudication in patients with lumbar canal stenosis

PubMed Central

Kobayashi, Shigeru

2014-01-01

Spinal nerve roots have a peculiar structure, different from the arrangements in the peripheral nerve. The nerve roots are devoid of lymphatic vessels but are immersed in the cerebrospinal fluid (CSF) within the subarachnoid space. The blood supply of nerve roots depends on the blood flow from both peripheral direction (ascending) and the spinal cord direction (descending). There is no hypovascular region in the nerve root, although there exists a so-called water-shed of the bloodstream in the radicular artery itself. Increased mechanical compression promotes the disturbance of CSF flow, circulatory disturbance starting from the venous congestion and intraradicular edema formation resulting from the breakdown of the blood-nerve barrier. Although this edema may diffuse into CSF when the subarachnoid space is preserved, the endoneurial fluid pressure may increase when the area is closed by increased compression. On the other hand, the nerve root tissue has already degenerated under the compression and the numerous macrophages releasing various chemical mediators, aggravating radicular symptoms that appear in the area of Wallerian degeneration. Prostaglandin E1 (PGE1) is a potent vasodilator as well as an inhibitor of platelet aggregation and has therefore attracted interest as a therapeutic drug for lumbar canal stenosis. However, investigations in the clinical setting have shown that PGE1 is effective in some patients but not in others, although the reason for this is unclear. PMID:24829876

Critical Ischemia Times and the Effect of Novel Preservation Solutions HTK-N and TiProtec on Tissues of a Vascularized Tissue Isograft.

PubMed

Messner, Franka; Hautz, Theresa; Blumer, Michael J F; Bitsche, Mario; Pechriggl, Elisabeth J; Hermann, Martin; Zelger, Bettina; Zelger, Bernhard; Öfner, Dietmar; Schneeberger, Stefan

2017-09-01

We herein investigate critical ischemia times and the effect of novel preservation solutions such as new histidine-tryptophan-ketoglutarate (HTK-N) and TiProtec on the individual tissues of a rat limb isograft. Orthotopic hind-limb transplantations were performed in male Lewis rats after 2 hours, 6 hours, or 10 hours of cold ischemia (CI). Limbs were flushed and stored in HTK-N, TiProtec, HTK, or saline solution. Muscle, nerve, vessel, skin, and bone samples were procured on day 10 for histology, immunohistochemistry, confocal and electron microscopy, and quantitative real-time polymerase chain reaction analysis. Histomorphology of the muscle showed a mainly perivascular inflammatory infiltrate, fibrotic degeneration, and neovascularization after 6 hours and 10 hours of CI. However, centrally aligned nuclei observed in muscle fibers suggest for muscle regeneration in these samples. In addition to Wallerian degeneration, nerve injury was significantly aggravated (P = 0.032) after prolonged CI. Proinflammatory and regulatory cytokines were most significantly upregulated after 2-hour CI. Our data suggest no superiority of novel perfusates HTK-N and TiProtec in terms of tissue preservation, compared with HTK and saline. Limiting CI time for less than 6 hours is the most significant factor to reduce tissue damage in vascularized tissue transplantation. Signs of muscle regeneration give rise that ischemic muscle damage in limb transplantation might be reversible to a certain extent.

Pathophysiology, diagnosis and treatment of intermittent claudication in patients with lumbar canal stenosis.

PubMed

Kobayashi, Shigeru

2014-04-18

Spinal nerve roots have a peculiar structure, different from the arrangements in the peripheral nerve. The nerve roots are devoid of lymphatic vessels but are immersed in the cerebrospinal fluid (CSF) within the subarachnoid space. The blood supply of nerve roots depends on the blood flow from both peripheral direction (ascending) and the spinal cord direction (descending). There is no hypovascular region in the nerve root, although there exists a so-called water-shed of the bloodstream in the radicular artery itself. Increased mechanical compression promotes the disturbance of CSF flow, circulatory disturbance starting from the venous congestion and intraradicular edema formation resulting from the breakdown of the blood-nerve barrier. Although this edema may diffuse into CSF when the subarachnoid space is preserved, the endoneurial fluid pressure may increase when the area is closed by increased compression. On the other hand, the nerve root tissue has already degenerated under the compression and the numerous macrophages releasing various chemical mediators, aggravating radicular symptoms that appear in the area of Wallerian degeneration. Prostaglandin E1 (PGE1) is a potent vasodilator as well as an inhibitor of platelet aggregation and has therefore attracted interest as a therapeutic drug for lumbar canal stenosis. However, investigations in the clinical setting have shown that PGE1 is effective in some patients but not in others, although the reason for this is unclear.

Mild (not severe) disc degeneration is implicated in the progression of bilateral L5 spondylolysis to spondylolisthesis.

PubMed

Ramakrishna, Vivek A S; Chamoli, Uphar; Viglione, Luke L; Tsafnat, Naomi; Diwan, Ashish D

2018-04-02

Spondylolytic (or lytic) spondylolisthesis is often associated with disc degeneration at the index-level; however, it is not clear if disc degeneration is the cause or the consequence of lytic spondylolisthesis. The main objective of this computed tomography based finite element modelling study was to examine the role of different grades of disc degeneration in the progression of a bilateral L5-lytic defect to spondylolisthesis. High-resolution computed tomography data of the lumbosacral spine from an anonymised healthy male subject (26 years old) were segmented to build a 3D-computational model of an INTACT L1-S1 spine. The INTACT model was manipulated to generate four more models representing a bilateral L5-lytic defect and the following states of the L5-S1 disc: nil degeneration (NOR LYTIC), mild degeneration (M-DEG LYTIC), mild degeneration with 50% disc height collapse (M-DEG-COL LYTIC), and severe degeneration with 50% disc height collapse(S-COL LYTIC). The models were imported into a finite element modelling software for pre-processing, running nonlinear-static solves, and post-processing of the results. Compared with the baseline INTACT model, M-DEG LYTIC model experienced the greatest increase in kinematics (Fx range of motion: 73% ↑, Fx intervertebral translation: 53%↑), shear stresses in the annulus (Fx anteroposterior: 163%↑, Fx posteroanterior: 31%↑), and strain in the iliolumbar ligament (Fx: 90%↑). The S-COL LYTIC model experienced a decrease in mobility (Fx range of motion: 48%↓, Fx intervertebral translation: 69%↓) and an increase in normal stresses in the annulus (Fx Tensile: 170%↑; Fx Compressive: 397%↑). No significant difference in results was noted between M-DEG-COL LYTIC and S-COL LYTIC models. In the presence of a bilateral L5 spondylolytic defect, a mildly degenerate index-level disc experienced greater intervertebral motions and shear stresses compared with a severely degenerate index-level disc in flexion and extension

Subacute combined degeneration of the cord due to folate deficiency: response to methyl folate treatment.

PubMed Central

Lever, E G; Elwes, R D; Williams, A; Reynolds, E H

1986-01-01

Subacute combined degeneration of the cord is a rare complication of folate deficiency. Disturbance of methylation reactions in nervous tissue probably underlie subacute combined degeneration of the cord arising from folate as well as vitamin B12 deficiency. Methyl tetrahydrofolate is the form in which folic acid is transported into the CNS. Therefore methyl tetrahydrofolate treatment of the neurological and psychiatric manifestations of folate deficiency would seem to be theoretically advantageous. A case of subacute combined degeneration of the cord due to dietary folate deficiency and associated with an organic brain syndrome is reported. There was striking haematological, neurological and psychiatric response to methyl folate treatment. PMID:3783183

Estrogen signalling in the pathogenesis of age-related macular degeneration.

PubMed

Kaarniranta, Kai; Machalińska, Anna; Veréb, Zoltán; Salminen, Antero; Petrovski, Goran; Kauppinen, Anu

2015-02-01

Age-related macular degeneration (AMD) is a multifactorial eye disease that is associated with aging, family history, smoking, obesity, cataract surgery, arteriosclerosis, hypertension, hypercholesterolemia and unhealthy diet. Gender has commonly been classified as a weak or inconsistent risk factor for AMD. This disease is characterized by degeneration of retinal pigment epithelial (RPE) cells, Bruch's membrane, and choriocapillaris, which secondarily lead to damage and death of photoreceptor cells and central visual loss. Pathogenesis of AMD involves constant oxidative stress, chronic inflammation, and increased accumulation of lipofuscin and drusen. Estrogen has both anti-oxidative and anti-inflammatory capacity and it regulates signaling pathways that are involved in the pathogenesis of AMD. In this review, we discuss potential cellular signaling targets of estrogen in retinal cells and AMD pathology.

Arbitrary amplitude nucleus-acoustic solitons in multi-ion quantum plasmas with relativistically degenerate electrons

NASA Astrophysics Data System (ADS)

Sultana, S.; Schlickeiser, R.

2018-02-01

A three component degenerate relativistic quantum plasma (consisting of relativistically degenerate electrons, nondegenerate inertial light nuclei, and stationary heavy nuclei) is considered to model the linear wave and also the electrostatic solitary waves in the light nuclei-scale length. A well-known normal mode analysis is employed to investigate the linear wave properties. A mechanical-motion analog (Sagdeev-type) pseudo-potential approach, which reveals the existence of large amplitude solitary excitations, is adopted to study the nonlinear wave properties. Only the positive potential solitary excitations are found to exist in the plasma medium under consideration. The basic properties of the arbitrary amplitude electrostatic acoustic modes in the light nuclei-scale length and their existence domain in terms of soliton speed (Mach number) are examined. The modifications of solitary wave characteristics and their existence domain with the variation of different key plasma configuration parameters (e.g., electrons degeneracy parameter, inertial light nuclei number density, and degenerate electron number density) are also analyzed. Our results, which may be helpful to explain the basic features of the nonlinear wave propagation in multi-component degenerate quantum plasmas, in connection with astrophysical compact objects (e.g., white dwarfs) are briefly discussed.

Immunology of age-related macular degeneration

PubMed Central

Ambati, Jayakrishna; Atkinson, John P.; Gelfand, Bradley D.

2014-01-01

Age-related macular degeneration (AMD) is a leading cause of blindness in aged individuals. Recent advances have highlighted the essential role of immune processes in the development, progression and treatment of AMD. In this Review we discuss recent discoveries related to the immunological aspects of AMD pathogenesis. We outline the diverse immune cell types, inflammatory activators and pathways that are involved. Finally, we discuss the future of inflammation-directed therapeutics to treat AMD in the growing aged population. PMID:23702979

WD40-repeat 47, a microtubule-associated protein, is essential for brain development and autophagy

PubMed Central

Kannan, Meghna; Bayam, Efil; Wagner, Christel; Rinaldi, Bruno; Kretz, Perrine F.; Tilly, Peggy; Roos, Marna; McGillewie, Lara; Bär, Séverine; Minocha, Shilpi; Chevalier, Claire; Po, Chrystelle; Chelly, Jamel; Mandel, Jean-Louis; Borgatti, Renato; Piton, Amélie; Loos, Ben; Adams, David J.; Hérault, Yann; Collins, Stephan C.; Godin, Juliette D.; Yalcin, Binnaz

2017-01-01

The family of WD40-repeat (WDR) proteins is one of the largest in eukaryotes, but little is known about their function in brain development. Among 26 WDR genes assessed, we found 7 displaying a major impact in neuronal morphology when inactivated in mice. Remarkably, all seven genes showed corpus callosum defects, including thicker (Atg16l1, Coro1c, Dmxl2, and Herc1), thinner (Kif21b and Wdr89), or absent corpus callosum (Wdr47), revealing a common role for WDR genes in brain connectivity. We focused on the poorly studied WDR47 protein sharing structural homology with LIS1, which causes lissencephaly. In a dosage-dependent manner, mice lacking Wdr47 showed lethality, extensive fiber defects, microcephaly, thinner cortices, and sensory motor gating abnormalities. We showed that WDR47 shares functional characteristics with LIS1 and participates in key microtubule-mediated processes, including neural stem cell proliferation, radial migration, and growth cone dynamics. In absence of WDR47, the exhaustion of late cortical progenitors and the consequent decrease of neurogenesis together with the impaired survival of late-born neurons are likely yielding to the worsening of the microcephaly phenotype postnatally. Interestingly, the WDR47-specific C-terminal to LisH (CTLH) domain was associated with functions in autophagy described in mammals. Silencing WDR47 in hypothalamic GT1-7 neuronal cells and yeast models independently recapitulated these findings, showing conserved mechanisms. Finally, our data identified superior cervical ganglion-10 (SCG10) as an interacting partner of WDR47. Taken together, these results provide a starting point for studying the implications of WDR proteins in neuronal regulation of microtubules and autophagy. PMID:29078390

Qualitative grading of disc degeneration by magnetic resonance in the lumbar and cervical spine: lack of correlation with histology in surgical cases.

PubMed

Davies, B M; Atkinson, R A; Ludwinski, F; Freemont, A J; Hoyland, J A; Gnanalingham, K K

2016-08-01

Clinically, magnetic resonance (MR) imaging is the most effective non-invasive tool for assessing IVD degeneration. Histological examination of the IVD provides a more detailed assessment of the pathological changes at a tissue level. However, very few reports have studied the relationship between these techniques. Identifying a relationship may allow more detailed staging of IVD degeneration, of importance in targeting future regenerative therapies. To investigate the relationship between MR and histological grading of IVD degeneration in the cervical and lumbar spine in patients undergoing discectomy. Lumbar (N = 99) and cervical (N = 106) IVD samples were obtained from adult patients undergoing discectomy surgery for symptomatic IVD herniation and graded to ascertain a histological grade of degeneration. The pre-operative MR images from these patients were graded for the degree of IVD (MR grade) and vertebral end-plate degeneration (Modic Changes, MC). The relationship between histological and MR grades of degeneration were studied. In lumbar and cervical IVD the majority of samples (93%) exhibited moderate levels of degeneration (ie MR grades 3-4) on pre-operative MR scans. Histologically, most specimens displayed moderate to severe grades of degeneration in lumbar (99%) and cervical spine (93%). MR grade was weakly correlated with patient age in lumbar and cervical study groups. MR and histological grades of IVD degeneration did not correlate in lumbar or cervical study groups. MC were more common in the lumbar than cervical spine (e.g. 39 versus 20% grade 2 changes; p < 0.05), but failed to correlate with MR or histological grades for degeneration. In this surgical series, the resected IVD tissue displayed moderate to severe degeneration, but there is no correlation between MR and histological grades using a qualitative classification system. There remains a need for a quantitative, non-invasive, pre-clinical measure of IVD degeneration that

Cervical Lordosis Actually Increases With Aging and Progressive Degeneration in Spinal Deformity Patients.

