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Sample records for prevent dendritic degeneration

  1. Prevention of age-related macular degeneration.

    Science.gov (United States)

    Wong, Ian Yat Hin; Koo, Simon Chi Yan; Chan, Clement Wai Nang

    2011-02-01

    Age-related macular degeneration (AMD) is one of the leading causes of blindness in the developed world. Although effective treatment modalities such as anti-VEGF treatment have been developed for neovascular AMD, there is still no effective treatment for geographical atrophy, and therefore the most cost-effective management of AMD is to start with prevention. This review looks at current evidence on preventive measures targeted at AMD. Modalities reviewed include (1) nutritional supplements such as the Age-Related Eye Disease Study (AREDS) formula, lutein and zeaxanthin, omega-3 fatty acid, and berry extracts, (2) lifestyle modifications, including smoking and body-mass-index, and (3) filtering sunlight, i.e. sunglasses and blue-blocking intraocular lenses. In summary, the only proven effective preventive measures are stopping smoking and the AREDS formula.

  2. GPR84 deficiency reduces microgliosis, but accelerates dendritic degeneration and cognitive decline in a mouse model of Alzheimer's disease.

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    Audoy-Rémus, Julie; Bozoyan, Lusine; Dumas, Aline; Filali, Mohammed; Lecours, Cynthia; Lacroix, Steve; Rivest, Serge; Tremblay, Marie-Eve; Vallières, Luc

    2015-05-01

    Microglia surrounds the amyloid plaques that form in the brains of patients with Alzheimer's disease (AD), but their role is controversial. Under inflammatory conditions, these cells can express GPR84, an orphan receptor whose pathophysiological role is unknown. Here, we report that GPR84 is upregulated in microglia of APP/PS1 transgenic mice, a model of AD. Without GPR84, these mice display both accelerated cognitive decline and a reduced number of microglia, especially in areas surrounding plaques. The lack of GPR84 affects neither plaque formation nor hippocampal neurogenesis, but promotes dendritic degeneration. Furthermore, GPR84 does not influence the clinical progression of other diseases in which its expression has been reported, i.e., experimental autoimmune encephalomyelitis (EAE) and endotoxic shock. We conclude that GPR84 plays a beneficial role in amyloid pathology by acting as a sensor for a yet unknown ligand that promotes microglia recruitment, a response affecting dendritic degeneration and required to prevent further cognitive decline. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Moderate traumatic brain injury causes acute dendritic and synaptic degeneration in the hippocampal dentate gyrus.

    Directory of Open Access Journals (Sweden)

    Xiang Gao

    Full Text Available Hippocampal injury-associated learning and memory deficits are frequent hallmarks of brain trauma and are the most enduring and devastating consequences following traumatic brain injury (TBI. Several reports, including our recent paper, showed that TBI brought on by a moderate level of controlled cortical impact (CCI induces immature newborn neuron death in the hippocampal dentate gyrus. In contrast, the majority of mature neurons are spared. Less research has been focused on these spared neurons, which may also be injured or compromised by TBI. Here we examined the dendrite morphologies, dendritic spines, and synaptic structures using a genetic approach in combination with immunohistochemistry and Golgi staining. We found that although most of the mature granular neurons were spared following TBI at a moderate level of impact, they exhibited dramatic dendritic beading and fragmentation, decreased number of dendritic branches, and a lower density of dendritic spines, particularly the mushroom-shaped mature spines. Further studies showed that the density of synapses in the molecular layer of the hippocampal dentate gyrus was significantly reduced. The electrophysiological activity of neurons was impaired as well. These results indicate that TBI not only induces cell death in immature granular neurons, it also causes significant dendritic and synaptic degeneration in pathohistology. TBI also impairs the function of the spared mature granular neurons in the hippocampal dentate gyrus. These observations point to a potential anatomic substrate to explain, in part, the development of posttraumatic memory deficits. They also indicate that dendritic damage in the hippocampal dentate gyrus may serve as a therapeutic target following TBI.

  4. Accumulation of Vesicle-Associated Human Tau in Distal Dendrites Drives Degeneration and Tau Secretion in an In Situ Cellular Tauopathy Model

    Directory of Open Access Journals (Sweden)

    Sangmook Lee

    2012-01-01

    Full Text Available We used a nontransgenic cellular tauopathy model in which individual giant neurons in the lamprey CNS (ABCs overexpress human tau isoforms cell autonomously to characterize the still poorly understood consequences of disease-associated tau processing in situ. In this model, tau colocalizes with endogenous microtubules and is nontoxic when expressed at low levels, but is misprocessed by a toxicity-associated alternative pathway when expressed above levels that saturate dendritic microtubules, causing abnormally phosphorylated, vesicle-associated tau to accumulate in ABC distal dendrites. This causes localized microtubule loss and eventually dendritic degeneration, which is preceded by tau secretion to the extracellular space. This sequence is reiterated at successively more proximal dendritic locations over time, suggesting that tau-induced dendritic degeneration is driven by distal dendritic accumulation of hyperphosphorylated, vesicle-associated tau perpetuated by localized microtubule loss. The implications for the diagnosis and treatment of human disease are discussed.

  5. Large-conductance calcium-dependent potassium channels prevent dendritic excitability in neocortical pyramidal neurons.

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    Benhassine, Narimane; Berger, Thomas

    2009-03-01

    Large-conductance calcium-dependent potassium channels (BK channels) are homogeneously distributed along the somatodendritic axis of layer 5 pyramidal neurons of the rat somatosensory cortex. The relevance of this conductance for dendritic calcium electrogenesis was studied in acute brain slices using somatodendritic patch clamp recordings and calcium imaging. BK channel activation reduces the occurrence of dendritic calcium spikes. This is reflected in an increased critical frequency of somatic spikes necessary to activate the distal initiation zone. Whilst BK channels repolarise the somatic spike, they dampen it only in the distal dendrite. Their activation reduces dendritic calcium influx via glutamate receptors. Furthermore, they prevent dendritic calcium electrogenesis and subsequent somatic burst discharges. However, the time window for coincident somatic action potential and dendritic input to elicit dendritic calcium events is not influenced by BK channels. Thus, BK channel activation in layer 5 pyramidal neurons affects cellular excitability primarily by establishing a high threshold at the distal action potential initiation zone.

  6. Curcumin prevents human dendritic cell response to immune stimulants

    International Nuclear Information System (INIS)

    Shirley, Shawna A.; Montpetit, Alison J.; Lockey, R.F.; Mohapatra, Shyam S.

    2008-01-01

    Curcumin, a compound found in the Indian spice turmeric, has anti-inflammatory and immunomodulatory properties, though the mechanism remains unclear. Dendritic cells (DCs) are important to generating an immune response and the effect of curcumin on human DCs has not been explored. The role curcumin in the DC response to bacterial and viral infection was investigated in vitro using LPS and Poly I:C as models of infection. CD14 + monocytes, isolated from human peripheral blood, were cultured in GM-CSF- and IL-4-supplemented medium to generate immature DCs. Cultures were incubated with curcumin, stimulated with LPS or Poly I:C and functional assays were performed. Curcumin prevents DCs from responding to immunostimulants and inducing CD4 + T cell proliferation by blocking maturation marker, cytokine and chemokine expression and reducing both migration and endocytosis. These data suggest a therapeutic role for curcumin as an immune suppressant

  7. Mitochondrial Calcium Dysregulation Contributes to Dendrite Degeneration Mediated by PD/LBD-Associated LRRK2 Mutants.

    Science.gov (United States)

    Verma, Manish; Callio, Jason; Otero, P Anthony; Sekler, Israel; Wills, Zachary P; Chu, Charleen T

    2017-11-15

    Mutations in leucine-rich repeat kinase 2 (LRRK2) contribute to development of late-onset familial Parkinson's disease (PD), with clinical features of motor and cognitive dysfunction indistinguishable from sporadic PD. Calcium dysregulation plays an important role in PD pathogenesis, but the mechanisms of neurodegeneration remain unclear. Recent reports indicate enhanced excitatory neurotransmission in cortical neurons expressing mutant LRRK2, which occurs before the well-characterized phenotype of dendritic shortening. As mitochondria play a major role in the rapid buffering of cytosolic calcium, we hypothesized that altered mitochondrial calcium handling contributes to dendritic retraction elicited by the LRRK2-G2019S and -R1441C mutations. In primary mouse cortical neurons, we observed increased depolarization-induced mitochondrial calcium uptake. We found that expression of mutant LRRK2 elicited transcriptional upregulation of the mitochondrial calcium uniporter (MCU) and the mitochondrial calcium uptake 1 protein (MICU1) with no change in levels of the mitochondrial calcium antiporter NCLX. Elevated MCU and MICU1 were also observed in LRRK2-mutated patient fibroblasts, along with increased mitochondrial calcium uptake, and in postmortem brains of sporadic PD/PDD patients of both sexes. Transcriptional upregulation of MCU and MICU1 was caused by activation of the ERK1/2 (MAPK3/1) pathway. Inhibiting ERK1/2 conferred protection against mutant LRRK2-induced neurite shortening. Pharmacological inhibitors or RNAi knockdown of MCU attenuated mitochondrial calcium uptake and dendritic/neuritic shortening elicited by mutant LRRK2, whereas expression of a constitutively active mutant of NCLX that enhances calcium export from mitochondria was neuroprotective. These data suggest that an increased susceptibility to mitochondrial calcium dysregulation contributes to dendritic injury in mutant LRRK2 pathogenesis. SIGNIFICANCE STATEMENT Cognitive dysfunction and dementia are

  8. Age-related macular degeneration: prevention and treatment. A review

    Directory of Open Access Journals (Sweden)

    K. A. Mirzabekova

    2014-07-01

    Full Text Available Age-related macular degeneration (AMD is a multifactorial disease. Age, light exposure, smoking, melanin levels and low-antioxidant diet are contributed to AMD development and progression. Cardiovascular disorders are of considerable importance as well. In macula, photoreceptor outer segments that are rich in polyunsaturated fatty acids (FA, particularly, docosahexaenoic acid (DHA, are susceptible to free radicals damage. High blood flow velocity and oxygen partial pressure as well as direct sunlight exposure induce oxidative processes. The source of free radicals in photoreceptor cells and retinal pigment epithelium (RPE is an extensive mitochondrial metabolism, photoreceptor outer segments phagocytosis, lipofuscin phototoxic activity and hemoglobin or protoporphyrin precursors photosensitization. Oxidative stress is considered as an universal component of cell depth in necrosis, apoptosis and toxic damage. Antioxidant protective system consists of enzymes (superoxide dismutase, glutathione peroxidase and catalase and non-enzymatic factors (ascorbic acid, alpha tocopherol, retinol, carotenoids. Specific antioxidant food supplement containing ascorbic acid (500 mg, vitamin E (400 IU and beta carotene (15 mg coupled with zinc (80 mg of zinc oxide and copper (2 mg of copper oxide results in 25 % decrease in late-stage AMD development rate. Amongst the agents that can protect retina from oxidative stress and AMD development, carotenoids are of special importance. Lutein and zeaxanthin containing in retina and lens screen blue light from central area of the retina. They also absorb blue light and inhibit free radicals generation thus preventing polyunsaturated FA light destruction. Association between lutein and zeaxanthin intake and late-stage AMD risk was revealed. Amongst the most important factors which deficiency favors macular degeneration are omega-3 FAs, i.e., DHA. DHA is the key component of visual pigment rhodopsin transformation. It

  9. Age-related macular degeneration: prevention and treatment. A review

    Directory of Open Access Journals (Sweden)

    K. A. Mirzabekova

    2014-01-01

    Full Text Available Age-related macular degeneration (AMD is a multifactorial disease. Age, light exposure, smoking, melanin levels and low-antioxidant diet are contributed to AMD development and progression. Cardiovascular disorders are of considerable importance as well. In macula, photoreceptor outer segments that are rich in polyunsaturated fatty acids (FA, particularly, docosahexaenoic acid (DHA, are susceptible to free radicals damage. High blood flow velocity and oxygen partial pressure as well as direct sunlight exposure induce oxidative processes. The source of free radicals in photoreceptor cells and retinal pigment epithelium (RPE is an extensive mitochondrial metabolism, photoreceptor outer segments phagocytosis, lipofuscin phototoxic activity and hemoglobin or protoporphyrin precursors photosensitization. Oxidative stress is considered as an universal component of cell depth in necrosis, apoptosis and toxic damage. Antioxidant protective system consists of enzymes (superoxide dismutase, glutathione peroxidase and catalase and non-enzymatic factors (ascorbic acid, alpha tocopherol, retinol, carotenoids. Specific antioxidant food supplement containing ascorbic acid (500 mg, vitamin E (400 IU and beta carotene (15 mg coupled with zinc (80 mg of zinc oxide and copper (2 mg of copper oxide results in 25 % decrease in late-stage AMD development rate. Amongst the agents that can protect retina from oxidative stress and AMD development, carotenoids are of special importance. Lutein and zeaxanthin containing in retina and lens screen blue light from central area of the retina. They also absorb blue light and inhibit free radicals generation thus preventing polyunsaturated FA light destruction. Association between lutein and zeaxanthin intake and late-stage AMD risk was revealed. Amongst the most important factors which deficiency favors macular degeneration are omega-3 FAs, i.e., DHA. DHA is the key component of visual pigment rhodopsin transformation. It

  10. Prolonged Prevention of Retinal Degeneration with Retinylamine Loaded Nanoparticles

    OpenAIRE

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

    2015-01-01

    Retinal degeneration impairs the vision of millions in all age groups worldwide. Increasing evidence suggests that the etiology of many retinal degenerative diseases is associated with impairment in biochemical reactions involved in the visual cycle, a metabolic pathway responsible for regeneration of the visual chromophore (11-cis-retinal). Inefficient clearance of toxic retinoid metabolites, especially all-trans-retinal, is considered responsible for photoreceptor cytotoxicity. Primary amin...

  11. Selection of probiotic bacteria for prevention of allergic diseases: immunomodulation of neonatal dendritic cells

    NARCIS (Netherlands)

    Niers, L. E. M.; Hoekstra, M. O.; Timmerman, H. M.; van Uden, N. O.; de Graaf, P. M. A.; Smits, H. H.; Kimpen, J. L. L.; Rijkers, G. T.

    2007-01-01

    Modification of intestinal microbiota early in life by administration of probiotic bacteria may be a potential approach to prevent allergic disease. To select probiotic bacteria for in vivo purposes, we investigated the capacity of probiotic bacteria to interact with neonatal dendritic cells (DC)

  12. Age related macular degeneration - modern diagnostic and therapeutic preventive approach

    OpenAIRE

    Gogelová, Blanka

    2009-01-01

    Age-related macular degeneration (AMD) is a disease associated with aging that gradually destroys sharp, central vision. Central vision is needed for seeing objects clearly and for common daily tasks such as reading and driving. AMD affects the macula, the part of the eye that alows seeing of fine details. AMD occurs in two form: dry and wet. In dry AMD, the light sensitive cells in the macula slowly break down. As fewer cells in the macula are able to function, people will see details less c...

  13. A systematic review on zinc for the prevention and treatment of age-related macular degeneration

    Science.gov (United States)

    Zinc is a potential candidate for the prevention and treatment of age-related macular degeneration (AMD) due to its high concentration in the retina and role as a cofactor for antioxidant enzymes. The objective of this work was to conduct a systematic review of studies that investigated dietary inta...

  14. Polygalae Radix Extract Prevents Axonal Degeneration and Memory Deficits in a Transgenic Mouse Model of Alzheimer's Disease.

    Science.gov (United States)

    Kuboyama, Tomoharu; Hirotsu, Keisuke; Arai, Tetsuya; Yamasaki, Hiroo; Tohda, Chihiro

    2017-01-01

    Memory impairments in Alzheimer's disease (AD) occur due to degenerated axons and disrupted neural networks. Since only limited recovery is possible after the destruction of neural networks, preventing axonal degeneration during the early stages of disease progression is necessary to prevent AD. Polygalae Radix (roots of Polygala tenuifolia ; PR) is a traditional herbal medicine used for sedation and amnesia. In this study, we aimed to clarify and analyze the preventive effects of PR against memory deficits in a transgenic AD mouse model, 5XFAD. 5XFAD mice demonstrated memory deficits at the age of 5 months. Thus, the water extract of Polygalae Radix (PR extract) was orally administered to 4-month-old 5XFAD mice that did not show signs of memory impairment. After consecutive administrations for 56 days, the PR extract prevented cognitive deficit and axon degeneration associated with the accumulation of amyloid β (Aβ) plaques in the perirhinal cortex of the 5XFAD mice. PR extract did not influence the formation of Aβ plaques in the brain of the 5XFAD mice. In cultured neurons, the PR extract prevented axonal growth cone collapse and axonal atrophy induced by Aβ. Additionally, it prevented Aβ-induced endocytosis at the growth cone of cultured neurons. Our previous study reported that endocytosis inhibition was enough to prevent Aβ-induced growth cone collapse, axonal degeneration, and memory impairments. Therefore, the PR extract possibly prevented axonal degeneration and memory impairment by inhibiting endocytosis. PR is the first preventive drug candidate for AD that inhibits endocytosis in neurons.

  15. Prevention and treatment of age-related macular degeneration: an update for pharmacists.

    Science.gov (United States)

    Marshall, Leisa L; Roach, J Michael

    2013-11-01

    Review the current recommendations for the prevention and treatment of age-related macular degeneration (AMD). Articles indexed in PubMed (National Library of Medicine), the Cochrane Reviews and Trials, Dynamed, and Iowa Drug Information Service (IDIS) in the last 10 years using the key words macular degeneration, agerelated macular degeneration (AMD), AMD and treatment, AMD and prevention. Sixty-nine published papers were reviewed, and criteria supporting the primary objective were used to identify useful resources. The literature included practice guidelines, original research articles, review articles, product prescribing information, and supplement product information for the prevention and treatment of AMD. AMD is a leading cause of visual impairment in older adults. At present there is no cure for advanced AMD, but intravitreal vascular endothelial growth factor inhibitors minimize and even reverse vision loss in patients with AMD of the neovascular type. In the Age-Related Eye Disease Study (AREDS), participants with intermediate AMD who received a supplement combination of vitamins C and E, beta-carotene, and zinc had a greater delay in progression to advanced AMD than those participants who received a portion of these supplements. In the second AREDS, AREDS2, the addition of lutein + zeaxanthin, docosahexaenoic acid (DHA) + eicosapentaenoic acid (EPA), or lutein + zeaxanthin and DHA + EPA to the complete AREDS formulation did not further reduce the risk of progression to advanced AMD. Subgroup analyses indicated that additional research with lutein + zeaxanthin supplementation is warranted as it was beneficial in participants with low dietary intake of lutein + zeaxanthin. A formulation without beta-carotene may be best for most patients, especially smokers or former smokers. Health care professionals will want to consider patient-specific information before recommending ocular health supplements.

  16. Prevention of age-related macular degeneration-like retinopathy by rapamycin in rats.

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    Kolosova, Nataliya G; Muraleva, Natalia A; Zhdankina, Anna A; Stefanova, Natalia A; Fursova, Anzhela Z; Blagosklonny, Mikhail V

    2012-08-01

    Age-related macular degeneration, a neurodegenerative and vascular retinal disease, is the most common cause of blindness in the Western countries. Evidence accumulates that target of rapamycin is involved in aging and age-related diseases, including neurodegeneration. The target of rapamycin inhibitor, rapamycin, suppresses the senescent cell phenotype and extends life span in diverse species, including mice. Rapamycin decreases senescence-associated phenotypes in retinal pigment epithelial cells in culture. Herein, we investigated the effect of rapamycin on spontaneous retinopathy in senescence-accelerated OXYS rats, an animal model of age-related macular degeneration. Rats were treated with either 0.1 or 0.5 mg/kg rapamycin, which was given orally as a food mixture. In a dose-dependent manner, rapamycin decreased the incidence and severity of retinopathy. Rapamycin improved some (but not all) histological abnormalities associated with retinopathy. Thus, in retinal pigment epithelial cell layers, rapamycin decreased nuclei heterogeneity and normalized intervals between nuclei. In photoreceptor cells, associated neurons, and radial glial cells, rapamycin prevented nuclear and cellular pyknosis. More important, rapamycin prevented destruction of ganglionar neurons in the retina. Rapamycin did not exert any adverse effects on the retina in control disease-free Wistar rats. Taken together, our data suggest the therapeutic potential of rapamycin for treatment and prevention of retinopathy. Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  17. Interventions for asymptomatic retinal breaks and lattice degeneration for preventing retinal detachment.

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    Wilkinson, Charles P

    2014-09-05

    Asymptomatic retinal breaks and lattice degeneration are visible lesions that are risk factors for later retinal detachment. Retinal detachments occur when fluid in the vitreous cavity passes through tears or holes in the retina and separates the retina from the underlying retinal pigment epithelium. Creation of an adhesion surrounding retinal breaks and lattice degeneration, with laser photocoagulation or cryotherapy, has been recommended as an effective means of preventing retinal detachment. This therapy is of value in the management of retinal tears associated with the symptoms of flashes and floaters and persistent vitreous traction upon the retina in the region of the retinal break, because such symptomatic retinal tears are associated with a high rate of progression to retinal detachment. Retinal tears and holes unassociated with acute symptoms and lattice degeneration are significantly less likely to be the sites of retinal breaks that are responsible for later retinal detachment. Nevertheless, treatment of these lesions frequently is recommended, in spite of the fact that the effectiveness of this therapy is unproven. The objective of this review was to assess the effectiveness and safety of techniques used to treat asymptomatic retinal breaks and lattice degeneration for the prevention of retinal detachment. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2014, Issue 2), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to February 2014), EMBASE (January 1980 to February 2014), PubMed (January 1948 to February 2014), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials

  18. Target-Derived Neurotrophins Coordinate Transcription and Transport of Bclw to Prevent Axonal Degeneration

    Science.gov (United States)

    Cosker, Katharina E.; Pazyra-Murphy, Maria F.; Fenstermacher, Sara J.

    2013-01-01

    Establishment of neuronal circuitry depends on both formation and refinement of neural connections. During this process, target-derived neurotrophins regulate both transcription and translation to enable selective axon survival or elimination. However, it is not known whether retrograde signaling pathways that control transcription are coordinated with neurotrophin-regulated actions that transpire in the axon. Here we report that target-derived neurotrophins coordinate transcription of the antiapoptotic gene bclw with transport of bclw mRNA to the axon, and thereby prevent axonal degeneration in rat and mouse sensory neurons. We show that neurotrophin stimulation of nerve terminals elicits new bclw transcripts that are immediately transported to the axons and translated into protein. Bclw interacts with Bax and suppresses the caspase6 apoptotic cascade that fosters axonal degeneration. The scope of bclw regulation at the levels of transcription, transport, and translation provides a mechanism whereby sustained neurotrophin stimulation can be integrated over time, so that axonal survival is restricted to neurons connected within a stable circuit. PMID:23516285

  19. Polygalae Radix Extract Prevents Axonal Degeneration and Memory Deficits in a Transgenic Mouse Model of Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Tomoharu Kuboyama

    2017-11-01

    Full Text Available Memory impairments in Alzheimer’s disease (AD occur due to degenerated axons and disrupted neural networks. Since only limited recovery is possible after the destruction of neural networks, preventing axonal degeneration during the early stages of disease progression is necessary to prevent AD. Polygalae Radix (roots of Polygala tenuifolia; PR is a traditional herbal medicine used for sedation and amnesia. In this study, we aimed to clarify and analyze the preventive effects of PR against memory deficits in a transgenic AD mouse model, 5XFAD. 5XFAD mice demonstrated memory deficits at the age of 5 months. Thus, the water extract of Polygalae Radix (PR extract was orally administered to 4-month-old 5XFAD mice that did not show signs of memory impairment. After consecutive administrations for 56 days, the PR extract prevented cognitive deficit and axon degeneration associated with the accumulation of amyloid β (Aβ plaques in the perirhinal cortex of the 5XFAD mice. PR extract did not influence the formation of Aβ plaques in the brain of the 5XFAD mice. In cultured neurons, the PR extract prevented axonal growth cone collapse and axonal atrophy induced by Aβ. Additionally, it prevented Aβ-induced endocytosis at the growth cone of cultured neurons. Our previous study reported that endocytosis inhibition was enough to prevent Aβ-induced growth cone collapse, axonal degeneration, and memory impairments. Therefore, the PR extract possibly prevented axonal degeneration and memory impairment by inhibiting endocytosis. PR is the first preventive drug candidate for AD that inhibits endocytosis in neurons.

  20. [Potential of melatonin for prevention of age-related macular degeneration: experimental study].

    Science.gov (United States)

    Stefanova, N A; Zhdankina, A A; Fursova, A Zh; Kolosova, N G

    2013-01-01

    Decline with age of the content of melatonin is considered as one of the leading mechanisms of aging and development of associated diseases, including age-related macular degeneration (AMD)--the disease, which becomes the most common cause of blindness and acuity of vision deterioration in elderly. The prospects of the use of melatonin in the prevention of AMD is being actively discussed, but as a rule on the basis of the results of the experiments on cells in retinal pigment epithelium (RPE). We showed previously that the senescence-accelerated OXYS rat is an adequate animal model of AMD, already used for identifying the relevant therapeutic targets. Here we have investigated the effect of Melatonin (Melaksen, 0,004 mg per kg--a dose equivalent to the recommended one for people) on the development of retinopathy similar to AMD in OXYS rats. Ophthalmoscopic examinations show that Melatonin supplementation decreased the incidence and severity of retinopathy and improved some (but not all) histological abnormalities associated with retinopathy. Thus, melatonin prevented the structural and functional changes in RPE cells, reduced the severity of microcirculatory disorders. Importantly, Melatonin prevented destruction of neurosensory cells, associative and gangliolar neurons in the retina. Taken together, our data suggest the therapeutic potential of Melatonin for treatment and prevention of AMD.

  1. Tenascin-C Prevents Articular Cartilage Degeneration in Murine Osteoarthritis Models.

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    Matsui, Yuriyo; Hasegawa, Masahiro; Iino, Takahiro; Imanaka-Yoshida, Kyoko; Yoshida, Toshimichi; Sudo, Akihiro

    2018-01-01

    Objective The objective of this study was to determine whether intra-articular injections of tenascin-C (TNC) could prevent cartilage damage in murine models of osteoarthritis (OA). Design Fluorescently labeled TNC was injected into knee joints and its distribution was examined at 1 day, 4 days, 1 week, 2 weeks, and 4 weeks postinjection. To investigate the effects of TNC on cartilage degeneration after surgery to knee joints, articular spaces were filled with 100 μg/mL (group I), 10 μg/mL (group II) of TNC solution, or control (group III). TNC solution of 10 μg/mL was additionally injected twice after 3 weeks (group IV) or weekly after 1 week, 2 weeks, and 3 weeks (group V). Joint tissues were histologically assessed using the Mankin score and the modified Chambers system at 2 to 8 weeks after surgery. Results Exogenous TNC was maintained in the cartilage and synovium for 1 week after administration. Histological scores in groups I and II were better than scores in group III at 4 and 6 weeks, but progressive cartilage damage was seen in all groups 8 weeks postoperatively. Sequential TNC injections (groups IV and V) showed significantly better Mankin score than single injection (group II) at 8 weeks. Conclusion TNC administered exogenously remained in the cartilage of knee joints for 1 week, and could decelerate articular cartilage degeneration in murine models of OA. We also showed that sequential administration of TNC was more effective than a single injection. TNC could be an important molecule for prevention of articular cartilage damage.

  2. Valproic acid prevents retinal degeneration in a murine model of normal tension glaucoma.

    Science.gov (United States)

    Kimura, Atsuko; Guo, Xiaoli; Noro, Takahiko; Harada, Chikako; Tanaka, Kohichi; Namekata, Kazuhiko; Harada, Takayuki

    2015-02-19

    Valproic acid (VPA) is widely used for treatment of epilepsy, mood disorders, migraines and neuropathic pain. It exerts its therapeutic benefits through modulation of multiple mechanisms including regulation of gamma-aminobutyric acid and glutamate neurotransmissions, activation of pro-survival protein kinases and inhibition of histone deacetylase. The evidence for neuroprotective properties associated with VPA is emerging. Herein, we investigated the therapeutic potential of VPA in a mouse model of normal tension glaucoma (NTG). Mice with glutamate/aspartate transporter gene deletion (GLAST KO mice) demonstrate progressive retinal ganglion cell (RGC) loss and optic nerve degeneration without elevated intraocular pressure, and exhibit glaucomatous pathology including glutamate neurotoxicity and oxidative stress in the retina. VPA (300mg/kg) or vehicle (PBS) was administered via intraperitoneal injection in GLAST KO mice daily for 2 weeks from the age of 3 weeks, which coincides with the onset of glaucomatous retinal degeneration. Following completion of the treatment period, the vehicle-treated GLAST KO mouse retina showed significant RGC death. Meanwhile, VPA treatment prevented RGC death and thinning of the inner retinal layer in GLAST KO mice. In addition, in vivo electrophysiological analyses demonstrated that visual impairment observed in vehicle-treated GLAST KO mice was ameliorated with VPA treatment, clearly establishing that VPA beneficially affects both histological and functional aspects of the glaucomatous retina. We found that VPA reduces oxidative stress induced in the GLAST KO retina and stimulates the cell survival signalling pathway associated with extracellular-signal-regulated kinases (ERK). This is the first study to report the neuroprotective effects of VPA in an animal model of NTG. Our findings raise intriguing possibilities that the widely prescribed drug VPA may be a novel candidate for treatment of glaucoma. Copyright © 2015 Elsevier

  3. Inhibition of the Rho/ROCK pathway prevents neuronal degeneration in vitro and in vivo following methylmercury exposure

    International Nuclear Information System (INIS)

    Fujimura, Masatake; Usuki, Fusako; Kawamura, Miwako; Izumo, Shuji

    2011-01-01

    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 associated 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.