PubMed

Kim, Han Jo; Lenke, Lawrence G; Oshima, Yasushi; Chuntarapas, Tapanut; Mesfin, Addisu; Hershman, Stuart; Fogelson, Jeremy L; Riew, K Daniel

2014-09-01

Retrospective. The authors hypothesized that cervical lordosis (CL) would decrease with aging and increasing degeneration. It is theorized that with age and degeneration, the cervical spine loses lordosis and becomes progressively more kyphotic; however, no studies support these conclusions in patients with various spinal deformities. The authors performed a radiographic analysis of asymptomatic adults (referring to their cervical spine) of varying ages, with differing forms of spinal deformity to the thoracic/lumbar spine to see how cervical lordosis changes with increasing age. A total of 104 total spine EOS X-rays of adult (aged >18 years) spinal deformity patients without documented neck pain, prior neck surgery, or cervical deformity were reviewed. The researchers only reviewed EOS X-rays because they allow complete visualization from occiput to feet. Cervical lordosis, standard Cobb measurements, sagittal balance parameters, and cervical degeneration were quantified radiographically by the method previously described by Gore et al. Statistical analysis was performed with 1-way analysis of variance to compare significant differences between groups aged <40, 40-60 and >60 years as well as changes in sagittal balance. A p-value < .05 was considered significant. Average CL actually increased with increasing age (10.3 ± 14.7, 15.4 ± 15.1, and 23.3 ± 1.6.7 for age < 40, 40-60, and > 60 years, respectively; p < .05). Average cervical degeneration score increased at all disc space levels from C2 to C7 across age groups (0.7 ± 1.2, 9.9 ± 69, and 16.3 ± 8.9 for age <40, 40-60, and >60 years, respectively; p < .01), with the highest degeneration at the C5-6 and C6-7 disc spaces (3.7 ± 3.3 and 3.2 ± 2.9, respectively; p < .01). This increase did not correlate with the increase in CL seen with aging (r = 0.02; p = .84). Cervical lordosis increased with aging in adult spinal deformity patients. There was no relationship between cervical degeneration and lordosis

Response solutions and quasi-periodic degenerate bifurcations for quasi-periodically forced systems

NASA Astrophysics Data System (ADS)

Si, Wen; Si, Jianguo

2018-06-01

This paper includes two parts. In the first part, we first focus on quasi-periodic time dependent perturbations of one-dimensional quasi-periodically forced systems with degenerate equilibrium. We study the system in two cases, for one of which system admits a response solution under a non-resonant condition on the frequency vector weaker than Brjuno–Rüssmann’s and for another of which system also admits a response solution without any non-resonant conditions. Next, we investigate the existence of response solutions of a quasi-periodic perturbed system with degenerate (including completely degenerate) equilibrium under Brjuno–Rüssmann’s non-resonant condition by using the Herman method. In the second part, we consider, firstly, the quasi-periodic perturbation of a universal unfolding of one-dimensional degenerate vector field . Secondly, we consider the perturbation of a universal unfolding of normal two-dimensional Hamiltonian system with completely degenerate equilibrium. With KAM theory and singularity theory, we show that these two classes of universal unfolding can persist on large Cantor sets under Brjuno–Rüssmann’s non-resonant condition, which implies all the invariant tori in the integrable part and all the bifurcation scenario can survive on large Cantor sets. The result for Hamiltonian system can apply directly to the response context for quasi-periodically forced systems. Our results in this paper can be regarded as an improvement with respect to several results in various literature (Broer et al 2005 Nonlinearity 18 1735–69 Broer et al 2006 J. Differ. Equ. 222 233–62 Wagener 2005 J. Differ. Equ. 216 216–81 Xu 2010 J. Differ. Equ. 250 551–71 Xu and Jiang 2010 Ergod. Theor. Dynam. Syst. 31 599–611 Lu and Xu 2014 Nonlinear Differ. Equ. Appl. 21 361–70). This work was partially supported by the National Natural Science Foundation of China (Grant Nos. 11171185, 11571201).

Early markers of retinal degeneration in rd/rd mice.

PubMed

Acosta, Monica L; Fletcher, Erica L; Azizoglu, Serap; Foster, Lisa E; Farber, Debora B; Kalloniatis, Michael

2005-09-06

In the rd/rd mouse, the cell death of rod photoreceptors has been correlated to abnormal levels of the cyclic nucleotide cGMP within photoreceptors. Given that cGMP is required for opening of the cationic channels, there is the possibility that a high cGMP concentration would maintain these channels open, at a high energy cost for the retina. We investigated whether cation channels were maintained in an open state in the rd/rd mouse retina by determining the labeling pattern of an organic cationic probe (agmatine, AGB) which selectively enters cells through open cationic channels. The metabolic activity of the rd/rd mice was measured by assaying lactate dehydrogenase (LDH) activity in several tissues and Na+/K+ ATPase activity was measured as a function of development and degeneration of the retina. AGB neuronal labeling showed a systematic increase consistent with the known neuronal functional maturation in the normal retina. There was a significant higher AGB labeling of photoreceptors in the rd/rd mouse retina from P6 supporting the possibility of open cationic channels from an early age. There were no changes in the LDH activity of tissues that contain PDE6 or that have a similar LDH distribution as the retina. However, LDH activity was significantly higher in the rd/rd mouse retina than in those of control mice from birth to P6, and it dramatically decreased from P9 as the photoreceptors degenerated. The predominant LDH isoenzyme changes and loss after degeneration appeared to be LDH5. ATPase activity increased with age, reaching adult levels by P16. Unlike LDH activity, there was no significant difference in Na+/K+ ATPase activity between control and rd/rd mice at any age examined. We conclude that AGB is a useful marker of photoreceptors destined to degenerate. We discard the possibility of a generalized metabolic effect in the rd/rd mice. However, the elevated LDH activity present before photoreceptor differentiation indicated altered retinal metabolic

Computational fluid dynamics simulation of transcatheter aortic valve degeneration.

PubMed

Dwyer, Harry A; Matthews, Peter B; Azadani, Ali; Jaussaud, Nicolas; Ge, Liang; Guy, T Sloane; Tseng, Elaine E

2009-08-01

Studied under clinical trials, transcatheter aortic valves (TAV) have demonstrated good short-term feasibility and results in high-risk surgical patients with severe aortic stenosis. However, their long-term safety and durability are unknown. The objective of this study is to evaluate hemodynamic changes within TAV created by bioprosthetic leaflet degeneration. Computational fluid dynamics (CFD) simulations were performed to evaluate the hemodynamics through TAV sclerosis (35% orifice reduction) and stenosis (78% orifice reduction). A three-dimensional surface mesh of the TAV within the aortic root was generated for each simulation. Leaflets were contained within an open, cylindrical body without attachment to the sinus commissures representing the stent. A continuous surface between the annulus and TAV excluded the geometry of the native calcified leaflets and prevented paravalvular leak. Unsteady control volume analysis throughout systole was used to calculate leaflet shear stress and total force on the TAV. Sclerosis increased total force on the TAV by 63% (0.602-0.98 N). Advancement of degeneration from sclerosis to stenosis was accompanied by an 86% increase in total force (1.82 N) but only a 32% increase in peak wall shear stress on the leaflets. Of the total force exerted on the TAV, 99% was in the direction of axial flow. Shear stresses on the TAV were greatest during peak systolic flow with stress concentrations on the tips of the leaflets. In the normal TAV, the aortic root geometry and physiologic flow dominate location and magnitude of shear stress. Following leaflet degeneration, the specific geometry of the stenosis dictates the profile of axial velocity leaving the TAV and shear stress on the leaflets. A dramatic increase in peak leaflet shear stress was observed (115 Pa stenosis vs. 87 Pa sclerosis and 29 Pa normal). CFD simulations in this study provide the first of its kind data quantifying hemodynamics within stenosed TAV. Stenosis leads to

Indices of Paraspinal Muscles Degeneration: Reliability and Association With Facet Joint Osteoarthritis: Feasibility Study.

PubMed

Kalichman, Leonid; Klindukhov, Alexander; Li, Ling; Linov, Lina

2016-11-01

A reliability and cross-sectional observational study. To introduce a scoring system for visible fat infiltration in paraspinal muscles; to evaluate intertester and intratester reliability of this system and its relationship with indices of muscle density; to evaluate the association between indices of paraspinal muscle degeneration and facet joint osteoarthritis. Current evidence suggests that the paraspinal muscles degeneration is associated with low back pain, facet joint osteoarthritis, spondylolisthesis, and degenerative disc disease. However, the evaluation of paraspinal muscles on computed tomography is not radiological routine, probably because of absence of simple and reliable indices of paraspinal degeneration. One hundred fifty consecutive computed tomography scans of the lower back (N=75) or abdomen (N=75) were evaluated. Mean radiographic density (in Hounsfield units) and SD of the density of multifidus and erector spinae were evaluated at the L4-L5 spinal level. A new index of muscle degeneration, radiographic density ratio=muscle density/SD of density, was calculated. To evaluate the visible fat infiltration in paraspinal muscles, we proposed a 3-graded scoring system. The prevalence of facet joint osteoarthritis was also evaluated. Intraclass correlation and κ statistics were used to evaluate inter-rater and intra-rater reliability. Logistic regression examined the association between paraspinal muscle indices and facet joint osteoarthritis. Intra-rater reliability for fat infiltration score (κ) ranged between 0.87 and 0.92; inter-rater reliability between 0.70 and 0.81. Intra-rater reliability (intraclass correlation) for mean density of paraspinal muscles ranged between 0.96 and 0.99, inter-rater reliability between 0.95 and 0.99; SD intra-rater reliability ranged between 0.82 and 0.91, inter-rater reliability between 0.80 and 0.89. Significant associations (P<0.01) were found between facet joint osteoarthritis, fat infiltration score, and

C1,1 regularity for degenerate elliptic obstacle problems

NASA Astrophysics Data System (ADS)

Daskalopoulos, Panagiota; Feehan, Paul M. N.

2016-03-01

The Heston stochastic volatility process is a degenerate diffusion process where the degeneracy in the diffusion coefficient is proportional to the square root of the distance to the boundary of the half-plane. The generator of this process with killing, called the elliptic Heston operator, is a second-order, degenerate-elliptic partial differential operator, where the degeneracy in the operator symbol is proportional to the distance to the boundary of the half-plane. In mathematical finance, solutions to the obstacle problem for the elliptic Heston operator correspond to value functions for perpetual American-style options on the underlying asset. With the aid of weighted Sobolev spaces and weighted Hölder spaces, we establish the optimal C 1 , 1 regularity (up to the boundary of the half-plane) for solutions to obstacle problems for the elliptic Heston operator when the obstacle functions are sufficiently smooth.

Degenerate stars and gravitational collapse in AdS/CFT

NASA Astrophysics Data System (ADS)

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

2011-01-01

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

Characterizing depth-dependent refractive index of articular cartilage subjected to mechanical wear or enzymic degeneration

NASA Astrophysics Data System (ADS)

Wang, Kuyu; Wu, Jianping; Day, Robert; Kirk, Thomas Brett; Hu, Xiaozhi

2016-09-01

Utilizing a laser scanning confocal microscope system, the refractive indices of articular cartilage (AC) with mechanical or biochemical degenerations were characterized to investigate whether potential correlations exist between refractive index (RI) and cartilage degeneration. The cartilage samples collected from the medial femoral condyles of kangaroo knees were mechanically degenerated under different loading patterns or digested in trypsin solution with different concentrations. The sequences of RI were then measured from cartilage surface to deep region and the fluctuations of RI were quantified considering combined effects of fluctuating frequency and amplitude. The compositional and microstructural alterations of cartilage samples were assessed with histological methods. Along with the loss of proteoglycans, the average RI of cartilage increased and the local fluctuation of RI became stronger. Short-term high-speed test induced little influence to both the depth fluctuation and overall level of RI. Long-term low-speed test increased the fluctuation of RI but the average RI was barely changed. The results substantially demonstrate that RI of AC varies with both compositional and structural alterations and is potentially an indicator for the degeneration of AC.

Finite-time blow-up for quasilinear degenerate Keller-Segel systems of parabolic-parabolic type

NASA Astrophysics Data System (ADS)

Hashira, Takahiro; Ishida, Sachiko; Yokota, Tomomi

2018-05-01

This paper deals with the quasilinear degenerate Keller-Segel systems of parabolic-parabolic type in a ball of RN (N ≥ 2). In the case of non-degenerate diffusion, Cieślak-Stinner [3,4] proved that if q > m + 2/N, where m denotes the intensity of diffusion and q denotes the nonlinearity, then there exist initial data such that the corresponding solution blows up in finite time. As to the case of degenerate diffusion, it is known that a solution blows up if q > m + 2/N (see Ishida-Yokota [13]); however, whether the blow-up time is finite or infinite has been unknown. This paper gives an answer to the unsolved problem. Indeed, the finite-time blow-up of energy solutions is established when q > m + 2/N.

Locus coeruleus degeneration exacerbates olfactory deficits in APP/PS1 transgenic mice.

PubMed

Rey, Nolwen L; Jardanhazi-Kurutz, Daniel; Terwel, Dick; Kummer, Markus P; Jourdan, Francois; Didier, Anne; Heneka, Michael T

2012-02-01

Neuronal loss in the locus coeruleus (LC) is 1 of the early pathological events in Alzheimer's disease (AD). Projections of noradrenergic neurons of the LC innervate the olfactory bulb (OB). Because olfactory deficits have been reported in early AD, we investigated the effect of induced LC degeneration on olfactory memory and discrimination in an AD mouse model. LC degeneration was induced by treating APP/PS1 mice with N-(2-chloroethyl)-N-ethyl-bromo-benzylamine (DSP4) repeatedly between 3 and 12 months of age. Short term odor retention, ability for spontaneous habituation to an odor, and spontaneous odor discrimination were assessed by behavioral tests. DSP4 treatment in APP/PS1 mice resulted in an exacerbation of short term olfactory memory deficits and more discrete weakening of olfactory discrimination abilities, suggesting that LC degeneration contributes to olfactory deficits observed in AD. Importantly, DSP4 treatment also increased amyloid β (Aβ) deposition in the olfactory bulb of APP/PS1 mice, which correlated with olfactory memory, not with discrimination deficits. Copyright © 2012 Elsevier Inc. All rights reserved.

HIGH-DOSE HIGH-FREQUENCY AFLIBERCEPT FOR RECALCITRANT NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PubMed

You, Qi Sheng; Gaber, Raouf; Meshi, Amit; Ramkumar, Hema L; Alam, Mostafa; Muftuoglu, Ilkay Kilic; Freeman, William R

2018-06-01

To determine the efficacy of monthly (0.1 mL/4 mg) aflibercept for refractory neovascular age-related macular degeneration (wet age-related macular degeneration). This was a retrospective interventional case series in which patients with wet age-related macular degeneration were treated with stepwise dose escalation. Nonvitrectomized patients resistant to monthly (Q4W) ranibizumab/bevacizumab were switched to 2 mg aflibercept every 8 weeks. With resistance, they were escalated to Q4W 2 mg aflibercept, then Q4W 4 mg (high dose high frequency, 4Q4W) aflibercept. Resistance was defined as ≥2 recurrences after being dry following ≥3 injections or persistent exudation on treatment of ≥5 injections. Thirty-three eyes of 28 patients were treated with 4Q4W aflibercept and followed for a mean of 16 months. A dry retina (no intraretinal or subretinal fluid) was achieved after initiating 4Q4W aflibercept treatment at a mean of 3.8 months. Central foveal thickness, maximum foveal thickness, intraretinal fluid, subretinal fluid, and retinal pigment detachment height decreased significantly at 1 month after initiating the 4Q4W aflibercept, and the morphologic therapeutic effect was sustained until the last visit. Forty-five percent of eyes had one or more lines of vision improvement. New geographic atrophy developed in 9% of eyes during follow-up. No ocular or systemic adverse events occurred after initiating 4Q4W aflibercept. Intravitreal high-dose high-frequency aflibercept is an effective treatment for patients with refractory wet age-related macular degeneration.

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

PubMed

Wishart, Thomas M; Rooney, Timothy M; Lamont, Douglas J; Wright, Ann K; Morton, A Jennifer; Jackson, Mandy; Freeman, Marc R; Gillingwater, Thomas H

2012-01-01

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

Study of degenerate four-quark states with SU(2) lattice Monte Carlo techniques

NASA Astrophysics Data System (ADS)

Green, A. M.; Lukkarinen, J.; Pennanen, P.; Michael, C.

1996-01-01

The energies of four-quark states are calculated for geometries in which the quarks are situated on the corners of a series of tetrahedra and also for geometries that correspond to gradually distorting these tetrahedra into a plane. The interest in tetrahedra arises because they are composed of three degenerate partitions of the four quarks into two two-quark color singlets. This is an extension of earlier work showing that geometries with two degenerate partitions (e.g., squares) experience a large binding energy. It is now found that even larger binding energies do not result, but that for the tetrahedra the ground and first excited states become degenerate in energy. The calculation is carried out using SU(2) for static quarks in the quenched approximation with β=2.4 on a 163×32 lattice. The results are analyzed using the correlation matrix between different Euclidean times and the implications of these results are discussed for a model based on two-quark potentials.

On degenerate coupled transport processes in porous media with memory phenomena

NASA Astrophysics Data System (ADS)

Beneš, Michal; Pažanin, Igor

2018-06-01

In this paper we prove the existence of weak solutions to degenerate parabolic systems arising from the fully coupled moisture movement, solute transport of dissolved species and heat transfer through porous materials. Physically relevant mixed Dirichlet-Neumann boundary conditions and initial conditions are considered. Existence of a global weak solution of the problem is proved by means of semidiscretization in time, proving necessary uniform estimates and by passing to the limit from discrete approximations. Degeneration occurs in the nonlinear transport coefficients which are not assumed to be bounded below and above by positive constants. Degeneracies in transport coefficients are overcome by proving suitable a-priori $L^{\\infty}$-estimates based on De Giorgi and Moser iteration technique.

Hyaline cartilage degenerates after autologous osteochondral transplantation.

PubMed

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

2004-11-01

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

Age-related memory decline is associated with vascular and microglial degeneration in aged rats.

PubMed

Zhang, Rong; Kadar, Tamar; Sirimanne, Ernest; MacGibbon, Alastair; Guan, Jian

2012-12-01

The hippocampus processes memory is an early target of aging-related biological and structural lesions, leading to memory decline. With absent neurodegeneration in the hippocampus, which identified in rodent model of normal aging the pathology underlying age-related memory impairment is not complete. The effective glial-vascular networks are the key for maintaining neuronal functions. The changes of glial cells and cerebral capillaries with age may contribute to memory decline. Thus we examined age associated changes in neurons, glial phenotypes and microvasculature in the hippocampus of aged rats with memory decline. Young adult (6 months) and aged (35 months) male rats (Fisher/Norway-Brown) were used. To evaluate memory, four days of acquisition phase of Morris water maze tasks were carried out in both age groups and followed by a probe trial 2 h after the acquisition. The brains were then collected for analysis using immunochemistry. The aged rats showed a delayed latency (p<0.001) and longer swimming path (p<0.001) to locate a hidden platform. They also spent less time in and made delayed and fewer entries into the correct quadrant during the probe trial. Without seen neuronal degeneration, the aged rats with memory impairments have displayed dopamine depletion, profound vascular and microglial degeneration with reduced vascular endothelial growth factor and elevated GFAP expression in the hippocampus. The data indicate the memory decline with age is associated with neuronal dysfunction, possibly due to impaired glial-vascular-neuronal networks, but not neuronal degeneration. Glial and vascular degeneration found in aged rats may represent early event of aging pathology prior to neuronal degeneration. Copyright © 2012 Elsevier B.V. All rights reserved.

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…

ANT: Software for Generating and Evaluating Degenerate Codons for Natural and Expanded Genetic Codes.

PubMed

Engqvist, Martin K M; Nielsen, Jens

2015-08-21

The Ambiguous Nucleotide Tool (ANT) is a desktop application that generates and evaluates degenerate codons. Degenerate codons are used to represent DNA positions that have multiple possible nucleotide alternatives. This is useful for protein engineering and directed evolution, where primers specified with degenerate codons are used as a basis for generating libraries of protein sequences. ANT is intuitive and can be used in a graphical user interface or by interacting with the code through a defined application programming interface. ANT comes with full support for nonstandard, user-defined, or expanded genetic codes (translation tables), which is important because synthetic biology is being applied to an ever widening range of natural and engineered organisms. The Python source code for ANT is freely distributed so that it may be used without restriction, modified, and incorporated in other software or custom data pipelines.

The role of orthodontics in the regeneration of the degenerated dentition.

PubMed

Melsen, B

2016-03-01

The demand for regeneration of a degenerated dentition has been increasing as a result of the development of societies, where the life expectancy is increasing and fighting age-related changes is in focus. Whereas removable dentures were acceptable and considered a norm earlier, patients do, to an increasing degree,demand fixed prosthetics; consequently, the development of implants has had an important impact. The balance in the chewing organ will change with time, due to age-related changes within the bone and the loss of teeth due to caries or periodontal disease, and malocclusions may develop or aggravate. The re-establishment of an aesthetical and functional satisfactory solution cannot be reached by replacing teeth by fixed prosthodontics and implants. The aim of this update was threefold: firstly, to demonstrate that age-related changes, often unnoticed by both the patient and the general dentist, can lead to degeneration of the dentition; secondly, to explain how an interdisciplinary approach can make regeneration of even severe degeneration possible; and finally, to show the importance of the general dentist in the maintenance of the obtained results. Treatments should not aim for short-term results but focus on maintainable results. © 2015 John Wiley & Sons Ltd.

Role of the vitreous in age-related macular degeneration.

PubMed

Ondeş, F; Yilmaz, G; Acar, M A; Unlü, N; Kocaoğlan, H; Arsan, A K

2000-01-01

To investigate the relationship between posterior vitreous detachment (PVD) and age-related macular degeneration (AMD). The condition of the vitreous was examined by slit-lamp funduscopy and ultrasonography in 93 eyes of 50 patients with AMD (exudative or dry) and 100 eyes of 50 controls. There was complete PVD in 31 of the 93 eyes (33.3%) of 50 patients with AMD and the posterior vitreous was attached in 62 of these eyes (66.6%). In the control group, in 50 eyes (50%) of 50 subjects there was posterior vitreous detachment. The prevalence of PVD in eyes with macular degeneration was significantly lower (P < .05). There was no statistically significant difference between the exudative and the nonexudative groups in respect to PVD. PVD may have a protective role against the development of AMD. Chronic vitreomacular traction and/or continuous exposure to free radicals and cytokines may possibly be one of the causes of AMD in eyes with attached vitreous.

Drosophila melanogaster White Mutant w 1118 Undergo Retinal Degeneration.

PubMed

Ferreiro, María José; Pérez, Coralia; Marchesano, Mariana; Ruiz, Santiago; Caputi, Angel; Aguilera, Pedro; Barrio, Rosa; Cantera, Rafael

2017-01-01

Key scientific discoveries have resulted from genetic studies of Drosophila melanogaster , using a multitude of transgenic fly strains, the majority of which are constructed in a genetic background containing mutations in the white gene. Here we report that white mutant flies from w 1118 strain undergo retinal degeneration. We observed also that w 1118 mutants have progressive loss of climbing ability, shortened life span, as well as impaired resistance to various forms of stress. Retinal degeneration was abolished by transgenic expression of mini-white + in the white null background w 1118 . We conclude that beyond the classical eye-color phenotype, mutations in Drosophila white gene could impair several biological functions affecting parameters like mobility, life span and stress tolerance. Consequently, we suggest caution and attentiveness during the interpretation of old experiments employing white mutant flies and when planning new ones, especially within the research field of neurodegeneration and neuroprotection. We also encourage that the use of w 1118 strain as a wild-type control should be avoided.

Accreting neutron stars, black holes, and degenerate dwarf stars.

PubMed

Pines, D

1980-02-08

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

Arbitrary amplitude electrostatic wave propagation in a magnetized dense plasma containing helium ions and degenerate electrons

NASA Astrophysics Data System (ADS)

Mahmood, S.; Sadiq, Safeer; Haque, Q.; Ali, Munazza Z.

2016-06-01

The obliquely propagating arbitrary amplitude electrostatic wave is studied in a dense magnetized plasma having singly and doubly charged helium ions with nonrelativistic and ultrarelativistic degenerate electrons pressures. The Fermi temperature for ultrarelativistic degenerate electrons described by N. M. Vernet [(Cambridge University Press, Cambridge, 2007), p. 57] is used to define ion acoustic speed in ultra-dense plasmas. The pseudo-potential approach is used to solve the fully nonlinear set of dynamic equations for obliquely propagating electrostatic waves in a dense magnetized plasma containing helium ions. The upper and lower Mach number ranges for the existence of electrostatic solitons are found which depends on the obliqueness of the wave propagation with respect to applied magnetic field and charge number of the helium ions. It is found that only compressive (hump) soliton structures are formed in all the cases and only subsonic solitons are formed for a singly charged helium ions plasma case with nonrelativistic degenerate electrons. Both subsonic and supersonic soliton hump structures are formed for doubly charged helium ions with nonrelativistic degenerate electrons and ultrarelativistic degenerate electrons plasma case containing singly as well as doubly charged helium ions. The effect of propagation direction on the soliton amplitude and width of the electrostatic waves is also presented. The numerical plots are also shown for illustration using dense plasma parameters of a compact star (white dwarf) from literature.

WD40-repeat 47, a microtubule-associated protein, is essential for brain development and autophagy.

PubMed

Kannan, Meghna; Bayam, Efil; Wagner, Christel; Rinaldi, Bruno; Kretz, Perrine F; Tilly, Peggy; Roos, Marna; McGillewie, Lara; Bär, Séverine; Minocha, Shilpi; Chevalier, Claire; Po, Chrystelle; Chelly, Jamel; Mandel, Jean-Louis; Borgatti, Renato; Piton, Amélie; Kinnear, Craig; Loos, Ben; Adams, David J; Hérault, Yann; Collins, Stephan C; Friant, Sylvie; Godin, Juliette D; Yalcin, Binnaz

2017-10-31

The family of WD40-repeat (WDR) proteins is one of the largest in eukaryotes, but little is known about their function in brain development. Among 26 WDR genes assessed, we found 7 displaying a major impact in neuronal morphology when inactivated in mice. Remarkably, all seven genes showed corpus callosum defects, including thicker ( Atg16l1 , Coro1c , Dmxl2 , and Herc1 ), thinner ( Kif21b and Wdr89 ), or absent corpus callosum ( Wdr47 ), revealing a common role for WDR genes in brain connectivity. We focused on the poorly studied WDR47 protein sharing structural homology with LIS1, which causes lissencephaly. In a dosage-dependent manner, mice lacking Wdr47 showed lethality, extensive fiber defects, microcephaly, thinner cortices, and sensory motor gating abnormalities. We showed that WDR47 shares functional characteristics with LIS1 and participates in key microtubule-mediated processes, including neural stem cell proliferation, radial migration, and growth cone dynamics. In absence of WDR47, the exhaustion of late cortical progenitors and the consequent decrease of neurogenesis together with the impaired survival of late-born neurons are likely yielding to the worsening of the microcephaly phenotype postnatally. Interestingly, the WDR47-specific C-terminal to LisH (CTLH) domain was associated with functions in autophagy described in mammals. Silencing WDR47 in hypothalamic GT1-7 neuronal cells and yeast models independently recapitulated these findings, showing conserved mechanisms. Finally, our data identified superior cervical ganglion-10 (SCG10) as an interacting partner of WDR47. Taken together, these results provide a starting point for studying the implications of WDR proteins in neuronal regulation of microtubules and autophagy. Published under the PNAS license.

Expression Profiling Analysis Reveals Key MicroRNA-mRNA Interactions in Early Retinal Degeneration in Retinitis Pigmentosa.

PubMed

Anasagasti, Ander; Ezquerra-Inchausti, Maitane; Barandika, Olatz; Muñoz-Culla, Maider; Caffarel, María M; Otaegui, David; López de Munain, Adolfo; Ruiz-Ederra, Javier

2018-05-01

The aim of this study was to identify differentially expressed microRNAs (miRNAs) that might play an important role in the etiology of retinal degeneration in a genetic mouse model of retinitis pigmentosa (rd10 mice) at initial stages of the disease. miRNAs-mRNA interaction networks were generated for analysis of biological pathways involved in retinal degeneration. Of more than 1900 miRNAs analyzed, we selected 19 miRNAs on the basis of (1) a significant differential expression in rd10 retinas compared with control samples and (2) an inverse expression relationship with predicted mRNA targets involved in biological pathways relevant to retinal biology and/or degeneration. Seven of the selected miRNAs have been associated with retinal dystrophies, whereas, to our knowledge, nine have not been previously linked to any disease. This study contributes to our understanding of the etiology and progression of retinal degeneration.

Evaluation of cartilage degeneration in a rat model of rotator cuff tear arthropathy

PubMed Central

Kramer, Erik J.; Bodendorfer, Blake M.; Laron, Dominique; Wong, Jason; Kim, Hubert T.; Liu, Xuhui; Feeley, Brian T.

2013-01-01

Introduction Rotator cuff tears are the most common injury seen by shoulder surgeons. Many late stage rotator cuff tear patients develop glenohumeral osteoarthritis as a result of torn cuff tendons, termed cuff tear arthropathy. However, the mechanisms of cuff tear arthropathy have not been fully established. It has been hypothesized that a combination of synovial and mechanical factors contribute equally to the development of cuff tear arthropathy. The goal of this study was to assess the utility of this model in investigating cuff-tear arthropathy. Methods We utilized a rat model which accurately reflects rotator cuff muscle degradation after massive rotator cuff tears through either infraspinatus and supraspinatus tenotomy or suprascapular nerve transection. Using a Modified-Mankin Scoring System (MMS), we found significant glenohumeral cartilage damage following both rotator cuff tenotomy and suprascapular nerve transection after only 12 weeks. Results Cartilage degeneration was similar between groups, and was present on both the humeral head and the glenoid. Denervation of the supraspinatus and infraspinatus muscles without opening the joint capsule caused cartilage degeneration similar to that found in the tendon transection group. Conclusions These results suggest that altered mechanical loading after rotator cuff tears is the primary factor in cartilage degeneration after rotator cuff tears. Clinically, understanding the process of cartilage degeneration after rotator cuff injury will help guide treatment decisions in the setting of rotator cuff tears. Level of evidence Basic Science Study, Animal Model PMID:23664745

Patterns of lumbar disc degeneration are different in degenerative disc disease and disc prolapse magnetic resonance imaging analysis of 224 patients.

PubMed

Kanna, Rishi M; Shetty, Ajoy Prasad; Rajasekaran, S

2014-02-01

Existing research on lumbar disc degeneration has remained inconclusive regarding its etiology, pathogenesis, symptomatology, prevention, and management. Degenerative disc disease (DDD) and disc prolapse (DP) are common diseases affecting the lumbar discs. Although they manifest clinically differently, existing studies on disc degeneration have included patients with both these features, leading to wide variations in observations. The possible relationship or disaffect between DDD and DP is not fully evaluated. To analyze the patterns of lumbar disc degeneration in patients with chronic back pain and DDD and those with acute DP. Prospective, magnetic resonance imaging-based radiological study. Two groups of patients (aged 20-50 years) were prospectively studied. Group 1 included patients requiring a single level microdiscectomy for acute DP. Group 2 included patients with chronic low back pain and DDD. Discs were assessed by magnetic resonance imaging through Pfirmann grading, Schmorl nodes, Modic changes, and the total end-plate damage score for all the five lumbar discs. Group 1 (DP) had 91 patients and group 2 (DDD) had 133 patients. DP and DDD patients differed significantly in the number, extent, and severity of degeneration. DDD patients had a significantly higher number of degenerated discs than DP patients (p<.000). The incidence of multilevel and pan-lumbar degeneration was also significantly higher in DDD group. The pattern of degeneration also differed in both the groups. DDD patients had predominant upper lumbar involvement, whereas DP patients had mainly lower lumbar degeneration. Modic changes were more common in DP patients, especially at the prolapsed level. Modic changes were present in 37% of prolapsed levels compared with 9.9% of normal discs (p<.00). The total end-plate damage score had a positive correlation with disc degeneration in both the groups. Further the mean total end-plate damage score at prolapsed level was also significantly higher

The consequences of neural degeneration regarding optimal cochlear implant position in scala tympani: a model approach.