  4. Do Nutritional Supplements Have a Role in Age Macular Degeneration Prevention?

    Directory of Open Access Journals (Sweden)

    Maria D. Pinazo-Durán

    2014-01-01

    Full Text Available Purpose. To review the proposed pathogenic mechanisms of age macular degeneration (AMD, as well as the role of antioxidants (AOX and omega-3 fatty acids (ω-3 supplements in AMD prevention. Materials and Methods. Current knowledge on the cellular/molecular mechanisms of AMD and the epidemiologic/experimental studies on the effects of AOX and ω-3 were addressed all together with the scientific evidence and the personal opinion of professionals involved in the Retina Group of the OFTARED (Spain. Results. High dietary intakes of ω-3 and macular pigments lutein/zeaxanthin are associated with lower risk of prevalence and incidence in AMD. The Age-Related Eye Disease study (AREDS showed a beneficial effect of high doses of vitamins C, E, beta-carotene, and zinc/copper in reducing the rate of progression to advanced AMD in patients with intermediate AMD or with one-sided late AMD. The AREDS-2 study has shown that lutein and zeaxanthin may substitute beta-carotene because of its potential relationship with increased lung cancer incidence. Conclusion. Research has proved that elder people with poor diets, especially with low AOX and ω-3 micronutrients intake and subsequently having low plasmatic levels, are more prone to developing AMD. Micronutrient supplementation enhances antioxidant defense and healthy eyes and might prevent/retard/modify AMD.

  5. Small heat shock protein αA-crystallin prevents photoreceptor degeneration in experimental autoimmune uveitis.

    Directory of Open Access Journals (Sweden)

    Narsing A Rao

    Full Text Available The small heat shock protein, αA-crystallin null (αA-/- mice are known to be more prone to retinal degeneration than the wild type mice in Experimental Autoimmune Uveoretinitis (EAU. In this report we demonstrate that intravenous administration of αA preserves retinal architecture and prevents photoreceptor damage in EAU. Interestingly, only αA and not αB-crystallin (αB, a closely related small heat shock protein works, pointing to molecular specificity in the observed retinal protection. The possible involvement of αA in retinal protection through immune modulation is corroborated by adaptive transfer experiments, (employing αA-/- and wild type mice with EAU as donors and Rag2-/- as the recipient mice, which indicate that αA protects against the autoimmune challenge by modulating the systemic B and T cell immunity. We show that αA administration causes marked reduction in Th1 cytokines (TNF-α, IL-12 and IFN-γ, both in the retina and in the spleen; notably, IL-17 was only reduced in the retina suggesting local intervention. Importantly, expression of Toll-like receptors and their associated adaptors is also inhibited suggesting that αA protection, against photoreceptor loss in EAU, is associated with systemic suppression of both the adaptive and innate immune responses.

  6. Small heat shock protein αA-crystallin prevents photoreceptor degeneration in experimental autoimmune uveitis.

    Science.gov (United States)

    Rao, Narsing A; Saraswathy, Sindhu; Pararajasegaram, Geeta; Bhat, Suraj P

    2012-01-01

    The small heat shock protein, αA-crystallin null (αA-/-) mice are known to be more prone to retinal degeneration than the wild type mice in Experimental Autoimmune Uveoretinitis (EAU). In this report we demonstrate that intravenous administration of αA preserves retinal architecture and prevents photoreceptor damage in EAU. Interestingly, only αA and not αB-crystallin (αB), a closely related small heat shock protein works, pointing to molecular specificity in the observed retinal protection. The possible involvement of αA in retinal protection through immune modulation is corroborated by adaptive transfer experiments, (employing αA-/- and wild type mice with EAU as donors and Rag2-/- as the recipient mice), which indicate that αA protects against the autoimmune challenge by modulating the systemic B and T cell immunity. We show that αA administration causes marked reduction in Th1 cytokines (TNF-α, IL-12 and IFN-γ), both in the retina and in the spleen; notably, IL-17 was only reduced in the retina suggesting local intervention. Importantly, expression of Toll-like receptors and their associated adaptors is also inhibited suggesting that αA protection, against photoreceptor loss in EAU, is associated with systemic suppression of both the adaptive and innate immune responses.

  7. [Prevention and preventive therapy of age-related macular degeneration through the beneficial effect of treatment of endothelial dysfunction].

    Science.gov (United States)

    Fischer, Tamás

    2006-12-24

    The beneficial effect achieved by the treatment of endothelial dysfunction in chronic cardiovascular diseases is already an evidence belonging to the basic treatment of the disease. Given the fact that the vascular system is uniform and consubstantial both physiologically, pathophysiologically and in terms of therapy, and that it plays a key role in age-related macular degeneration (AMD) - a disease leading to tragic loss of vision with its etiology and therapy being unknown -, endothelial dysfunction should be treated. The pleiotropic effects of ACE-inhibitors, AR-blockers and statins help to restitute the balance between vasodilators and vasoconstrictors in endothelial dysfunction caused by oxidative stress, the balance of growth factors and their inhibitors, pro- and anti-inflammatory substances and prothrombotic and fibrinolytic factors, inhibit the formation of oxidative stress and its harmful effects; while aspirin with its pleiotropic effects acting as an antiaggregation substance on platelets helps to set the endothelial layer back to its normal balance regarding its vasodilating, antithrombotic, anti-adhesive and anti-inflammatory functions. For the above reasons it is suggested that, as a part of long term primary and/or secondary prevention, the following groups of patients with AMD receive - taking into consideration all possible side effects - ACE-inhibitor and/or AR-blocker and statin and aspirin treatment: 1) those without maculopathy but being over the age of 50 and having risk factors inducing endothelial dysfunction; 2) those, who already developed AMD in one eye as a prevention in the second, unaffected eye; and 3) those patients who developed AMD in both eyes in order to ameliorate or merely slow the progression of the disease. Besides, it is advisory to inhibit AMD risk factors inducing oxidative stress with consecutive endothelial dysfunction.

  8. Low Vision Depression Prevention Trial in Age-Related Macular Degeneration

    Science.gov (United States)

    Rovner, Barry W.; Casten, Robin J.; Hegel, Mark T.; Massof, Robert W.; Leiby, Benjamin E.; Ho, Allen C.; Tasman, William S.

    2014-01-01

    Purpose To compare the efficacy of behavior activation (BA) + low vision rehabilitation (LVR) with supportive therapy (ST) + LVR to prevent depressive disorders in patients with age-related macular degeneration (AMD). Design Single-masked, attention-controlled, randomized, clinical trial with outcome assessment at 4 months. Participants Patients with AMD and subsyndromal depressive symptoms attending retina practices (n = 188). Interventions Before randomization, all subjects had 2 outpatient LVR visits, and were then randomized to in-home BA+LVR or ST+LVR. Behavior activation is a structured behavioral treatment that aims to increase adaptive behaviors and achieve valued goals. Supportive therapy is a nondirective, psychological treatment that provides emotional support and controls for attention. Main Outcome Measures The Diagnostic and Statistical Manual IV defined depressive disorder based on the Patient Health Questionnaire-9 (primary outcome), Activities Inventory, National Eye Institute Vision Function Questionnaire–25 plus Supplement (NEI-VFQ), and NEI-VFQ quality of life (secondary outcomes). Results At 4 months, 11 BA+LVR subjects (12.6%) and 18 ST+LVR subjects (23.4%) developed a depressive disorder (relative risk [RR], 0.54; 95% CI, 0.27–1.06; P = 0.067). In planned adjusted analyses the RR was 0.51 (95% CI, 0.27–0.98; P = 0.04). A mediational analysis suggested that BA+LVR prevented depression to the extent that it enabled subjects to remain socially engaged. In addition, BA+LVR was associated with greater improvements in functional vision than ST+LVR, although there was no significant between-group difference. There was no significant change or between-group difference in quality of life. Conclusions An integrated mental health and low vision intervention halved the incidence of depressive disorders relative to standard outpatient LVR in patients with AMD. As the population ages, the number of persons with AMD and the adverse effects of comorbid

  9. Low vision depression prevention trial in age-related macular degeneration: a randomized clinical trial.

    Science.gov (United States)

    Rovner, Barry W; Casten, Robin J; Hegel, Mark T; Massof, Robert W; Leiby, Benjamin E; Ho, Allen C; Tasman, William S

    2014-11-01

    To compare the efficacy of behavior activation (BA) + low vision rehabilitation (LVR) with supportive therapy (ST) + LVR to prevent depressive disorders in patients with age-related macular degeneration (AMD). Single-masked, attention-controlled, randomized, clinical trial with outcome assessment at 4 months. Patients with AMD and subsyndromal depressive symptoms attending retina practices (n = 188). Before randomization, all subjects had 2 outpatient LVR visits, and were then randomized to in-home BA+LVR or ST+LVR. Behavior activation is a structured behavioral treatment that aims to increase adaptive behaviors and achieve valued goals. Supportive therapy is a nondirective, psychological treatment that provides emotional support and controls for attention. The Diagnostic and Statistical Manual IV defined depressive disorder based on the Patient Health Questionnaire-9 (primary outcome), Activities Inventory, National Eye Institute Vision Function Questionnaire-25 plus Supplement (NEI-VFQ), and NEI-VFQ quality of life (secondary outcomes). At 4 months, 11 BA+LVR subjects (12.6%) and 18 ST+LVR subjects (23.4%) developed a depressive disorder (relative risk [RR], 0.54; 95% CI, 0.27-1.06; P = 0.067). In planned adjusted analyses the RR was 0.51 (95% CI, 0.27-0.98; P = 0.04). A mediational analysis suggested that BA+LVR prevented depression to the extent that it enabled subjects to remain socially engaged. In addition, BA+LVR was associated with greater improvements in functional vision than ST+LVR, although there was no significant between-group difference. There was no significant change or between-group difference in quality of life. An integrated mental health and low vision intervention halved the incidence of depressive disorders relative to standard outpatient LVR in patients with AMD. As the population ages, the number of persons with AMD and the adverse effects of comorbid depression will increase. Promoting interactions between ophthalmology, optometry

  10. Characteristics of choroidal neovascularization in the complications of age-related macular degeneration prevention trial.

    Science.gov (United States)

    Maguire, Maureen G; Alexander, Judith; Fine, Stuart L

    2008-09-01

    To describe the characteristics of incident choroidal neovascularization (CNV) in observed and treated eyes in the Complications of Age-related Macular Degeneration Prevention Trial (CAPT). Cross-sectional descriptive study within a multicenter, randomized clinical trial. Patients who developed CNV during CAPT follow-up. Inclusion criteria for CAPT specified bilateral large drusen (>or=10 drusen at least 125 micro), visual acuity >or=20/40 in each eye, and age >or=50. Exclusion criteria included CNV and geographic atrophy >1 Macular Photocoagulation Study (MPS) disc area or within 500 micro of the foveal center. One eye of each person was selected randomly for low-intensity laser treatment and the contralateral eye was observed. Fluorescein angiography was performed at baseline, annually for >or=5 years, and whenever there were symptoms of CNV. Trained readers at the CAPT Photograph Reading Center assessed color stereo photographs and angiogram negatives to identify CNV. Choroidal neovascularization was classified by type (predominantly classic CNV, minimally classic CNV, occult only CNV, or scar), location, and area. Visual acuity was measured by certified examiners. Symmetry of characteristics between eyes of bilaterally affected patients was examined. Choroidal neovascularization developed in 282 eyes of 225 patients. At the time of detection, 192 (68%) of the lesions were occult only, 153 (54%) were subfoveal, and 157 (56%) were or=20/40 in 123 (69%) of 179 eyes with visual acuity measured at the time of detection. Choroidal neovascularization developed in both eyes in 57 patients (25%) during CAPT follow-up. Lesions in eyes of bilaterally affected patients were no more similar to each other than affected eyes in 2 different patients. When patients are monitored closely, many CNV lesions can be detected outside of the fovea and when they are relatively small. Early detection may lead to improved long-term visual acuity.

  11. ROLE OF DIETARY SUPPLEMENTATION IN PREVENTING PROGRESSION OF AGE-RELATED MACULAR DEGENERATION

    Directory of Open Access Journals (Sweden)

    N. A. Ermakova

    2016-01-01

    Full Text Available Age-related macular degeneration (AMD is a chronic, progressive, degenerative eye disease affecting the central retina. It is the leading cause of blindness among individuals of 65 years and older. In the early stage patients have drusen and/or alterations of pigmentation in the macular region. This disease can progress to geographic atrophy and/or choroidal neovascularization. It has been shown that oxidative stress and hypoxia are important in the pathogenesis of AMD. Patients may gain some visual improvement with inhibitors of vascular endothelial growth factor, but complete restoration of visual function is achieved only in small cases. No effective therapies are known for atrophic AMD. Many large observational studies have shown that dietary antioxidant supplementation is beneficial in preventing the progression of AMD from early to late stages. The Age-Related Eye Disease Study (AREDS demonstrated that daily oral supplementation with vitamins C (500 mg and E (400 IU, beta carotene (15 mg, zinc (80 mg and copper (2 mg reduced the risk of progression to advanced AMD by 25% at 5 years. In primary analyses AREDS II failed to show further reduce of this risk by addition of lutein (10 mg and zeaxanthin (2mg, or/and omega-3 long-chain polyunsaturated fatty acids [docosahexaenoic acid (350 mg DHA and eicosapentaenoic acid 650 mg (EPA] to the AREDS formulation. But there was no true placebo group. The simultaneous administration of beta carotene, lutein and zeaxanthin may suppress tissue level of the both laters because of competitive absorption of carotenoids. Subgroup analyses revealed that dietary supplementation with lutein, zeaxanthin and AREDS formulation without beta carotene may reduce the risk of progression to advanced AMD.The LUNA (Lutein nutrition effects measured by autofluorescence study demonstrated that supplementation with lutein (12 mg, zeaxanthin (1 mg, vitamin C (120 mg, vitamin E (17,6 mg, zinc (10 mg, selenium (40 mg resulted

  12. Scanning Ultrasound (SUS Causes No Changes to Neuronal Excitability and Prevents Age-Related Reductions in Hippocampal CA1 Dendritic Structure in Wild-Type Mice.

    Directory of Open Access Journals (Sweden)

    Robert John Hatch

    Full Text Available Scanning ultrasound (SUS is a noninvasive approach that has recently been shown to ameliorate histopathological changes and restore memory functions in an Alzheimer's disease mouse model. Although no overt neuronal damage was reported, the short- and long-term effects of SUS on neuronal excitability and dendritic tree morphology had not been investigated. To address this, we performed patch-clamp recordings from hippocampal CA1 pyramidal neurons in wild-type mice 2 and 24 hours after a single SUS treatment, and one week and 3 months after six weekly SUS treatments, including sham treatments as controls. In both treatment regimes, no changes in CA1 neuronal excitability were observed in SUS-treated neurons when compared to sham-treated neurons at any time-point. For the multiple treatment groups, we also determined the dendritic morphology and spine densities of the neurons from which we had recorded. The apical trees of sham-treated neurons were reduced at the 3 month time-point when compared to one week; however, surprisingly, no longitudinal change was detected in the apical dendritic trees of SUS-treated neurons. In contrast, the length and complexity of the basal dendritic trees were not affected by SUS treatment at either time-point. The apical dendritic spine densities were reduced, independent of the treatment group, at 3 months compared to one week. Collectively, these data suggest that ultrasound can be employed to prevent an age-associated loss of dendritic structure without impairing neuronal excitability.

  13. Preventive and therapeutic effects of SkQ1-containing Visomitin eye drops against light-induced retinal degeneration.

    Science.gov (United States)

    Novikova, Yu P; Gancharova, O S; Eichler, O V; Philippov, P P; Grigoryan, E N

    2014-10-01

    The human retina is constantly affected by light of varying intensity, this being especially true for photoreceptor cells and retinal pigment epithelium. Traditionally, photoinduced damages of the retina are induced by visible light of high intensity in albino rats using the LIRD (light-induced retinal degeneration) model. This model allows study of pathological processes in the retina and the search for retinoprotectors preventing retinal photodamage. In addition, the etiology and mechanisms of retina damage in the LIRD model have much in common with the mechanisms of the development of age-related retinal disorders, in particular, with age-related macular degeneration (AMD). We have studied preventive and therapeutic effects of Visomitin eye drops (based on the mitochondria-targeted antioxidant SkQ1) on albino rat retinas damaged by bright light. In the first series of experiments, rats receiving Visomitin for two weeks prior to illumination demonstrated significantly less expressed atrophic and degenerative changes in the retina compared to animals receiving similar drops with no SkQ1. In the second series, the illuminated rats were treated for two weeks with Visomitin or similar drops without SkQ1. The damaged retinas of the experimental animals were repaired much more effectively than those of the control animals. Therefore, we conclude that Visomitin SkQ1-containing eye drops have pronounced preventive and therapeutic effects on the photodamaged retina and might be recommended as a photoprotector and a pharmaceutical preparation for the treatment of AMD in combination with conventional medicines.

  14. Regulation of dendrite growth and maintenance by exocytosis

    OpenAIRE

    Peng, Yun; Lee, Jiae; Rowland, Kimberly; Wen, Yuhui; Hua, Hope; Carlson, Nicole; Lavania, Shweta; Parrish, Jay Z.; Kim, Michael D.

    2015-01-01

    Dendrites lengthen by several orders of magnitude during neuronal development, but how membrane is allocated in dendrites to facilitate this growth remains unclear. Here, we report that Ras opposite (Rop), the Drosophila ortholog of the key exocytosis regulator Munc18-1 (also known as STXBP1), is an essential factor mediating dendrite growth. Neurons with depleted Rop function exhibit reduced terminal dendrite outgrowth followed by primary dendrite degeneration, suggestive of differential req...

  15. Antioxidant vitamin and mineral supplements for preventing age-related macular degeneration.

    Science.gov (United States)

    Evans, Jennifer R; Lawrenson, John G

    2017-07-30

    There is inconclusive evidence from observational studies to suggest that people who eat a diet rich in antioxidant vitamins (carotenoids, vitamins C, and E) or minerals (selenium and zinc) may be less likely to develop age-related macular degeneration (AMD). To determine whether or not taking antioxidant vitamin or mineral supplements, or both, prevent the development of AMD. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2017, Issue 2), MEDLINE Ovid (1946 to 29 March 2017), Embase Ovid (1947 to 29 March 2017), AMED (Allied and Complementary Medicine Database) (1985 to 29 March 2017), OpenGrey (System for Information on Grey Literature in Europe) (www.opengrey.eu/); searched 29 March 2017, the ISRCTN registry (www.isrctn.com/editAdvancedSearch); searched 29 March 2017, ClinicalTrials.gov (www.clinicaltrials.gov); searched 29 March 2017 and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en); searched 29 March 2017. We did not use any date or language restrictions in the electronic searches for trials. We included all randomised controlled trials (RCTs) comparing an antioxidant vitamin or mineral supplement (alone or in combination) to control. Both review authors independently assessed risk of bias in the included studies and extracted data. One author entered data into RevMan 5; the other author checked the data entry. We pooled data using a fixed-effect model. We graded the certainty of the evidence using GRADE. We included a total of five RCTs in this review with data available for 76,756 people. The trials were conducted in Australia, Finland, and the USA, and investigated vitamin C, vitamin E, beta-carotene, and multivitamin supplements. All trials were judged to be at low risk of bias.Four studies reported the comparison of vitamin E with placebo. Average treatment and follow-up duration ranged from 4 to 10 years. Data were

  16. Laser treatment of drusen to prevent progression to advanced age-related macular degeneration.

    Science.gov (United States)

    Virgili, Gianni; Michelessi, Manuele; Parodi, Maurizio B; Bacherini, Daniela; Evans, Jennifer R

    2015-10-23

    Drusen are amorphous yellowish deposits beneath the sensory retina. People with drusen, particularly large drusen, are at higher risk of developing age-related macular degeneration (AMD). The most common complication in AMD is choroidal neovascularisation (CNV), the growth of new blood vessels in the centre of the macula. The risk of CNV is higher among people who are already affected by CNV in one eye.It has been observed clinically that laser photocoagulation of drusen leads to their disappearance and may prevent the occurrence of advanced disease (CNV or geographic atrophy) associated with visual loss. To examine the effectiveness and adverse effects of laser photocoagulation of drusen in AMD. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2015, Issue 7), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to August 2015), EMBASE (January 1980 to August 2015), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to August 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 3 August 2015. Randomised controlled trials (RCTs) of laser treatment of drusen in AMD in which laser treatment had been compared with no intervention or sham treatment. Two types of trials were included. Some trials studied one eye of each participant (unilateral studies); other studies recruited participants with bilateral drusen and randomised one eye to photocoagulation or control and the fellow eye to the other group. Two review authors independently selected studies and extracted data. We pooled data from unilateral and bilateral

  17. Edaravone Prevents Retinal Degeneration in Adult Mice Following Optic Nerve Injury.

    Science.gov (United States)

    Akiyama, Goichi; Azuchi, Yuriko; Guo, Xiaoli; Noro, Takahiko; Kimura, Atsuko; Harada, Chikako; Namekata, Kazuhiko; Harada, Takayuki

    2017-09-01

    To assess the therapeutic potential of edaravone, a free radical scavenger that is used for the treatment of acute brain infarction and amyotrophic lateral sclerosis, in a mouse model of optic nerve injury (ONI). Two microliters of edaravone (7.2 mM) or vehicle were injected intraocularly 3 minutes after ONI. Optical coherence tomography, retrograde labeling of retinal ganglion cells (RGCs), histopathology, and immunohistochemical analyses of phosphorylated apoptosis signal-regulating kinase-1 (ASK1) and p38 mitogen-activated protein kinase (MAPK) in the retina were performed after ONI. Reactive oxygen species (ROS) levels were assessed with a CellROX Green Reagent. Edaravone ameliorated ONI-induced ROS production, RGC death, and inner retinal degeneration. Also, activation of the ASK1-p38 MAPK pathway that induces RGC death following ONI was suppressed with edaravone treatment. The results of this study suggest that intraocular administration of edaravone may be a useful treatment for posttraumatic complications.

  18. Prevention and Treatment of Spontaneous Mammary Carcinoma with Dendritic Tumor Fusion Cell Vaccine

    National Research Council Canada - National Science Library

    Gong, Jianlin

    2002-01-01

    In the present study, the prevention of cancer development by vaccination with fusion cells was evaluated In a genetically engineered murine model which develops spontaneous mammary carcinomas. The mice (MMT...

  19. Targeted delivery of antigen to intestinal dendritic cells induces oral tolerance and prevents autoimmune diabetes in NOD mice.

    Science.gov (United States)

    Chen, Yulin; Wu, Jie; Wang, Jiajia; Zhang, Wenjing; Xu, Bohui; Xu, Xiaojun; Zong, Li

    2018-03-15

    The intestinal immune system is an ideal target to induce immune tolerance physiologically. However, the efficiency of oral protein antigen delivery is limited by degradation of the antigen in the gastrointestinal tract and poor uptake by antigen-presenting cells. Gut dendritic cells (DCs) are professional antigen-presenting cells that are prone to inducing antigen-specific immune tolerance. In this study, we delivered the antigen heat shock protein 65-6×P277 (H6P) directly to the gut DCs of NOD mice through oral vaccination with H6P-loaded targeting nanoparticles (NPs), and investigated the ability of this antigen to induce immune tolerance to prevent autoimmune diabetes in NOD mice. A targeting NP delivery system was developed to encapsulate H6P, and the ability of this system to protect and facilitate H6P delivery to gut DCs was assessed. NOD mice were immunised with H6P-loaded targeting NPs orally once a week for 7 weeks and the onset of diabetes was assessed by monitoring blood glucose levels. H6P-loaded targeting NPs protected the encapsulated H6P from degradation in the gastrointestinal tract environment and significantly increased the uptake of H6P by DCs in the gut Peyer's patches (4.1 times higher uptake compared with the control H6P solution group). Oral vaccination with H6P-loaded targeting NPs induced antigen-specific T cell tolerance and prevented diabetes in 100% of NOD mice. Immune deviation (T helper [Th]1 to Th2) and CD4 + CD25 + FOXP3 + regulatory T cells were found to participate in the induction of immune tolerance. In this study, we successfully induced antigen-specific T cell tolerance and prevented the onset of diabetes in NOD mice. To our knowledge, this is the first attempt at delivering antigen to gut DCs using targeting NPs to induce T cell tolerance.

  20. Sirtuin 6 prevents matrix degradation through inhibition of the NF-κB pathway in intervertebral disc degeneration

    International Nuclear Information System (INIS)

    Kang, Liang; Hu, Jia; Weng, Yuxiong; Jia, Jie; Zhang, Yukun

    2017-01-01

    Intervertebral disc degeneration (IDD) is marked by imbalanced metabolism of the extracellular matrix (ECM) in the nucleus pulposus (NP) of intervertebral discs. This study aimed to determine whether sirtuin 6 (SIRT6), a member of the sirtuin family of nicotinamide adenine dinucleotide-dependent deacetylases, protects the NP from ECM degradation in IDD. Our study showed that expression of SIRT6 markedly decreased during IDD progression. Overexpression of wild-type SIRT6, but not a catalytically inactive mutant, prevented IL-1β-induced NP ECM degradation. SIRT6 depletion by RNA interference in NP cells caused ECM degradation. Moreover, SIRT6 physically interacted with nuclear factor-κB (NF-κB) catalytic subunit p65, transcriptional activity of which was significantly suppressed by SIRT6 overexpression. These results suggest that SIRT6 prevented NP ECM degradation in vitro via inhibiting NF-κB-dependent transcriptional activity and that this effect depended on its deacetylase activity. - Highlights: • SIRT6 expression is decreased in degenerative nucleus pulposus (NP) tissues. • SIRT6 overexpression lowers IL-1β-induced matrix degradation of NP. • SIRT6 inhibition induces matrix degradation of NP. • SIRT6 prevents matrix degradation of NP via the NF-κB signaling pathway.

  1. Sirtuin 6 prevents matrix degradation through inhibition of the NF-κB pathway in intervertebral disc degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Liang [Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China); Hu, Jia [Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China); Weng, Yuxiong [Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China); Jia, Jie [Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China); Zhang, Yukun, E-mail: zhangyukuncom@126.com [Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China)

    2017-03-15

    Intervertebral disc degeneration (IDD) is marked by imbalanced metabolism of the extracellular matrix (ECM) in the nucleus pulposus (NP) of intervertebral discs. This study aimed to determine whether sirtuin 6 (SIRT6), a member of the sirtuin family of nicotinamide adenine dinucleotide-dependent deacetylases, protects the NP from ECM degradation in IDD. Our study showed that expression of SIRT6 markedly decreased during IDD progression. Overexpression of wild-type SIRT6, but not a catalytically inactive mutant, prevented IL-1β-induced NP ECM degradation. SIRT6 depletion by RNA interference in NP cells caused ECM degradation. Moreover, SIRT6 physically interacted with nuclear factor-κB (NF-κB) catalytic subunit p65, transcriptional activity of which was significantly suppressed by SIRT6 overexpression. These results suggest that SIRT6 prevented NP ECM degradation in vitro via inhibiting NF-κB-dependent transcriptional activity and that this effect depended on its deacetylase activity. - Highlights: • SIRT6 expression is decreased in degenerative nucleus pulposus (NP) tissues. • SIRT6 overexpression lowers IL-1β-induced matrix degradation of NP. • SIRT6 inhibition induces matrix degradation of NP. • SIRT6 prevents matrix degradation of NP via the NF-κB signaling pathway.

  2. Interleukin-17 retinotoxicity is prevented by gene transfer of a soluble interleukin-17 receptor acting as a cytokine blocker: implications for age-related macular degeneration.

    Directory of Open Access Journals (Sweden)

    Daniel Ardeljan

    Full Text Available Age-related macular degeneration (AMD is a common yet complex retinal degeneration that causes irreversible central blindness in the elderly. Pathology is widely believed to follow loss of retinal pigment epithelium (RPE and photoreceptor degeneration. Here we report aberrant expression of interleukin-17A (IL17A and the receptor IL17RC in the macula of AMD patients. In vitro, IL17A induces RPE cell death characterized by the accumulation of cytoplasmic lipids and autophagosomes with subsequent activation of pro-apoptotic Caspase-3 and Caspase-9. This pathology is reduced by siRNA knockdown of IL17RC. IL17-dependent retinal degeneration in a mouse model of focal retinal degeneration can be prevented by gene therapy with adeno-associated virus vector encoding soluble IL17 receptor. This intervention rescues RPE and photoreceptors in a MAPK-dependent process. The IL17 pathway plays a key role in RPE and photoreceptor degeneration and could hold therapeutic potential in AMD.