PubMed

Briaire, Jeroen J; Frijns, Johan H M

2006-04-01

Cochlear implant research endeavors to optimize the spatial selectivity, threshold and dynamic range with the objective of improving the speech perception performance of the implant user. One of the ways to achieve some of these goals is by electrode design. New cochlear implant electrode designs strive to bring the electrode contacts into close proximity to the nerve fibers in the modiolus: this is done by placing the contacts on the medial side of the array and positioning the implant against the medial wall of scala tympani. The question remains whether this is the optimal position for a cochlea with intact neural fibers and, if so, whether it is also true for a cochlea with degenerated neural fibers. In this study a computational model of the implanted human cochlea is used to investigate the optimal position of the array with respect to threshold, dynamic range and spatial selectivity for a cochlea with intact nerve fibers and for degenerated nerve fibers. In addition, the model is used to evaluate the predictive value of eCAP measurements for obtaining peri-operative information on the neural status. The model predicts improved threshold, dynamic range and spatial selectivity for the peri-modiolar position at the basal end of the cochlea, with minimal influence of neural degeneration. At the apical end of the array (1.5 cochlear turns), the dynamic range and the spatial selectivity are limited due to the occurrence of cross-turn stimulation, with the exception of the condition without neural degeneration and with the electrode array along the lateral wall of scala tympani. The eCAP simulations indicate that a large P(0) peak occurs before the N(1)P(1) complex when the fibers are not degenerated. The absence of this peak might be used as an indicator for neural degeneration.

Early Events in Retinal Degeneration Caused by Rhodopsin Mutation or Pigment Epithelium Malfunction: Differences and Similarities

PubMed Central

Di Pierdomenico, Johnny; García-Ayuso, Diego; Pinilla, Isabel; Cuenca, Nicolás; Vidal-Sanz, Manuel; Agudo-Barriuso, Marta; Villegas-Pérez, María P.

2017-01-01

To study the course of photoreceptor cell death and macro and microglial reactivity in two rat models of retinal degeneration with different etiologies. Retinas from P23H-1 (rhodopsin mutation) and Royal College of Surgeon (RCS, pigment epithelium malfunction) rats and age-matched control animals (Sprague-Dawley and Pievald Viro Glaxo, respectively) were cross-sectioned at different postnatal ages (from P10 to P60) and rhodopsin, L/M- and S-opsin, ionized calcium-binding adapter molecule 1 (Iba1), glial fibrillary acid protein (GFAP), and proliferating cell nuclear antigen (PCNA) proteins were immunodetected. Photoreceptor nuclei rows and microglial cells in the different retinal layers were quantified. Photoreceptor degeneration starts earlier and progresses quicker in P23H-1 than in RCS rats. In both models, microglial cell activation occurs simultaneously with the initiation of photoreceptor death while GFAP over-expression starts later. As degeneration progresses, the numbers of microglial cells increase in the retina, but decreasing in the inner retina and increasing in the outer retina, more markedly in RCS rats. Interestingly, and in contrast with healthy animals, microglial cells reach the outer nuclei and outer segment layers. The higher number of microglial cells in dystrophic retinas cannot be fully accounted by intraretinal migration and PCNA immunodetection revealed microglial proliferation in both models but more importantly in RCS rats. The etiology of retinal degeneration determines the initiation and pattern of photoreceptor cell death and simultaneously there is microglial activation and migration, while the macroglial response is delayed. The actions of microglial cells in the degeneration cannot be explained only in the basis of photoreceptor death because they participate more actively in the RCS model. Thus, the retinal degeneration caused by pigment epithelium malfunction is more inflammatory and would probably respond better to interventions

Inhibition of Cathepsin B Alleviates Secondary Degeneration in Ipsilateral Thalamus After Focal Cerebral Infarction in Adult Rats.

PubMed

Zuo, Xialin; Hou, Qinghua; Jin, Jizi; Zhan, Lixuan; Li, Xinyu; Sun, Weiwen; Lin, Kunqin; Xu, En

2016-09-01

Secondary degeneration in areas beyond ischemic foci can inhibit poststroke recovery. The cysteine protease Cathepsin B (CathB) regulates cell death and intracellular protein catabolism. To investigate the roles of CathB in the development of secondary degeneration in the ventroposterior nucleus (VPN) of the ipsilateral thalamus after focal cerebral infarction, infarct volumes, immunohistochemistry and immunofluorescence, and Western blotting analyses were conducted in a distal middle cerebral artery occlusion (dMCAO) stroke model in adult rats. We observed marked neuron loss and gliosis in the ipsilateral thalamus after dMCAO, and the expression of CathB and cleaved caspase-3 in the VPN was significantly upregulated; glial cells were the major source of CathB. Although it had no effect on infarct volume, delayed intracerebroventricular treatment with the membrane-permeable CathB inhibitor CA-074Me suppressed the expression of CathB and cleaved caspase-3 in ipsilateral VPN and accordingly alleviated the secondary degeneration. These data indicate that CathB mediates a novel mechanism of secondary degeneration in the VPN of the ipsilateral thalamus after focal cortical infarction and suggest that CathB might be a therapeutic target for the prevention of secondary degeneration in patients after stroke. © 2016 American Association of Neuropathologists, Inc. All rights reserved.

ALS-associated mutant FUS induces selective motor neuron degeneration through toxic gain of function

PubMed Central

Sharma, Aarti; Lyashchenko, Alexander K.; Lu, Lei; Nasrabady, Sara Ebrahimi; Elmaleh, Margot; Mendelsohn, Monica; Nemes, Adriana; Tapia, Juan Carlos; Mentis, George Z.; Shneider, Neil A.

2016-01-01

Mutations in FUS cause amyotrophic lateral sclerosis (ALS), including some of the most aggressive, juvenile-onset forms of the disease. FUS loss-of-function and toxic gain-of-function mechanisms have been proposed to explain how mutant FUS leads to motor neuron degeneration, but neither has been firmly established in the pathogenesis of ALS. Here we characterize a series of transgenic FUS mouse lines that manifest progressive, mutant-dependent motor neuron degeneration preceded by early, structural and functional abnormalities at the neuromuscular junction. A novel, conditional FUS knockout mutant reveals that postnatal elimination of FUS has no effect on motor neuron survival or function. Moreover, endogenous FUS does not contribute to the onset of the ALS phenotype induced by mutant FUS. These findings demonstrate that FUS-dependent motor degeneration is not due to loss of FUS function, but to the gain of toxic properties conferred by ALS mutations. PMID:26842965

Prophylactic laser in age-related macular degeneration: the past, the present and the future.

PubMed

Findlay, Quan; Jobling, Andrew I; Vessey, Kirstan A; Greferath, Ursula; Phipps, Joanna A; Guymer, Robyn H; Fletcher, Erica L

2018-05-01

The presence of drusen in the posterior eye is a hallmark feature of the early stages of age-related macular degeneration and their size is an indicator of risk of progression to vision-threatening forms of the disease. Since the initial observations that laser treatment can resolve drusen, there has been great interest in whether laser treatment can be used to reduce the progression of age-related macular degeneration. In this article, we review the development of lasers for the treatment of those with age-related macular degeneration. We provide an overview of the clinical trial results that demonstrated drusen resolution but that had mixed effects on progression of disease. In addition, we provide a summary of the recent developments in pulsed lasers that are designed to reduce the energy applied to the posterior eye to provide the therapeutic effects of conventional continuous wave lasers while reducing the secondary tissue effects.

ALS-associated mutant FUS induces selective motor neuron degeneration through toxic gain of function.

PubMed

Sharma, Aarti; Lyashchenko, Alexander K; Lu, Lei; Nasrabady, Sara Ebrahimi; Elmaleh, Margot; Mendelsohn, Monica; Nemes, Adriana; Tapia, Juan Carlos; Mentis, George Z; Shneider, Neil A

2016-02-04

Mutations in FUS cause amyotrophic lateral sclerosis (ALS), including some of the most aggressive, juvenile-onset forms of the disease. FUS loss-of-function and toxic gain-of-function mechanisms have been proposed to explain how mutant FUS leads to motor neuron degeneration, but neither has been firmly established in the pathogenesis of ALS. Here we characterize a series of transgenic FUS mouse lines that manifest progressive, mutant-dependent motor neuron degeneration preceded by early, structural and functional abnormalities at the neuromuscular junction. A novel, conditional FUS knockout mutant reveals that postnatal elimination of FUS has no effect on motor neuron survival or function. Moreover, endogenous FUS does not contribute to the onset of the ALS phenotype induced by mutant FUS. These findings demonstrate that FUS-dependent motor degeneration is not due to loss of FUS function, but to the gain of toxic properties conferred by ALS mutations.

Retinal Remodeling in the Tg P347L Rabbit, a Large-Eye Model of Retinal Degeneration

PubMed Central

Jones, Bryan William; Kondo, Mineo; Terasaki, Hiroko; Watt, Carl Brock; Rapp, Kevin; Anderson, James; Lin, Yanhua; Shaw, Marguerite Victoria; Yang, Jia-Hui; Marc, Robert Edward

2013-01-01

Retinitis pigmentosa (RP) is an inherited blinding disease characterized by progressive loss of retinal photo-receptors. There are numerous rodent models of retinal degeneration, but most are poor platforms for interventions that will translate into clinical practice. The rabbit possesses a number of desirable qualities for a model of retinal disease including a large eye and an existing and substantial knowledge base in retinal circuitry, anatomy, and ophthalmology. We have analyzed degeneration, remodeling, and reprogramming in a rabbit model of retinal degeneration, expressing a rhodopsin proline 347 to leucine transgene in a TgP347L rabbit as a powerful model to study the pathophysiology and treatment of retinal degeneration. We show that disease progression in the TgP347L rabbit closely tracks human cone-sparing RP, including the cone-associated preservation of bipolar cell signaling and triggering of reprogramming. The relatively fast disease progression makes the TgP347L rabbit an excellent model for gene therapy, cell biological intervention, progenitor cell transplantation, surgical interventions, and bionic prosthetic studies. PMID:21681749

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

Advancing Research and Treatment for Frontotemporal Lobar Degeneration (ARTFL)

ClinicalTrials.gov

2018-05-01

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)

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…

Dichromatic Langmuir waves in degenerate quantum plasma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dubinov, A. E., E-mail: dubinov-ae@yandex.ru; 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.

Independent degeneration of photoreceptors and retinal pigment epithelium in conditional knockout mouse models of choroideremia

PubMed Central

Tolmachova, Tanya; Anders, Ross; Abrink, Magnus; Bugeon, Laurence; Dallman, Margaret J.; Futter, Clare E.; Ramalho, José S.; Tonagel, Felix; Tanimoto, Naoyuki; Seeliger, Mathias W.; Huxley, Clare; Seabra, Miguel C.

2006-01-01

Choroideremia (CHM) is an X-linked degeneration of the retinal pigment epithelium (RPE), photoreceptors, and choroid, caused by loss of function of the CHM/REP1 gene. REP1 is involved in lipid modification (prenylation) of Rab GTPases, key regulators of intracellular vesicular transport and organelle dynamics. To study the pathogenesis of CHM and to develop a model for assessing gene therapy, we have created a conditional mouse knockout of the Chm gene. Heterozygous-null females exhibit characteristic hallmarks of CHM: progressive degeneration of the photoreceptors, patchy depigmentation of the RPE, and Rab prenylation defects. Using tamoxifen-inducible and tissue-specific Cre expression in combination with floxed Chm alleles, we show that CHM pathogenesis involves independently triggered degeneration of photoreceptors and the RPE, associated with different subsets of defective Rabs. PMID:16410831

Lumbar disc degeneration was not related to spine and hip bone mineral densities in Chinese: facet joint osteoarthritis may confound the association.

PubMed

Pan, Jianjiang; Lu, Xuan; Yang, Ge; Han, Yongmei; Tong, Xiang; Wang, Yue

2017-12-01

A sample of 512 Chinese was studied and we observed that greater disc degeneration on MRI was associated with greater spine DXA BMD. Yet, this association may be confounded by facet joint osteoarthritis. BMD may not be a risk factor for lumbar disc degeneration in Chinese. Evidence suggested that lumbar vertebral bone and intervertebral disc interact with each other in multiple ways. The current paper aims to determine the association between bone mineral density (BMD) and lumbar disc degeneration using a sample of Chinese. We studied 165 patients with back disorders and 347 general subjects from China. All subjects had lumbar spine magnetic resonance (MR) imaging and dual- energy X-ray absorptiometry (DXA) spine BMD studies, and a subset of general subjects had additional hip BMD measurements. On T2-weighted MR images, Pfirrmann score was used to evaluate the degree of lumbar disc degeneration and facet joint osteoarthritis was assessed as none, slight-moderate, and severe. Regression analyses were used to examine the associations between lumbar and hip BMD and disc degeneration, adjusting for age, gender, body mass index (BMI), lumbar region, and facet joint osteoarthritis. Greater facet joint osteoarthritis was associated with greater spine BMD (P < 0.01) in both patients and general subjects. For general subjects, greater spine BMD was associated with severe disc degeneration, controlling for age, gender, BMI, and lumbar region. When facet joint osteoarthritis entered the regression model, however, greater spine BMD was associated with greater facet joint osteoarthritis (P < 0.01) but not greater disc degeneration (P > 0.05). No statistical association was observed between spine BMD and lumbar disc degeneration in patients with back disorders (P > 0.05), and between hip BMD and disc degeneration in general subjects (P > 0.05). BMD may not be a risk factor for lumbar disc degeneration in Chinese. Facet joint osteoarthritis inflates DXA spine BMD

Value-based medicine and interventions for macular degeneration.

PubMed

Brown, Melissa M; Brown, Gary C; Brown, Heidi

2007-05-01

The aim of this article is to review the patient value conferred by interventions for neovascular macular degeneration. Value-based medicine is the practice of medicine based upon the patient value (improvement in quality of life and length of life) conferred by an intervention. For ophthalmologic interventions, in which length-of-life is generally unaffected, the value gain is equivalent to the improvement in quality of life. Photodynamic therapy delivers a value gain (improvement in quality of life) of 8.1% for the average person with classic subfoveal choroidal neovascularization, while laser photocoagulation for the same entity confers a 4.4% improvement in quality of life. Preliminary data suggest the value gain for the treatment of occult/minimally classic choroidal neovascularization with ranibizumab is greater than 15%. The average value gain for statins for the treatment of hyperlipidemia is 3.9%, while that for the use of biphosphonates for the treatment of osteoporosis is 1.1% and that for drugs to treat benign prostatic hyperplasia is 1-2%. Interventions, especially ranibizumab therapy, for neovascular macular degeneration appear to deliver an extraordinary degree of value compared with many other interventions across healthcare.

Quasi-degenerate perturbation theory using matrix product states

NASA Astrophysics Data System (ADS)

Sharma, Sandeep; Jeanmairet, Guillaume; Alavi, Ali

2016-01-01

In this work, we generalize the recently proposed matrix product state perturbation theory (MPSPT) for calculating energies of excited states using quasi-degenerate (QD) perturbation theory. Our formulation uses the Kirtman-Certain-Hirschfelder canonical Van Vleck perturbation theory, which gives Hermitian effective Hamiltonians at each order, and also allows one to make use of Wigner's 2n + 1 rule. Further, our formulation satisfies Granovsky's requirement of model space invariance which is important for obtaining smooth potential energy curves. Thus, when we use MPSPT with the Dyall Hamiltonian, we obtain a model space invariant version of quasi-degenerate n-electron valence state perturbation theory (NEVPT), a property that the usual formulation of QD-NEVPT2 based on a multipartitioning technique lacked. We use our method on the benchmark problems of bond breaking of LiF which shows ionic to covalent curve crossing and the twist around the double bond of ethylene where significant valence-Rydberg mixing occurs in the excited states. In accordance with our previous work, we find that multi-reference linearized coupled cluster theory is more accurate than other multi-reference theories of similar cost.

Symmetry, stability, and computation of degenerate lasing modes

NASA Astrophysics Data System (ADS)

Liu, David; Zhen, Bo; Ge, Li; Hernandez, Felipe; Pick, Adi; Burkhardt, Stephan; Liertzer, Matthias; Rotter, Stefan; Johnson, Steven G.

2017-02-01

We present a general method to obtain the stable lasing solutions for the steady-state ab initio lasing theory (SALT) for the case of a degenerate symmetric laser in two dimensions (2D). We find that under most regimes (with one pathological exception), the stable solutions are clockwise and counterclockwise circulating modes, generalizing previously known results of ring lasers to all 2D rotational symmetry groups. Our method uses a combination of semianalytical solutions close to lasing threshold and numerical solvers to track the lasing modes far above threshold. Near threshold, we find closed-form expressions for both circulating modes and other types of lasing solutions as well as for their linearized Maxwell-Bloch eigenvalues, providing a simple way to determine their stability without having to do a full nonlinear numerical calculation. Above threshold, we show that a key feature of the circulating mode is its "chiral" intensity pattern, which arises from spontaneous symmetry breaking of mirror symmetry, and whose symmetry group requires that the degeneracy persists even when nonlinear effects become important. Finally, we introduce a numerical technique to solve the degenerate SALT equations far above threshold even when spatial discretization artificially breaks the degeneracy.

Heat capacity of free electrons at the degenerate-nondegenerate transition

NASA Astrophysics Data System (ADS)

Nimtz, G.; Stadler, J. P.

1985-04-01

In this Brief Report the heat capacity of an electron gas at the degenerate-nondegenerate transition is presented. The values are deduced from hot-carrier data of InSb with ~=1014 electrons/cm3 determined by Maneval, Zylberstejn, and Budd.

Expression Profiling Analysis Reveals Key MicroRNA–mRNA Interactions in Early Retinal Degeneration in Retinitis Pigmentosa

PubMed Central

Anasagasti, Ander; Ezquerra-Inchausti, Maitane; Barandika, Olatz; Muñoz-Culla, Maider; Caffarel, María M.; Otaegui, David; López de Munain, Adolfo

2018-01-01

Purpose The aim of this study was to identify differentially expressed microRNAs (miRNAs) that might play an important role in the etiology of retinal degeneration in a genetic mouse model of retinitis pigmentosa (rd10 mice) at initial stages of the disease. Methods miRNAs–mRNA interaction networks were generated for analysis of biological pathways involved in retinal degeneration. Results Of more than 1900 miRNAs analyzed, we selected 19 miRNAs on the basis of (1) a significant differential expression in rd10 retinas compared with control samples and (2) an inverse expression relationship with predicted mRNA targets involved in biological pathways relevant to retinal biology and/or degeneration. Seven of the selected miRNAs have been associated with retinal dystrophies, whereas, to our knowledge, nine have not been previously linked to any disease. Conclusions This study contributes to our understanding of the etiology and progression of retinal degeneration. PMID:29847644

ANTERIOR CHAMBER FLARE DURING BEVACIZUMAB TREATMENT IN EYES WITH EXUDATIVE AGE-RELATED MACULAR DEGENERATION.

PubMed

Hautamäki, Asta; Luoma, Arto; Immonen, Ilkka

2016-11-01

To study the anterior chamber flare during bevacizumab treatment of exudative age-related macular degeneration. During a 2-year prospective follow-up, 50 patients recently diagnosed with exudative age-related macular degeneration were treated at once-a-month visits if subretinal or intraretinal fluid or a new hemorrhage was present in the lesion area. Flare was measured weekly during the first month and then monthly in both eyes. Higher flare was associated with older age (P = 0.007, Linear Mixed Model), higher number of smoking pack-years (P = 0.019), macular cysts (P = 0.041), and pseudophakia (P = 0.003). The levels gradually increased during the follow-up (P < 0.0001) but less in the eyes with classic CNV (P = 0.011). Flare decreased during treatment-free periods lasting for at least two consecutive visits (P = 0.005). A peak in flare was observed 1 week after the first injection (P = 0.034, Wilcoxon signed rank test). In the fellow eyes, higher flare values in the beginning of the follow-up were associated with later conversion into exudative age-related macular degeneration (P = 0.015, Mann-Whitney U test). Anterior chamber flare correlated poorly with the CNV activity. Higher levels may, however, precede or exist early in the process that leads to the development of exudative age-related macular degeneration.

SALT HRS discovery of a long-period double-degenerate binary in the planetary nebula NGC 1360

NASA Astrophysics Data System (ADS)

Miszalski, B.; Manick, R.; Mikołajewska, J.; Iłkiewicz, K.; Kamath, D.; Van Winckel, H.

2018-01-01

Whether planetary nebulae (PNe) are predominantly the product of binary stellar evolution as some population synthesis models (PSM) suggest remains an open question. Around 50 short-period binary central stars (P ∼ 1 d) are known, but with only four with measured orbital periods over 10 d, our knowledge is severely incomplete. Here we report on the first discovery from a systematic Southern African Large Telescope (SALT) High Resolution Spectrograph (HRS) survey for long-period binary central stars. We find a 142 d orbital period from radial velocities of the central star of NGC 1360, HIP 16566. NGC 1360 appears to be the product of common-envelope (CE) evolution, with nebula features similar to post-CE PNe, albeit with an orbital period considerably longer than expected to be typical of post-CE PSM. The most striking feature is a newly identified ring of candidate low-ionization structures. Previous spatiokinematic modelling of the nebula gives a nebula inclination of 30° ± 10°, and assuming the binary nucleus is coplanar with the nebula, multiwavelength observations best fit a more massive, evolved white dwarf (WD) companion. A WD companion in a 142 d orbit is not the focus of many PSM, making NGC 1360 a valuable system with which to improve future PSM work. HIP 16566 is amongst many central stars in which large radial velocity variability was found by low-resolution surveys. The discovery of its binary nature may indicate long-period binaries may be more common than PSM models predict.

Auditory analysis of xeroderma pigmentosum 1971-2012: hearing function, sun sensitivity and DNA repair predict neurological degeneration.

PubMed

Totonchy, Mariam B; Tamura, Deborah; Pantell, Matthew S; Zalewski, Christopher; Bradford, Porcia T; Merchant, Saumil N; Nadol, Joseph; Khan, Sikandar G; Schiffmann, Raphael; Pierson, Tyler Mark; Wiggs, Edythe; Griffith, Andrew J; DiGiovanna, John J; Kraemer, Kenneth H; Brewer, Carmen C

2013-01-01

To assess the role of DNA repair in maintenance of hearing function and neurological integrity, we examined hearing status, neurological function, DNA repair complementation group and history of acute burning on minimal sun exposure in all patients with xeroderma pigmentosum, who had at least one complete audiogram, examined at the National Institutes of Health from 1971 to 2012. Seventy-nine patients, aged 1-61 years, were diagnosed with xeroderma pigmentosum (n = 77) or xeroderma pigmentosum/Cockayne syndrome (n = 2). A total of 178 audiograms were included. Clinically significant hearing loss (>20 dB) was present in 23 (29%) of 79 patients. Of the 17 patients with xeroderma pigmentosum-type neurological degeneration, 13 (76%) developed hearing loss, and all 17 were in complementation groups xeroderma pigmentosum type A or type D and reported acute burning on minimal sun exposure. Acute burning on minimal sun exposure without xeroderma pigmentosum-type neurological degeneration was present in 18% of the patients (10/55). Temporal bone histology in a patient with severe xeroderma pigmentosum-type neurological degeneration revealed marked atrophy of the cochlear sensory epithelium and neurons. The 19-year mean age of detection of clinically significant hearing loss in the patients with xeroderma pigmentosum with xeroderma pigmentosum-type neurological degeneration was 54 years younger than that predicted by international norms. The four frequency (0.5/1/2/4 kHz) pure-tone average correlated with degree of neurodegeneration (P < 0.001). In patients with xeroderma pigmentosum, aged 4-30 years, a four-frequency pure-tone average ≥10 dB hearing loss was associated with a 39-fold increased risk (P = 0.002) of having xeroderma pigmentosum-type neurological degeneration. Severity of hearing loss parallels neurological decline in patients with xeroderma pigmentosum-type neurological degeneration. Audiometric findings, complementation group, acute burning on minimal sun

Current knowledge and trends in age-related macular degeneration: genetics, epidemiology, and prevention.

PubMed

Velez-Montoya, Raul; Oliver, Scott C N; Olson, Jeffrey L; Fine, Stuart L; Quiroz-Mercado, Hugo; Mandava, Naresh

2014-03-01

To address the most dynamic and current issues concerning human genetics, risk factors, pharmacoeconomics, and prevention regarding age-related macular degeneration. An online review of the database Pubmed and Ovid was performed, searching for the key words: age-related macular degeneration, AMD, pharmacoeconomics, risk factors, VEGF, prevention, genetics and their compound phrases. The search was limited to articles published since 1985 to date. All returned articles were carefully screened and their references were manually reviewed for additional relevant data. The webpage www.clinicaltrials.gov was also accessed in search of relevant research trials. A total of 366 articles were reviewed, including 64 additional articles extracted from the references and 25 webpages and online databases from different institutions. At the end, only 244 references were included in this review. Age-related macular degeneration is a complex multifactorial disease that has an uneven manifestation around the world but with one common denominator, it is increasing and spreading. The economic burden that this disease poses in developed nations will increase in the coming years. Effective preventive therapies need to be developed in the near future.

Quantitative metabolomics of photoreceptor degeneration and the effects of stem cell-derived retinal pigment epithelium transplantation

PubMed Central

Wang, Junhua; Westenskow, Peter D.; Fang, Mingliang; Friedlander, Martin

2016-01-01

Photoreceptor degeneration is characteristic of vision-threatening diseases including age-related macular degeneration. Photoreceptors are metabolically demanding cells in the retina, but specific details about their metabolic behaviours are unresolved. The quantitative metabolomics of retinal degeneration could provide valuable insights and inform future therapies. Here, we determined the metabolomic ‘fingerprint’ of healthy and dystrophic retinas in rat models using optimized metabolite extraction techniques. A number of classes of metabolites were consistently dysregulated during degeneration: vitamin A analogues, fatty acid amides, long-chain polyunsaturated fatty acids, acyl carnitines and several phospholipid species. For the first time, a distinct temporal trend of several important metabolites including DHA (4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoic acid), all-trans-retinal and its toxic end-product N-retinyl-N-retinylidene-ethanolamine were observed between healthy and dystrophic retinas. In this study, metabolomics was further used to determine the temporal effects of the therapeutic intervention of grafting stem cell-derived retinal pigment epithelium (RPE) in dystrophic retinas, which significantly prevented photoreceptor atrophy in our previous studies. The result revealed that lipid levels such as phosphatidylethanolamine in eyes were restored in those animals receiving the RPE grafts. In conclusion, this study provides insight into the metabolomics of retinal degeneration, and further understanding of the efficacy of RPE transplantation. This article is part of the themed issue ‘Quantitative mass spectrometry’. PMID:27644974

Arbitrary amplitude electrostatic wave propagation in a magnetized dense plasma containing helium ions and degenerate electrons

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mahmood, S., E-mail: shahzadm100@gmail.com; Sadiq, Safeer; Haque, Q.

2016-06-15

The obliquely propagating arbitrary amplitude electrostatic wave is studied in a dense magnetized plasma having singly and doubly charged helium ions with nonrelativistic and ultrarelativistic degenerate electrons pressures. The Fermi temperature for ultrarelativistic degenerate electrons described by N. M. Vernet [(Cambridge University Press, Cambridge, 2007), p. 57] is used to define ion acoustic speed in ultra-dense plasmas. The pseudo-potential approach is used to solve the fully nonlinear set of dynamic equations for obliquely propagating electrostatic waves in a dense magnetized plasma containing helium ions. The upper and lower Mach number ranges for the existence of electrostatic solitons are found whichmore » depends on the obliqueness of the wave propagation with respect to applied magnetic field and charge number of the helium ions. It is found that only compressive (hump) soliton structures are formed in all the cases and only subsonic solitons are formed for a singly charged helium ions plasma case with nonrelativistic degenerate electrons. Both subsonic and supersonic soliton hump structures are formed for doubly charged helium ions with nonrelativistic degenerate electrons and ultrarelativistic degenerate electrons plasma case containing singly as well as doubly charged helium ions. The effect of propagation direction on the soliton amplitude and width of the electrostatic waves is also presented. The numerical plots are also shown for illustration using dense plasma parameters of a compact star (white dwarf) from literature.« less

Voltage-gated calcium channel autoimmune cerebellar degeneration

PubMed Central

McKasson, Marilyn; Clawson, Susan A.; Hill, Kenneth E.; Wood, Blair; Carlson, Noel; Bromberg, Mark; Greenlee, John E.

2016-01-01

Objectives: To describe response to treatment in a patient with autoantibodies against voltage-gated calcium channels (VGCCs) who presented with autoimmune cerebellar degeneration and subsequently developed Lambert-Eaton myasthenic syndrome (LEMS), and to study the effect of the patient's autoantibodies on Purkinje cells in rat cerebellar slice cultures. Methods: Case report and study of rat cerebellar slice cultures incubated with patient VGCC autoantibodies. Results: A 53-year-old man developed progressive incoordination with ataxic speech. Laboratory evaluation revealed VGCC autoantibodies without other antineuronal autoantibodies. Whole-body PET scans 6 and 12 months after presentation detected no malignancy. The patient improved significantly with IV immunoglobulin G (IgG), prednisone, and mycophenolate mofetil, but worsened after IV IgG was halted secondary to aseptic meningitis. He subsequently developed weakness with electrodiagnostic evidence of LEMS. The patient's IgG bound to Purkinje cells in rat cerebellar slice cultures, followed by neuronal death. Reactivity of the patient's autoantibodies with VGCCs was confirmed by blocking studies with defined VGCC antibodies. Conclusions: Autoimmune cerebellar degeneration associated with VGCC autoantibodies may precede onset of LEMS and may improve with immunosuppressive treatment. Binding of anti-VGCC antibodies to Purkinje cells in cerebellar slice cultures may be followed by cell death. Patients with anti-VGCC autoantibodies may be at risk of irreversible neurologic injury over time, and treatment should be initiated early. PMID:27088118

Retinopathy of prematurity: inflammation, choroidal degeneration, and novel promising therapeutic strategies.