  3. The FTLD risk factor TMEM106B and MAP6 control dendritic trafficking of lysosomes

    Science.gov (United States)

    Schwenk, Benjamin M; Lang, Christina M; Hogl, Sebastian; Tahirovic, Sabina; Orozco, Denise; Rentzsch, Kristin; Lichtenthaler, Stefan F; Hoogenraad, Casper C; Capell, Anja; Haass, Christian; Edbauer, Dieter

    2014-01-01

    TMEM106B is a major risk factor for frontotemporal lobar degeneration with TDP-43 pathology. TMEM106B localizes to lysosomes, but its function remains unclear. We show that TMEM106B knockdown in primary neurons affects lysosomal trafficking and blunts dendritic arborization. We identify microtubule-associated protein 6 (MAP6) as novel interacting protein for TMEM106B. MAP6 over-expression inhibits dendritic branching similar to TMEM106B knockdown. MAP6 knockdown fully rescues the dendritic phenotype of TMEM106B knockdown, supporting a functional interaction between TMEM106B and MAP6. Live imaging reveals that TMEM106B knockdown and MAP6 overexpression strongly increase retrograde transport of lysosomes in dendrites. Downregulation of MAP6 in TMEM106B knockdown neurons restores the balance of anterograde and retrograde lysosomal transport and thereby prevents loss of dendrites. To strengthen the link, we enhanced anterograde lysosomal transport by expressing dominant-negative Rab7-interacting lysosomal protein (RILP), which also rescues the dendrite loss in TMEM106B knockdown neurons. Thus, TMEM106B/MAP6 interaction is crucial for controlling dendritic trafficking of lysosomes, presumably by acting as a molecular brake for retrograde transport. Lysosomal misrouting may promote neurodegeneration in patients with TMEM106B risk variants. PMID:24357581

  4. Functional Outcomes of the Low Vision Depression Prevention Trial in Age-Related Macular Degeneration.

    Science.gov (United States)

    Deemer, Ashley D; Massof, Robert W; Rovner, Barry W; Casten, Robin J; Piersol, Catherine V

    2017-03-01

    To compare the efficacy of behavioral activation (BA) plus low vision rehabilitation with an occupational therapist (OT-LVR) with supportive therapy (ST) on visual function in patients with age-related macular degeneration (AMD). Single-masked, attention-controlled, randomized clinical trial with AMD patients with subsyndromal depressive symptoms (n = 188). All subjects had two outpatient low vision rehabilitation optometry visits, then were randomized to in-home BA + OT-LVR or ST. Behavioral activation is a structured behavioral treatment aiming to increase adaptive behaviors and achieve valued goals. Supportive therapy is a nondirective, psychological treatment that provides emotional support and controls for attention. Functional vision was assessed with the activity inventory (AI) in which participants rate the difficulty level of goals and corresponding tasks. Participants were assessed at baseline and 4 months. Improvements in functional vision measures were seen in both the BA + OT-LVR and ST groups at the goal level (d = 0.71; d = 0.56 respectively). At the task level, BA + OT-LVR patients showed more improvement in reading, inside-the-home tasks and outside-the-home tasks, when compared to ST patients. The greatest effects were seen in the BA + OT-LVR group in subjects with a visual acuity ≥20/70 (d = 0.360 reading; d = 0.500 inside the home; d = 0.468 outside the home). Based on the trends of the AI data, we suggest that BA + OT-LVR services, provided by an OT in the patient's home following conventional low vision optometry services, are more effective than conventional optometric low vision services alone for those with mild visual impairment. (ClinicalTrials.gov number, NCT00769015.).

  5. A systematic review on zinc for the prevention and treatment of age-related macular degeneration.

    Science.gov (United States)

    Vishwanathan, Rohini; Chung, Mei; Johnson, Elizabeth J

    2013-06-12

    The objective of this systematic review was to examine the evidence on zinc intake from foods and supplements in the primary prevention and treatment of AMD. Randomized controlled trials (RCTs), prospective cohort, retrospective cohort, and case-control studies that investigated zinc intake from foods and/or supplements, and AMD in men and women with a mean age of 50 years or older were included. Medline and Cochrane Central were searched from inception to February 2012 and November 2012, respectively. Data extraction and quality appraisal were done on all eligible studies. TEN STUDIES WERE INCLUDED: four RCTs, four prospective cohort, and two retrospective cohort studies. Age-related Eye Disease Study (AREDS) showed zinc treatment to significantly reduce the risk of progression to advanced AMD. The risk of visual acuity loss was of similar magnitude, but not statistically significant. Two RCTs reported statistically significant increases in visual acuity in early AMD patients and one RCT showed no effect of zinc treatment on visual acuity in advanced AMD patients. Results from six cohort studies on associations between zinc intake and incidence of AMD were inconsistent. Current evidence on zinc intake for the prevention of AMD is inconclusive. Based on the strength of AREDS, we can conclude that zinc treatment may be effective in preventing progression to advanced AMD. Zinc supplementation alone may not be sufficient to produce clinically meaningful changes in visual acuity.

  6. Laser treatment in patients with bilateral large drusen: the complications of age-related macular degeneration prevention trial.

    Science.gov (United States)

    2006-11-01

    To evaluate the efficacy and safety of low-intensity laser treatment in the prevention of visual acuity (VA) loss among participants with bilateral large drusen. Multicenter randomized clinical trial. One eye of each participant was assigned to treatment, and the contralateral eye was assigned to observation. A total of 1052 participants who had > or =10 large (>125 microm) drusen and VA> or =20/40 in each eye enrolled through 22 clinical centers. The initial laser treatment protocol specified 60 barely visible burns applied in a grid pattern within an annulus between 1500 and 2500 mum from the foveal center. At 12 months, eyes assigned to treatment that had sufficient drusen remaining were retreated with 30 burns by targeting drusen within an annulus between 1000 and 2000 mum from the foveal center. Proportion of eyes at 5 years with loss of > or =3 lines of VA from baseline. Secondary outcome measures included the development of choroidal neovascularization or geographic atrophy (GA), change in contrast threshold, change in critical print size, and incidence of ocular adverse events. At 5 years, 188 (20.5%) treated eyes and 188 (20.5%) observed eyes had VA scores > or = 3 lines worse than at the initial visit (P = 1.00). Cumulative 5-year incidence rates for treated and observed eyes were 13.3% and 13.3% (P = 0.95) for choroidal neovascularization and 7.4% and 7.8% (P = 0.64) for GA, respectively. The contrast threshold doubled in 23.9% of treated eyes and in 20.5% of observed eyes (P = 0.40). The critical print size doubled in 29.6% of treated eyes and in 28.4% of observed eyes (P = 0.70). Seven treated eyes and 14 observed eyes had an adverse event of a > or =6-line loss in VA in the absence of late age-related macular degeneration or cataract. As applied in the Complications of Age-Related Macular Degeneration Prevention Trial, low-intensity laser treatment did not demonstrate a clinically significant benefit for vision in eyes of people with bilateral large

  7. Development of a risk score for geographic atrophy in complications of the age-related macular degeneration prevention trial.

    Science.gov (United States)

    Ying, Gui-Shuang; Maguire, Maureen G

    2011-02-01

    To develop a risk score for developing geographic atrophy (GA) involving easily obtainable information among patients with bilateral large drusen. Cohort study within a multicenter randomized clinical trial. We included 1052 participants with ≥ 10 large (>125 μm) drusen and visual acuity ≥ 20/40 in each eye. In the Complications of Age-related Macular Degeneration (AMD) Prevention Trial (CAPT), 1 eye of each participant was randomly assigned to laser treatment and the contralateral eye was assigned to observation to evaluate whether laser treatment of drusen could prevent vision loss. Gradings by a reading center were used to identify: CAPT end point GA (total area of GA [>250 μm] > 1 disc area), GA (>175 μm) involving the foveal center (CGA), and GA of any size and location (any GA). Established risk factors (age, smoking status, hypertension, Age-related Eye Disease Study simple severity scale score), both with and without a novel risk factor (night vision score), were used in assigning risk points. The risk scores were evaluated for the ability to discriminate and calibrate GA risk. Development of end point GA, CGA, and any GA. Among 942 CAPT participants who completed 5 years of follow-up and did not have any GA at baseline, 6.8% participants developed CAPT end point GA, 9.6% developed CGA, and 34.4% developed any GA. The 5-year incidence of end point GA in 1 or both eyes of a participant increased with the 15-point GA risk score, from 0.6% for prevention of GA and for clinical assessment of GA risk in early AMD patients. Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  8. Kartogenin treatment prevented joint degeneration in a rodent model of osteoarthritis: A pilot study.

    Science.gov (United States)

    Mohan, Geetha; Magnitsky, Sergey; Melkus, Gerd; Subburaj, Karupppasamy; Kazakia, Galateia; Burghardt, Andrew J; Dang, Alexis; Lane, Nancy E; Majumdar, Sharmila

    2016-10-01

    Osteoarthritis (OA) is a major degenerative joint disease characterized by progressive loss of articular cartilage, synovitis, subchondral bone changes, and osteophyte formation. Currently there is no treatment for OA except temporary pain relief and end-stage joint replacement surgery. We performed a pilot study to determine the effect of kartogenin (KGN, a small molecule) on both cartilage and subchondral bone in a rat model of OA using multimodal imaging techniques. OA was induced in rats (OA and KGN treatment group) by anterior cruciate ligament transection (ACLT) surgery in the right knee joint. Sham surgery was performed on the right knee joint of control group rats. KGN group rats received weekly intra-articular injection of 125 μM KGN 1 week after surgery until week 12. All rats underwent in vivo magnetic resonance imaging (MRI) at 3, 6, and 12 weeks after surgery. Quantitative MR relaxation measures (T 1ρ and T 2 ) were determined to evaluate changes in articular cartilage. Cartilage and bone turnover markers (COMP and CTX-I) were determined at baseline, 3, 6, and 12 weeks. Animals were sacrificed at week 12 and the knee joints were removed for micro-computed tomography (micro-CT) and histology. KGN treatment significantly lowered the T 1ρ and T 2 relaxation times indicating decreased cartilage degradation. KGN treatment significantly decreased COMP and CTX-I levels indicating decreased cartilage and bone turnover rate. KGN treatment also prevented subchondral bone changes in the ACLT rat model of OA. Thus, kartogenin is a potential drug to prevent joint deterioration in post-traumatic OA. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1780-1789, 2016. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  9. Using vitamin E to prevent the impairment in behavioral test, cell loss and dendrite changes in medial prefrontal cortex induced by tartrazine in rats.

    Science.gov (United States)

    Rafati, Ali; Nourzei, Nasrin; Karbalay-Doust, Saied; Noorafshan, Ali

    2017-03-01

    Tartrazine is a food color that may adversely affect the nervous system. Vitamin E is a neuro-protective agent. This study aimed to evaluate the effects of tartrazine and vitamin E on the performance of rats in memory and learning tests as well as the structure of medial Prefrontal Cortex (mPFC). The rats were first divided into seven groups which received the followings for a period of seven weeks: distilled water, corn oil, vitamin E (100mg/kg/day), a low dose (50mg/kg/day) and a high dose (50mg/kg/day) of tartrazine with and without vitamin E. Behavioral tests were conducted and the brain was extracted for stereological methods The high dose of tartrazine decreased the exploration time of novel objects (Ptartrazine led into an increase in working and reference memory errors in acquisition and retention phases (eight-arm radial maze) compared to distilled water group (Ptartrazine induced a reduction in the volume of mPFC (∼13%) and its subdivision. Not only that, but the number of neurons and glial cells (∼14%) as well as the mushroom and thin spines per dendrite length declined. The length of dendrites per neuron also reduced in comparison to the distilled water group (Ptartrazine prevented the above-mentioned changes. An acceptable daily dose of tartrazine could induce impairment in spatial memory and dendrite structure. Moreover, a high dose of tartrazine may defect the visual memory, mPFC structure, the spatial memory and also cause dendrite changes. Vitamin E could prevent the behavioral and structural changes. Copyright © 2017 Elsevier GmbH. All rights reserved.

  10. [A new possible strategy for prevention and preventive treatment of age-related macular degeneration resting on recent clinical and pathophysiological observations].

    Science.gov (United States)

    Fischer, Tamás

    2009-03-15

    The beneficial effect achieved by the treatment of endothelial dysfunction in chronic cardiovascular diseases is already an evidence belonging to the basic treatment of the disease. Given the fact that the vascular system is uniform and consubstantial both physiologically, pathophysiologically and in terms of therapy, and that it plays a key role in age-related macular degeneration (AMD)--a disease leading to tragic loss of vision with its etiology and therapy being unknown--endothelial dysfunction should be treated. The pleiotropic effects of ACE-inhibitors, AR-blockers and statins and third generation beta blockers help to restitute the balance between vasodilators and vasoconstrictors in endothelial dysfunction caused by oxidative stress, the balance of growth factors and their inhibitors, pro- and anti-inflammatory substances and prothrombotic and fibrinolytic factors, inhibit the formation of oxidative stress and its harmful effects; while aspirin with its pleiotropic effects acting as an antiaggregation substance on platelets helps to set the endothelial layer back to its normal balance regarding its vasodilating, antithrombotic, antiadhesive and anti-inflammatory functions; trimetazidine as an adjuvant agent helps to normalize, to restore the disturbed metabolism of the retinal tissue functioning insufficiently, in the end. The angiotensin II receptor blocker telmisartan with its peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist effect inhibits the development of choroidal neovascularisation (CNV) and improves it clinically favourably. The third generation beta adrenergic receptor blocker carvedilol and nebivolol as well as the peroxisome proliferator-activated receptor-gamma agonist pioglitazone elicit their antioxidant vascular protective effects mitochondrially. For the above reasons it is suggested that, as a part of long term primary and/or secondary prevention, the following groups of patients with AMD receive--taking into

  11. Dendritic cell-based immunotherapy induces transient clinical response in advanced rat fibrosarcoma - comparison with preventive anti-tumour vaccination

    Czech Academy of Sciences Publication Activity Database

    Kučera, A.; Pýcha, K.; Pajer, Petr; Špíšek, R.; Škába, R.

    2009-01-01

    Roč. 55, č. 4 (2009), s. 119-125 ISSN 0015-5500 Institutional research plan: CEZ:AV0Z50520514 Keywords : dendritic cells * immunotherapy * cancer immunotherapy * chemotherapy Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.924, year: 2009

  12. Critical rate of electrolyte circulation for preventing zinc dendrite formation in a zinc-bromine redox flow battery

    Science.gov (United States)

    Yang, Hyeon Sun; Park, Jong Ho; Ra, Ho Won; Jin, Chang-Soo; Yang, Jung Hoon

    2016-09-01

    In a zinc-bromine redox flow battery, a nonaqueous and dense polybromide phase formed because of bromide oxidation in the positive electrolyte during charging. This formation led to complicated two-phase flow on the electrode surface. The polybromide and aqueous phases led to different kinetics of the Br/Br- redox reaction; poor mixing of the two phases caused uneven redox kinetics on the electrode surface. As the Br/Br- redox reaction was coupled with the zinc deposition reaction, the uneven redox reaction on the positive electrode was accompanied by nonuniform zinc deposition and zinc dendrite formation, which degraded battery stability. A single-flow cell was operated at varying electrolyte circulation rates and current densities. Zinc dendrite formation was observed after cell disassembly following charge-discharge testing. In addition, the flow behavior in the positive compartment was observed by using a transparent version of the cell. At low rate of electrolyte circulation, the polybromide phase clearly separated from the aqueous phase and accumulated at the bottom of the flow frame. In the corresponding area on the negative electrode, a large amount of zinc dendrites was observed after charge-discharge testing. Therefore, a minimum circulation rate should be considered to avoid poor mixing of the positive electrolyte.

  13. Striatonigral Degeneration

    Science.gov (United States)

    ... See More About Research The NINDS supports and conducts research on disorders of the brain and nervous system such as striatonigral degeneration. This research ... Publications Definition Striatonigral ...

  14. Oral docosahexaenoic acid in the prevention of exudative age-related macular degeneration: the Nutritional AMD Treatment 2 study.

    Science.gov (United States)

    Souied, Eric H; Delcourt, Cécile; Querques, Giuseppe; Bassols, Ana; Merle, Bénédicte; Zourdani, Alain; Smith, Theodore; Benlian, Pascale

    2013-08-01

    To evaluate the efficacy of docosahexaenoic acid (DHA)-enriched oral supplementation in preventing exudative age-related macular degeneration (AMD). The Nutritional AMD Treatment 2 study was a randomized, placebo-controlled, double-blind, parallel, comparative study. Two hundred sixty-three patients 55 years of age or older and younger than 85 years with early lesions of age-related maculopathy and visual acuity better than 0.4 logarithm of minimum angle of resolution units in the study eye and neovascular AMD in the fellow eye. Patients were assigned randomly to receive either 840 mg/day DHA and 270 mg/day eicosapentaenoic acid (EPA) from fish oil capsules or the placebo (olive oil capsules) for 3 years. The primary outcome measure was time to occurrence of choroidal neovascularization (CNV) in the study eye. Secondary outcome measures in the study eye were: incidence of CNV developing in patients, changes in visual acuity, occurrence and progression of drusen, and changes in EPA plus DHA level in red blood cell membrane (RBCM). Time to occurrence and incidence of CNV in the study eye were not significantly different between the DHA group (19.5±10.9 months and 28.4%, respectively) and the placebo group (18.7±10.6 months and 25.6%, respectively). In the DHA group, EPA plus DHA levels increased significantly in RBCM (+70%; P<0.001), suggesting that DHA easily penetrated cells, but this occurred unexpectedly also in the placebo group (+9%; P = 0.007). In the DHA-allocated group, patients steadily achieving the highest tertile of EPA plus DHA levels in RBCM had significantly lower risk (-68%; P = 0.047; hazard ratio, 0.32; 95% confidence interval, 0.10-0.99) of CNV developing over 3 years. No marked changes from baseline in best-corrected visual acuity, drusen progression, or geographic atrophy in the study eye were observed throughout the study in either group. In patients with unilateral exudative AMD, 3 years of oral DHA-enriched supplementation had the same

  15. Cerebellar Degeneration

    Science.gov (United States)

    ... FARA) National Ataxia Foundation (NAF) National Multiple Sclerosis Society See all related organizations Publications Degeneración cerebelosa Order NINDS Publications Definition Cerebellar degeneration is a process in which neurons ( ...

  16. Macular degeneration

    Science.gov (United States)

    The macula is the part of the retina that distinguishes fine details at the center of the field of vision. Macular degeneration results from a partial breakdown of the insulating layer between the retina and the choroid layer of ...

  17. Regulation of dendrite growth and maintenance by exocytosis

    Science.gov (United States)

    Peng, Yun; Lee, Jiae; Rowland, Kimberly; Wen, Yuhui; Hua, Hope; Carlson, Nicole; Lavania, Shweta; Parrish, Jay Z.; Kim, Michael D.

    2015-01-01

    ABSTRACT Dendrites lengthen by several orders of magnitude during neuronal development, but how membrane is allocated in dendrites to facilitate this growth remains unclear. Here, we report that Ras opposite (Rop), the Drosophila ortholog of the key exocytosis regulator Munc18-1 (also known as STXBP1), is an essential factor mediating dendrite growth. Neurons with depleted Rop function exhibit reduced terminal dendrite outgrowth followed by primary dendrite degeneration, suggestive of differential requirements for exocytosis in the growth and maintenance of different dendritic compartments. Rop promotes dendrite growth together with the exocyst, an octameric protein complex involved in tethering vesicles to the plasma membrane, with Rop–exocyst complexes and exocytosis predominating in primary dendrites over terminal dendrites. By contrast, membrane-associated proteins readily diffuse from primary dendrites into terminals, but not in the reverse direction, suggesting that diffusion, rather than targeted exocytosis, supplies membranous material for terminal dendritic growth, revealing key differences in the distribution of materials to these expanding dendritic compartments. PMID:26483382

  18. Benefits, Potential Harms, and Optimal Use of Nutritional Supplementation for Preventing Progression of Age-Related Macular Degeneration.

    Science.gov (United States)

    Rojas-Fernandez, Carlos H; Tyber, Kevin

    2017-03-01

    To briefly review age-related macular degeneration (AMD), the main findings from the Age Related Eye Disease Study (AREDS) report number 8 on the use of nutritional supplements for AMD, and to focus on data suggesting that supplement use should be guided using genetic testing of AMD risk genes. A literature search (January 2001 through October 26, 2016) was conducted using MEDLINE and the following MeSH terms: Antioxidants/therapeutic use, Genotype, Macular Degeneration/drug therapy, Macular degeneration/genetics, Dietary Supplements, Proteins/genetics, and Zinc Compounds/therapeutic use. Bibliographies of publications identified were also reviewed. English-language studies assessing AREDS supplement response in patients with AMD in relation to complement factor H gene ( CFH) and age-related maculopathy susceptibility 2 gene ( ARMS2) risk alleles were evaluated. Three of the 4 studies demonstrated a treatment interaction between ARMS2 and CFH genotypes and a differential response to supplements. The fourth study documented an interaction for the CFH genotype only. Reported response interactions included attenuated response, no response, and good response, whereas a subset showed increased progression of AMD. Conversely, one study reported no interactions between CFH and ARMS2 risk alleles and response to supplements. The weight of the evidence supports using genetic testing to guide selection of ocular vitamin use. This approach will avoid using supplements that could speed the progression of AMD in vulnerable patients, avoid using supplements that will have little to no effect in others, and result in appropriately using supplements in those that are likely to derive meaningful benefits.

  19. Tolerogenic interactions between CD8+ dendritic cells and NKT cells prevent rejection of bone marrow and organ grafts.

    Science.gov (United States)

    Hongo, David; Tang, Xiaobin; Zhang, Xiangyue; Engleman, Edgar G; Strober, Samuel

    2017-03-23

    The combination of total lymphoid irradiation and anti-T-cell antibodies safely induces immune tolerance to combined hematopoietic cell and organ allografts in humans. Our mouse model required host natural killer T (NKT) cells to induce tolerance. Because NKT cells normally depend on signals from CD8 + dendritic cells (DCs) for their activation, we used the mouse model to test the hypothesis that, after lymphoid irradiation, host CD8 + DCs play a requisite role in tolerance induction through interactions with NKT cells. Selective deficiency of either CD8 + DCs or NKT cells abrogated chimerism and organ graft acceptance. After radiation, the CD8 + DCs increased expression of surface molecules required for NKT and apoptotic cell interactions and developed suppressive immune functions, including production of indoleamine 2,3-deoxygenase. Injection of naive mice with apoptotic spleen cells generated by irradiation led to DC changes similar to those induced by lymphoid radiation, suggesting that apoptotic body ingestion by CD8 + DCs initiates tolerance induction. Tolerogenic CD8 + DCs induced the development of tolerogenic NKT cells with a marked T helper 2 cell bias that, in turn, regulated the differentiation of the DCs and suppressed rejection of the transplants. Thus, reciprocal interactions between CD8 + DCs and invariant NKT cells are required for tolerance induction in this system that was translated into a successful clinical protocol. © 2017 by The American Society of Hematology.

  20. Deficiency in plasmacytoid dendritic cells and type I interferon signalling prevents diet-induced obesity and insulin resistance in mice.

    Science.gov (United States)

    Hannibal, Tine D; Schmidt-Christensen, Anja; Nilsson, Julia; Fransén-Pettersson, Nina; Hansen, Lisbeth; Holmberg, Dan

    2017-10-01

    Obesity is associated with glucose intolerance and insulin resistance and is closely linked to the increasing prevalence of type 2 diabetes. In mouse models of diet-induced obesity (DIO) and type 2 diabetes, an increased fat intake results in adipose tissue expansion and the secretion of proinflammatory cytokines. The innate immune system not only plays a crucial role in obesity-associated chronic low-grade inflammation but it is also proposed to play a role in modulating energy metabolism. However, little is known about how the modulation of metabolism by the immune system may promote increased adiposity in the early stages of increased dietary intake. Here we aimed to define the role of type I IFNs in DIO and insulin resistance. Mice lacking the receptor for IFN-α (IFNAR -/- ) and deficient in plasmacytoid dendritic cells (pDCs) (B6.E2-2 fl/fl .Itgax-cre) were fed a diet with a high fat content or normal chow. The mice were analysed in vivo and in vitro using cellular, biochemical and molecular approaches. We found that the development of obesity was inhibited by an inability to respond to type I IFNs. Furthermore, the development of obesity and insulin resistance in this model was associated with pDC recruitment to the fatty tissues and liver of obese mice (a 4.3-fold and 2.7-fold increase, respectively). Finally, we demonstrated that the depletion of pDCs protects mice from DIO and from developing obesity-associated metabolic complications. Our results provide genetic evidence that pDCs, via type I IFNs, regulate energy metabolism and promote the development of obesity.

  1. Dibucaine mitigates spreading depolarization in human neocortical slices and prevents acute dendritic injury in the ischemic rodent neocortex.

    Directory of Open Access Journals (Sweden)

    W Christopher Risher

    Full Text Available Spreading depolarizations that occur in patients with malignant stroke, subarachnoid/intracranial hemorrhage, and traumatic brain injury are known to facilitate neuronal damage in metabolically compromised brain tissue. The dramatic failure of brain ion homeostasis caused by propagating spreading depolarizations results in neuronal and astroglial swelling. In essence, swelling is the initial response and a sign of the acute neuronal injury that follows if energy deprivation is maintained. Choosing spreading depolarizations as a target for therapeutic intervention, we have used human brain slices and in vivo real-time two-photon laser scanning microscopy in the mouse neocortex to study potentially useful therapeutics against spreading depolarization-induced injury.We have shown that anoxic or terminal depolarization, a spreading depolarization wave ignited in the ischemic core where neurons cannot repolarize, can be evoked in human slices from pediatric brains during simulated ischemia induced by oxygen/glucose deprivation or by exposure to ouabain. Changes in light transmittance (LT tracked terminal depolarization in time and space. Though spreading depolarizations are notoriously difficult to block, terminal depolarization onset was delayed by dibucaine, a local amide anesthetic and sodium channel blocker. Remarkably, the occurrence of ouabain-induced terminal depolarization was delayed at a concentration of 1 µM that preserves synaptic function. Moreover, in vivo two-photon imaging in the penumbra revealed that, though spreading depolarizations did still occur, spreading depolarization-induced dendritic injury was inhibited by dibucaine administered intravenously at 2.5 mg/kg in a mouse stroke model.Dibucaine mitigated the effects of spreading depolarization at a concentration that could be well-tolerated therapeutically. Hence, dibucaine is a promising candidate to protect the brain from ischemic injury with an approach that does not rely on

  2. Can Vitamin A be Improved to Prevent Blindness due to Age-Related Macular Degeneration, Stargardt Disease and Other Retinal Dystrophies?

    Science.gov (United States)

    Saad, Leonide; Washington, Ilyas

    2016-01-01

    We discuss how an imperfect visual cycle results in the formation of vitamin A dimers, thought to be involved in the pathogenesis of various retinal diseases, and summarize how slowing vitamin A dimerization has been a therapeutic target of interest to prevent blindness. To elucidate the molecular mechanism of vitamin A dimerization, an alternative form of vitamin A, one that forms dimers more slowly yet maneuvers effortlessly through the visual cycle, was developed. Such a vitamin A, reinforced with deuterium (C20-D3-vitamin A), can be used as a non-disruptive tool to understand the contribution of vitamin A dimers to vision loss. Eventually, C20-D3-vitamin A could become a disease-modifying therapy to slow or stop vision loss associated with dry age-related macular degeneration (AMD), Stargardt disease and retinal diseases marked by such vitamin A dimers. Human clinical trials of C20-D3-vitamin A (ALK-001) are underway.

  3. [Lattice degeneration of the retina].

    Science.gov (United States)

    Boĭko, E V; Suetov, A A; Mal'tsev, D S

    2014-01-01

    Lattice degeneration of the retina is a clinically important type of peripheral retinal dystrophies due to its participation in the pathogenesis of rhegmatogenous retinal detachment. In spite of extensive epidemiological, morphological, and clinical data, the question on causes of this particular type of retinal dystrophies currently remains debatable. Existing hypotheses on pathogenesis of retinal structural changes in lattice degeneration explain it to a certain extent. In clinical ophthalmology it is necessary to pay close attention to this kind of degenerations and distinguish between cases requiring preventive treatment and those requiring monitoring.

  4. RIG-I Helicase-Independent Pathway in Sendai Virus-Activated Dendritic Cells Is Critical for Preventing Lung Metastasis of AT6.3 Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Tomonori Kato

    2010-11-01

    Full Text Available We recently demonstrated highly efficient antitumor immunity against dermal tumors of B16F10 murine melanoma with the use of dendritic cells (DCs activated by replication-competent, as well as nontransmissible-type, recombinant Sendai viruses (rSeV, and proposed a new concept, “immunostimulatory virotherapy,” for cancer immunotherapy. However, there has been little information on the efficacies of thismethod: 1 inmore clinically relevant situations including metastatic diseases, 2 on other tumor types and other animal species, and 3 on the related molecular/cellular mechanisms. In this study, therefore, we investigated the efficacy of vaccinating DCs activated by fusion gene-deleted nontransmissible rSeV on a rat model of lung metastasis using a highly malignant subline of Dunning R-3327 prostate cancer, AT6.3. rSeV/dF-green fluorescent protein (GFP-activated bone marrow-derived DCs (rSeV/dF-GFP-DC, consistent with results previously observed in murine DCs. Vaccination of rSeV/dF-GFP-DC was highly effective at preventing lung metastasis after intravenous loading of R-3327 tumor cells, compared with the effects observed with immature DCs or lipopolysaccharide-activated DCs. Interestingly, neither CTL activity nor DC trafficking showed any apparent difference among groups. Notably, rSeV/dF-DCs expressing a dominant-negative mutant of retinoic acid-inducible gene I (RIG-I (rSeV/dF-RIGIC-DC, an RNA helicase that recognizes the rSeV genome for inducing type I interferons, largely lost the expression of proinflammatory cytokines without any impairment of antitumor activity. These results indicate the essential role of RIG-I-independent signaling on antimetastatic effect induced by rSeV-activated DCs and may provide important insights to DC-based immunotherapy for advanced malignancies.