PubMed

Rivera, José Carlos; Holm, Mari; Austeng, Dordi; Morken, Tora Sund; Zhou, Tianwei Ellen; Beaudry-Richard, Alexandra; Sierra, Estefania Marin; Dammann, Olaf; Chemtob, Sylvain

2017-08-22

Retinopathy of prematurity (ROP) is an important cause of childhood blindness globally, and the incidence is rising. The disease is characterized by initial arrested retinal vascularization followed by neovascularization and ensuing retinal detachment causing permanent visual loss. Although neovascularization can be effectively treated via retinal laser ablation, it is unknown which children are at risk of entering this vision-threatening phase of the disease. Laser ablation may itself induce visual field deficits, and there is therefore a need to identify targets for novel and less destructive treatments of ROP. Inflammation is considered a key contributor to the pathogenesis of ROP. A large proportion of preterm infants with ROP will have residual visual loss linked to loss of photoreceptor (PR) and the integrity of the retinal pigment epithelium (RPE) in the macular region. Recent studies using animal models of ROP suggest that choroidal degeneration may be associated with a loss of integrity of the outer retina, a phenomenon so far largely undescribed in ROP pathogenesis. In this review, we highlight inflammatory and neuron-derived factors related to ROP progression, as well, potential targets for new treatment strategies. We also introduce choroidal degeneration as a significant cause of residual visual loss following ROP. We propose that ROP should no longer be considered an inner retinal vasculopathy only, but also a disease of choroidal degeneration affecting both retinal pigment epithelium and photoreceptor integrity.

Knee degeneration in concrete reinforcement workers.

PubMed Central

Wickström, G; Hänninen, K; Mattsson, T; Niskanen, T; Riihimäki, H; Waris, P; Zitting, A

1983-01-01

The loads on the knees in concrete reinforcement work and maintenance painting were analysed on eight construction work sites. A total of 352 reinforcement workers and 231 painters. Finnish men aged 20-64, were clinically and radiologically examined to determine the condition of the knee joints in active workers. The loads on the knees and the occurrence of minor injuries and accidents were higher in reinforcement work than in painting, but the occurrence of symptoms, clinical signs, and radiological findings was equally common in both groups. Reinforcement work seemed to provoke more symptoms from degenerated knees than painting. PMID:6830721

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.

Intacs for early pellucid marginal degeneration.

PubMed

Kymionis, George D; Aslanides, Ioannis M; Siganos, Charalambos S; Pallikaris, Ioannis G

2004-01-01

A 42-year-old man had Intacs (Addition Technology Inc.) implantation for early pellucid marginal degeneration (PMD). Two Intacs segments (0.45 mm thickness) were inserted uneventfully in the fashion typically used for low myopia correction (nasal-temporal). Eleven months after the procedure, the uncorrected visual acuity was 20/200, compared with counting fingers preoperatively, while the best spectacle-corrected visual acuity improved to 20/25 from 20/50. Corneal topographic pattern also improved. Although the results are encouraging, concern still exists regarding the long-term effect of this approach for the management of patients with PMD.

SOCIETAL COSTS ASSOCIATED WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION IN THE UNITED STATES.

PubMed

Brown, Melissa M; Brown, Gary C; Lieske, Heidi B; Tran, Irwin; Turpcu, Adam; Colman, Shoshana

2016-02-01

The purpose of this study was to use a cross-sectional prevalence-based health care economic survey to ascertain the annual, incremental, societal ophthalmic costs associated with neovascular age-related macular degeneration. Consecutive patients (n = 200) with neovascular age-related macular degeneration were studied. A Control Cohort included patients with good (20/20-20/25) vision, while Study Cohort vision levels included Subcohort 1: 20/30 to 20/50, Subcohort 2: 20/60 to 20/100, Subcohort 3: 20/200 to 20/400, and Subcohort 4: 20/800 to no light perception. An interviewer-administered, standardized, written survey assessed 1) direct ophthalmic medical, 2) direct nonophthalmic medical, 3) direct nonmedical, and 4) indirect medical costs accrued due solely to neovascular age-related macular degeneration. The mean annual societal cost for the Control Cohort was $6,116 and for the Study Cohort averaged $39,910 (P < 0.001). Study Subcohort 1 costs averaged $20,339, while Subcohort 4 costs averaged $82,984. Direct ophthalmic medical costs comprised 17.9% of Study Cohort societal ophthalmic costs, versus 74.1% of Control Cohort societal ophthalmic costs (P < 0.001) and 10.4% of 20/800 to no light perception subcohort costs. Direct nonmedical costs, primarily caregiver, comprised 67.1% of Study Cohort societal ophthalmic costs, versus 21.3% ($1,302/$6,116) of Control Cohort costs (P < 0.001) and 74.1% of 20/800 to no light perception subcohort costs. Total societal ophthalmic costs associated with neovascular age-related macular degeneration dramatically increase as vision in the better-seeing eye decreases.

Magnetic resonance imaging of degeneration of uterine adenomyosis during pregnancy and post-partum period.

PubMed

Hirashima, Hiroto; Ohkuchi, Akihide; Usui, Rie; Kijima, Shigeyoshi; Matsubara, Shigeki

2018-03-08

Degeneration of adenomyosis during pregnancy and the post-partum period is very rare. A 42-year-old Japanese parous woman with four normal-term deliveries, who presented with abdominal pain and fever at 22 weeks of gestation with transient increases of the white blood cell count and C-reactive protein, demonstrated sustained inflammation after cesarean section at 29 weeks of gestation due to the occurrence of gestational hypertension with late deceleration. The noncontrast-enhanced magnetic resonance imaging (MRI) at 22 weeks demonstrated a poorly demarcated hypointense area at the posterior uterine wall on T1- and T2-weighted imaging. The 2nd MRI 2 weeks after the cesarean section showed hypointensity on a T1-weighted image and hyperintensity on a T2-weighted image, allowing confirmation of the diagnosis of degeneration of adenomyosis. Repeated MRIs were clinically useful to diagnose the degeneration of adenomyosis. © 2018 Japan Society of Obstetrics and Gynecology.

Incompressible limit of the degenerate quantum compressible Navier-Stokes equations with general initial data

NASA Astrophysics Data System (ADS)

Kwon, Young-Sam; Li, Fucai

2018-03-01

In this paper we study the incompressible limit of the degenerate quantum compressible Navier-Stokes equations in a periodic domain T3 and the whole space R3 with general initial data. In the periodic case, by applying the refined relative entropy method and carrying out the detailed analysis on the oscillations of velocity, we prove rigorously that the gradient part of the weak solutions (velocity) of the degenerate quantum compressible Navier-Stokes equations converge to the strong solution of the incompressible Navier-Stokes equations. Our results improve considerably the ones obtained by Yang, Ju and Yang [25] where only the well-prepared initial data case is considered. While for the whole space case, thanks to the Strichartz's estimates of linear wave equations, we can obtain the convergence of the weak solutions of the degenerate quantum compressible Navier-Stokes equations to the strong solution of the incompressible Navier-Stokes/Euler equations with a linear damping term. Moreover, the convergence rates are also given.

Optomechanical entanglement via non-degenerate parametric interactions

NASA Astrophysics Data System (ADS)

Ahmed, Rizwan; Qamar, Shahid

2017-10-01

We present a scheme for the optomechanical entanglement between a micro-mechanical mirror and the field inside a bimodal cavity system using a non-degenerate optical parametric amplifier (NOPA). Our results show that the introduction of NOPA makes the entanglement stronger or more robust against the mean number of average thermal phonons and cavity decay. Interestingly, macroscopic entanglement depends upon the choice of the phase associated with classical field driving NOPA. We also consider the effects of input laser power on optomechanical entanglement.

Approach of Turkish ophthalmologists to micronutrition in age-related macular degeneration.

PubMed

Muhammed, Şahin; Yüksel, Harun; Şahin, Alparslan; Cingü, Abdullah Kürşat; Türkcü, Fatih Mehmet; Özkurt, Zeynep Gürsel; Çaça, İhsan

2015-01-01

To evaluate the knowledge and behaviors of ophthalmologists in Turkey concerning micronutrition support in patients with age related macular degeneration (ARMD). This study involved 1,845 ophthalmologists. A scientific poll was sent to all participants by email. The survey covered the following: demographic features, subspecialty knowledge about micronutrition preference for prescribing micronutrition to age related macular degeneration patients, and the reason for this preference. If a participant indicated that he or she prescribed micronutrition, the participant was also asked to indicate the source of the treatment and supplemental treatments. Of 1,845 ophthalmologists, 249 responded to the survey. Of the respondents, 9% (22) never, 43% (107) sometimes, 37% (92) frequently, and 11% (27) always used micronutrition. The most frequent prescribing subgroup was general ophthalmology (22%), followed by the retina-uvea subspecialty (13.9%). The micronutrition prescribing ratio was 54.8% in retina-uvea specialists when the "frequent" and "always" responses were combined. There was no statistically significant difference between subgroups with respect to prescribing micronutrition. Among the ophthalmologists prescribing micronutrition, 57.1% of them did not use the Age-Related Eye Disease Study-1 (AREDS) criteria, and only 31.3% prescribe micronutrition according to AREDS criteria. The results for the general ophthalmologist and retina-uvea specialist subgroups were similar, 56.3% vs 20.2%, and 54.1% vs 36.1%, respectively. Micronutrition was not recommended for the following reasons: expensive (55.4%), low patient expectancy (40%), no effect (30%), and low patient drug compliance (25.4%). Moreover, 55.2% of the clinicians recommended physical activities, dietary changes, and smoking cessation; 7.3% did not recommend these behavioral changes. This survey demonstrated that micronutrition preference in age related macular degeneration was low in ophthalmologists in Turkey

Characterization of cytochrome c as marker for retinal cell degeneration by uv/vis spectroscopic imaging

NASA Astrophysics Data System (ADS)

Hollmach, Julia; Schweizer, Julia; Steiner, Gerald; Knels, Lilla; Funk, Richard H. W.; Thalheim, Silko; Koch, Edmund

2011-07-01

Retinal diseases like age-related macular degeneration have become an important cause of visual loss depending on increasing life expectancy and lifestyle habits. Due to the fact that no satisfying treatment exists, early diagnosis and prevention are the only possibilities to stop the degeneration. The protein cytochrome c (cyt c) is a suitable marker for degeneration processes and apoptosis because it is a part of the respiratory chain and involved in the apoptotic pathway. The determination of the local distribution and oxidative state of cyt c in living cells allows the characterization of cell degeneration processes. Since cyt c exhibits characteristic absorption bands between 400 and 650 nm wavelength, uv/vis in situ spectroscopic imaging was used for its characterization in retinal ganglion cells. The large amount of data, consisting of spatial and spectral information, was processed by multivariate data analysis. The challenge consists in the identification of the molecular information of cyt c. Baseline correction, principle component analysis (PCA) and cluster analysis (CA) were performed in order to identify cyt c within the spectral dataset. The combination of PCA and CA reveals cyt c and its oxidative state. The results demonstrate that uv/vis spectroscopic imaging in conjunction with sophisticated multivariate methods is a suitable tool to characterize cyt c under in situ conditions.

Dark-matter admixed white dwarfs

NASA Astrophysics Data System (ADS)

Leung, Shing Chi; Chu, Ming Chung; Lin, Lap Ming; Wong, Ka Wing

2014-03-01

We study the equilibrium structures of white dwarfs (WD) with dark matter cores formed by non-self-annihilating dark matter (DM) particles with masses ranging from 1 GeV to 100 GeV, assuming in form of an ideal degenerate Fermi gas inside the stars. For DM particles of mass 10 GeV and 100 GeV, we find that stable stellar models exist only if the mass of the DM core inside the star is less than O and -3)Msun , respectively. The global properties of these stars, and the corresponding Chandrasekhar mass (CM) limits, are essentially the same as those of traditional WD models without DM. Nevertheless, in the 10 GeV case, the gravitational attraction of the DM core is strong enough to squeeze the normal matter in the core region to densities above neutron drip. For the 1 GeV case, the DM core inside the star can be as massive as O and affects the global structure of the star significantly. The radius of a stellar model with DM can be about two times smaller than that of a traditional WD. Furthermore, the CM limit can be decreased by as much as 40%. Our results may have implications on the extent to which type Ia supernovae can be regarded as standard candles. This work is partially supported by a grant from the Research Grant Council of the Hong Kong Special Administrative Region, China (Project No. 400910).

Lipocalin 2 Plays an Important Role in Regulating Inflammation in Retinal Degeneration.

PubMed

Parmar, Tanu; Parmar, Vipul M; Perusek, Lindsay; Georges, Anouk; Takahashi, Masayo; Crabb, John W; Maeda, Akiko

2018-05-01

It has become increasingly important to understand how retinal inflammation is regulated because inflammation plays a role in retinal degenerative diseases. Lipocalin 2 (LCN2), an acute stress response protein with multiple innate immune functions, is increased in ATP-binding cassette subfamily A member 4 ( Abca4 ) -/- retinol dehydrogenase 8 ( Rdh8 ) -/- double-knockout mice, an animal model for Stargardt disease and age-related macular degeneration (AMD). To examine roles of LCN2 in retinal inflammation and degeneration, Lcn2 -/- Abca4 -/- Rdh8 -/- triple-knockout mice were generated. Exacerbated inflammation following light exposure was observed in Lcn2 -/- Abca4 -/- Rdh8 -/- mice as compared with Abca4 -/- Rdh8 -/- mice, with upregulation of proinflammatory genes and microglial activation. RNA array analyses revealed an increase in immune response molecules such as Ccl8 , Ccl2 , and Cxcl10 To further probe a possible regulatory role for LCN2 in retinal inflammation, we examined the in vitro effects of LCN2 on NF-κB signaling in human retinal pigmented epithelial (RPE) cells differentiated from induced pluripotent stem cells derived from healthy donors. We found that LCN2 induced expression of antioxidant enzymes heme oxygenase 1 and superoxide dismutase 2 in these RPE cells and could inhibit the cytotoxic effects of H 2 O 2 and LPS. ELISA revealed increased LCN2 levels in plasma of patients with Stargardt disease, retinitis pigmentosa, and age-related macular degeneration as compared with healthy controls. Finally, overexpression of LCN2 in RPE cells displayed protection from cell death. Overall these results suggest that LCN2 is involved in prosurvival responses during cell stress and plays an important role in regulating inflammation during retinal degeneration. Copyright © 2018 by The American Association of Immunologists, Inc.

Spectropathology-corroborated multimodal quantitative imaging biomarkers for neuroretinal degeneration in diabetic retinopathy

PubMed Central

Guha Mazumder, Arpan; Chatterjee, Swarnadip; Chatterjee, Saunak; Gonzalez, Juan Jose; Bag, Swarnendu; Ghosh, Sambuddha; Mukherjee, Anirban; Chatterjee, Jyotirmoy

2017-01-01

Introduction Image-based early detection for diabetic retinopathy (DR) needs value addition due to lack of well-defined disease-specific quantitative imaging biomarkers (QIBs) for neuroretinal degeneration and spectropathological information at the systemic level. Retinal neurodegeneration is an early event in the pathogenesis of DR. Therefore, development of an integrated assessment method for detecting neuroretinal degeneration using spectropathology and QIBs is necessary for the early diagnosis of DR. Methods The present work explored the efficacy of intensity and textural features extracted from optical coherence tomography (OCT) images after selecting a specific subset of features for the precise classification of retinal layers using variants of support vector machine (SVM). Fourier transform infrared (FTIR) spectroscopy and nuclear magnetic resonance (NMR) spectroscopy were also performed to confirm the spectropathological attributes of serum for further value addition to the OCT, fundoscopy, and fluorescein angiography (FA) findings. The serum metabolomic findings were also incorporated for characterizing retinal layer thickness alterations and vascular asymmetries. Results Results suggested that OCT features could differentiate the retinal lesions indicating retinal neurodegeneration with high sensitivity and specificity. OCT, fundoscopy, and FA provided geometrical as well as optical features. NMR revealed elevated levels of ribitol, glycerophosphocholine, and uridine diphosphate N-acetyl glucosamine, while the FTIR of serum samples confirmed the higher expressions of lipids and β-sheet-containing proteins responsible for neoangiogenesis, vascular fragility, vascular asymmetry, and subsequent neuroretinal degeneration in DR. Conclusion Our data indicated that disease-specific spectropathological alterations could be the major phenomena behind the vascular attenuations observed through fundoscopy and FA, as well as the variations in the intensity and

Analysis of the RPE sheet in the rd10 retinal degeneration model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jiang, Yi

2011-01-04

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

Cellular regeneration strategies for macular degeneration: past, present and future.

PubMed

Chichagova, Valeria; Hallam, Dean; Collin, Joseph; Zerti, Darin; Dorgau, Birthe; Felemban, Majed; Lako, Majlinda; Steel, David H

2018-05-01

Despite considerable effort and significant therapeutic advances, age-related macular degeneration (AMD) remains the commonest cause of blindness in the developed world. Progressive late-stage AMD with outer retinal degeneration currently has no proven treatment. There has been significant interest in the possibility that cellular treatments may slow or reverse visual loss in AMD. A number of modes of action have been suggested, including cell replacement and rescue, as well as immune modulation to delay the neurodegenerative process. Their appeal in this enigmatic disease relate to their generic, non-pathway-specific effects. The outer retina in particular has been at the forefront of developments in cellular regenerative therapies being surgically accessible, easily observable, as well as having a relatively simple architecture. Both the retinal pigment epithelium (RPE) and photoreceptors have been considered for replacement therapies as both sheets and cell suspensions. Studies using autologous RPE, and to a lesser extent, foetal retina, have shown proof of principle. A wide variety of cell sources have been proposed with pluripotent stem cell-derived cells currently holding the centre stage. Recent early-phase trials using these cells for RPE replacement have met safety endpoints and hinted at possible efficacy. Animal studies have confirmed the promise that photoreceptor replacement, even in a completely degenerated outer retina may restore some vision. Many challenges, however, remain, not least of which include avoiding immune rejection, ensuring long-term cellular survival and maximising effect. This review provides an overview of progress made, ongoing studies and challenges ahead.

Treatment of dry age-related macular degeneration with dobesilate

PubMed Central

Cuevas, P; Outeiriño, L A; Angulo, J; Giménez-Gallego, G

2012-01-01

The authors present anatomical and functional evidences of dry age-macular degeneration improvement, after intravitreal treatment with dobesilate. Main outcomes measures were normalisation of retinal structure and function, assessed by optical coherence tomography, fundus-monitored microperimetry, electrophysiology and visual acuity. The effect might be related to the normalisation of the outer retinal architecture. PMID:22729337

Association between menopause and lumbar disc degeneration: an MRI study of 1,566 women and 1,382 men.

PubMed

Lou, Chao; Chen, Hongliang; Mei, Liangwei; Yu, Weiyang; Zhu, Kejun; Liu, Feijun; Chen, Zhenzhong; Xiang, Guangheng; Chen, Minjiang; Weng, Qiaoyou; He, Dengwei

2017-10-01

The aim of this study was to revisit and further investigate the association between menopause and disc degeneration in the lumbar spine using a magnetic resonance imaging-based eight-level grading system. This study cohort comprised of 1,566 women and 1,382 age-matched men who were admitted for low back pain from June 2013 to October 2016. Data on age, weight, height, body mass index, age at natural menopause, and years since menopause (YSM) were obtained. Lumbar disc degeneration was assessed using a magnetic resonance imaging-based eight-level grading system. After adjustment for the confounding factors of age, height, and weight, young age-matched men were more susceptible to disc degeneration than premenopausal women (P < 0.05). However, after menopause, postmenopausal women had a significant tendency to develop more severe disc degeneration than their age-matched men (P < 0.05), and also compared with premenopausal and perimenopausal women (P < 0.01). Postmenopausal women were divided into nine subgroups by every 5 YSM. When YSM was less than 15 years, a positive trend was observed between YSM and severity of disc degeneration, respectively, at L1/L2 (r = 0.241), L2/L3 (r = 0.193), L3/L4 (r = 0.191), L4/L5 (r = 0.165), L5/S1 (r = 0.153), and all lumbar discs (r = 0.237) (P < 0.05 or 0.01). The analysis of covariance indicated a significant difference in each disc level (P < 0.05 or 0.01) between every two groups. When YSM was more than 15 years, the significant difference, however, disappeared in each disc level (P > 0.05). Menopause is associated with lumbar disc degeneration. The association occurred in the first 15 YSM, suggesting estrogen deficiency might be a risk factor of disc degeneration of the lumbar spine. Further studies need to be carried out for deciding whether age or menopause plays a more important role in the progression of disc degeneration in the lumbar spine.

Drosophila melanogaster White Mutant w1118 Undergo Retinal Degeneration

PubMed Central

Ferreiro, María José; Pérez, Coralia; Marchesano, Mariana; Ruiz, Santiago; Caputi, Angel; Aguilera, Pedro; Barrio, Rosa; Cantera, Rafael

2018-01-01

Key scientific discoveries have resulted from genetic studies of Drosophila melanogaster, using a multitude of transgenic fly strains, the majority of which are constructed in a genetic background containing mutations in the white gene. Here we report that white mutant flies from w1118 strain undergo retinal degeneration. We observed also that w1118 mutants have progressive loss of climbing ability, shortened life span, as well as impaired resistance to various forms of stress. Retinal degeneration was abolished by transgenic expression of mini-white+ in the white null background w1118. We conclude that beyond the classical eye-color phenotype, mutations in Drosophila white gene could impair several biological functions affecting parameters like mobility, life span and stress tolerance. Consequently, we suggest caution and attentiveness during the interpretation of old experiments employing white mutant flies and when planning new ones, especially within the research field of neurodegeneration and neuroprotection. We also encourage that the use of w1118 strain as a wild-type control should be avoided. PMID:29354028

Genetic control of an epigenetic cell degeneration syndrome in Podospora anserina.

PubMed

Haedens, Vicki; Malagnac, Fabienne; Silar, Philippe

2005-06-01

Filamentous fungi frequently present degenerative processes, whose molecular basis is very often unknown. Here, we present three mutant screens that result in the identification of 29 genes that directly or indirectly control Crippled Growth (CG), an epigenetic cell degeneration of the filamentous ascomycete Podospora anserina. Two of these genes were previously shown to encode a MAP kinase kinase kinase and an NADPH oxidase involved in a signal transduction cascade that participates in stationary phase differentiations, fruiting body development and defence against fungal competitors. The numerous genes identified can be incorporated in a model in which CG results from the sustained activation of the MAP kinase cascade. Our data also emphasize the complex regulatory network underlying three interconnected processes in P. anserina: sexual reproduction, defence against competitors, and cell degeneration.

On the dispersion characteristics of extraordinary mode in a relativistic fully degenerate electron plasma

NASA Astrophysics Data System (ADS)

Noureen, S.; Abbas, G.; Sarfraz, M.

2018-01-01

The study of relativistic degenerate plasmas is important in many astrophysical and laboratory environments. Using linearized relativistic Vlasov-Maxwell equations, a generalized expression for the plasma conductivity tensor is derived. Employing Fermi-Dirac distribution at zero temperature, the dispersion relation of the extraordinary mode in a relativistic degenerate electron plasma is investigated. The propagation characteristics are examined in different relativistic density ranges. The shifting of cutoff points due to relativistic effects is observed analytically and graphically. Non-relativistic and ultra-relativistic limiting cases are also presented.

[The misery of degeneration: Buffon's materialism and the 'limitations' of his transformism].

PubMed

Caponi, Gustavo

2009-01-01

In "Of the degeneration of animals" (1766), Buffon espoused a kind of limited transformism. Yet twelve years later, in Epochs of Nature, he supplemented this with a materialist theory on the origin of life that left no room for this alternative: the conditions under which living beings develop could explain how the different species within each animal genus had formed through the degeneration of an originating species. But the formation of these multiple, originating varieties could only be explained by a sudden process of spontaneous generation. A limitation inherent to the very system of ideas that had taken Buffon to limited transformism the underlying theory of generation and reproduction -preempted the possibility of its radicalization.

A prefoldin-associated WD-repeat protein (WDR92) is required for the correct architectural assembly of motile cilia

PubMed Central

Patel-King, Ramila S.; King, Stephen M.

2016-01-01

WDR92 is a highly conserved WD-repeat protein that has been proposed to be involved in apoptosis and also to be part of a prefoldin-like cochaperone complex. We found that WDR92 has a phylogenetic signature that is generally compatible with it playing a role in the assembly or function of specifically motile cilia. To test this hypothesis, we performed an RNAi-based knockdown of WDR92 gene expression in the planarian Schmidtea mediterranea and were able to achieve a robust reduction in mRNA expression to levels undetectable under our standard RT-PCR conditions. We found that this treatment resulted in a dramatic reduction in the rate of organismal movement that was caused by a switch in the mode of locomotion from smooth, cilia-driven gliding to muscle-based, peristaltic contractions. Although the knockdown animals still assembled cilia of normal length and in similar numbers to controls, these structures had reduced beat frequency and did not maintain hydrodynamic coupling. By transmission electron microscopy we observed that many cilia had pleiomorphic defects in their architecture, including partial loss of dynein arms, incomplete closure of the B-tubule, and occlusion or replacement of the central pair complex by accumulated electron-dense material. These observations suggest that WDR92 is part of a previously unrecognized cytoplasmic chaperone system that is specifically required to fold key components necessary to build motile ciliary axonemes. PMID:26912790

A Novel Method to Simulate the Progression of Collagen Degeneration of Cartilage in the Knee: Data from the Osteoarthritis Initiative

NASA Astrophysics Data System (ADS)

Mononen, Mika E.; Tanska, Petri; Isaksson, Hanna; Korhonen, Rami K.

2016-02-01

We present a novel algorithm combined with computational modeling to simulate the development of knee osteoarthritis. The degeneration algorithm was based on excessive and cumulatively accumulated stresses within knee joint cartilage during physiological gait loading. In the algorithm, the collagen network stiffness of cartilage was reduced iteratively if excessive maximum principal stresses were observed. The developed algorithm was tested and validated against experimental baseline and 4-year follow-up Kellgren-Lawrence grades, indicating different levels of cartilage degeneration at the tibiofemoral contact region. Test groups consisted of normal weight and obese subjects with the same gender and similar age and height without osteoarthritic changes. The algorithm accurately simulated cartilage degeneration as compared to the Kellgren-Lawrence findings in the subject group with excess weight, while the healthy subject group’s joint remained intact. Furthermore, the developed algorithm followed the experimentally found trend of cartilage degeneration in the obese group (R2 = 0.95, p < 0.05 experiments vs. model), in which the rapid degeneration immediately after initiation of osteoarthritis (0-2 years, p < 0.001) was followed by a slow or negligible degeneration (2-4 years, p > 0.05). The proposed algorithm revealed a great potential to objectively simulate the progression of knee osteoarthritis.

A Novel Method to Simulate the Progression of Collagen Degeneration of Cartilage in the Knee: Data from the Osteoarthritis Initiative

PubMed Central

Mononen, Mika E.; Tanska, Petri; Isaksson, Hanna; Korhonen, Rami K.

2016-01-01

We present a novel algorithm combined with computational modeling to simulate the development of knee osteoarthritis. The degeneration algorithm was based on excessive and cumulatively accumulated stresses within knee joint cartilage during physiological gait loading. In the algorithm, the collagen network stiffness of cartilage was reduced iteratively if excessive maximum principal stresses were observed. The developed algorithm was tested and validated against experimental baseline and 4-year follow-up Kellgren-Lawrence grades, indicating different levels of cartilage degeneration at the tibiofemoral contact region. Test groups consisted of normal weight and obese subjects with the same gender and similar age and height without osteoarthritic changes. The algorithm accurately simulated cartilage degeneration as compared to the Kellgren-Lawrence findings in the subject group with excess weight, while the healthy subject group’s joint remained intact. Furthermore, the developed algorithm followed the experimentally found trend of cartilage degeneration in the obese group (R2 = 0.95, p < 0.05; experiments vs. model), in which the rapid degeneration immediately after initiation of osteoarthritis (0–2 years, p < 0.001) was followed by a slow or negligible degeneration (2–4 years, p > 0.05). The proposed algorithm revealed a great potential to objectively simulate the progression of knee osteoarthritis. PMID:26906749

The WD40 Domain Protein MSI1 Functions in a Histone Deacetylase Complex to Fine-Tune Abscisic Acid Signaling.

PubMed

Mehdi, Saher; Derkacheva, Maria; Ramström, Margareta; Kralemann, Lejon; Bergquist, Jonas; Hennig, Lars

2016-01-01

MSI1 belongs to a family of histone binding WD40-repeat proteins. Arabidopsis thaliana contains five genes encoding MSI1-like proteins, but their functions in diverse chromatin-associated complexes are poorly understood. Here, we show that MSI1 is part of a histone deacetylase complex. We copurified HISTONE DEACETYLASE19 (HDA19) with MSI1 and transcriptional regulatory SIN3-like proteins and provide evidence that MSI1 and HDA19 associate into the same complex in vivo. These data suggest that MSI1, HDA19, and HISTONE DEACETYLATION COMPLEX1 protein form a core complex that can integrate various SIN3-like proteins. We found that reduction of MSI1 or HDA19 causes upregulation of abscisic acid (ABA) receptor genes and hypersensitivity of ABA-responsive genes. The MSI1-HDA19 complex fine-tunes ABA signaling by binding to the chromatin of ABA receptor genes and by maintaining low levels of acetylation of histone H3 at lysine 9, thereby affecting the expression levels of ABA receptor genes. Reduced MSI1 or HDA19 levels led to increased tolerance to salt stress corresponding to the increased ABA sensitivity of gene expression. Together, our results reveal the presence of an MSI1-HDA19 complex that fine-tunes ABA signaling in Arabidopsis. © 2016 American Society of Plant Biologists. All rights reserved.

Complement pathway biomarkers and age-related macular degeneration

PubMed Central

Gemenetzi, M; Lotery, A J

2016-01-01

In the age-related macular degeneration (AMD) ‘inflammation model', local inflammation plus complement activation contributes to the pathogenesis and progression of the disease. Multiple genetic associations have now been established correlating the risk of development or progression of AMD. Stratifying patients by their AMD genetic profile may facilitate future AMD therapeutic trials resulting in meaningful clinical trial end points with smaller sample sizes and study duration. PMID:26493033

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.