  5. Cost-effectiveness of anti-oxidant vitamins plus zinc treatment to prevent the progression of intermediate age-related macular degeneration. A Singapore perspective.

    Science.gov (United States)

    Saxena, Nakul; George, Pradeep Paul; Heng, Bee Hoon; Lim, Tock Han; Yong, Shao Onn

    2015-06-01

    To determine if providing high dose anti-oxidant vitamins and zinc treatment age-related eye disease study (AREDS formulation) to patients with intermediate age-related macular degeneration (AMD) aged 40-79 years from Singapore is cost-effective in preventing progression to wet AMD. A hypothetical cohort of category 3 and 4 AMD patients from Singapore was followed for 5 calendar years to determine the number of patients who would progress to wet AMD given the following treatment scenarios: (a) AREDS formulation or placebo followed by ranibizumab (as needed) for wet AMD. (b) AREDS formulation or placebo followed by bevacizumab (monthly) for wet AMD. (c) AREDS formulation or placebo followed by aflibercept (VIEW I and II trial treatment regimen). Costs were estimated for the above scenarios from the providers' perspective, and cost-effectiveness was measured by cost per disability-adjusted life year (DALY) averted with a disability weight of 0.22 for wet AMD. The costs were discounted at an annual rate of 3%. Over 5400 patients could be prevented from progressing to wet AMD cumulatively if AREDS formulation were prescribed. AREDS formulation followed by ranibizumab was cost-effective compared to placebo-ranibizumab or placebo-aflibercept combinations (cost per DALY averted: SGD$23,662.3 and SGD$21,138.8, respectively). However, bevacizumab (monthly injections) alone was more cost-effective compared to AREDS formulation followed by bevacizumab. Prophylactic treatment with AREDS formulation for intermediate AMD patients followed by ranibizumab or for patients who progressed to wet AMD was found to be cost-effective. These findings have implications for intermediate AMD screening, treatment and healthcare planning in Singapore.

  6. Chronic caffeine consumption prevents cognitive decline from young to middle age in rats, and is associated with increased length, branching, and spine density of basal dendrites in CA1 hippocampal neurons.

    Science.gov (United States)

    Vila-Luna, S; Cabrera-Isidoro, S; Vila-Luna, L; Juárez-Díaz, I; Bata-García, J L; Alvarez-Cervera, F J; Zapata-Vázquez, R E; Arankowsky-Sandoval, G; Heredia-López, F; Flores, G; Góngora-Alfaro, J L

    2012-01-27

    Chronic caffeine consumption has been inversely associated with the risk of developing dementia and Alzheimer's disease. Here we assessed whether chronic caffeine treatment prevents the behavioral and cognitive decline that male Wistar rats experience from young (≈3 months) to middle age (≈10 months). When animals were young they were evaluated at weekly intervals in three tests: motor activity habituation in the open field (30-min sessions at the same time on consecutive days), continuous spontaneous alternation in the Y-maze (8 min), and elevated plus-maze (5 min). Afterward, rats from the same litter were randomly assigned either to a caffeine-treated group (n=13) or a control group (n=11), which received only tap water. Caffeine treatment (5 mg/kg/day) began when animals were ≈4 months old, and lasted for 6 months. Behavioral tests were repeated from day 14 to day 28 after caffeine withdrawal, a time period that is far in excess for the full excretion of a caffeine dose in this species. Thirty days after caffeine discontinuation brains were processed for Golgi-Cox staining. Compared with controls, we found that middle-aged rats that had chronically consumed low doses of caffeine (1) maintained their locomotor habituation during the second consecutive day exposure to the open field (an index of non-associative learning), (2) maintained their exploratory drive to complete the conventional minimum of nine arm visits required to calculate the alternation performance in the Y-maze in a greater proportion, (3) maintained their alternation percentage above chance level (an index of working memory), and (4) did not increase the anxiety indexes assessed by measuring the time spent in the open arms of the elevated plus maze. In addition, morphometric analysis of hippocampal neurons revealed that dendritic branching (90-140 μm from the soma), length of 4th and 5th order branches, total dendritic length, and spine density in distal dendritic branches were greater in

  7. Extra-virgin olive oil diet and mild physical activity prevent cartilage degeneration in an osteoarthritis model: an in vivo and in vitro study on lubricin expression.

    Science.gov (United States)

    Musumeci, Giuseppe; Trovato, Francesca Maria; Pichler, Karin; Weinberg, Annelie Martina; Loreto, Carla; Castrogiovanni, Paola

    2013-12-01

    Mediterranean diet includes a relatively high fat consumption mostly from monounsaturated fatty acids mainly provided by olive oil, the principal source of culinary and dressing fat. The beneficial effects of olive oil have been widely studied and could be due to its phytochemicals, which have been shown to possess anti-inflammatory properties. Lubricin is a chondroprotective glycoprotein and it serves as a critical boundary lubricant between opposing cartilage surfaces. A joint injury causes an initial flare of cytokines, which decreases lubricin expression and predisposes to cartilage degeneration such as osteoarthritis. The aim of this study was to evaluate the role of extra-virgin olive oil diet and physical activity on inflammation and expression of lubricin in articular cartilage of rats after injury. In this study we used histomorphometric, histological, immunocytochemical, immunohistochemical, western blot and biochemical analysis for lubricin and interleukin-1 evaluations in the cartilage and in the synovial fluid. We report the beneficial effect of physical activity (treadmill training) and extra-virgin olive oil supplementation, on the articular cartilage. The effects of anterior cruciate ligament transection decrease drastically the expression of lubricin and increase the expression of interleukin-1 in rats, while after physical activity and extra-virgin olive oil supplemented diet, the values return to a normal level compared to the control group. With our results we can confirm the importance of the physical activity in conjunction with extra-virgin olive oil diet in medical therapy to prevent osteoarthritis disease in order to preserve the articular cartilage and then the entire joint.

  8. Dendritic cell vaccines.

    Science.gov (United States)

    Mosca, Paul J; Lyerly, H Kim; Clay, Timothy M; Morse, Michael A; Lyerly, H Kim

    2007-05-01

    Dendritic cells are antigen-presenting cells that have been shown to stimulate tumor antigen-specific T cell responses in preclinical studies. Consequently, there has been intense interest in developing dendritic cell based cancer vaccines. A variety of methods for generating dendritic cells, loading them with tumor antigens, and administering them to patients have been described. In recent years, a number of early phase clinical trials have been performed and have demonstrated the safety and feasibility of dendritic cell immunotherapies. A number of these trials have generated valuable preliminary data regarding the clinical and immunologic response to DC-based immunotherapy. The emphasis of dendritic cell immunotherapy research is increasingly shifting toward the development of strategies to increase the potency of dendritic cell vaccine preparations.

  9. Macular degeneration (image)

    Science.gov (United States)

    ... macula in the back of the eye. The macula is important for clear central vision, allowing an individual to see fine details. There are two types of macular degeneration, dry and wet. Dry macular degeneration is more ...

  10. Age-related macular degeneration

    DEFF Research Database (Denmark)

    la Cour, Morten; Kiilgaard, Jens Folke; Nissen, Mogens Holst

    2002-01-01

    Age-related macular degeneration (AMD) is a common macular disease affecting elderly people in the Western world. It is characterised by the appearance of drusen in the macula, accompanied by choroidal neovascularisation (CNV) or geographic atrophy. The disease is more common in Caucasian....... Smoking is probably also a risk factor. Preventive strategies using macular laser photocoagulation are under investigation, but their efficacy in preventing visual loss is as yet unproven. There is no treatment with proven efficacy for geographic atrophy. Optimal treatment for exudative AMD requires...

  11. Berberine prevents nitric oxide-induced rat chondrocyte apoptosis and cartilage degeneration in a rat osteoarthritis model via AMPK and p38 MAPK signaling.

    Science.gov (United States)

    Zhou, Yan; Liu, Shi-Qing; Yu, Ling; He, Bin; Wu, Shi-Hao; Zhao, Qi; Xia, Shao-Qiang; Mei, Hong-Jun

    2015-09-01

    Chondrocyte apoptosis is an important mechanism involved in osteoarthritis (OA). Berberine (BBR), a plant alkaloid derived from Chinese medicine, is characterized by multiple pharmacological effects, such as anti-inflammatory and anti-apoptotic activities. This study aimed to evaluate the chondroprotective effect and underlying mechanisms of BBR on sodium nitroprusside (SNP)-stimulated chondrocyte apoptosis and surgically-induced rat OA model. The in vitro results revealed that BBR suppressed SNP-stimulated chondrocyte apoptosis as well as cytoskeletal remodeling, down-regulated expressions of inducible nitric oxide synthase (iNOS) and caspase-3, and up-regulated Bcl-2/Bax ratio and Type II collagen (Col II) at protein levels, which were accompanied by increased adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and decreased phosphorylation of p38 mitogen-activated protein kinase (MAPK). Furthermore, the anti-apoptotic effect of BBR was blocked by AMPK inhibitor Compound C (CC) and adenosine-9-β-D-arabino-furanoside (Ara A), and enhanced by p38 MAPK inhibitor SB203580. In vivo experiment suggested that BBR ameliorated cartilage degeneration and exhibited an anti-apoptotic effect on articular cartilage in a rat OA model, as demonstrated by histological analyses, TUNEL assay and immunohistochemical analyses of caspase-3, Bcl-2 and Bax expressions. These findings suggest that BBR suppresses SNP-stimulated chondrocyte apoptosis and ameliorates cartilage degeneration via activating AMPK signaling and suppressing p38 MAPK activity.

  12. Degeneration of the osteocyte network in the C57BL/6 mouse model of aging.

    Science.gov (United States)

    Tiede-Lewis, LeAnn M; Xie, Yixia; Hulbert, Molly A; Campos, Richard; Dallas, Mark R; Dusevich, Vladimir; Bonewald, Lynda F; Dallas, Sarah L

    2017-10-26

    Age-related bone loss and associated fracture risk are major problems in musculoskeletal health. Osteocytes have emerged as key regulators of bone mass and as a therapeutic target for preventing bone loss. As aging is associated with changes in the osteocyte lacunocanalicular system, we focused on the responsible cellular mechanisms in osteocytes. Bone phenotypic analysis was performed in young-(5mo) and aged-(22mo) C57BL/6 mice and changes in bone structure/geometry correlated with alterations in osteocyte parameters determined using novel multiplexed-3D-confocal imaging techniques. Age-related bone changes analogous to those in humans were observed, including increased cortical diameter, decreased cortical thickness, reduced trabecular BV/TV and cortical porosities. This was associated with a dramatic reduction in osteocyte dendrite number and cell density, particularly in females, where osteocyte dendricity decreased linearly from 5, 12, 18 to 22mo and correlated significantly with cortical bone parameters. Reduced dendricity preceded decreased osteocyte number, suggesting dendrite loss may trigger loss of viability. Age-related degeneration of osteocyte networks may impair bone anabolic responses to loading and gender differences in osteocyte cell body and lacunar fluid volumes we observed in aged mice may lead to gender-related differences in mechanosensitivity. Therapies to preserve osteocyte dendricity and viability may be beneficial for bone health in aging.

  13. RAB-10 Regulates Dendritic Branching by Balancing Dendritic Transport

    Science.gov (United States)

    Taylor, Caitlin A.; Yan, Jing; Howell, Audrey S.; Dong, Xintong; Shen, Kang

    2015-01-01

    The construction of a large dendritic arbor requires robust growth and the precise delivery of membrane and protein cargoes to specific subcellular regions of the developing dendrite. How the microtubule-based vesicular trafficking and sorting systems are regulated to distribute these dendritic development factors throughout the dendrite is not well understood. Here we identify the small GTPase RAB-10 and the exocyst complex as critical regulators of dendrite morphogenesis and patterning in the C. elegans sensory neuron PVD. In rab-10 mutants, PVD dendritic branches are reduced in the posterior region of the cell but are excessive in the distal anterior region of the cell. We also demonstrate that the dendritic branch distribution within PVD depends on the balance between the molecular motors kinesin-1/UNC-116 and dynein, and we propose that RAB-10 regulates dendrite morphology by balancing the activity of these motors to appropriately distribute branching factors, including the transmembrane receptor DMA-1. PMID:26633194

  14. Late complications following cryotherapy of lattice degeneration.

    Science.gov (United States)

    Benson, W E; Morse, P H; Nantawan, P

    1977-10-01

    We observed 341 patients who had received cryotherapy for lattice degeneration in order to identify possible late complications. Sequelae such as retinal tears posterior to an operculum or flap tears within treated areas showed that treatment did not necessarily prevent subsequent vitreous traction. Moreover, the newly created flap tears may extend beyond the treated area and can cause retinal detachment. Even scleral buckling did not necesserily prevent further traction. Therefore, we concluded that when cryotherapy is used to treat lattice degeneration, an adequate margin of surrounding retina should be treated and the treatment should extend to the ora serrata.

  15. Disruption of Early Tumor Necrosis Factor Alpha Signaling Prevents Classical Activation of Dendritic Cells in Lung-Associated Lymph Nodes and Development of Protective Immunity against Cryptococcal Infection

    Directory of Open Access Journals (Sweden)

    Jintao Xu

    2016-07-01

    Full Text Available Anti-tumor necrosis factor alpha (anti-TNF-α therapies have been increasingly used to treat inflammatory diseases and are associated with increased risk of invasive fungal infections, including Cryptococcus neoformans infection. Using a mouse model of cryptococcal infection, we investigated the mechanism by which disruption of early TNF-α signaling results in the development of nonprotective immunity against C. neoformans. We found that transient depletion of TNF-α inhibited pulmonary fungal clearance and enhanced extrapulmonary dissemination of C. neoformans during the adaptive phase of the immune response. Higher fungal burdens in TNF-α-depleted mice were accompanied by markedly impaired Th1 and Th17 responses in the infected lungs. Furthermore, early TNF-α depletion also resulted in disrupted transcriptional initiation of the Th17 polarization program and subsequent upregulation of Th1 genes in CD4+ T cells in the lung-associated lymph nodes (LALN of C. neoformans-infected mice. These defects in LALN T cell responses were preceded by a dramatic shift from a classical toward an alternative activation of dendritic cells (DC in the LALN of TNF-α-depleted mice. Taken together, our results indicate that early TNF-α signaling is required for optimal DC activation, and the initial Th17 response followed by Th1 transcriptional prepolarization of T cells in the LALN, which further drives the development of protective immunity against cryptococcal infection in the lungs. Thus, administration of anti-TNF-α may introduce a particularly greater risk for newly acquired fungal infections that require generation of protective Th1/Th17 responses for their containment and clearance.

  16. Conceitos atuais e perspectivas na prevenção da degeneração macular relacionada à idade Current concepts and perspectives in the prevention of age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Rogil José de Almeida Torres

    2008-06-01

    Full Text Available Os autores fazem revisão bibliográfica a respeito dos principais antioxidantes utilizados na prática diária atualmente para prevenção da progressão da degeneração macular relacionada com a idade (DMRI, enfatizando o mecanismo de ação de cada substância bem como as possíveis complicações relacionadas ao uso excessivo destes componentes.The authors prepare a literature review about the main antioxidants used in daily practice for the prevention of age-related macular degeneration progression (AMD, emphasizing the mechanism of action of each substance as well as the possible complications related to the overuse of such components.

  17. Dendritic cell neoplasms: an overview.

    Science.gov (United States)

    Kairouz, Sebastien; Hashash, Jana; Kabbara, Wadih; McHayleh, Wassim; Tabbara, Imad A

    2007-10-01

    Dendritic cell neoplasms are rare tumors that are being recognized with increasing frequency. They were previously classified as lymphomas, sarcomas, or histiocytic neoplasms. The World Health Organization (WHO) classifies dendritic cell neoplasms into five groups: Langerhans' cell histiocytosis, Langerhans' cell sarcoma, Interdigitating dendritic cell sarcoma/tumor, Follicular dendritic cell sarcoma/tumor, and Dendritic cell sarcoma, not specified otherwise (Jaffe, World Health Organization classification of tumors 2001; 273-289). Recently, Pileri et al. provided a comprehensive immunohistochemical classification of histiocytic and dendritic cell tumors (Pileri et al., Histopathology 2002;59:161-167). In this article, a concise overview regarding the pathological, clinical, and therapeutic aspects of follicular dendritic, interdigitating dendritic, and Langerhans' cell tumors is presented.

  18. Degenerate nonlinear diffusion equations

    CERN Document Server

    Favini, Angelo

    2012-01-01

    The aim of these notes is to include in a uniform presentation style several topics related to the theory of degenerate nonlinear diffusion equations, treated in the mathematical framework of evolution equations with multivalued m-accretive operators in Hilbert spaces. The problems concern nonlinear parabolic equations involving two cases of degeneracy. More precisely, one case is due to the vanishing of the time derivative coefficient and the other is provided by the vanishing of the diffusion coefficient on subsets of positive measure of the domain. From the mathematical point of view the results presented in these notes can be considered as general results in the theory of degenerate nonlinear diffusion equations. However, this work does not seek to present an exhaustive study of degenerate diffusion equations, but rather to emphasize some rigorous and efficient techniques for approaching various problems involving degenerate nonlinear diffusion equations, such as well-posedness, periodic solutions, asympt...

  19. Rapid glutamate receptor 2 trafficking during retinal degeneration

    Directory of Open Access Journals (Sweden)

    Lin Yanhua

    2012-02-01

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

  20. Modification of dendritic development.

    Science.gov (United States)

    Feria-Velasco, Alfredo; del Angel, Alma Rosa; Gonzalez-Burgos, Ignacio

    2002-01-01

    Since 1890 Ramón y Cajal strongly defended the theory that dendrites and their processes and spines had a function of not just nutrient transport to the cell body, but they had an important conductive role in neural impulse transmission. He extensively discussed and supported this theory in the Volume 1 of his extraordinary book Textura del Sistema Nervioso del Hombre y de los Vertebrados. Also, Don Santiago significantly contributed to a detailed description of the various neural components of the hippocampus and cerebral cortex during development. Extensive investigation has been done in the last Century related to the functional role of these complex brain regions, and their association with learning, memory and some limbic functions. Likewise, the organization and expression of neuropsychological qualities such as memory, exploratory behavior and spatial orientation, among others, depend on the integrity and adequate functional activity of the cerebral cortex and hippocampus. It is known that brain serotonin synthesis and release depend directly and proportionally on the availability of its precursor, tryptophan (TRY). By using a chronic TRY restriction model in rats, we studied their place learning ability in correlation with the dendritic spine density of pyramidal neurons in field CA1 of the hippocampus during postnatal development. We have also reported alterations in the maturation pattern of the ability for spontaneous alternation and task performance evaluating short-term memory, as well as adverse effects on the density of dendritic spines of hippocampal CA1 field pyramidal neurons and on the dendritic arborization and the number of dendritic spines of pyramidal neurons from the third layer of the prefrontal cortex using the same model of TRY restriction. The findings obtained in these studies employing a modified Golgi method, can be interpreted as a trans-synaptic plastic response due to understimulation of serotoninergic receptors located in the

  1. Mitochondria-Targeted Antioxidant SS31 Prevents Amyloid Beta-Induced Mitochondrial Abnormalities and Synaptic Degeneration in Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Marcus J. Calkins

    2012-10-01

    Full Text Available In neuronal systems, the health and activity of mitochondria and synapses are tightly coupled. For this reason, it has been postulated that mitochondrial abnormalities may, at least in part, drive neurodegeneration in conditions such as Alzheimer’s disease (AD. Mounting evidence from multiple Alzheimer’s disease cell and mouse models and postmortem brains suggest that loss of mitochondrial integrity may be a key factor that mediates synaptic loss. Therefore, the prevention or rescue of mitochondrial dysfunction may help delay or altogether prevent AD-associated neurodegeneration. Since mitochondrial health is heavily dependent on antioxidant defenses, researchers have begun to explore the use of mitochondria-targeted antioxidants as therapeutic tools to prevent neurodegenerative diseases. This review will highlight advances made using a model mitochondria-targeted antioxidant peptide, SS31, as a potential treatment for AD.

  2. [Prevention and treatment of age-related macular degeneration by extract of Fructus lycii and its constituents lutein/zeaxanthin: an in vive and in vitro experimental research].

    Science.gov (United States)

    Huang, Bing-Lin; Ding, Shu-Hua; Hang, Li; Zheng, Shi-Zhong; Li, Wei; Xu, Xin-rong

    2013-04-01

    To investigate the in vivo inhibition of extract of Fructus lycii (FL) on the expressions of cathepsin B (Cat B) and cystatin C (Cys C) in high-fat diet and hydroquinone (HQ) induced model mice with age-related macular degeneration (AMD), and to explore the in vitro effects of lutein and zeaxanthin on hydrogen peroxide (H2O2,) induced expressions of matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of metalloproteinase 2 (TIMP-2) on ARPE-19 cells. Fifty female 8-month-old C57BL/6 mice were recruited in this research. Ten mice fed with regular diet was taken as the age control group. The rest 40 mice were fed with high fat diet for 6 months, followed by adding HQ (0. 8%) in the drinking water for 3 consecutive months. Then the modeled mice were randomly divided into the model control group (n =10), the high (at the daily dose of 3.75 g/kg), middle (at the daily dose of 2.50 g/kg), and low dose (at the daily dose of 1.25 g/kg) FL groups, 10 in each group. The extract of FL at each dose was respectively administered to mice by gastrogavage for 3 successive months. By the end of the experiment, the mice were killed and their eyeballs were removed. The protein expressions of Cat B and Cys C were observed by immunohistochemical assay. The mRNA and protein expressions of Cat B and Cys C were detected by real-time PCR and Western blot respectively. The drug concentrations of H2O2, lutein, and zeaxanthin were screened and detected using the activity of cell proliferation. The protein expressions of MMP-2 and TIMP-2 were detected using Western blot. Compared with the age control group, the mRNA and protein expressions of Cat B and Cys C were significantly higher in the in vivo model control group (P <0.05, P <0.01). The mRNA expressions of Cat B and Cys C were weaker in the middle and high dose FL groups than in the model control group (P <0. 05, P <0. 01). In in vitro cells, lutein and zeaxanthin could down-regulate the protein expressions of MMP-2 and TIMP-2 in H202

  3. [Peripheral retinal degenerations--treatment recommendations].

    Science.gov (United States)

    Joussen, A M; Kirchhof, B

    2004-10-01

    This report reviews the clinical appearance of degenerative diseases of the peripheral retina in relationship to the risk of developing a rhegmatogenous retinal detachment. We present recommendations for preventive treatment in eyes at increased risk of developing retinal detachment. Retinal degenerations are common lesions involving the peripheral retina but most of them are clinically insignificant. Lattice degeneration, degenerative retinoschisis, cystic retinal tufts, and very rarely zonular traction tufts can result in rhegmatogenous retinal detachment. Therefore, these lesions have been considered for prophylactic treatment; however, adequate studies have not been performed to date. Most of the peripheral retinal degenerations may not require treatment except in rare, high-risk situations. According to current knowledge there is no higher incidence of secondary pucker or other side effects after laser coagulation. Therefore, generous laser indication is recommended if risk factors apply.

  4. Laenderyggens degeneration og radiologi

    DEFF Research Database (Denmark)

    Jacobsen, Steffen; Gosvig, Kasper Kjaerulf; Sonne-Holm, Stig

    2006-01-01

    Low back pain (LBP) is one of the most common conditions, and at the same time one of the most complex nosological entities. The lifetime prevalence is approximately 80%, and radiological features of lumbar degeneration are almost universal in adults. The individual risk factors for LBP and signi...... is cyclic: exacerbations relieved by asymptomatic periods. New imaging modalities, including the combination of MR imaging and multiplanar 3-D CT scans, have broadened our awareness of possible pain-generating degenerative processes of the lumbar spine other than disc degeneration....

  5. The role of subchondral bone remodeling in osteoarthritis: reduction of cartilage degeneration and prevention of osteophyte formation by alendronate in the rat anterior cruciate ligament transection model.

    Science.gov (United States)

    Hayami, Tadashi; Pickarski, Maureen; Wesolowski, Gregg A; McLane, Julia; Bone, Ashleigh; Destefano, James; Rodan, Gideon A; Duong, Le T

    2004-04-01

    It has been suggested that subchondral bone remodeling plays a role in the progression of osteoarthritis (OA). To test this hypothesis, we characterized the changes in the rat anterior cruciate ligament transection (ACLT) model of OA and evaluated the effects of alendronate (ALN), a potent inhibitor of bone resorption, on cartilage degradation and on osteophyte formation. Male Sprague-Dawley rats underwent ACLT or sham operation of the right knee. Animals were then treated with ALN (0.03 and 0.24 microg/kg/week subcutaneously) and necropsied at 2 or 10 weeks postsurgery. OA changes were evaluated. Subchondral bone volume and osteophyte area were measured by histomorphometric analysis. Coimmunostaining for transforming growth factor beta (TGF beta), matrix metalloproteinase 9 (MMP-9), and MMP-13 was performed to investigate the effect of ALN on local activation of TGF beta. ALN was chondroprotective at both dosages, as determined by histologic criteria and collagen degradation markers. ALN suppressed subchondral bone resorption, which was markedly increased 2 weeks postsurgery, and prevented the subsequent increase in bone formation 10 weeks postsurgery, in the untreated tibial plateau of ACLT joints. Furthermore, ALN reduced the incidence and area of osteophytes in a dose-dependent manner. ALN also inhibited vascular invasion into the calcified cartilage in rats with OA and blocked osteoclast recruitment to subchondral bone and osteophytes. ALN treatment reduced the local release of active TGF beta, possibly via inhibition of MMP-13 expression in articular cartilage and MMP-9 expression in subchondral bone. Subchondral bone remodeling plays an important role in the pathogenesis of OA. ALN or other inhibitors of bone resorption could potentially be used as disease-modifying agents in the treatment of OA.

  6. On Degenerate Partial Differential Equations

    OpenAIRE

    Chen, Gui-Qiang G.

    2010-01-01

    Some of recent developments, including recent results, ideas, techniques, and approaches, in the study of degenerate partial differential equations are surveyed and analyzed. Several examples of nonlinear degenerate, even mixed, partial differential equations, are presented, which arise naturally in some longstanding, fundamental problems in fluid mechanics and differential geometry. The solution to these fundamental problems greatly requires a deep understanding of nonlinear degenerate parti...

  7. Laenderyggens degeneration og radiologi

    DEFF Research Database (Denmark)

    Jacobsen, Steffen; Gosvig, Kasper Kjaerulf; Sonne-Holm, Stig

    2006-01-01

    Low back pain (LBP) is one of the most common conditions, and at the same time one of the most complex nosological entities. The lifetime prevalence is approximately 80%, and radiological features of lumbar degeneration are almost universal in adults. The individual risk factors for LBP and signi......Low back pain (LBP) is one of the most common conditions, and at the same time one of the most complex nosological entities. The lifetime prevalence is approximately 80%, and radiological features of lumbar degeneration are almost universal in adults. The individual risk factors for LBP...... and significant relationships between radiological findings and subjective symptoms have both been notoriously difficult to identify. The lack of consensus on clinical criteria and radiological definitions has hampered the undertaking of properly executed epidemiological studies. The natural history of LBP...

  8. Quantum degenerate systems

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-10-15

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

  9. Laenderyggens degeneration og radiologi

    DEFF Research Database (Denmark)

    Jacobsen, Steffen; Gosvig, Kasper Kjaerulf; Sonne-Holm, Stig

    2006-01-01

    and significant relationships between radiological findings and subjective symptoms have both been notoriously difficult to identify. The lack of consensus on clinical criteria and radiological definitions has hampered the undertaking of properly executed epidemiological studies. The natural history of LBP...... is cyclic: exacerbations relieved by asymptomatic periods. New imaging modalities, including the combination of MR imaging and multiplanar 3-D CT scans, have broadened our awareness of possible pain-generating degenerative processes of the lumbar spine other than disc degeneration....

  10. Preventing Food Allergies by Tricking Dendritic Cells

    Science.gov (United States)

    Food allergies are adverse responses to components (usually proteins) within the foods we eat, which result in a self-damaging response from our immune system. A myriad of cellular and molecular components are involved in the decision to tolerate or respond to foreign molecules that pass through the...

  11. Extrinsic Repair of Injured Dendrites as a Paradigm for Regeneration by Fusion in Caenorhabditis elegans

    Science.gov (United States)

    Oren-Suissa, Meital; Gattegno, Tamar; Kravtsov, Veronika; Podbilewicz, Benjamin

    2017-01-01

    Injury triggers regeneration of axons and dendrites. Research has identified factors required for axonal regeneration outside the CNS, but little is known about regeneration triggered by dendrotomy. Here, we study neuronal plasticity triggered by dendrotomy and determine the fate of complex PVD arbors following laser surgery of dendrites. We find that severed primary dendrites grow toward each other and reconnect via branch fusion. Simultaneously, terminal branches lose self-avoidance and grow toward each other, meeting and fusing at the tips via an AFF-1-mediated process. Ectopic branch growth is identified as a step in the regeneration process required for bypassing the lesion site. Failure of reconnection to the severed dendrites results in degeneration of the distal end of the neuron. We discover pruning of excess branches via EFF-1 that acts to recover the original wild-type arborization pattern in a late stage of the process. In contrast, AFF-1 activity during dendritic auto-fusion is derived from the lateral seam cells and not autonomously from the PVD neuron. We propose a model in which AFF-1-vesicles derived from the epidermal seam cells fuse neuronal dendrites. Thus, EFF-1 and AFF-1 fusion proteins emerge as new players in neuronal arborization and maintenance of arbor connectivity following injury in Caenorhabditis elegans. Our results demonstrate that there is a genetically determined multi-step pathway to repair broken dendrites in which EFF-1 and AFF-1 act on different steps of the pathway. EFF-1 is essential for dendritic pruning after injury and extrinsic AFF-1 mediates dendrite fusion to bypass injuries. PMID:28283540

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

    Science.gov (United States)

    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.