Fertility depression among cheese‐making Penicillium roqueforti strains suggests degeneration during domestication

PubMed Central

Ropars, Jeanne; Lo, Ying‐Chu; Dumas, Emilie; Snirc, Alodie; Begerow, Dominik; Rollnik, Tanja; Lacoste, Sandrine; Dupont, Joëlle; Giraud, Tatiana; López‐Villavicencio, Manuela

2016-01-01

Genetic differentiation occurs when gene flow is prevented, due to reproductive barriers or asexuality. Investigating the early barriers to gene flow is important for understanding the process of speciation. Here, we therefore investigated reproductive isolation between different genetic clusters of the fungus Penicillium roqueforti, used for maturing blue cheeses, and also occurring as food spoiler or in silage. We investigated premating and postmating fertility between and within three genetic clusters (two from cheese and one from other substrates), and we observed sexual structures under scanning electron microscopy. All intercluster types of crosses showed some fertility, suggesting that no intersterility has evolved between domesticated and wild populations despite adaptation to different environments and lack of gene flow. However, much lower fertility was found in crosses within the cheese clusters than within the noncheese cluster, suggesting reduced fertility of cheese strains, which may constitute a barrier to gene flow. Such degeneration may be due to bottlenecks during domestication and/or to the exclusive clonal replication of the strains in industry. This study shows that degeneration has occurred rapidly and independently in two lineages of a domesticated species. Altogether, these results inform on the processes and tempo of degeneration and speciation. PMID:27470007

Changes in morphology of retinal ganglion cells with eccentricity in retinal degeneration.

PubMed

Anderson, E E; Greferath, U; Fletcher, E L

2016-05-01

Ganglion cells are the output neurons of the retina and are known to remodel during the subtle plasticity changes that occur following the death of photoreceptors in inherited retinal degeneration. We examine the influence of retinal eccentricity on anatomical remodelling and ganglion cell morphology well after photoreceptor loss. Rd1 mice that have a mutation in the β subunit of phosphodiesterase 6 were used as a model of retinal degeneration and gross remodelling events were examined by processing serial sections for immunocytochemistry. Retinal wholemounts from rd1-Thy1 and control Thy1 mice that contained a fluorescent protein labelling a subset of ganglion cells were processed for immunohistochemistry at 11 months of age. Ganglion cells were classified based on their soma size, dendritic field size and dendritic branching pattern and their dendritic fields were analysed for their length, area and quantity of branching points. Overall, more remodelling was found in the central compared with the peripheral retina. In addition, the size and complexity of A2, B1, C1 and D type ganglion cells located in the central region of the retina decreased. We propose that the changes in ganglion cell morphology are correlated with remodelling events in these regions and impact the function of retinal circuitry in the degenerated retina.

Optical coherence tomography angiography in age-related macular degeneration: The game changer.

PubMed

Lupidi, Marco; Cerquaglia, Alessio; Chhablani, Jay; Fiore, Tito; Singh, Sumit Randhir; Cardillo Piccolino, Felice; Corbucci, Roberta; Coscas, Florence; Coscas, Gabriel; Cagini, Carlo

2018-04-01

Optical coherence tomography angiography is one of the biggest advances in ophthalmic imaging. It enables a depth-resolved assessment of the retinal and choroidal blood flow, far exceeding the levels of detail commonly obtained with dye angiographies. One of the first applications of optical coherence tomography angiography was in detecting the presence of choroidal neovascularization in age-related macular degeneration and establishing its position in relation to the retinal pigmented epithelium and Bruch's membrane, and thereby classifying the CNV as type 1, type 2, type 3, or mixed lesions. Optical coherence tomography angiograms, due to the longer wavelength used by optical coherence tomography, showed a more distinct choroidal neovascularization vascular pattern than fluorescein angiography, since there is less suffering from light scattering or is less obscured by overlying subretinal hemorrhages or exudation. Qualitative and quantitative assessments of optical coherence tomography angiography findings in exudative and nonexudative age-related macular degeneration have been largely investigated within the past 3 years both in clinical and experimental settings. This review constitutes an up-to-date of all the potential applications of optical coherence tomography angiography in age-related macular degeneration in order to better understand how to translate its theoretical usefulness into the current clinical practice.

RISK FACTORS AND CLINICAL SIGNIFICANCE OF PRECHOROIDAL CLEFT IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PubMed

Kim, Jong Min; Kang, Se Woong; Son, Dae Yong; Bae, Kunho

2017-11-01

To investigate the risk factors associated with prechoroidal cleft occurrence after treatment for neovascular age-related macular degeneration (nAMD) and to elucidate its clinical significance. Two hundred thirty-four subjects who were treated for neovascular age-related macular degeneration were assessed to identify prechoroidal cleft on optical coherence tomography. Clinical variables were compared between patients manifesting a cleft (cleft group) and patients who did not (control group). Prechoroidal cleft was detected in 29 of 234 patients (8.1%). Although the baseline visual acuity was not different between the 2 groups, logMAR visual acuity at final visit was 0.89 ± 0.74 (with approximate Snellen equivalent of 20/160) in the cleft group and 0.65 ± 0.69 (with approximate Snellen equivalent of 20/100) in controls (P < 0.05). Within cleft group, the early-onset (<6 months) subgroup had even worse visual outcomes than the late-onset subgroup (P < 0.05). Multiple logistic regression analyses revealed that the incidence of prechoroidal cleft was positively correlated with having received intravitreal gas injection to displace a submacular hemorrhage and a diagnosis of retinal angiomatous proliferation and typical neovascular age-related macular degeneration (P < 0.05). Diagnosis of retinal angiomatous proliferation and typical neovascular age-related macular degeneration, and a submacular hemorrhage treated by pneumatic displacement were the independent risk factors for development of prechoroidal cleft. Eyes with a cleft, especially clefts that develop early, generally had worse prognoses than eyes without clefts.

Inhibition of the Rho/ROCK pathway prevents neuronal degeneration in vitro and in vivo following methylmercury exposure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fujimura, Masatake, E-mail: fujimura@nimd.go.jp; Usuki, Fusako; Kawamura, Miwako

Methylmercury (MeHg) is an environmental neurotoxicant which induces neuropathological changes in both the central nervous and peripheral sensory nervous systems. Our recent study demonstrated that down-regulation of Ras-related C3 botulinum toxin substrate 1 (Rac1), which is known to promote neuritic extension, preceded MeHg-induced damage in cultured cortical neurons, suggesting that MeHg-mediated axonal degeneration is due to the disturbance of neuritic extension. Therefore we hypothesized that MeHg-induced axonal degeneration might be caused by neuritic extension/retraction incoordination. This idea brought our attention to the Ras homolog gene (Rho)/Rho-associated coiled coil-forming protein kinase (ROCK) pathway because it has been known to be associatedmore » with the development of axon and apoptotic neuronal cell death. Here we show that inhibition of the Rho/ROCK pathway prevents MeHg-intoxication both in vitro and in vivo. A Rho inhibitor, C3 toxin, and 2 ROCK inhibitors, Fasudil and Y-27632, significantly protected against MeHg-induced axonal degeneration and apoptotic neuronal cell death in cultured cortical neuronal cells exposed to 100 nM MeHg for 3 days. Furthermore, Fasudil partially prevented the loss of large pale neurons in dorsal root ganglia, axonal degeneration in dorsal spinal root nerves, and vacuolar degeneration in the dorsal columns of the spinal cord in MeHg-intoxicated model rats (20 ppm MeHg in drinking water for 28 days). Hind limb crossing sign, a characteristic MeHg-intoxicated sign, was significantly suppressed in this model. The results suggest that inhibition of the Rho/ROCK pathway rescues MeHg-mediated neuritic extension/retraction incoordination and is effective for the prevention of MeHg-induced axonal degeneration and apoptotic neuronal cell death.« less

Degenerate SDEs with singular drift and applications to Heisenberg groups

NASA Astrophysics Data System (ADS)

Huang, Xing; Wang, Feng-Yu

2018-09-01

By using the ultracontractivity of a reference diffusion semigroup, Krylov's estimate is established for a class of degenerate SDEs with singular drifts, which leads to existence and pathwise uniqueness by means of Zvonkin's transformation. The main result is applied to singular SDEs on generalized Heisenberg groups.

Infectious agents is a risk factor for myxomatous mitral valve degeneration: A case control study.

PubMed

Tiveron, Marcos Gradim; Pomerantzeff, Pablo Maria Alberto; de Lourdes Higuchi, Maria; Reis, Marcia Martins; de Jesus Pereira, Jaqueline; Kawakami, Joyce Tieko; Ikegami, Renata Nishiyama; de Almeida Brandao, Carlos Manuel; Jatene, Fabio Biscegli

2017-04-21

The etiology of myxomatous mitral valve degeneration (MVD) is not fully understood and may depend on time or environmental factors for which the interaction of infectious agents has not been documented. The purpose of the study is to analyze the effect of Mycoplasma pneumoniae (Mp), Chlamydophila pneumoniae (Cp) and Borrelia burgdorferi (Bb) on myxomatous mitral valve degeneration pathogenesis and establish whether increased in inflammation and collagen degradation in myxomatous mitral valve degeneration etiopathogenesis. An immunohistochemical test was performed to detect the inflammatory cells (CD20, CD45, CD68) and Mp, Bb and MMP9 antigens in two groups. The in situ hybridization was performed to detect Chlamydophila pneumoniae and the bacteria study was performed using transmission electron microscopy. Group 1 (n = 20), surgical specimen composed by myxomatous mitral valve degeneration, and group 2 (n = 20), autopsy specimen composed by normal mitral valve. The data were analyzed using SigmaStat version 20 (SPSS Inc., Chicago, IL, USA). The groups were compared using Student's t test, Mann-Whitney test. A correlation analysis was performed using Spearman's correlation test. P values lower than 0.05 were considered statistically significant. By immunohistochemistry, there was a higher inflammatory cells/mm2 for CD20 and CD45 in group 1, and CD68 in group 2. Higher number of Mp and Cp antigens was observed in group 1 and more Bb antigens was detected in group 2. The group 1 exhibited a positive correlation between the Bb and MVD percentage, between CD45 and Mp, and between MMP9 with Mp. These correlations were not observed in the group 2. Electron microscopy revealed the presence of structures compatible with microorganisms that feature Borrelia and Mycoplasma characteristics. The presence of infectious agents, inflammatory cells and collagenases in mitral valves appear to contribute to the pathogenesis of MVD. Mycoplasma pneumoniae was strongly related with

Sudden acquired retinal degeneration syndrome in western Canada: 93 cases.

PubMed

Leis, Marina L; Lucyshyn, Danica; Bauer, Bianca S; Grahn, Bruce H; Sandmeyer, Lynne S

2017-11-01

This study reviewed clinical data from dogs diagnosed with sudden acquired retinal degeneration syndrome (SARDS) in western Canada. Medical records from the Western College of Veterinary Medicine from 2002 to 2016 showed that 93 cases of SARDS were diagnosed based on presentation for sudden blindness and a bilaterally extinguished electroretinogram. The most common pure breeds were the miniature schnauzer, dachshund, and pug. The mean age at diagnosis was 8.1 years and males and females were equally affected. Most of the dogs were presented with normal non-chromatic, but abnormal chromatic pupillary light reflexes. The incidence of retinal degeneration as detected via ophthalmoscopy increased over time after SARDS diagnosis. Polyuria, polydipsia, polyphagia, weight gain, elevated liver enzyme values, isosthenuria, and proteinuria were common clinical and laboratory findings. Chromatic pupillary light reflex testing may be more valuable than non-chromatic pupillary light testing in detecting pupil response abnormalities in dogs with SARDS, although electroretinography remains the definitive diagnostic test.

Modulation of Mcl-1 expression reduces age-related cochlear degeneration

PubMed Central

Yang, Wei Ping; Xu, Yang; Guo, Wei Wei; Liu, Hui Zhan; Hu, Bo Hua

2013-01-01

Mcl-1 is an anti-apoptotic member of the Bcl-2 family that modulates apoptosis-related signaling pathways and promotes cell survival. We have previously demonstrated a reduction of Mcl-1 expression in aging cochleae. To investigate whether restoring Mcl-1 expression would reduce aging-related cochlear degeneration, we developed a rat model of Mcl-1 overexpression. A plasmid encoding human Mcl-1/enhanced green fluorescent protein was applied to the round window of the cochlea. This in vivo treatment transfected both the sensory and supporting cells of the cochlear sensory epithelium and enhanced Mcl-1 expression at both the mRNA and the protein level. The upregulation of Mcl-1 expression reduced the progression of age-related cochlear dysfunction and sensory cell death. Furthermore, the transfection of Mcl-1 exerted its protective effect by suppressing cochlear apoptosis at the mitochondrial level. This study demonstrates that the genetic modulation of Mcl-1 expression reduces the progression of age-related cochlear degeneration. PMID:23790646

Sudden acquired retinal degeneration syndrome in western Canada: 93 cases

PubMed Central

Leis, Marina L.; Lucyshyn, Danica; Bauer, Bianca S.; Grahn, Bruce H.; Sandmeyer, Lynne S.

2017-01-01

This study reviewed clinical data from dogs diagnosed with sudden acquired retinal degeneration syndrome (SARDS) in western Canada. Medical records from the Western College of Veterinary Medicine from 2002 to 2016 showed that 93 cases of SARDS were diagnosed based on presentation for sudden blindness and a bilaterally extinguished electroretinogram. The most common pure breeds were the miniature schnauzer, dachshund, and pug. The mean age at diagnosis was 8.1 years and males and females were equally affected. Most of the dogs were presented with normal non-chromatic, but abnormal chromatic pupillary light reflexes. The incidence of retinal degeneration as detected via ophthalmoscopy increased over time after SARDS diagnosis. Polyuria, polydipsia, polyphagia, weight gain, elevated liver enzyme values, isosthenuria, and proteinuria were common clinical and laboratory findings. Chromatic pupillary light reflex testing may be more valuable than non-chromatic pupillary light testing in detecting pupil response abnormalities in dogs with SARDS, although electroretinography remains the definitive diagnostic test. PMID:29089658

Rare earth nanoparticles prevent retinal degeneration induced by intracellular peroxides:

NASA Astrophysics Data System (ADS)

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

2006-11-01

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

Fin degeneration of young-of-the-year Alosa pseudoharengus (Clupeidae) in southern Lake Michigan

USGS Publications Warehouse

Brown, Edward H.; Norden, Carroll R.

1970-01-01

Young-of-the-year alewives, Alosa pseudoharengus, with extremely shortened caudal fins were observed at four locations in southern Lake Michigan between 1964 and 1968. Some of the fins appeared stunted or underdeveloped, but microscopic examination revealed a deterioration of the fins and not an ontogenetic abnormality. Deterioration of the caudal fin was frequently accompanied by degeneration of the dorsal and anal fins. Degenerate fins were not found on other species nor on older alewives, with the exception of one known yearling alewife at Waukegan and possibly a few of the larger fish at Milwaukee.

Density matrix renormalization group for a highly degenerate quantum system: Sliding environment block approach

NASA Astrophysics Data System (ADS)

Schmitteckert, Peter

2018-04-01

We present an infinite lattice density matrix renormalization group sweeping procedure which can be used as a replacement for the standard infinite lattice blocking schemes. Although the scheme is generally applicable to any system, its main advantages are the correct representation of commensurability issues and the treatment of degenerate systems. As an example we apply the method to a spin chain featuring a highly degenerate ground-state space where the new sweeping scheme provides an increase in performance as well as accuracy by many orders of magnitude compared to a recently published work.

Present and future treatment possibilities in macular degeneration

NASA Astrophysics Data System (ADS)

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