  13. Dendrite Injury Triggers DLK-Independent Regeneration

    Directory of Open Access Journals (Sweden)

    Michelle C. Stone

    2014-01-01

    Full Text Available Axon injury triggers regeneration through activation of a conserved kinase cascade, which includes the dual leucine zipper kinase (DLK. Although dendrites are damaged during stroke, traumatic brain injury, and seizure, it is not known whether mature neurons monitor dendrite injury and initiate regeneration. We probed the response to dendrite damage using model Drosophila neurons. Two larval neuron types regrew dendrites in distinct ways after all dendrites were removed. Dendrite regeneration was also triggered by injury in adults. Next, we tested whether dendrite injury was initiated with the same machinery as axon injury. Surprisingly, DLK, JNK, and fos were dispensable for dendrite regeneration. Moreover, this MAP kinase pathway was not activated by injury to dendrites. Thus, neurons respond to dendrite damage and initiate regeneration without using the conserved DLK cascade that triggers axon regeneration.

  14. Commitment to glycolysis sustains survival of NO-producing inflammatory dendritic cells

    NARCIS (Netherlands)

    Everts, Bart; Amiel, Eyal; van der Windt, Gerritje J. W.; Freitas, Tori C.; Chott, Robert; Yarasheski, Kevin E.; Pearce, Erika L.; Pearce, Edward J.

    2012-01-01

    TLR agonists initiate a rapid activation program in dendritic cells (DCs) that requires support from metabolic and bioenergetic resources. We found previously that TLR signaling promotes aerobic glycolysis and a decline in oxidative phosphorylation (OXHPOS) and that glucose restriction prevents

  15. Macular Degeneration Prevention and Risk Factors

    Science.gov (United States)

    ... that nourish the retina, restricting oxygen flow. Eye Color People with light-colored eyes are more likely ... Advice Expert Eye Diseases that Can Cause Legal Blindness What is legal blindness? This article defines the ...

  16. Degenerate band edge laser

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    Mathew, David J; Sarma, Saurabh Kumar; Basaiawmoit, Jennifer V

    2016-07-01

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

  18. Changes in intrinsic excitability of ganglion cells in degenerated retinas of RCS rats

    Directory of Open Access Journals (Sweden)

    Yi-Ming Ren

    2018-05-01

    Full Text Available AIM: To evaluate the intrinsic excitability of retinal ganglion cells (RGCs in degenerated retinas. METHODS: The intrinsic excitability of various morphologically defined RGC types using a combination of patch-clamp recording and the Lucifer yellow tracer in retinal whole-mount preparations harvested from Royal College of Surgeons (RCS rats, a common retinitis pigmentosa (RP model, in a relatively late stage of retinal degeneration (P90 were investigated. Several parameters of RGC morphologies and action potentials (APs were measured and compared to those of non-dystrophic control rats, including dendritic stratification, dendritic field diameter, peak amplitude, half width, resting membrane potential, AP threshold, depolarization to threshold, and firing rates. RESULTS: Compared with non-dystrophic control RGCs, more depolarizations were required to reach the AP threshold in RCS RGCs with low spontaneous spike rates and in RCS OFF cells (especially A2o cells, and RCS RGCs maintained their dendritic morphologies, resting membrane potentials and capabilities to generate APs. CONCLUSION: RGCs are relatively well preserved morphologically and functionally, and some cells are more susceptible to decreased excitability during retinal degeneration. These findings provide valuable considerations for optimizing RP therapeutic strategies.

  19. Intervertebral disc degeneration in dogs

    NARCIS (Netherlands)

    Bergknut, N.

    2011-01-01

    Back pain is common in both dogs and humans, and is often associated with intervertebral disc (IVD) degeneration. The IVDs are essential structures of the spine and degeneration can ultimately result in diseases such as IVD herniation or spinal instability. In order to design new treatments halting

  20. Intervertebral disc degeneration in dogs

    NARCIS (Netherlands)

    Bergknut, Niklas

    Back pain is common in both dogs and humans, and is often associated with intervertebral disc (IVD) degeneration. The IVDs are essential structures of the spine and degeneration can ultimately result in diseases such as IVD herniation or spinal instability. In order to design new treatments halting

  1. Second order degenerate elliptic equations

    International Nuclear Information System (INIS)

    Duong Minh Duc.

    1988-08-01

    Using an improved Sobolev inequality we study a class of elliptic operators which is degenerate inside the domain and strongly degenerate near the boundary of the domain. Our results are applicable to the L 2 -boundary value problem and the mixed boundary problem. (author). 18 refs

  2. Cdk5 Is Essential for Amphetamine to Increase Dendritic Spine Density in Hippocampal Pyramidal Neurons

    Directory of Open Access Journals (Sweden)

    Soledad Ferreras

    2017-11-01

    Full Text Available Psychostimulant drugs of abuse increase dendritic spine density in reward centers of the brain. However, little is known about their effects in the hippocampus, where activity-dependent changes in the density of dendritic spine are associated with learning and memory. Recent reports suggest that Cdk5 plays an important role in drug addiction, but its role in psychostimulant’s effects on dendritic spines in hippocampus remain unknown. We used in vivo and in vitro approaches to demonstrate that amphetamine increases dendritic spine density in pyramidal neurons of the hippocampus. Primary cultures and organotypic slice cultures were used for cellular, molecular, pharmacological and biochemical analyses of the role of Cdk5/p25 in amphetamine-induced dendritic spine formation. Amphetamine (two-injection protocol increased dendritic spine density in hippocampal neurons of thy1-green fluorescent protein (GFP mice, as well as in hippocampal cultured neurons and organotypic slice cultures. Either genetic or pharmacological inhibition of Cdk5 activity prevented the amphetamine–induced increase in dendritic spine density. Amphetamine also increased spine density in neurons overexpressing the strong Cdk5 activator p25. Finally, inhibition of calpain, the protease necessary for the conversion of p35 to p25, prevented amphetamine’s effect on dendritic spine density. We demonstrate, for the first time, that amphetamine increases the density of dendritic spine in hippocampal pyramidal neurons in vivo and in vitro. Moreover, we show that the Cdk5/p25 signaling and calpain activity are both necessary for the effect of amphetamine on dendritic spine density. The identification of molecular mechanisms underlying psychostimulant effects provides novel and promising therapeutic approaches for the treatment of drug addiction.

  3. Double Degenerate Stars

    International Nuclear Information System (INIS)

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

    2008-01-01

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

  4. Coding and decoding with dendrites.

    Science.gov (United States)

    Papoutsi, Athanasia; Kastellakis, George; Psarrou, Maria; Anastasakis, Stelios; Poirazi, Panayiota

    2014-02-01

    Since the discovery of complex, voltage dependent mechanisms in the dendrites of multiple neuron types, great effort has been devoted in search of a direct link between dendritic properties and specific neuronal functions. Over the last few years, new experimental techniques have allowed the visualization and probing of dendritic anatomy, plasticity and integrative schemes with unprecedented detail. This vast amount of information has caused a paradigm shift in the study of memory, one of the most important pursuits in Neuroscience, and calls for the development of novel theories and models that will unify the available data according to some basic principles. Traditional models of memory considered neural cells as the fundamental processing units in the brain. Recent studies however are proposing new theories in which memory is not only formed by modifying the synaptic connections between neurons, but also by modifications of intrinsic and anatomical dendritic properties as well as fine tuning of the wiring diagram. In this review paper we present previous studies along with recent findings from our group that support a key role of dendrites in information processing, including the encoding and decoding of new memories, both at the single cell and the network level. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Age-related macular degeneration.

    Science.gov (United States)

    Cheung, Lily K; Eaton, Angie

    2013-08-01

    Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, and the prevalence of the disease increases exponentially with every decade after age 50 years. It is a multifactorial disease involving a complex interplay of genetic, environmental, metabolic, and functional factors. Besides smoking, hypertension, obesity, and certain dietary habits, a growing body of evidence indicates that inflammation and the immune system may play a key role in the development of the disease. AMD may progress from the early form to the intermediate form and then to the advanced form, where two subtypes exist: the nonneovascular (dry) type and the neovascular (wet) type. The results from the Age-Related Eye Disease Study have shown that for the nonneovascular type of AMD, supplementation with high-dose antioxidants (vitamin C, vitamin E, and β-carotene) and zinc is recommended for those with the intermediate form of AMD in one or both eyes or with advanced AMD or vision loss due to AMD in one eye. As for the neovascular type of the advanced AMD, the current standard of therapy is intravitreal injections of vascular endothelial growth factor inhibitors. In addition, lifestyle and dietary modifications including improved physical activity, reduced daily sodium intake, and reduced intake of solid fats, added sugars, cholesterol, and refined grain foods are recommended. To date, no study has demonstrated that AMD can be cured or effectively prevented. Clearly, more research is needed to fully understand the pathophysiology as well as to develop prevention and treatment strategies for this devastating disease. © 2013 Pharmacotherapy Publications, Inc.

  6. Dscam1-mediated self-avoidance counters netrin-dependent targeting of dendrites in Drosophila.

    Science.gov (United States)

    Matthews, Benjamin J; Grueber, Wesley B

    2011-09-13

    Dendrites and axons show precise targeting and spacing patterns for proper reception and transmission of information in the nervous system. Self-avoidance promotes complete territory coverage and nonoverlapping spacing between processes from the same cell [1, 2]. Neurons that lack Drosophila Down syndrome cell adhesion molecule 1 (Dscam1) show aberrant overlap, fasciculation, and accumulation of dendrites and axons, demonstrating a role in self-recognition and repulsion leading to self-avoidance [3-11]. Fasciculation and accumulation of processes suggested that Dscam1 might promote process spacing by counterbalancing developmental signals that otherwise promote self-association [9, 12]. Here we show that Dscam1 functions to counter Drosophila sensory neuron dendritic targeting signals provided by secreted Netrin-B and Frazzled, a netrin receptor. Loss of Dscam1 function resulted in aberrant dendrite accumulation at a Netrin-B-expressing target, whereas concomitant loss of Frazzled prevented accumulation and caused severe deficits in dendritic territory coverage. Netrin misexpression was sufficient to induce ectopic dendritic targeting in a Frazzled-dependent manner, whereas Dscam1 was required to prevent ectopic accumulation, consistent with separable roles for these receptors. Our results suggest that Dscam1-mediated self-avoidance counters extrinsic signals that are required for normal dendritic patterning, but whose action would otherwise favor neurite accumulation. Counterbalancing roles for Dscam1 may be deployed in diverse contexts during neural circuit formation. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. Divergent Effects of Dendritic Cells on Pancreatitis

    Science.gov (United States)

    2015-09-01

    role of dendritic cells in pancreatitis. Dendritic cells are professional antigen presenting cells which initiate innate and adaptive immune... Lymphoid -tissue-specific homing of bone- marrow-derived dendritic cells . Blood. 113:6638–6647. http://dx.doi .org/10.1182/blood-2009-02-204321 Dapito...Award Number: W81XWH-12-1-0313 TITLE: Divergent Effects of Dendritic Cells on Pancreatitis PRINCIPAL INVESTIGATOR: Dr. George Miller

  8. An inverse approach for elucidating dendritic function

    Directory of Open Access Journals (Sweden)

    Benjamin Torben-Nielsen

    2010-09-01

    Full Text Available We outline an inverse approach for investigating dendritic function-structure relationships by optimizing dendritic trees for a-priori chosen computational functions. The inverse approach can be applied in two different ways. First, we can use it as a `hypothesis generator' in which we optimize dendrites for a function of general interest. The optimization yields an artificial dendrite that is subsequently compared to real neurons. This comparison potentially allows us to propose hypotheses about the function of real neurons. In this way, we investigated dendrites that optimally perform input-order detection. Second, we can use it as a `function confirmation' by optimizing dendrites for functions hypothesized to be performed by classes of neurons. If the optimized, artificial, dendrites resemble the dendrites of real neurons the artificial dendrites corroborate the hypothesized function of the real neuron. Moreover, properties of the artificial dendrites can lead to predictions about yet unmeasured properties. In this way, we investigated wide-field motion integration performed by the VS cells of the fly visual system. In outlining the inverse approach and two applications, we also elaborate on the nature of dendritic function. We furthermore discuss the role of optimality in assigning functions to dendrites and point out interesting future directions.

  9. Human CNS cultures exposed to HIV-1 gp120 reproduce dendritic injuries of HIV-1-associated dementia

    Directory of Open Access Journals (Sweden)

    Hammond Robert R

    2004-05-01

    Full Text Available Abstract HIV-1-associated dementia remains a common subacute to chronic central nervous system degeneration in adult and pediatric HIV-1 infected populations. A number of viral and host factors have been implicated including the HIV-1 120 kDa envelope glycoprotein (gp120. In human post-mortem studies using confocal scanning laser microscopy for microtubule-associated protein 2 and synaptophysin, neuronal dendritic pathology correlated with dementia. In the present study, primary human CNS cultures exposed to HIV-1 gp120 at 4 weeks in vitro suffered gliosis and dendritic damage analogous to that described in association with HIV-1-associated dementia.

  10. Development and degeneration of cone bipolar cells are independent of cone photoreceptors in a mouse model of retinitis pigmentosa.

    Directory of Open Access Journals (Sweden)

    Miao Chen

    Full Text Available Retinal photoreceptors die during retinal synaptogenesis in a portion of retinal degeneration. Whether cone bipolar cells establish regular retinal mosaics and mature morphologies, and resist degeneration are not completely understood. To explore these issues, we backcrossed a transgenic mouse expressing enhanced green fluorescent protein (EGFP in one subset of cone bipolar cells (type 7 into rd1 mice, a classic mouse model of retinal degeneration, to examine the development and survival of cone bipolar cells in a background of retinal degeneration. Our data revealed that both the development and degeneration of cone bipolar cells are independent of the normal activity of cone photoreceptors. We found that type 7 cone bipolar cells achieved a uniform tiling of the retinal surface and developed normal dendritic and axonal arbors without the influence of cone photoreceptor innervation. On the other hand, degeneration of type 7 cone bipolar cells, contrary to our belief of central-to-peripheral progression, was spatially uniform across the retina independent of the spatiotemporal pattern of cone degeneration. The results have important implications for the design of more effective therapies to restore vision in retinal degeneration.

  11. Prevention

    DEFF Research Database (Denmark)

    Halken, S; Høst, A

    2001-01-01

    , breastfeeding should be encouraged for 4-6 months. In high-risk infants a documented extensively hydrolysed formula is recommended if exclusive breastfeeding is not possible for the first 4 months of life. There is no evidence for preventive dietary intervention neither during pregnancy nor lactation...... populations. These theories remain to be documented in proper, controlled and prospective studies. Breastfeeding and the late introduction of solid foods (>4 months) is associated with a reduced risk of food allergy, atopic dermatitis, and recurrent wheezing and asthma in early childhood. In all infants....... Preventive dietary restrictions after the age of 4-6 months are not scientifically documented....

  12. Macular degeneration - age-related

    Science.gov (United States)

    ... AMD occurs when the blood vessels under the macula become thin and brittle. Small yellow deposits, called drusen, form. Almost all people with macular degeneration start with the dry form. Wet AMD occurs ...

  13. Neutrophils, dendritic cells and Toxoplasma.

    Science.gov (United States)

    Denkers, Eric Y; Butcher, Barbara A; Del Rio, Laura; Bennouna, Soumaya

    2004-03-09

    Toxoplasma gondii rapidly elicits strong Type 1 cytokine-based immunity. The necessity for this response is well illustrated by the example of IFN-gamma and IL-12 gene knockout mice that rapidly succumb to the effects of acute infection. The parasite itself is skilled at sparking complex interactions in the innate immune system that lead to protective immunity. Neutrophils are one of the first cell types to arrive at the site of infection, and the cells release several proinflammatory cytokines and chemokines in response to Toxoplasma. Dendritic cells are an important source of IL-12 during infection with T. gondii and other microbial pathogens, and they are also specialized for high-level antigen presentation to T lymphocytes. Tachyzoites express at least two types of molecules that trigger innate immune cell cytokine production. One of these involves Toll-like receptor/MyD88 pathways common to many microbial pathogens. The second pathway is less conventional and involves molecular mimicry between a parasite cyclophilin and host CC chemokine receptor 5-binding ligands. Neutrophils, dendritic cells and Toxoplasma work together to elicit the immune response required for host survival. Cytokine and chemokine cross-talk between parasite-triggered neutrophils and dendritic cells results in recruitment, maturation and activation of the latter. Neutrophil-empowered dendritic cells possess properties expected of highly potent antigen presenting cells that drive T helper 1 generation.

  14. Advanced dendritic web growth development

    Science.gov (United States)

    Hopkins, R. H.

    1985-01-01

    A program to develop the technology of the silicon dendritic web ribbon growth process is examined. The effort is being concentrated on the area rate and quality requirements necessary to meet the JPL/DOE goals for terrestrial PV applications. Closed loop web growth system development and stress reduction for high area rate growth is considered.

  15. Computed tomography of Wallerian degeneration

    International Nuclear Information System (INIS)

    Uchino, Akira; Maeda, Fumihiko

    1986-01-01

    CT findings of wallerian degeneration of the pyramidal tract at the midbrain (atrophy of cerebral peduncle following cerebrovascular accident) were studied in 34 patients (44 CT scans) with old cerebrovascular accidents. Severe atrophy of cerebral peduncle was noted when the ipsilateral motor cortex was involved. However, when the posterior limb of the internal capsule was involved, atrophy of the ipsilateral cerebral peduncle was mild. In this series, the shortest interval between cerebrovascular accident and wallerian degeneration was 8 month. (author)

  16. What Is Age-Related Macular Degeneration?

    Science.gov (United States)

    ... Eye Health / Eye Health A-Z Age-Related Macular Degeneration Sections What Is Macular Degeneration? How is AMD ... What Does Macular Degeneration Look Like? What Is Macular Degeneration? Leer en Español: ¿Qué es la degeneración macular ...

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

    Science.gov (United States)

    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…

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

    Science.gov (United States)

    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.

  19. Microtubule nucleation and organization in dendrites

    Science.gov (United States)

    Delandre, Caroline; Amikura, Reiko; Moore, Adrian W.

    2016-01-01

    ABSTRACT Dendrite branching is an essential process for building complex nervous systems. It determines the number, distribution and integration of inputs into a neuron, and is regulated to create the diverse dendrite arbor branching patterns characteristic of different neuron types. The microtubule cytoskeleton is critical to provide structure and exert force during dendrite branching. It also supports the functional requirements of dendrites, reflected by differential microtubule architectural organization between neuron types, illustrated here for sensory neurons. Both anterograde and retrograde microtubule polymerization occur within growing dendrites, and recent studies indicate that branching is enhanced by anterograde microtubule polymerization events in nascent branches. The polarities of microtubule polymerization events are regulated by the position and orientation of microtubule nucleation events in the dendrite arbor. Golgi outposts are a primary microtubule nucleation center in dendrites and share common nucleation machinery with the centrosome. In addition, pre-existing dendrite microtubules may act as nucleation sites. We discuss how balancing the activities of distinct nucleation machineries within the growing dendrite can alter microtubule polymerization polarity and dendrite branching, and how regulating this balance can generate neuron type-specific morphologies. PMID:27097122

  20. Phase field modeling of dendritic coarsening during isothermal

    Directory of Open Access Journals (Sweden)

    Zhang Yutuo

    2011-08-01

    Full Text Available Dendritic coarsening in Al-2mol%Si alloy during isothermal solidification at 880K was investigated by phase field modeling. Three coarsening mechanisms operate in the alloy: (a melting of small dendrite arms; (b coalescence of dendrites near the tips leading to the entrapment of liquid droplets; (c smoothing of dendrites. Dendrite melting is found to be dominant in the stage of dendritic growth, whereas coalescence of dendrites and smoothing of dendrites are dominant during isothermal holding. The simulated results provide a better understanding of dendrite coarsening during isothermal solidification.

  1. D1 receptors regulate dendritic morphology in normal and stressed prelimbic cortex.

    Science.gov (United States)

    Lin, Grant L; Borders, Candace B; Lundewall, Leslie J; Wellman, Cara L

    2015-01-01

    Both stress and dysfunction of prefrontal cortex are linked to psychological disorders, and structure and function of medial prefrontal cortex (mPFC) are altered by stress. Chronic restraint stress causes dendritic retraction in the prelimbic region (PL) of mPFC in rats. Dopamine release in mPFC increases during stress, and chronic administration of dopaminergic agonists results in dendritic remodeling. Thus, stress-induced alterations in dopaminergic transmission in PL may contribute to dendritic remodeling. We examined the effects of dopamine D1 receptor (D1R) blockade in PL during daily restraint stress on dendritic morphology in PL. Rats either underwent daily restraint stress (3h/day, 10 days) or remained unstressed. In each group, rats received daily infusions of either the D1R antagonist SCH23390 or vehicle into PL prior to restraint; unstressed and stressed rats that had not undergone surgery were also examined. On the final day of restraint, rats were euthanized and brains were processed for Golgi histology. Pyramidal neurons in PL were reconstructed and dendritic morphology was quantified. Vehicle-infused stressed rats demonstrated dendritic retraction compared to unstressed rats, and D1R blockade in PL prevented this effect. Moreover, in unstressed rats, D1R blockade produced dendritic retraction. These effects were not due to attenuation of the HPA axis response to acute stress: plasma corticosterone levels in a separate group of rats that underwent acute restraint stress with or without D1R blockade were not significantly different. These findings indicate that dopaminergic transmission in mPFC during stress contributes directly to the stress-induced retraction of apical dendrites, while dopamine transmission in the absence of stress is important in maintaining normal dendritic morphology. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Thermosolutal convection during dendritic solidification

    Science.gov (United States)

    Heinrich, J. C.; Nandapurkar, P.; Poirier, D. R.; Felicelli, S.

    1989-01-01

    This paper presents a mathematical model for directional solidification of a binary alloy including a dendritic region underlying an all-liquid region. It is assumed initially that there exists a nonconvecting state with planar isotherms and isoconcentrates solidifying at a constant velocity. The stability of this system has been analyzed and nonlinear calculations are performed that show the effect of convection in the solidification process when the system is unstable. Results of calculations for various cases defined by the initial temperature gradient at the dendrite tips and varying strength of the gravitational field are presented for systems involving lead-tin alloys. The results show that the systems are stable for a gravitational constant of 0.0001 g(0) and that convection can be suppressed by appropriate choice of the container's size for higher values of the gravitational constant. It is also concluded that for the lead-tin systems considered, convection in the mushy zone is not significant below the upper 20 percent of the dendritic zone, if al all.

  3. Notochord Cells in Intervertebral Disc Development and Degeneration

    Science.gov (United States)

    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

  4. Notochord Cells in Intervertebral Disc Development and Degeneration

    Directory of Open Access Journals (Sweden)

    Matthew R. McCann

    2016-01-01

    Full Text Available 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.

  5. Orientations of dendritic growth during solidification

    Science.gov (United States)

    Lee, Dong Nyung

    2017-03-01

    Dendrites are crystalline forms which grow far from the limit of stability of the plane front and adopt an orientation which is as close as possible to the heat flux direction. Dendritic growth orientations for cubic metals, bct Sn, and hcp Zn, can be controlled by thermal conductivity, Young's modulus, and surface energy. The control factors have been elaborated. Since the dendrite is a single crystal, its properties such as thermal conductivity that influences the heat flux direction, the minimum Young's modulus direction that influences the strain energy minimization, and the minimum surface energy plane that influences the crystal/liquid interface energy minimization have been proved to control the dendritic growth direction. The dendritic growth directions of cubic metals are determined by the minimum Young's modulus direction and/or axis direction of symmetry of the minimum crystal surface energy plane. The dendritic growth direction of bct Sn is determined by its maximum thermal conductivity direction and the minimum surface energy plane normal direction. The primary dendritic growth direction of hcp Zn is determined by its maximum thermal conductivity direction and the minimum surface energy plane normal direction and the secondary dendrite arm direction of hcp Zn is normal to the primary dendritic growth direction.

  6. Age-Related Macular Degeneration.

    Science.gov (United States)

    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.

  7. Degenerated differential pair with controllable transconductance

    NARCIS (Netherlands)

    Mensink, Clemens; Mensink, Clemens H.J.; Nauta, Bram

    1998-01-01

    A differential pair with input transistors and provided with a variable degeneration resistor. The degeneration resistor comprises a series arrangement of two branches of coupled resistors which are shunted in mutually corresponding points by respective control transistors whose gates are

  8. Effect of the dendritic morphology on hot tearing of carbon steels

    International Nuclear Information System (INIS)

    Ridolfi, M R

    2016-01-01

    Hot tears form during solidification in the brittle region of the dendritic front. Most hot tearing criteria are based on solid and fluid mechanics, being the phenomenon strictly depending on the solid resistance to applied strains and on the liquid capability of filling the void spaces. Modelling both mechanisms implies the precise description of the dendritic morphology. To this scope, the theory of coalescence of the dendritic arms at grain boundaries of Rappaz et al. has been applied, in this work, to the columnar growth of carbon steels by means of a simple mathematical model. Depending on the alloy composition, solid bridging starts at solid fractions down to about 0.8 and up to above 0.995 (very low carbon). The morphology of the brittle region changes drastically with increasing carbon and adding other solutes. In particular, ferritic dendrites, typical of low carbon steels, tend to offer short and wide interdendritic spaces to the surrounding liquid making possible their complete filling, and few solid bridges; peritectic steels show the rise of austenite growing and bridging rapidly in the interdendritic spaces, preventing void formation; austenitic dendrites form long and narrow interdendritic spaces difficult to reach for the liquid and with a lot of solid bridges. Sulphur addition mainly acts in delaying the coalescence end, more markedly in ferritic dendrites. (paper)

  9. Recrystallization phenomena of solution grown paraffin dendrites

    NARCIS (Netherlands)

    Hollander, F.F.A.; Hollander, F.; Stasse, O.; van Suchtelen, J.; van Enckevort, W.J.P.

    2001-01-01

    Paraffin crystals were grown from decane solutions using a micro-Bridgman set up for in-situ observation of the morphology at the growth front. It is shown that for large imposed velocities, dendrites are obtained. After dendritic growth, aging or recrystallization processes set in rather quickly,

  10. Vertical solidification of dendritic binary alloys

    Science.gov (United States)

    Heinrich, J. C.; Felicelli, S.; Poirier, D. R.

    1991-01-01

    Three numerical techniques are employed to analyze the influence of thermosolutal convection on defect formation in directionally solidified (DS) alloys. The finite-element models are based on the Boussinesq approximation and include the plane-front model and two plane-front models incorporating special dendritic regions. In the second model the dendritic region has a time-independent volume fraction of liquid, and in the last model the dendritic region evolves as local conditions dictate. The finite-element models permit the description of nonlinear thermosolutal convection by treating the dendritic regions as porous media with variable porosities. The models are applied to lead-tin alloys including DS alloys, and severe segregation phenomena such as freckles and channels are found to develop in the DS alloys. The present calculations and the permeability functions selected are shown to predict behavior in the dendritic regions that qualitatively matches that observed experimentally.

  11. Light and inherited retinal degeneration

    OpenAIRE

    Paskowitz, D M; LaVail, M M; Duncan, J L

    2006-01-01

    Light deprivation has long been considered a potential treatment for patients with inherited retinal degenerative diseases, but no therapeutic benefit has been demonstrated to date. In the few clinical studies that have addressed this issue, the underlying mutations were unknown. Our rapidly expanding knowledge of the genes and mechanisms involved in retinal degeneration have made it possible to reconsider the potential value of light restriction in specific genetic contexts. This review summ...

  12. Dendritic Actin Cytoskeleton: Structure, Functions, and Regulations

    Directory of Open Access Journals (Sweden)

    Anja Konietzny

    2017-05-01

    Full Text Available Actin is a versatile and ubiquitous cytoskeletal protein that plays a major role in both the establishment and the maintenance of neuronal polarity. For a long time, the most prominent roles that were attributed to actin in neurons were the movement of growth cones, polarized cargo sorting at the axon initial segment, and the dynamic plasticity of dendritic spines, since those compartments contain large accumulations of actin filaments (F-actin that can be readily visualized using electron- and fluorescence microscopy. With the development of super-resolution microscopy in the past few years, previously unknown structures of the actin cytoskeleton have been uncovered: a periodic lattice consisting of actin and spectrin seems to pervade not only the whole axon, but also dendrites and even the necks of dendritic spines. Apart from that striking feature, patches of F-actin and deep actin filament bundles have been described along the lengths of neurites. So far, research has been focused on the specific roles of actin in the axon, while it is becoming more and more apparent that in the dendrite, actin is not only confined to dendritic spines, but serves many additional and important functions. In this review, we focus on recent developments regarding the role of actin in dendrite morphology, the regulation of actin dynamics by internal and external factors, and the role of F-actin in dendritic protein trafficking.

  13. Age-related macular degeneration: epidemiology and optimal treatment

    DEFF Research Database (Denmark)

    la Cour, Morten; Kiilgaard, Jens Folke; Nissen, Mogens Holst

    2002-01-01

    Age-related macular degeneration (AMD) is a common macular disease affecting elderly people in the Western world. It is characterised by the appearance of drusen in the macula, accompanied by choroidal neovascularisation (CNV) or geographic atrophy. The disease is more common in Caucasian....... Smoking is probably also a risk factor. Preventive strategies using macular laser photocoagulation are under investigation, but their efficacy in preventing visual loss is as yet unproven. There is no treatment with proven efficacy for geographic atrophy. Optimal treatment for exudative AMD requires...

  14. Disc degeneration: current surgical options

    Directory of Open Access Journals (Sweden)

    C Schizas

    2010-10-01

    Full Text Available Chronic low back pain attributed to lumbar disc degeneration poses a serious challenge to physicians. Surgery may be indicated in selected cases following failure of appropriate conservative treatment. For decades, the only surgical option has been spinal fusion, but its results have been inconsistent. Some prospective trials show superiority over usual conservative measures while others fail to demonstrate its advantages. In an effort to improve results of fusion and to decrease the incidence of adjacent segment degeneration, total disc replacement techniques have been introduced and studied extensively. Short-term results have shown superiority over some fusion techniques. Mid-term results however tend to show that this approach yields results equivalent to those of spinal fusion. Nucleus replacement has gained some popularity initially, but evidence on its efficacy is scarce. Dynamic stabilisation, a technique involving less rigid implants than in spinal fusion and performed without the need for bone grafting, represents another surgical option. Evidence again is lacking on its superiority over other surgical strategies and conservative measures. Insertion of interspinous devices posteriorly, aiming at redistributing loads and relieving pain, has been used as an adjunct to disc removal surgery for disc herniation. To date however, there is no clear evidence on their efficacy. Minimally invasive intradiscal thermocoagulation techniques have also been tried, but evidence of their effectiveness is questioned. Surgery using novel biological solutions may be the future of discogenic pain treatment. Collaboration between clinicians and basic scientists in this multidisciplinary field will undoubtedly shape the future of treating symptomatic disc degeneration.

  15. Lattice degeneration of the retina.

    Science.gov (United States)

    Byer, N E

    1979-01-01

    Lattice degeneration of the retina is the most important of all clinically distinct entities that effect the peripheral fundus and are related to retinal detachment. The purpose of this review is to survey the extensive literature, to evaluate the many diverse opinions on this subject, and to correlate and summarize all the known facts regarding this disease entity. The disease is fully defined and described, both clinically and histologically. Some aspects of the disease are still poorly understood, and some remain controversial, especially in the area of management. For this reason, the indications for treatment are discussed under eight subsections, with a view toward providing practical guidelines for recommendations in management.

  16. Dendritic ion channelopathy in acquired epilepsy

    Science.gov (United States)

    Poolos, Nicholas P.; Johnston, Daniel

    2012-01-01

    Summary Ion channel dysfunction or “channelopathy” is a proven cause of epilepsy in the relatively uncommon genetic epilepsies with Mendelian inheritance. But numerous examples of acquired channelopathy in experimental animal models of epilepsy following brain injury have also been demonstrated. Our understanding of channelopathy has grown due to advances in electrophysiology techniques that have allowed the study of ion channels in the dendrites of pyramidal neurons in cortex and hippocampus. The apical dendrites of pyramidal neurons comprise the vast majority of neuronal surface membrane area, and thus the majority of the neuronal ion channel population. Investigation of dendritic ion channels has demonstrated remarkable plasticity in ion channel localization and biophysical properties in epilepsy, many of which produce hyperexcitability and may contribute to the development and maintenance of the epileptic state. Here we review recent advances in dendritic physiology and cell biology, and their relevance to epilepsy. PMID:23216577

  17. Sequence learning in differentially activated dendrites

    DEFF Research Database (Denmark)

    Nielsen, Bjørn Gilbert

    2003-01-01

    . It is proposed that the neural machinery required in such a learning/retrieval mechanism could involve the NMDA receptor, in conjunction with the ability of dendrites to maintain differentially activated regions. In particular, it is suggested that such a parcellation of the dendrite allows the neuron......Differentially activated areas of a dendrite permit the existence of zones with distinct rates of synaptic modification, and such areas can be individually accessed using a reference signal which localizes synaptic plasticity and memory trace retrieval to certain subregions of the dendrite...... to participate in multiple sequences, which can be learned without suffering from the 'wash-out' of synaptic efficacy associated with superimposition of training patterns. This is a biologically plausible solution to the stability-plasticity dilemma of learning in neural networks....

  18. Con-nectin axons and dendrites.

    Science.gov (United States)

    Beaudoin, Gerard M J

    2006-07-03

    Unlike adherens junctions, synapses are asymmetric connections, usually between axons and dendrites, that rely on various cell adhesion molecules for structural stability and function. Two cell types of adhesion molecules found at adherens junctions, cadherins and nectins, are thought to mediate homophilic interaction between neighboring cells. In this issue, Togashi et al. (see p. 141) demonstrate that the differential localization of two heterophilic interacting nectins mediates the selective attraction of axons and dendrites in cooperation with cadherins.

  19. Dendritic growth forms of borax crystals

    International Nuclear Information System (INIS)

    Takoo, R.K.; Patel, B.R.; Joshi, M.S.

    1983-01-01

    A variety of dendritic forms of borax grown from solutions by the film formation method is given. The changing growth morphology is followed as a function of concentration and temperature. The initial, intermediate and final growth morphologies are described and discussed. Influence of evaporation rate and supersaturation on the mechanism of growth is assessed. It is suggested that under all crystallization conditions, borax crystals have dendritic form in the initial stages of growth. (author)

  20. Degree of tendon degeneration and stage of rotator cuff disease.

    Science.gov (United States)

    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 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 the study is that strategies and goals of the treatment for rotator cuff disease should be specific to its stage, in order to prevent disease progression for tendinopathy and pRCT, as

  1. Synaptic Control of Secretory Trafficking in Dendrites

    Directory of Open Access Journals (Sweden)

    Cyril Hanus

    2014-06-01

    Full Text Available Localized signaling in neuronal dendrites requires tight spatial control of membrane composition. Upon initial synthesis, nascent secretory cargo in dendrites exits the endoplasmic reticulum (ER from local zones of ER complexity that are spatially coupled to post-ER compartments. Although newly synthesized membrane proteins can be processed locally, the mechanisms that control the spatial range of secretory cargo transport in dendritic segments are unknown. Here, we monitored the dynamics of nascent membrane proteins in dendritic post-ER compartments under regimes of low or increased neuronal activity. In response to activity blockade, post-ER carriers are highly mobile and are transported over long distances. Conversely, increasing synaptic activity dramatically restricts the spatial scale of post-ER trafficking along dendrites. This activity-induced confinement of secretory cargo requires site-specific phosphorylation of the kinesin motor KIF17 by Ca2+/calmodulin-dependent protein kinases (CaMK. Thus, the length scales of early secretory trafficking in dendrites are tuned by activity-dependent regulation of microtubule-dependent transport.

  2. Early increase and late decrease of purkinje cell dendritic spine density in prion-infected organotypic mouse cerebellar cultures.

    Science.gov (United States)

    Campeau, Jody L; Wu, Gengshu; Bell, John R; Rasmussen, Jay; Sim, Valerie L

    2013-01-01

    Prion diseases are infectious neurodegenerative diseases associated with the accumulation of protease-resistant prion protein, neuronal loss, spongiform change and astrogliosis. In the mouse model, the loss of dendritic spines is one of the earliest pathological changes observed in vivo, occurring 4-5 weeks after the first detection of protease-resistant prion protein in the brain. While there are cell culture models of prion infection, most do not recapitulate the neuropathology seen in vivo. Only the recently developed prion organotypic slice culture assay has been reported to undergo neuronal loss and the development of some aspects of prion pathology, namely small vacuolar degeneration and tubulovesicular bodies. Given the rapid replication of prions in this system, with protease-resistant prion protein detectable by 21 days, we investigated whether the dendritic spine loss and altered dendritic morphology seen in prion disease might also develop within the lifetime of this culture system. Indeed, six weeks after first detection of protease-resistant prion protein in tga20 mouse cerebellar slice cultures infected with RML prion strain, we found a statistically significant loss of Purkinje cell dendritic spines and altered dendritic morphology in infected cultures, analogous to that seen in vivo. In addition, we found a transient but statistically significant increase in Purkinje cell dendritic spine density during infection, at the time when protease-resistant prion protein was first detectable in culture. Our findings support the use of this slice culture system as one which recapitulates prion disease pathology and one which may facilitate study of the earliest stages of prion disease pathogenesis.

  3. Multidendritic sensory neurons in the adult Drosophila abdomen: origins, dendritic morphology, and segment- and age-dependent programmed cell death

    Directory of Open Access Journals (Sweden)

    Sugimura Kaoru

    2009-10-01

    Full Text Available Abstract Background For the establishment of functional neural circuits that support a wide range of animal behaviors, initial circuits formed in early development have to be reorganized. One way to achieve this is local remodeling of the circuitry hardwiring. To genetically investigate the underlying mechanisms of this remodeling, one model system employs a major group of Drosophila multidendritic sensory neurons - the dendritic arborization (da neurons - which exhibit dramatic dendritic pruning and subsequent growth during metamorphosis. The 15 da neurons are identified in each larval abdominal hemisegment and are classified into four categories - classes I to IV - in order of increasing size of their receptive fields and/or arbor complexity at the mature larval stage. Our knowledge regarding the anatomy and developmental basis of adult da neurons is still fragmentary. Results We identified multidendritic neurons in the adult Drosophila abdomen, visualized the dendritic arbors of the individual neurons, and traced the origins of those cells back to the larval stage. There were six da neurons in abdominal hemisegment 3 or 4 (A3/4 of the pharate adult and the adult just after eclosion, five of which were persistent larval da neurons. We quantitatively analyzed dendritic arbors of three of the six adult neurons and examined expression in the pharate adult of key transcription factors that result in the larval class-selective dendritic morphologies. The 'baseline design' of A3/4 in the adult was further modified in a segment-dependent and age-dependent manner. One of our notable findings is that a larval class I neuron, ddaE, completed dendritic remodeling in A2 to A4 and then underwent caspase-dependent cell death within 1 week after eclosion, while homologous neurons in A5 and in more posterior segments degenerated at pupal stages. Another finding is that the dendritic arbor of a class IV neuron, v'ada, was immediately reshaped during post

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

    Science.gov (United States)

    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.

  5. Dendritic cell-based immunotherapy.

    Science.gov (United States)

    Osada, Takuya; Clay, Timothy M; Woo, Christopher Y; Morse, Michael A; Lyerly, H Kim

    2006-01-01

    Dendritic cells (DCs) play a crucial role in the induction of antigen-specific T-cell responses, and therefore their use for the active immunotherapy of malignancies has been studied with considerable interest. More than a decade has passed since the publication of the first clinical data of DC-based vaccines, and through this and subsequent studies, a number of important developmental insights have been gleaned. These include the ideal source and type of DCs, the discovery of novel antigens and methods of loading DCs, the role of DC maturation, and the most efficient route of immunization. The generation of immune responses against tumor antigens after DC immunization has been demonstrated, and favorable clinical responses have been reported in some patients; however, it is difficult to pool the results as a whole, and thus the body of data remains inconclusive, in part because of varying DC preparation and vaccination protocols, the use of different forms of antigens, and, most importantly, a lack of rigorous criteria for defining clinical responses. As such, the standardization of clinical and immunologic criteria utilized, as well as DC preparations employed, will allow for the comparison of results across multiple clinical studies and is required in order for future trials to measure the true value and role of this treatment modality. In addition, issues regarding the optimal dose and clinical setting for the application of DC vaccines remain to be resolved, and recent clinical studies have been designed to begin to address these questions.

  6. Genetics of Frontotemporal Lobar Degeneration

    Directory of Open Access Journals (Sweden)

    Daniela eGalimberti

    2012-04-01

    Full Text Available Frontotemporal Lobar Degeneration (FTLD is the most frequent neurodegenerative disorder with a presenile onset. It presents with a spectrum of clinical manifestations, ranging from behavioural and executive impairment to language disorders and motor dysfunction. Familial aggregation is frequently reported in FTLD, and about 10% of cases have an autosomal dominant transmission. Microtubule Associated Protein Tau gene (MAPT mutations have been the first ones identified and are generally associated with early onset behavioural variant Frontotemporal Dementia (bvFTD phenotype. More recently, progranulin gene (GRN mutations were recognized in association with familial form of FTLD. In addition, other genes are linked to rare cases of familial FTLD. Lastly, a number of genetic risk factors for sporadic forms have also been identified.

  7. Frontotemporal Degeneration in a Child.

    Science.gov (United States)

    Terrill, Tyler; Pascual, Juan M

    2017-07-01

    There is a predilection for the frontal and temporal lobes in certain cases of dementia in the adult, leading to the syndrome of frontotemporal dementia. However, this syndrome has seemed to elude the developing brain until now. We describe an example of apparently selective neurodegeneration of the frontal and temporal regions during development associated with some of the clinical, magnetic resonance imaging, and fludeoxyglucose positron emission tomography (FDG PET) scan features of canonical frontotemporal dementia in the adult. This patient does not have any of the common frontotemporal dementia-causing mutations or known progressive brain disorders of children. This patient illustrates that symptomatic, selective, and progressive vulnerability of the frontal and temporal lobes is not restricted to adulthood, expanding the phenotype of frontotemporal degeneration. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Naturalness of nearly degenerate neutrinos

    International Nuclear Information System (INIS)

    Casas, J.A.; Espinosa, J.R.; Ibarra, A.; Navarro, I.

    1999-01-01

    If neutrinos are to play a relevant cosmological role, they must be essentially degenerate. We study whether radiative corrections can or cannot be responsible for the small mass splittings, in agreement with all the available experimental data. We perform an exhaustive exploration of the bimaximal mixing scenario, finding that (i) the vacuum oscillations solution to the solar neutrino problem is always excluded; (ii) if the mass matrix is produced by a see-saw mechanism, there are large regions of the parameter space consistent with the large angle MSW solution, providing a natural origin for the Δm sol 2 atm 2 hierarchy; (iii) the bimaximal structure becomes then stable under radiative corrections. We also provide analytical expressions for the mass splittings and mixing angles and present a particularly simple see-saw ansatz consistent with all observations

  9. Eigenstate Thermalization for Degenerate Observables

    Science.gov (United States)

    Anza, Fabio; Gogolin, Christian; Huber, Marcus

    2018-04-01

    Under unitary time evolution, expectation values of physically reasonable observables often evolve towards the predictions of equilibrium statistical mechanics. The eigenstate thermalization hypothesis (ETH) states that this is also true already for individual energy eigenstates. Here we aim at elucidating the emergence of the ETH for observables that can realistically be measured due to their high degeneracy, such as local, extensive, or macroscopic observables. We bisect this problem into two parts, a condition on the relative overlaps and one on the relative phases between the eigenbases of the observable and Hamiltonian. We show that the relative overlaps are unbiased for highly degenerate observables and demonstrate that unless relative phases conspire to cumulative effects, this makes such observables verify the ETH. Through this we elucidate potential pathways towards proofs of thermalization.

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

    Science.gov (United States)

    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

  11. On degenerate metrics, dark matter and unification

    Science.gov (United States)

    Searight, Trevor P.

    2017-12-01

    A five-dimensional theory of relativity is presented which suggests that gravitation and electromagnetism may be unified using a degenerate metric. There are four fields (in the four-dimensional sense): a tensor field, two vector fields, and a scalar field, and they are unified with a combination of a gauge-like invariance and a reflection symmetry which means that both vector fields are photons. The gauge-like invariance implies that the fifth dimension is not directly observable; it also implies that charge is a constant of motion. The scalar field is analogous to the Brans-Dicke scalar field, and the theory tends towards the Einstein-Maxwell theory in the limit as the coupling constant tends to infinity. As there is some scope for fields to vary in the fifth dimension, it is possible for the photons to have wave behaviour in the fifth dimension. The wave behaviour has two effects: it gives mass to the photons, and it prevents them from interacting directly with normal matter. These massive photons still act as a source of gravity, however, and therefore they are candidates for dark matter.

  12. The Complete Reconfiguration of Dendritic Gold

    Science.gov (United States)

    Paneru, Govind; Flanders, Bret

    2014-03-01

    Reconfigurability-by-design is an important strategy in modern materials science, as materials with this capability could potentially be used to confer hydrophobic, lipophobic, or anti-corrosive character to substrates in a regenerative manner. The present work extends the directed electrochemical nanowire assembly (DENA) methodology, which is a technique that employs alternating voltages to grow single crystalline metallic nanowires and nano-dendrites from simple salt solutions, to enable the complete dissolution of macroscopic arrays of metallic dendrites following their growth. Our main finding is that structural reconfiguration of dendritic gold is induced by changes in the MHz-level frequencies of voltages that are applied to the dendrites. Cyclic voltammetry and micro-Raman spectroscopy have been used to show that dendritic gold grows and dissolves by the same chemical mechanisms as bulk gold. Hence, the redox chemistry that occurs at the crystal-solution interface is no different than the established electrochemistry of gold. What differs in this process and allows for reconfiguration to occur is the diffusive behavior of the gold chloride molecules in the solution adjacent to the interface. We will present a simple model that captures the physics of this behavior.

  13. Isoflurane reversibly destabilizes hippocampal dendritic spines by an actin-dependent mechanism.

    Directory of Open Access Journals (Sweden)

    Jimcy Platholi

    Full Text Available General anesthetics produce a reversible coma-like state through modulation of excitatory and inhibitory synaptic transmission. Recent evidence suggests that anesthetic exposure can also lead to sustained cognitive dysfunction. However, the subcellular effects of anesthetics on the structure of established synapses are not known. We investigated effects of the widely used volatile anesthetic isoflurane on the structural stability of hippocampal dendritic spines, a postsynaptic structure critical to excitatory synaptic transmission in learning and memory. Exposure to clinical concentrations of isoflurane induced rapid and non-uniform shrinkage and loss of dendritic spines in mature cultured rat hippocampal neurons. Spine shrinkage was associated with a reduction in spine F-actin concentration. Spine loss was prevented by either jasplakinolide or cytochalasin D, drugs that prevent F-actin disassembly. Isoflurane-induced spine shrinkage and loss were reversible upon isoflurane elimination. Thus, isoflurane destabilizes spine F-actin, resulting in changes to dendritic spine morphology and number. These findings support an actin-based mechanism for isoflurane-induced alterations of synaptic structure in the hippocampus. These reversible alterations in dendritic spine structure have important implications for acute anesthetic effects on excitatory synaptic transmission and synaptic stability in the hippocampus, a locus for anesthetic-induced amnesia, and have important implications for anesthetic effects on synaptic plasticity.

  14. Stress-driven lithium dendrite growth mechanism and dendrite mitigation by electroplating on soft substrates

    Science.gov (United States)

    Wang, Xu; Zeng, Wei; Hong, Liang; Xu, Wenwen; Yang, Haokai; Wang, Fan; Duan, Huigao; Tang, Ming; Jiang, Hanqing

    2018-03-01

    Problems related to dendrite growth on lithium-metal anodes such as capacity loss and short circuit present major barriers to next-generation high-energy-density batteries. The development of successful lithium dendrite mitigation strategies is impeded by an incomplete understanding of the Li dendrite growth mechanisms, and in particular, Li-plating-induced internal stress in Li metal and its effect on Li growth morphology are not well addressed. Here, we reveal the enabling role of plating residual stress in dendrite formation through depositing Li on soft substrates and a stress-driven dendrite growth model. We show that dendrite growth is mitigated on such soft substrates through surface-wrinkling-induced stress relaxation in the deposited Li film. We demonstrate that this dendrite mitigation mechanism can be utilized synergistically with other existing approaches in the form of three-dimensional soft scaffolds for Li plating, which achieves higher coulombic efficiency and better capacity retention than that for conventional copper substrates.

  15. Transformation of Leaf-like Zinc Dendrite in Oxidation and Reduction Cycle

    International Nuclear Information System (INIS)

    Nakata, Akiyoshi; Murayama, Haruno; Fukuda, Katsutoshi; Yamane, Tomokazu; Arai, Hajime; Hirai, Toshiro; Uchimoto, Yoshiharu; Yamaki, Jun-ichi; Ogumi, Zempachi

    2015-01-01

    Highlights: • Leaf-like zinc dendrites change to leaf-like residual oxides at high oxidation current density (10 mA cm −2 ) whereas it completely dissolves at low oxidation current density (1 mA cm −2 ). • Leaf-like residual oxide products is transformed to zinc deposits with particulate morphology, resulting in good rechargeability. • The residual zinc oxide provides sufficient zincate on its reduction, preventing the diffusion-limited condition that causes leaf-like dendrite formation. - Abstract: Zinc is a promising negative electrode material for aqueous battery systems whereas it shows insufficient rechargeability for use in secondary batteries. It has been reported that leaf-like dendrite deposits are often the origin of cell-failure, however, their nature and behavior on discharge (oxidation) - charge (reduction) cycling have been only poorly understood. Here we investigate the transformation of the leaf-like zinc dendrites using ex-situ scanning electron microscopy, X-ray computational tomography and in-situ X-ray diffraction. It is shown that the leaf-like zinc dendrites obtained under diffusion-limited conditions are nearly completely dissolved at a low oxidation current density of 1 mA cm −2 and cause re-evolution of the zinc dendrites. Oxidation at a high current density of 10 mA cm −2 leads to the formation of leaf-like zinc oxide residual products that result in particulate zinc deposits in the following reduction process, enabling good rechargeability. The reaction behavior of this oxide residue is detailed and discussed for the development of long-life zinc electrodes

  16. Frontotemporal lobar degeneration: current perspectives

    Directory of Open Access Journals (Sweden)

    Riedl L

    2014-02-01

    Full Text Available Lina Riedl,1 Ian R Mackenzie,2 Hans Förstl,1 Alexander Kurz,1 Janine Diehl-Schmid1 1Center for Cognitive Disorders, Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, Technische Universität München, Munich, Germany; 2Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada Abstract: The term frontotemporal lobar degeneration (FTLD refers to a group of progressive brain diseases, which preferentially involve the frontal and temporal lobes. Depending on the primary site of atrophy, the clinical manifestation is dominated by behavior alterations or impairment of language. The onset of symptoms usually occurs before the age of 60 years, and the mean survival from diagnosis varies between 3 and 10 years. The prevalence is estimated at 15 per 100,000 in the population aged between 45 and 65 years, which is similar to the prevalence of Alzheimer's disease in this age group. There are two major clinical subtypes, behavioral-variant frontotemporal dementia and primary progressive aphasia. The neuropathology underlying the clinical syndromes is also heterogeneous. A common feature is the accumulation of certain neuronal proteins. Of these, the microtubule-associated protein tau (MAPT, the transactive response DNA-binding protein, and the fused in sarcoma protein are most important. Approximately 10% to 30% of FTLD shows an autosomal dominant pattern of inheritance, with mutations in the genes for MAPT, progranulin (GRN, and in the chromosome 9 open reading frame 72 (C9orf72 accounting for more than 80% of familial cases. Although significant advances have been made in recent years regarding diagnostic criteria, clinical assessment instruments, neuropsychological tests, cerebrospinal fluid biomarkers, and brain imaging techniques, the clinical diagnosis remains a challenge. To date, there is no specific pharmacological treatment for FTLD. Some evidence has been provided for serotonin reuptake

  17. From neurodevelopment to neurodegeneration: the interaction of neurofibromin and valosin-containing protein/p97 in regulation of dendritic spine formation

    Directory of Open Access Journals (Sweden)

    Hsueh Yi-Ping

    2012-03-01

    Full Text Available Abstract Both Neurofibromatosis type I (NF1 and inclusion body myopathy with Paget's disease of bone and frontotemporal dementia (IBMPFD are autosomal dominant genetic disorders. These two diseases are fully penetrant but with high heterogeneity in phenotypes, suggesting the involvement of genetic modifiers in modulating patients' phenotypes. Although NF1 is recognized as a developmental disorder and IBMPFD is associated with degeneration of multiple tissues, a recent study discovered the direct protein interaction between neurofibromin, the protein product of the NF1 gene, and VCP/p97, encoded by the causative gene of IBMPFD. Both NF1 and VCP/p97 are critical for dendritic spine formation, which provides the cellular mechanism explaining the cognitive deficits and dementia found in patients. Moreover, disruption of the interaction between neurofibromin and VCP impairs dendritic spinogenesis. Neurofibromin likely influences multiple downstream pathways to control dendritic spinogenesis. One is to activate the protein kinase A pathway to initiate dendritic spine formation; another is to regulate the synaptic distribution of VCP and control the activity of VCP in dendritic spinogenesis. Since neurofibromin and VCP/p97 also regulate cell growth and bone metabolism, the understanding of neurofibromin and VCP/p97 in neurons may be applied to study of cancer and bone. Statin treatment rescues the spine defects caused by VCP deficiency, suggesting the potential role of statin in clinical treatment for these two diseases.

  18. From neurodevelopment to neurodegeneration: the interaction of neurofibromin and valosin-containing protein/p97 in regulation of dendritic spine formation.

    Science.gov (United States)

    Hsueh, Yi-Ping

    2012-03-26

    Both Neurofibromatosis type I (NF1) and inclusion body myopathy with Paget's disease of bone and frontotemporal dementia (IBMPFD) are autosomal dominant genetic disorders. These two diseases are fully penetrant but with high heterogeneity in phenotypes, suggesting the involvement of genetic modifiers in modulating patients' phenotypes. Although NF1 is recognized as a developmental disorder and IBMPFD is associated with degeneration of multiple tissues, a recent study discovered the direct protein interaction between neurofibromin, the protein product of the NF1 gene, and VCP/p97, encoded by the causative gene of IBMPFD. Both NF1 and VCP/p97 are critical for dendritic spine formation, which provides the cellular mechanism explaining the cognitive deficits and dementia found in patients. Moreover, disruption of the interaction between neurofibromin and VCP impairs dendritic spinogenesis. Neurofibromin likely influences multiple downstream pathways to control dendritic spinogenesis. One is to activate the protein kinase A pathway to initiate dendritic spine formation; another is to regulate the synaptic distribution of VCP and control the activity of VCP in dendritic spinogenesis. Since neurofibromin and VCP/p97 also regulate cell growth and bone metabolism, the understanding of neurofibromin and VCP/p97 in neurons may be applied to study of cancer and bone. Statin treatment rescues the spine defects caused by VCP deficiency, suggesting the potential role of statin in clinical treatment for these two diseases.

  19. Apparatus for growing a dendritic web

    International Nuclear Information System (INIS)

    Duncan, C.S.; Mchugh, J.P.; Piotrowski, P.A.; Skutch, M.E.

    1983-01-01

    A melt system including a susceptor-crucible assembly having improved gradient control when melt replenishment is used during dendritic web growth. The improvement lies in the formation of a thermal barrier in the base of the receptor which is in the form of a vertical slot in the region of the susceptor underlying the crucible at the location of a compartmental separator dividing the crucible into a growth compartment and a melt replenishment compartment. The result achieved is a step change in temperature gradient in the melt thereby providing a more uniform temperature in the growth compartment from which the dendritic web is drawn

  20. Dendrite tungsten liquation in molybdenum alloys

    International Nuclear Information System (INIS)

    Kantor, M.M.; Ageeva, E.N.; Kolotinskij, V.N.

    1992-01-01

    A study was made on primary crystallization structure of ingots of Mo-W-B system alloys with electron microscopy were used to establish, that cells and cellular dendrites were the main elements of primary crystallization structure. Method of local X-ray spectral analysis enabled to establish, that intracrystallite liquation at cellular growth developed more intensively, as compared to the case of cellular dendrite formation. Change of boron content in alloys didn't practically affect the degree of development of intracrystallite W liquation in Mo

  1. Research status of conbercept treating age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Hai-Yan He

    2015-08-01

    Full Text Available Age-related macular degeneration(AMDis one of the major reasons of blindness among the elderly in the developed countries. As AMD patients are increasing year by year, AMD has become one of the important topics of ophthalmic research to prevent blindness. Its pathogenesis is not fully understood, but many studies have shown that vascular endothelial growth factor(VEGFplays an important role in the pathogenesis. With the development and application of anti-VEGF drugs, there are a variety of drugs applied to the disease. This article introduces conbercept for the treatment of AMD.

  2. Motor axon excitability during Wallerian degeneration

    DEFF Research Database (Denmark)

    Moldovan, Mihai; Alvarez, Susana; Krarup, Christian

    2008-01-01

    Axonal loss and degeneration are major factors in determining long-term outcome in patients with peripheral nerve disorders or injury. Following loss of axonal continuity, the isolated nerve stump distal to the lesion undergoes Wallerian degeneration in several phases. In the initial 'latent' phase......, action potential propagation and structural integrity of the distal segment are maintained. The aim of this study was to investigate in vivo the changes in membrane function of motor axons during the 'latent' phase of Wallerian degeneration. Multiple indices of axonal excitability of the tibial nerve...

  3. Disk degeneration in 14 year old children

    International Nuclear Information System (INIS)

    Erkintalo, M.; Salminen, J.J.; Paajanen, H.; Terho, P.; Kormano, M.

    1989-01-01

    This paper reports low back symptoms of 1,500 school children (14 years old) evaluated with a questionnaire and with a standardized clinical examination. Forty children who complained of recurrent and/or persistent low back pain and 40 matching symptomless controls were randomly chosen to undergo MR imaging of the lumbar spine. Premature disk degeneration was seen in 25.5% of asymptomatic children and in 40% of those with low back pain. The difference was statistically not significant. Disk degeneration is a surprisingly frequent MR finding in symptomless children. Premature disk degeneration may be the cause of low back pain in some children but is not always symptomatic in childhood

  4. Total absorption by degenerate critical coupling

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-06-23

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

  5. Transient potentials in dendritic systems of arbitrary geometry.

    Science.gov (United States)

    Butz, E G; Cowan, J D

    1974-09-01

    A simple graphical calculus is developed that generates analytic solutions for membrane potential transforms at any point on the dendritic tree of neurons with arbitrary dendritic geometries, in response to synaptic "current" inputs. Such solutions permit the computation of transients in neurons with arbitrary geometry and may facilitate analysis of the role of dendrites in such cells.

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

    Science.gov (United States)

    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.

  7. Genetics of frontotemporal lobar degeneration

    Directory of Open Access Journals (Sweden)

    Aswathy P

    2010-10-01

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

  8. Degeneration of biogenic superparamagnetic magnetite.

    Science.gov (United States)

    Li, Y-L; Pfiffner, S M; Dyar, M D; Vali, H; Konhauser, K; Cole, D R; Rondinone, A J; Phelps, T J

    2009-01-01

    Magnetite crystals precipitated as a consequence of Fe(III) reduction by Shewanella algae BrY after 265 h incubation and 5-year anaerobic storage were investigated with transmission electron microscopy, Mössbauer spectroscopy and X-ray diffraction. The magnetite crystals were typically superparamagnetic with an approximate size of 13 nm. The lattice constants of the 265 h and 5-year crystals are 8.4164A and 8.3774A, respectively. The Mössbauer spectra indicated that the 265 h magnetite had excess Fe(II) in its crystal-chemistry (Fe(3+) (1.990)Fe(2+) (1.015)O(4)) but the 5-year magnetite was Fe(II)-deficient in stoichiometry (Fe(3+) (2.388)Fe(2+) (0.419)O(4)). Such crystal-chemical changes may be indicative of the degeneration of superparamagnetic magnetite through the aqueous oxidization of Fe(II) anaerobically, and the concomitant oxidation of the organic phases (fatty acid methyl esters) that were present during the initial formation of the magnetite. The observation of a corona structure on the aged magnetite corroborates the anaerobic oxidation of Fe(II) on the outer layers of magnetite crystals. These results suggest that there may be a possible link between the enzymatic activity of the bacteria and the stability of Fe(II)-excess magnetite, which may help explain why stable nano-magnetite grains are seldom preserved in natural environments.

  9. Degeneration of Biogenic Superparamagnetic Magnetite

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-01-01

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

  10. Serotonin receptor and dendritic plasticity in the spinal cord mediated by chronic serotonergic pharmacotherapy combined with exercise following complete SCI in the adult rat.

    Science.gov (United States)

    Ganzer, Patrick D; Beringer, Carl R; Shumsky, Jed S; Nwaobasi, Chiemela; Moxon, Karen A

    2018-06-01

    Severe spinal cord injury (SCI) damages descending motor and serotonin (5-HT) fiber projections leading to paralysis and serotonin depletion. 5-HT receptors (5-HTRs) subsequently upregulate following 5-HT fiber degeneration, and dendritic density decreases indicative of atrophy. 5-HT pharmacotherapy or exercise can improve locomotor behavior after SCI. One might expect that 5-HT pharmacotherapy acts on upregulated spinal 5-HTRs to enhance function, and that exercise alone can influence dendritic atrophy. In the current study, we assessed locomotor recovery and spinal proteins influenced by SCI and therapy. 5-HT, 5-HT 2A R, 5-HT 1A R, and dendritic densities were quantified both early (1 week) and late (9 weeks) after SCI, and also following therapeutic interventions (5-HT pharmacotherapy, bike therapy, or a combination). Interestingly, chronic 5-HT pharmacotherapy largely normalized spinal 5-HTR upregulation following injury. Improvement in locomotor behavior was not correlated to 5-HTR density. These results support the hypothesis that chronic 5-HT pharmacotherapy can mediate recovery following SCI, despite acting on largely normal spinal 5-HTR levels. We next assessed spinal dendritic plasticity and its potential role in locomotor recovery. Single therapies did not normalize the loss of dendritic density after SCI. Groups displaying significantly atrophied dendritic processes were rarely able to achieve weight supported open-field locomotion. Only a combination of 5-HT pharmacotherapy and bike therapy enabled significant open-field weigh-supported stepping, mediated in part by restoring spinal dendritic density. These results support the use of combined therapies to synergistically impact multiple markers of spinal plasticity and improve motor recovery. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. Dendritic spikes amplify the synaptic signal to enhance detection of motion in a simulation of the direction-selective ganglion cell.

    Directory of Open Access Journals (Sweden)

    Michael J Schachter

    2010-08-01

    Full Text Available The On-Off direction-selective ganglion cell (DSGC in mammalian retinas responds most strongly to a stimulus moving in a specific direction. The DSGC initiates spikes in its dendritic tree, which are thought to propagate to the soma with high probability. Both dendritic and somatic spikes in the DSGC display strong directional tuning, whereas somatic PSPs (postsynaptic potentials are only weakly directional, indicating that spike generation includes marked enhancement of the directional signal. We used a realistic computational model based on anatomical and physiological measurements to determine the source of the enhancement. Our results indicate that the DSGC dendritic tree is partitioned into separate electrotonic regions, each summing its local excitatory and inhibitory synaptic inputs to initiate spikes. Within each local region the local spike threshold nonlinearly amplifies the preferred response over the null response on the basis of PSP amplitude. Using inhibitory conductances previously measured in DSGCs, the simulation results showed that inhibition is only sufficient to prevent spike initiation and cannot affect spike propagation. Therefore, inhibition will only act locally within the dendritic arbor. We identified the role of three mechanisms that generate directional selectivity (DS in the local dendritic regions. First, a mechanism for DS intrinsic to the dendritic structure of the DSGC enhances DS on the null side of the cell's dendritic tree and weakens it on the preferred side. Second, spatially offset postsynaptic inhibition generates robust DS in the isolated dendritic tips but weak DS near the soma. Third, presynaptic DS is apparently necessary because it is more robust across the dendritic tree. The pre- and postsynaptic mechanisms together can overcome the local intrinsic DS. These local dendritic mechanisms can perform independent nonlinear computations to make a decision, and there could be analogous mechanisms within

  12. Dendritic spikes amplify the synaptic signal to enhance detection of motion in a simulation of the direction-selective ganglion cell.

    Science.gov (United States)

    Schachter, Michael J; Oesch, Nicholas; Smith, Robert G; Taylor, W Rowland

    2010-08-19

    The On-Off direction-selective ganglion cell (DSGC) in mammalian retinas responds most strongly to a stimulus moving in a specific direction. The DSGC initiates spikes in its dendritic tree, which are thought to propagate to the soma with high probability. Both dendritic and somatic spikes in the DSGC display strong directional tuning, whereas somatic PSPs (postsynaptic potentials) are only weakly directional, indicating that spike generation includes marked enhancement of the directional signal. We used a realistic computational model based on anatomical and physiological measurements to determine the source of the enhancement. Our results indicate that the DSGC dendritic tree is partitioned into separate electrotonic regions, each summing its local excitatory and inhibitory synaptic inputs to initiate spikes. Within each local region the local spike threshold nonlinearly amplifies the preferred response over the null response on the basis of PSP amplitude. Using inhibitory conductances previously measured in DSGCs, the simulation results showed that inhibition is only sufficient to prevent spike initiation and cannot affect spike propagation. Therefore, inhibition will only act locally within the dendritic arbor. We identified the role of three mechanisms that generate directional selectivity (DS) in the local dendritic regions. First, a mechanism for DS intrinsic to the dendritic structure of the DSGC enhances DS on the null side of the cell's dendritic tree and weakens it on the preferred side. Second, spatially offset postsynaptic inhibition generates robust DS in the isolated dendritic tips but weak DS near the soma. Third, presynaptic DS is apparently necessary because it is more robust across the dendritic tree. The pre- and postsynaptic mechanisms together can overcome the local intrinsic DS. These local dendritic mechanisms can perform independent nonlinear computations to make a decision, and there could be analogous mechanisms within cortical circuitry.

  13. Magnetic resonance imaging of intervertebral disc degeneration

    International Nuclear Information System (INIS)

    Maeda, Hiroshi; Noguchi, Masao; Kira, Hideaki; Fujiki, Hiroshi; Shimokawa, Isao; Hinoue, Kaichi.

    1993-01-01

    The aim of this study was to correlate the degree of lumbar intervertebral disc degeneration with findings of magnetic resonance imaging (MRI). Seventeen autopsied (from 7 patients) and 21 surgical (from 20 patients) intervertebral discs were used as specimens for histopathological examination. In addition, 21 intervertebral discs were examined on T2-weighted images. Histopathological findings from both autopsied and surgical specimens were well correlated with MRI findings. In particular, T2-weighted images reflected increased collagen fibers and rupture within the fibrous ring accurately. However, when severely degenerated intervertebral discs and hernia protruding the posterior longitudinal ligament existed, histological findings were not concordant well with T2-weighted images. Morphological appearances of autopsy specimens, divided into four on T2-weighted images, were well consistent with histological degeneration. This morphological classification, as shown on T2-weighted images, could also be used in the evaluation of intervertebral disc degeneration. (N.K.)

  14. Magnetic resonance imaging of intervertebral disc degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Maeda, Hiroshi; Noguchi, Masao (Kitakyushu City Yahata Hospital, Fukuoka (Japan)); Kira, Hideaki; Fujiki, Hiroshi; Shimokawa, Isao; Hinoue, Kaichi

    1993-02-01

    The aim of this study was to correlate the degree of lumbar intervertebral disc degeneration with findings of magnetic resonance imaging (MRI). Seventeen autopsied (from 7 patients) and 21 surgical (from 20 patients) intervertebral discs were used as specimens for histopathological examination. In addition, 21 intervertebral discs were examined on T2-weighted images. Histopathological findings from both autopsied and surgical specimens were well correlated with MRI findings. In particular, T2-weighted images reflected increased collagen fibers and rupture within the fibrous ring accurately. However, when severely degenerated intervertebral discs and hernia protruding the posterior longitudinal ligament existed, histological findings were not concordant well with T2-weighted images. Morphological appearances of autopsy specimens, divided into four on T2-weighted images, were well consistent with histological degeneration. This morphological classification, as shown on T2-weighted images, could also be used in the evaluation of intervertebral disc degeneration. (N.K.).

  15. Genetics Home Reference: Stargardt macular degeneration

    Science.gov (United States)

    ... recognizing faces. In most people with Stargardt macular degeneration , a fatty yellow pigment (lipofuscin) builds up in cells underlying the macula. Over time, the abnormal accumulation of this substance ...

  16. Ataxias and Cerebellar or Spinocerebellar Degeneration

    Science.gov (United States)

    ... and conducts a broad range of basic and clinical research on cerebellar and spinocerebellar degeneration, including work aimed at finding the cause(s) of ataxias and ways to ... Publications Definition Ataxia ...

  17. Hamiltonization of theories with degenerate coordinates

    International Nuclear Information System (INIS)

    Gitman, D.M.; Tyutin, I.V.

    2002-01-01

    We consider a class of Lagrangian theories where part of the coordinates does not have any time derivatives in the Lagrange function (we call such coordinates degenerate). We advocate that it is reasonable to reconsider the conventional definition of singularity based on the usual Hessian and, moreover, to simplify the conventional hamiltonization procedure. In particular, in such a procedure, it is not necessary to complete the degenerate coordinates with the corresponding conjugate momenta

  18. Hamiltonization of theories with degenerate coordinates

    Energy Technology Data Exchange (ETDEWEB)

    Gitman, D.M. E-mail: gitman@fma.if.usp.br; Tyutin, I.V. E-mail: tyutin@lpi.ru

    2002-05-27

    We consider a class of Lagrangian theories where part of the coordinates does not have any time derivatives in the Lagrange function (we call such coordinates degenerate). We advocate that it is reasonable to reconsider the conventional definition of singularity based on the usual Hessian and, moreover, to simplify the conventional hamiltonization procedure. In particular, in such a procedure, it is not necessary to complete the degenerate coordinates with the corresponding conjugate momenta.

  19. Splitting deformations of degenerations of complex curves towards the classification of atoms of degenerations

    CERN Document Server

    2006-01-01

    The author develops a deformation theory for degenerations of complex curves; specifically, he treats deformations which induce splittings of the singular fiber of a degeneration. He constructs a deformation of the degeneration in such a way that a subdivisor is "barked" (peeled) off from the singular fiber. These "barking deformations" are related to deformations of surface singularities (in particular, cyclic quotient singularities) as well as the mapping class groups of Riemann surfaces (complex curves) via monodromies. Important applications, such as the classification of atomic degenerations, are also explained.

  20. Peptides and proteins in dendritic assemblies

    NARCIS (Netherlands)

    Baal, van I.

    2007-01-01

    Multiple, simultaneous interactions are often used in biology to enhance the affinity and specificity of binding, an effect referred to as multivalency. This multivalency can be mimicked by anchoring multiple peptides and proteins onto synthetic dendritic scaffolds. The aim of this research was to

  1. Targeting nanoparticles to dendritic cells for immunotherapy.

    NARCIS (Netherlands)

    Cruz, L.J.; Tacken, P.J.; Rueda, F.; Domingo, J.C.; Albericio, F.; Figdor, C.G.

    2012-01-01

    Dendritic cells (DCs) are key players in the initiation of adaptive immune responses and are currently exploited in immunotherapy for treatment of cancer and infectious diseases. Development of targeted nanodelivery systems carrying vaccine components, including antigens and adjuvants, to DCs in

  2. Antigen dynamics of follicular dendritic cells

    NARCIS (Netherlands)

    Heesters, B.A.

    2015-01-01

    Stromal-derived follicular dendritic cells (FDCs) are a major depot for antigen that are essential for formation of germinal centers, the site where memory and effector B cells differentiate and high-affinity antibody production takes place. Historically, FDCs have been characterized as ‘accessory’

  3. Dendritic cells: biology of the skin

    NARCIS (Netherlands)

    Toebak, M.J.; Gibbs, S.; Bruynzeel, D.P.; Scheper, R.J.; Rustemeyer, T.

    2009-01-01

    Allergic contact dermatitis results from a T-cell-mediated, delayed-type hypersensitivity immune response induced by allergens. Skin dendritic cells (DCs) play a central role in the initiation of allergic skin responses. Following encounter with an allergen, DCs become activated and undergo

  4. Thermosolutal convection and macrosegregation in dendritic alloys

    Science.gov (United States)

    Poirier, David R.; Heinrich, J. C.

    1993-01-01

    A mathematical model of solidification, that simulates the formation of channel segregates or freckles, is presented. The model simulates the entire solidification process, starting with the initial melt to the solidified cast, and the resulting segregation is predicted. Emphasis is given to the initial transient, when the dendritic zone begins to develop and the conditions for the possible nucleation of channels are established. The mechanisms that lead to the creation and eventual growth or termination of channels are explained in detail and illustrated by several numerical examples. A finite element model is used for the simulations. It uses a single system of equations to deal with the all-liquid region, the dendritic region, and the all-solid region. The dendritic region is treated as an anisotropic porous medium. The algorithm uses the bilinear isoparametric element, with a penalty function approximation and a Petrov-Galerkin formulation. The major task was to develop the solidification model. In addition, other tasks that were performed in conjunction with the modeling of dendritic solidification are briefly described.

  5. Dendritic cells in peripheral tolerance and immunity

    DEFF Research Database (Denmark)

    Gad, Monika; Claesson, Mogens Helweg; Pedersen, Anders Elm

    2003-01-01

    Dendritic cells capable of influencing immunity exist as functionally distinct subsets, T cell-tolerizing and T cell-immunizing subsets. The present paper reviews how these subsets of DCs develop, differentiate and function in vivo and in vitro at the cellular and molecular level. In particular...

  6. Dendritic cells modified by vitamin D

    DEFF Research Database (Denmark)

    Pedersen, Ayako Wakatsuki; Claesson, Mogens Helweg; Zocca, Mai-Britt

    2011-01-01

    Dendritic cells (DCs), the most potent antigen-presenting cells of the immune system, express nuclear receptors for 1,25-dihydroxyvitamin D(3) (VD3) and they are one of its main targets. In the presence of VD3, DCs differentiate into a phenotype that resembles semimature DCs, with reduced T cell ...

  7. Randomly oriented twin domains in electrodeposited silver dendrites

    Directory of Open Access Journals (Sweden)

    Ivanović Evica R.

    2015-01-01

    Full Text Available Silver dendrites were prepared by electrochemical deposition. The structures of Ag dendrites, the type of twins and their distribution were investigated by scanning electron microscopy (SEM, Z-contrast high angle annular dark field transmission electron microscopy (HAADF, and crystallografically sensitive orientation imaging microscopy (OIM. The results revealed that silver dendrites are characterized by the presence of randomly distributed 180° rotational twin domains. The broad surface of dendrites was of the {111} type. Growth directions of the main dendrite stem and all branches were of type. [Projekat Ministarstva nauke Republike Srbije, br. 172054

  8. Activity-dependent trafficking of lysosomes in dendrites and dendritic spines.

    Science.gov (United States)

    Goo, Marisa S; Sancho, Laura; Slepak, Natalia; Boassa, Daniela; Deerinck, Thomas J; Ellisman, Mark H; Bloodgood, Brenda L; Patrick, Gentry N

    2017-08-07

    In neurons, lysosomes, which degrade membrane and cytoplasmic components, are thought to primarily reside in somatic and axonal compartments, but there is little understanding of their distribution and function in dendrites. Here, we used conventional and two-photon imaging and electron microscopy to show that lysosomes traffic bidirectionally in dendrites and are present in dendritic spines. We find that lysosome inhibition alters their mobility and also decreases dendritic spine number. Furthermore, perturbing microtubule and actin cytoskeletal dynamics has an inverse relationship on the distribution and motility of lysosomes in dendrites. We also find trafficking of lysosomes is correlated with synaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptors. Strikingly, lysosomes traffic to dendritic spines in an activity-dependent manner and can be recruited to individual spines in response to local activation. These data indicate the position of lysosomes is regulated by synaptic activity and thus plays an instructive role in the turnover of synaptic membrane proteins. © 2017 Goo et al.

  9. Centralization of extruded medial meniscus delays cartilage degeneration in rats.

    Science.gov (United States)

    Ozeki, Nobutake; Muneta, Takeshi; Kawabata, Kenichi; Koga, Hideyuki; Nakagawa, Yusuke; Saito, Ryusuke; Udo, Mio; Yanagisawa, Katsuaki; Ohara, Toshiyuki; Mochizuki, Tomoyuki; Tsuji, Kunikazu; Saito, Tomoyuki; Sekiya, Ichiro

    2017-05-01

    Meniscus extrusion often observed in knee osteoarthritis has a strong correlation with the progression of cartilage degeneration and symptom in the patients. We recently reported a novel procedure "arthroscopic centralization" in which the capsule was sutured to the edge of the tibial plateau to reduce meniscus extrusion in the human knee. However, there is no animal model to study the efficacy of this procedure. The purposes of this study were [1] to establish a model of centralization for the extruded medial meniscus in a rat model; and [2] to investigate the chondroprotective effect of this procedure. Medial meniscus extrusion was induced by the release of the anterior synovial capsule and the transection of the meniscotibial ligament. Centralization was performed by the pulled-out suture technique. Alternatively, control rats had only the medial meniscus extrusion surgery. Medial meniscus extrusion was evaluated by micro-CT and macroscopic findings. Cartilage degeneration of the medial tibial plateau was evaluated macroscopically and histologically. By micro-CT analysis, the medial meniscus extrusion was significantly improved in the centralization group in comparison to the extrusion group throughout the study. Both macroscopically and histologically, the cartilage lesion of the medial tibial plateau was prevented in the centralization group but was apparent in the control group. We developed medial meniscus extrusion in a rat model, and centralization of the extruded medial meniscus by the pull-out suture technique improved the medial meniscus extrusion and delayed cartilage degeneration, though the effect was limited. Centralization is a promising treatment to prevent the progression of osteoarthritis. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    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.

  11. Esterified dendritic TAM radicals with very high stability and enhanced oxygen sensitivity.

    Science.gov (United States)

    Song, Yuguang; Liu, Yangping; Hemann, Craig; Villamena, Frederick A; Zweier, Jay L

    2013-02-15

    In this work, we have developed a new class of dendritic TAM radicals (TG, TdG, and dTdG) through a convergent method based on the TAM core CT-03 or its deuterated analogue dCT-03 and trifurcated Newkome-type monomer. Among these radicals, dTdG exhibits the best EPR properties with sharpest EPR singlet and highest O(2) sensitivity due to deuteration of both the ester linker groups and the TAM core CT-03. Like the previous dendritic TAM radicals, these new compounds also show extremely high stability toward various reactive species owing to the dendritic encapsulation. The highly charged nature of these molecules resulting from nine carboxylate groups prevents concentration-dependent EPR line broadening at physiological pH. Furthermore, we demonstrate that these TAM radicals can be easily derivatized (e.g., PEGylation) at the nine carboxylate groups and the resulting PEGylated analogue dTdG-PEG completely inhibits the albumin binding, thereby enhancing suitability for in vivo applications. These new dendritic TAM radicals show great potential for in vivo EPR oximetric applications and provide insights on approaches to develop improved and targeted EPR oximetric probes for biomedical applications.

  12. Phospholipid Homeostasis Regulates Dendrite Morphogenesis in Drosophila Sensory Neurons

    Directory of Open Access Journals (Sweden)

    Shan Meltzer

    2017-10-01

    Full Text Available Disruptions in lipid homeostasis have been observed in many neurodevelopmental disorders that are associated with dendrite morphogenesis defects. However, the molecular mechanisms of how lipid homeostasis affects dendrite morphogenesis are unclear. We find that easily shocked (eas, which encodes a kinase with a critical role in phospholipid phosphatidylethanolamine (PE synthesis, and two other enzymes in this synthesis pathway are required cell autonomously in sensory neurons for dendrite growth and stability. Furthermore, we show that the level of Sterol Regulatory Element-Binding Protein (SREBP activity is important for dendrite development. SREBP activity increases in eas mutants, and decreasing the level of SREBP and its transcriptional targets in eas mutants largely suppresses the dendrite growth defects. Furthermore, reducing Ca2+ influx in neurons of eas mutants ameliorates the dendrite morphogenesis defects. Our study uncovers a role for EAS kinase and reveals the in vivo function of phospholipid homeostasis in dendrite morphogenesis.

  13. Indian hedgehog contributes to human cartilage endplate degeneration.

    Science.gov (United States)

    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.

  14. The mucosal factors retinoic acid and TGF-B induce phenotypically and functionally distinct dendritic cell types

    NARCIS (Netherlands)

    Hartog, den C.G.; Altena, van S.E.C.; Savelkoul, H.F.J.; Neerven, van R.J.J.

    2013-01-01

    Non-inflammatory dendritic cell (DC) subsets play an essential role in preventing massive inflammation in mucosal tissues. We investigated whether mucosa-related factors, namely retinoic acid (RA) and transforming growth factor-ß (TGF-ß1), can induce such DC types. DCs were differentiated from

  15. Mesenchymal stem cells induce mature dendritic cells into a novel Jagged-2-dependent regulatory dendritic cell population.

    Science.gov (United States)

    Zhang, Bin; Liu, Rui; Shi, Dan; Liu, Xingxia; Chen, Yuan; Dou, Xiaowei; Zhu, Xishan; Lu, Chunhua; Liang, Wei; Liao, Lianming; Zenke, Martin; Zhao, Robert C H

    2009-01-01

    Mesenchymal stem cells (MSCs), in addition to their multilineage differentiation, exert immunomodulatory effects on immune cells, even dendritic cells (DCs). However, whether they influence the destiny of full mature DCs (maDCs) remains controversial. Here we report that MSCs vigorously promote proliferation of maDCs, significantly reduce their expression of Ia, CD11c, CD80, CD86, and CD40 while increasing CD11b expression. Interestingly, though these phenotypes clearly suggest their skew to immature status, bacterial lipopolysaccharide (LPS) stimulation could not reverse this trend. Moreover, high endocytosic capacity, low immunogenicity, and strong immunoregulatory function of MSC-treated maDCs (MSC-DCs) were also observed. Furthermore we found that MSCs, partly via cell-cell contact, drive maDCs to differentiate into a novel Jagged-2-dependent regulatory DC population and escape their apoptotic fate. These results further support the role of MSCs in preventing rejection in organ transplantation and treatment of autoimmune disease.

  16. Transgenic Mice Over-Expressing RBP4 Have RBP4-Dependent and Light-Independent Retinal Degeneration.

    Science.gov (United States)

    Du, Mei; Phelps, Eric; Balangue, Michael J; Dockins, Aaron; Moiseyev, Gennadiy; Shin, Younghwa; Kane, Shelley; Otalora, Laura; Ma, Jian-Xing; Farjo, Rafal; Farjo, Krysten M

    2017-08-01

    Transgenic mice overexpressing serum retinol-binding protein (RBP4-Tg) develop progressive retinal degeneration, characterized by microglia activation, yet the precise mechanisms underlying retinal degeneration are unclear. Previous studies showed RBP4-Tg mice have normal ocular retinoid levels, suggesting that degeneration is independent of the retinoid visual cycle or light exposure. The present study addresses whether retinal degeneration is light-dependent and RBP4-dependent by testing the effects of dark-rearing and pharmacological lowering of serum RBP4 levels, respectively. RBP4-Tg mice reared on normal mouse chow in normal cyclic light conditions were directly compared to RBP4-Tg mice exposed to chow supplemented with the RBP4-lowering compound A1120 or dark-rearing conditions. Quantitative retinal histological analysis was conducted to assess retinal degeneration, and electroretinography (ERG) and optokinetic tracking (OKT) tests were performed to assess retinal and visual function. Ocular retinoids and bis-retinoid A2E were quantified. Dark-rearing RBP4-Tg mice effectively reduced ocular bis-retinoid A2E levels, but had no significant effect on retinal degeneration or dysfunction in RBP4-Tg mice, demonstrating that retinal degeneration is light-independent. A1120 treatment lowered serum RBP4 levels similar to wild-type mice, and prevented structural retinal degeneration. However, A1120 treatment did not prevent retinal dysfunction in RBP4-Tg mice. Moreover, RBP4-Tg mice on A1120 diet had significant worsening of OKT response and loss of cone photoreceptors compared to RBP4-Tg mice on normal chow. This may be related to the very significant reduction in retinyl ester levels in the retina of mice on A1120-supplemented diet. Retinal degeneration in RBP4-Tg mice is RBP4-dependent and light-independent.

  17. Nutritional supplements in age-related macular degeneration.

    Science.gov (United States)

    Schmidl, Doreen; Garhöfer, Gerhard; Schmetterer, Leopold

    2015-03-01

    Age-related macular degeneration (AMD) is the most frequent cause of blindness in the Western World. While with new therapies that are directed towards vascular endothelial growth factor (VEGF), a potentially efficient treatment option for the wet form of the disease has been introduced, a therapeutic regimen for dry AMD is still lacking. There is evidence from several studies that oral intake of supplements is beneficial in preventing progression of the disease. Several formulations of micronutrients are currently available. The present review focuses on the role of supplements in the treatment and prevention of AMD and sums up the current knowledge about the most frequently used micronutrients. In addition, regulatory issues are discussed, and future directions for the role of supplementation in AMD are highlighted. © 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  18. Dendritic excitability modulates dendritic information processing in a purkinje cell model.

    Science.gov (United States)

    Coop, Allan D; Cornelis, Hugo; Santamaria, Fidel

    2010-01-01

    Using an electrophysiological compartmental model of a Purkinje cell we quantified the contribution of individual active dendritic currents to processing of synaptic activity from granule cells. We used mutual information as a measure to quantify the information from the total excitatory input current (I(Glu)) encoded in each dendritic current. In this context, each active current was considered an information channel. Our analyses showed that most of the information was encoded by the calcium (I(CaP)) and calcium activated potassium (I(Kc)) currents. Mutual information between I(Glu) and I(CaP) and I(Kc) was sensitive to different levels of excitatory and inhibitory synaptic activity that, at the same time, resulted in the same firing rate at the soma. Since dendritic excitability could be a mechanism to regulate information processing in neurons we quantified the changes in mutual information between I(Glu) and all Purkinje cell currents as a function of the density of dendritic Ca (g(CaP)) and Kca (g(Kc)) conductances. We extended our analysis to determine the window of temporal integration of I(Glu) by I(CaP) and I(Kc) as a function of channel density and synaptic activity. The window of information integration has a stronger dependence on increasing values of g(Kc) than on g(CaP), but at high levels of synaptic stimulation information integration is reduced to a few milliseconds. Overall, our results show that different dendritic conductances differentially encode synaptic activity and that dendritic excitability and the level of synaptic activity regulate the flow of information in dendrites.

  19. Differential activation behavior of dermal dendritic cells underlies the strain-specific Th1 responses to single epicutaneous immunization.

    Science.gov (United States)

    Lee, Chih-Hung; Chen, Jau-Shiuh; Chiu, Hsien-Ching; Hong, Chien-Hui; Liu, Ching-Yi; Ta, Yng-Cun; Wang, Li-Fang

    2016-12-01

    Epicutaneous immunization with allergens is an important sensitization route for atopic dermatitis. We recently showed in addition to the Th2 response following single epicutaneous immunization, a remarkable Th1 response is induced in B6 mice, but not in BALB/c mice, mimicking the immune response to allergens in human non-atopics and atopics. We investigated the underlying mechanisms driving this differential Th1 response between BALB/c and B6 mice. We characterized dermal dendritic cells by flow cytometric analysis. We measured the induced Th1/Th2 responses by measuring the IFN-γ/IL-13 contents of supernatants of antigen reactivation cultures of lymph node cells. We demonstrate that more dermal dendritic cells with higher activation status migrate into draining lymph nodes of B6 mice compared to BALB/c mice. Dermal dendritic cells of B6 mice have a greater ability to capture protein antigen than those of BALB/c mice. Moreover, increasing the activation status or amount of captured antigen in dermal dendritic cells induced a Th1 response in BALB/c mice. Further, differential activation behavior, but not antigen-capturing ability of dermal dendritic cells between BALB/c and B6 mice is dendritic cell-intrinsic. These results show that the differential activation behavior of dermal dendritic cells underlies the strain-specific Th1 responses following single epicutaneous immunization. Furthermore, our findings highlight the potential differences between human atopics and non-atopics and provide useful information for the prediction and prevention of atopic diseases. Copyright © 2016 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  20. RAB-10-Dependent Membrane Transport Is Required for Dendrite Arborization

    Science.gov (United States)

    Zou, Wei; Yadav, Smita; DeVault, Laura; Jan, Yuh Nung; Sherwood, David R.

    2015-01-01

    Formation of elaborately branched dendrites is necessary for the proper input and connectivity of many sensory neurons. Previous studies have revealed that dendritic growth relies heavily on ER-to-Golgi transport, Golgi outposts and endocytic recycling. How new membrane and associated cargo is delivered from the secretory and endosomal compartments to sites of active dendritic growth, however, remains unknown. Using a candidate-based genetic screen in C. elegans, we have identified the small GTPase RAB-10 as a key regulator of membrane trafficking during dendrite morphogenesis. Loss of rab-10 severely reduced proximal dendritic arborization in the multi-dendritic PVD neuron. RAB-10 acts cell-autonomously in the PVD neuron and localizes to the Golgi and early endosomes. Loss of function mutations of the exocyst complex components exoc-8 and sec-8, which regulate tethering, docking and fusion of transport vesicles at the plasma membrane, also caused proximal dendritic arborization defects and led to the accumulation of intracellular RAB-10 vesicles. In rab-10 and exoc-8 mutants, the trans-membrane proteins DMA-1 and HPO-30, which promote PVD dendrite stabilization and branching, no longer localized strongly to the proximal dendritic membranes and instead were sequestered within intracellular vesicles. Together these results suggest a crucial role for the Rab10 GTPase and the exocyst complex in controlling membrane transport from the secretory and/or endosomal compartments that is required for dendritic growth. PMID:26394140

  1. New approaches and potential treatments for dry age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Francisco Max Damico

    2012-02-01

    Full Text Available Emerging treatments for dry age-related macular degeneration (AMD and geographi c atrophy focus on two strategies that target components involved in physiopathological pathways: prevention of photoreceptors and retinal pigment epithelium loss (neuroprotection induction, oxidative damage prevention, and visual cycle modification and suppression of inflammation. Neuroprotective drugs, such as ciliary neurotrophic factor, brimonidine tartrate, tandospirone, and anti-amyloid β antibodies, aim to prevent apoptosis of retinal cells. Oxidative stress and depletion of essential micronutrients are targeted by the Age-Related Eye Disease Study (AREDS formulation. Visual cycle modulators reduce the activity of the photoreceptors and retinal accumulation of toxic fluorophores and lipofuscin. Eyes with dry age-related macular degeneration present chronic inflammation and potential treatments include corticosteroid and complement inhibition. We review the current concepts and rationale of dry age-related macular degeneration treatment that will most likely include a combination of drugs targeting different pathways involved in the development and progression of age-related macular degeneration.

  2. Sleeping dendrites: fiber-optic measurements of dendritic calcium activity in freely moving and sleeping animals

    Directory of Open Access Journals (Sweden)

    Julie Seibt

    2014-03-01

    Full Text Available Dendrites are the post-synaptic sites of most excitatory and inhibitory synapses in the brain, making them the main location of cortical information processing and synaptic plasticity. Although current hypotheses suggest a central role for sleep in proper cognitive function and brain plasticity, virtually nothing is known about changes in dendritic activity across the sleep-wake cycle and how waking experience modifies this activity. To start addressing these questions, we developed a method that allows long-term recordings of EEGs/EMG combined with in vivo cortical calcium (Ca2+ activity in freely moving and sleeping rats. We measured Ca2+ activity from populations of dendrites of layer (L 5 pyramidal neurons (n = 13 rats that we compared with Ca2+ activity from populations of neurons in L2/3 (n = 11 rats. L5 and L2/3 neurons were labelled using bolus injection of OGB1-AM or GCaMP6 (1. Ca2+ signals were detected using a fiber-optic system (cannula diameter = 400µm, transmitting the changes in fluorescence to a photodiode. Ca2+ fluctuations could then be correlated with ongoing changes in brain oscillatory activity during 5 major brain states: active wake [AW], quiet wake [QW], NREM, REM and NREM-REM transition (or intermediate state, [IS]. Our Ca2+ recordings show large transients in L5 dendrites and L2/3 neurons that oscillate predominantly at frequencies In summary, we show that this technique is successful in monitoring fluctuations in ongoing dendritic Ca2+ activity during natural brain states and allows, in principle, to combine behavioral measurement with imaging from various brain regions (e.g. deep structures in freely behaving animals. Using this method, we show that Ca2+ transients from populations of L2/3 neurons and L5 dendrites are deferentially regulated across the sleep/wake cycle, with dendritic activity being the highest during the IS sleep. Our correlation analysis suggests that specific sleep EEG activity during NREM and IS

  3. A Genome-Wide Screen for Dendritically Localized RNAs Identifies Genes Required for Dendrite Morphogenesis

    Directory of Open Access Journals (Sweden)

    Mala Misra

    2016-08-01

    Full Text Available Localizing messenger RNAs at specific subcellular sites is a conserved mechanism for targeting the synthesis of cytoplasmic proteins to distinct subcellular domains, thereby generating the asymmetric protein distributions necessary for cellular and developmental polarity. However, the full range of transcripts that are asymmetrically distributed in specialized cell types, and the significance of their localization, especially in the nervous system, are not known. We used the EP-MS2 method, which combines EP transposon insertion with the MS2/MCP in vivo fluorescent labeling system, to screen for novel localized transcripts in polarized cells, focusing on the highly branched Drosophila class IV dendritic arborization neurons. Of a total of 541 lines screened, we identified 55 EP-MS2 insertions producing transcripts that were enriched in neuronal processes, particularly in dendrites. The 47 genes identified by these insertions encode molecularly diverse proteins, and are enriched for genes that function in neuronal development and physiology. RNAi-mediated knockdown confirmed roles for many of the candidate genes in dendrite morphogenesis. We propose that the transport of mRNAs encoded by these genes into the dendrites allows their expression to be regulated on a local scale during the dynamic developmental processes of dendrite outgrowth, branching, and/or remodeling.

  4. Evaluating Local Primary Dendrite Arm Spacing Characterization Techniques Using Synthetic Directionally Solidified Dendritic Microstructures

    Science.gov (United States)

    Tschopp, Mark A.; Miller, Jonathan D.; Oppedal, Andrew L.; Solanki, Kiran N.

    2015-10-01

    Microstructure characterization continues to play an important bridge to understanding why particular processing routes or parameters affect the properties of materials. This statement certainly holds true in the case of directionally solidified dendritic microstructures, where characterizing the primary dendrite arm spacing is vital to developing the process-structure-property relationships that can lead to the design and optimization of processing routes for defined properties. In this work, four series of simulations were used to examine the capability of a few Voronoi-based techniques to capture local microstructure statistics (primary dendrite arm spacing and coordination number) in controlled (synthetically generated) microstructures. These simulations used both cubic and hexagonal microstructures with varying degrees of disorder (noise) to study the effects of length scale, base microstructure, microstructure variability, and technique parameters on the local PDAS distribution, local coordination number distribution, bulk PDAS, and bulk coordination number. The Voronoi tesselation technique with a polygon-side-length criterion correctly characterized the known synthetic microstructures. By systematically studying the different techniques for quantifying local primary dendrite arm spacings, we have evaluated their capability to capture this important microstructure feature in different dendritic microstructures, which can be an important step for experimentally correlating with both processing and properties in single crystal nickel-based superalloys.

  5. Sensitivity of Dendritic Cells to Microenvironment Signals

    Directory of Open Access Journals (Sweden)

    Juliana Maria Motta

    2016-01-01

    Full Text Available Dendritic cells are antigen-presenting cells capable of either activating the immune response or inducing and maintaining immune tolerance. They do this by integrating stimuli from the environment and changing their functional status as a result of plasticity. The modifications suffered by these cells have consequences in the way the organism may respond. In the present work two opposing situations known to affect dendritic cells are analyzed: tumor growth, leading to a microenvironment that favors the induction of a tolerogenic profile, and organ transplantation, which leads to a proinflammatory profile. Lessons learned from these situations may help to understand the mechanisms of modulation resulting not only from the above circumstances, but also from other pathologies.

  6. Role of Dendritic Cells in Immune Dysfunction

    Science.gov (United States)

    Savary, Cherylyn A.

    1997-01-01

    Specific aims include: (1) Application of the bioreactor to enhance cytokine-regulated proliferation and maturation of dendritic cells (DC); (2) Based on clues from spaceflight: compare the frequency and function of DC in normal donors and immunocompromised cancer patients; and (3) Initiate studies on the efficiency of cytokine therapy and DC-assisted immunotherapy (using bioreactor-expanded DC) in animal models of experimental fungal infections.

  7. Fabrication of dendritic silver-coated copper powders by galvanic displacement reaction and their thermal stability against oxidation

    Energy Technology Data Exchange (ETDEWEB)

    Park, Yu-Seon [School of Chemical Engineering, Sungkyunkwan University, Suwon 16419 (Korea, Republic of); Farad Materials Co., Ltd., Suwon 16419 (Korea, Republic of); An, Chang Yong; Kannan, Padmanathan Karthick; Seo, Nary [School of Chemical Engineering, Sungkyunkwan University, Suwon 16419 (Korea, Republic of); Zhuo, Kai [School of Chemical Engineering, Sungkyunkwan University, Suwon 16419 (Korea, Republic of); Farad Materials Co., Ltd., Suwon 16419 (Korea, Republic of); Yoo, Tae Kyong [School of Chemical Engineering, Sungkyunkwan University, Suwon 16419 (Korea, Republic of); Chung, Chan-Hwa, E-mail: chchung@skku.edu [School of Chemical Engineering, Sungkyunkwan University, Suwon 16419 (Korea, Republic of); Farad Materials Co., Ltd., Suwon 16419 (Korea, Republic of)

    2016-12-15

    Highlights: • The dendritic silver-coated copper powders with high specific surface area have been prepared using a simple wet chemical reduction process at room temperature. • It is found that the Cu starts to be oxidized into Cu{sub 2}O followed by CuO at elevated temperatures. • The more amount of Ag-coating provides the less oxidation, which confirms that the Ag-shell prevents the Cu-core from oxidation. • The resistivity of dendritic 33.27 wt.% Ag-coated Cu powders was measured to 25.67 μΩ cm after the annealing at 150 °C for 30 min. - Abstract: Two steps of wet chemical processes have been developed for the preparation of core-shell nanostructures of copper and silver, which is a facile and low cost method for the production of large quantity of dendritic powders. First step involves a galvanic displacement reaction with hydrogen evolution which is the motive force of spontaneous electrochemical reaction. To achieve the core-shell structure, silver has been coated on the dendritic copper using the galvanic displacement reaction. The dendritic silver-coated copper powders exhibit high surface-area, excellent conductivity, and good oxidation resistance. It has been found that silver-coated copper powders maintain the electrical conductivity even after annealing at 150 °C for several to tens of minutes, thus it is a promising material and an alternative to pure silver powders in printed electronics application.

  8. Fabrication of dendritic silver-coated copper powders by galvanic displacement reaction and their thermal stability against oxidation

    International Nuclear Information System (INIS)

    Park, Yu-Seon; An, Chang Yong; Kannan, Padmanathan Karthick; Seo, Nary; Zhuo, Kai; Yoo, Tae Kyong; Chung, Chan-Hwa

    2016-01-01

    Highlights: • The dendritic silver-coated copper powders with high specific surface area have been prepared using a simple wet chemical reduction process at room temperature. • It is found that the Cu starts to be oxidized into Cu_2O followed by CuO at elevated temperatures. • The more amount of Ag-coating provides the less oxidation, which confirms that the Ag-shell prevents the Cu-core from oxidation. • The resistivity of dendritic 33.27 wt.% Ag-coated Cu powders was measured to 25.67 μΩ cm after the annealing at 150 °C for 30 min. - Abstract: Two steps of wet chemical processes have been developed for the preparation of core-shell nanostructures of copper and silver, which is a facile and low cost method for the production of large quantity of dendritic powders. First step involves a galvanic displacement reaction with hydrogen evolution which is the motive force of spontaneous electrochemical reaction. To achieve the core-shell structure, silver has been coated on the dendritic copper using the galvanic displacement reaction. The dendritic silver-coated copper powders exhibit high surface-area, excellent conductivity, and good oxidation resistance. It has been found that silver-coated copper powders maintain the electrical conductivity even after annealing at 150 °C for several to tens of minutes, thus it is a promising material and an alternative to pure silver powders in printed electronics application.

  9. Families and degenerations of conformal field theories

    Energy Technology Data Exchange (ETDEWEB)

    Roggenkamp, D.

    2004-09-01

    In this work, moduli spaces of conformal field theories are investigated. In the first part, moduli spaces corresponding to current-current deformation of conformal field theories are constructed explicitly. For WZW models, they are described in detail, and sigma model realizations of the deformed WZW models are presented. The second part is devoted to the study of boundaries of moduli spaces of conformal field theories. For this purpose a notion of convergence of families of conformal field theories is introduced, which admits certain degenerated conformal field theories to occur as limits. To such a degeneration of conformal field theories, a degeneration of metric spaces together with additional geometric structures can be associated, which give rise to a geometric interpretation. Boundaries of moduli spaces of toroidal conformal field theories, orbifolds thereof and WZW models are analyzed. Furthermore, also the limit of the discrete family of Virasoro minimal models is investigated. (orig.)

  10. Intramuscular degeneration process in Duchenne muscular dystrophy

    International Nuclear Information System (INIS)

    Hasegawa, Takeshi; Matsumra, Kiichiro; Hashimoto, Takahiro; Ikehira, Hiroo; Fukuda, Hiroshi; Tateno, Yukio.

    1992-01-01

    Intramuscular degeneration process of Duchenne dystrophy skeletal muscles was investigated by longitudinal skeletal muscle imaging with high-field-strength NMR-CT of 1.5 Tesla. Thigh muscles in 10 cases ranging in age from 4 to 19 years were examined by T 1 -weighted longitudinal images (TR=215∼505 ms, TE=19∼20 ms). The following results were obtained. Skeletal muscle degeneration was depicted as high signal intensity area reflecting its high fat contents. These high signal intensity areas had a longitudinally streaky appearance in parallel direction with myofibers. These findings were more prominent toward myotendon junction than muscle bellies. Skeletal muscle degeneration progressed rapidly between 7 to 10 years of age, and reached a plateau after that. (author)

  11. Inorganic arsenic impairs differentiation and functions of human dendritic cells

    Energy Technology Data Exchange (ETDEWEB)

    Macoch, Mélinda; Morzadec, Claudie [UMR INSERM U1085, Institut de Recherche sur la Santé, l' Environnement et le Travail (IRSET), Université de Rennes 1, 2 avenue du Professeur Léon Bernard, 35043 Rennes (France); Fardel, Olivier [UMR INSERM U1085, Institut de Recherche sur la Santé, l' Environnement et le Travail (IRSET), Université de Rennes 1, 2 avenue du Professeur Léon Bernard, 35043 Rennes (France); Pôle Biologie, Centre Hospitalier Universitaire (CHU) Rennes, 2 rue Henri Le Guilloux, 35033 Rennes (France); Vernhet, Laurent, E-mail: laurent.vernhet@univ-rennes1.fr [UMR INSERM U1085, Institut de Recherche sur la Santé, l' Environnement et le Travail (IRSET), Université de Rennes 1, 2 avenue du Professeur Léon Bernard, 35043 Rennes (France)

    2013-01-15

    Experimental studies have demonstrated that the antileukemic trivalent inorganic arsenic prevents the development of severe pro-inflammatory diseases mediated by excessive Th1 and Th17 cell responses. Differentiation of Th1 and Th17 subsets is mainly regulated by interleukins (ILs) secreted from dendritic cells (DCs) and the ability of inorganic arsenic to impair interferon-γ and IL-17 secretion by interfering with the physiology of DCs is unknown. In the present study, we demonstrate that high concentrations of sodium arsenite (As(III), 1–2 μM) clinically achievable in plasma of arsenic-treated patients, block differentiation of human peripheral blood monocytes into immature DCs (iDCs) by inducing their necrosis. Differentiation of monocytes in the presence of non-cytotoxic concentrations of As(III) (0.1 to 0.5 μM) only slightly impacts endocytotic activity of iDCs or expression of co-stimulatory molecules in cells activated with lipopolysaccharide. However, this differentiation in the presence of As(III) strongly represses secretion of IL-12p70 and IL-23, two major regulators of Th1 and Th17 activities, from iDCs stimulated with different toll-like receptor (TLR) agonists in metalloid-free medium. Such As(III)-exposed DCs also exhibit reduced mRNA levels of IL12A and/or IL12B genes when activated with TLR agonists. Finally, differentiation of monocytes with non-cytotoxic concentrations of As(III) subsequently reduces the ability of activated DCs to stimulate the release of interferon-γ and IL-17 from Th cells. In conclusion, our results demonstrate that clinically relevant concentrations of inorganic arsenic markedly impair in vitro differentiation and functions of DCs, which may contribute to the putative beneficial effects of the metalloid towards inflammatory autoimmune diseases. Highlights: ► Inorganic arsenic impairs differentiation and functions of human dendritic cells (DCs) ► Arsenite (> 1 μM) blocks differentiation of dendritic cells by

  12. Inorganic arsenic impairs differentiation and functions of human dendritic cells

    International Nuclear Information System (INIS)

    Macoch, Mélinda; Morzadec, Claudie; Fardel, Olivier; Vernhet, Laurent

    2013-01-01

    Experimental studies have demonstrated that the antileukemic trivalent inorganic arsenic prevents the development of severe pro-inflammatory diseases mediated by excessive Th1 and Th17 cell responses. Differentiation of Th1 and Th17 subsets is mainly regulated by interleukins (ILs) secreted from dendritic cells (DCs) and the ability of inorganic arsenic to impair interferon-γ and IL-17 secretion by interfering with the physiology of DCs is unknown. In the present study, we demonstrate that high concentrations of sodium arsenite (As(III), 1–2 μM) clinically achievable in plasma of arsenic-treated patients, block differentiation of human peripheral blood monocytes into immature DCs (iDCs) by inducing their necrosis. Differentiation of monocytes in the presence of non-cytotoxic concentrations of As(III) (0.1 to 0.5 μM) only slightly impacts endocytotic activity of iDCs or expression of co-stimulatory molecules in cells activated with lipopolysaccharide. However, this differentiation in the presence of As(III) strongly represses secretion of IL-12p70 and IL-23, two major regulators of Th1 and Th17 activities, from iDCs stimulated with different toll-like receptor (TLR) agonists in metalloid-free medium. Such As(III)-exposed DCs also exhibit reduced mRNA levels of IL12A and/or IL12B genes when activated with TLR agonists. Finally, differentiation of monocytes with non-cytotoxic concentrations of As(III) subsequently reduces the ability of activated DCs to stimulate the release of interferon-γ and IL-17 from Th cells. In conclusion, our results demonstrate that clinically relevant concentrations of inorganic arsenic markedly impair in vitro differentiation and functions of DCs, which may contribute to the putative beneficial effects of the metalloid towards inflammatory autoimmune diseases. Highlights: ► Inorganic arsenic impairs differentiation and functions of human dendritic cells (DCs) ► Arsenite (> 1 μM) blocks differentiation of dendritic cells by

  13. Taurine Provides Neuroprotection against Retinal Ganglion Cell Degeneration

    Science.gov (United States)

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

    2012-01-01

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

  14. The Isothermal Dendritic Growth Experiment Archive

    Science.gov (United States)

    Koss, Matthew

    2009-03-01

    The growth of dendrites is governed by the interplay between two simple and familiar processes---the irreversible diffusion of energy, and the reversible work done in the formation of new surface area. To advance our understanding of these processes, NASA sponsored a project that flew on the Space Shuttle Columbia is 1994, 1996, and 1997 to record and analyze benchmark data in an apparent-microgravity ``laboratory.'' In this laboratory, energy transfer by gravity driven convection was essentially eliminated and one could test independently, for the first time, both components of dendritic growth theory. The analysis of this data shows that although the diffusion of energy can be properly accounted for, the results from interfacial physics appear to be in disagreement and alternate models should receive increased attention. Unfortunately, currently and for the foreseeable future, there is no access or financial support to develop and conduct additional experiments of this type. However, the benchmark data of 35mm photonegatives, video, and all supporting instrument data are now available at the IDGE Archive at the College of the Holy Cross. This data may still have considerable relevance to researchers working specifically with dendritic growth, and more generally those working in the synthesis, growth & processing of materials, multiscale computational modeling, pattern formation, and systems far from equilibrium.

  15. Epoxiconazole-induced degeneration in rat placenta and the effects of estradiol supplementation.

    Science.gov (United States)

    Rey Moreno, Maria Cecilia; Fussell, Karma C; Gröters, Sibylle; Schneider, Steffen; Strauss, Volker; Stinchcombe, Stefan; Fegert, Ivana; Veras, Mariana; van Ravenzwaay, Bennard

    2013-06-01

    Epoxiconazole (CAS-No. 133855-98-8) was recently shown to cause both a marked depletion of maternal estradiol blood levels and a significantly increased incidence of late fetal mortality when administered to pregnant rats throughout gestation (GD 7-18 or 21); estradiol supplementation prevented this epoxiconazole effect in rats (Stinchcombe et al., 2013), indicating that epoxiconazole-mediated estradiol depletion is a critical key event for induction of late fetal resorptions in rats. For further elucidation of the mode of action, the placentas from these modified prenatal developmental toxicity experiments with 23 and 50 mg/kg bw/d epoxiconazole were subjected to a detailed histopathological examination. This revealed dose-dependent placental degeneration characterized by cystic dilation of maternal sinuses in the labyrinth, leading to rupture of the interhemal membrane. Concomitant degeneration occurred in the trophospongium. Both placentas supporting live fetuses and late fetal resorptions were affected; the highest degree of severity was observed in placentas with late resorptions. Placental degeneration correlated with a severe decline in maternal serum estradiol concentration. Supplementation with 0.5 and 1.0 μg of the synthetic estrogen estradiol cyclopentylpropionate per day reduced the severity of the degeneration in placentas with live fetuses. The present study demonstrates that both the placental degeneration and the increased incidence of late fetal resorptions are due to decreased levels of estrogen, since estrogen supplementation ameliorates the former and abolishes the latter. © 2013 Wiley Periodicals, Inc.

  16. Morphological and physiological retinal degeneration induced by intravenous delivery of vitamin A dimers in rabbits

    Directory of Open Access Journals (Sweden)

    Jackie Penn

    2015-02-01

    Full Text Available The eye uses vitamin A as a cofactor to sense light and, during this process, some vitamin A molecules dimerize, forming vitamin A dimers. A striking chemical signature of retinas undergoing degeneration in major eye diseases such as age-related macular degeneration (AMD and Stargardt disease is the accumulation of these dimers in the retinal pigment epithelium (RPE and Bruch’s membrane (BM. However, it is not known whether dimers of vitamin A are secondary symptoms or primary insults that drive degeneration. Here, we present a chromatography-free method to prepare gram quantities of the vitamin A dimer, A2E, and show that intravenous administration of A2E to the rabbit results in retinal degeneration. A2E-damaged photoreceptors and RPE cells triggered inflammation, induced remolding of the choroidal vasculature and triggered a decline in the retina’s response to light. Data suggest that vitamin A dimers are not bystanders, but can be primary drivers of retinal degeneration. Thus, preventing dimer formation could be a preemptive strategy to address serious forms of blindness.

  17. Retinal Cell Degeneration in Animal Models

    Directory of Open Access Journals (Sweden)

    Masayuki Niwa

    2016-01-01

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

  18. Kinematic control of robot with degenerate wrist

    Science.gov (United States)

    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.

  19. Genetics of lattice degeneration of the retina.

    Science.gov (United States)

    Murakami, F; Ohba, N

    1982-01-01

    First-degree relatives of proband patients with lattice degeneration of the retina revealed a significantly higher prevalence of the disease than the prevalence in the general population: the former had the disease about three times as frequently as the latter. The observed data were analyzed in terms of their accordance with recognized genetic models. The inheritance pattern did not fit well to a monogenic mode of inheritance, and it was hypothesized that a polygenic or multifactorial mode of inheritance is the most likely for lattice degeneration of the retina.

  20. CT of sarcomatous degeneration in neurofibromatosis

    International Nuclear Information System (INIS)

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

    1983-01-01

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

  1. Molecular identity of dendritic voltage-gated sodium channels.

    Science.gov (United States)

    Lorincz, Andrea; Nusser, Zoltan

    2010-05-14

    Active invasion of the dendritic tree by action potentials (APs) generated in the axon is essential for associative synaptic plasticity and neuronal ensemble formation. In cortical pyramidal cells (PCs), this AP back-propagation is supported by dendritic voltage-gated Na+ (Nav) channels, whose molecular identity is unknown. Using a highly sensitive electron microscopic immunogold technique, we revealed the presence of the Nav1.6 subunit in hippocampal CA1 PC proximal and distal dendrites. Here, the subunit density is lower by a factor of 35 to 80 than that found in axon initial segments. A gradual decrease in Nav1.6 density along the proximodistal axis of the dendritic tree was also detected without any labeling in dendritic spines. Our results reveal the characteristic subcellular distribution of the Nav1.6 subunit, identifying this molecule as a key substrate enabling dendritic excitability.

  2. Gelidium amansii promotes dendritic spine morphology and synaptogenesis, and modulates NMDA receptor-mediated postsynaptic current.

    Science.gov (United States)

    Hannan, Md Abdul; Mohibbullah, Md; Hong, Yong-Ki; Nam, Joo Hyun; Moon, Il Soo

    2014-01-01

    Neurotrophic factors are essential for the differentiation and maturation of developing neurons as well as providing survival support to the mature neurons. Moreover, therapeutically neurotrophic factors are promising to reconstruct partially damaged neuronal networks in neurodegenerative diseases. In the previous study, we reported that the ethanol extract of an edible marine alga, Gelidium amansii (GAE) had shown promising effects in the development and maturation of both axon and dendrites of hippocampal neurons. Here, we demonstrate that in primary culture of hippocampal neurons (1) GAE promotes a significant increase in the number of filopodia and dendritic spines; (2) promotes synaptogenesis; (3) enhances N-methyl-D-aspartic acid (NMDA) receptor recruitment; and (4) modulates NMDA-receptor-mediated postsynaptic current. Taken together these findings that GAE might be involved in both morphological and functional maturation of neurons suggest the possibility that GAE may constitute a promising candidate for novel compounds for the prevention and treatment of neurodegenerative diseases.

  3. Sensory Neuron Fates Are Distinguished by a Transcriptional Switch that Regulates Dendrite Branch Stabilization

    Science.gov (United States)

    Smith, Cody J.; O’Brien, Timothy; Chatzigeorgiou, Marios; Spencer, W. Clay; Feingold-Link, Elana; Husson, Steven J.; Hori, Sayaka; Mitani, Shohei; Gottschalk, Alexander; Schafer, William R.; Miller, David M.

    2013-01-01

    SUMMARY Sensory neurons adopt distinct morphologies and functional modalities to mediate responses to specific stimuli. Transcription factors and their downstream effectors orchestrate this outcome but are incompletely defined. Here, we show that different classes of mechanosensory neurons in C. elegans are distinguished by the combined action of the transcription factors MEC-3, AHR-1, and ZAG-1. Low levels of MEC-3 specify the elaborate branching pattern of PVD nociceptors, whereas high MEC-3 is correlated with the simple morphology of AVM and PVM touch neurons. AHR-1 specifies AVM touch neuron fate by elevating MEC-3 while simultaneously blocking expression of nociceptive genes such as the MEC-3 target, the claudin-like membrane protein HPO-30, that promotes the complex dendritic branching pattern of PVD. ZAG-1 exercises a parallel role to prevent PVM from adopting the PVD fate. The conserved dendritic branching function of the Drosophila AHR-1 homolog, Spineless, argues for similar pathways in mammals. PMID:23889932

  4. Suppressive effects of primed eosinophils on single epicutaneous sensitization through regulation of dermal dendritic cells.

    Science.gov (United States)

    Lin, Jing-Yi; Ta, Yng-Cun; Liu, I-Lin; Chen, Hsi-Wen; Wang, Li-Fang

    2016-07-01

    Eosinophils are multifunctional innate immune cells involved in many aspects of innate and adaptive immunity. Epicutaneous sensitization with protein allergen is an important sensitization route for atopic dermatitis. In this study, using a murine single protein-patch model, we show that eosinophils of a primed status accumulate in draining lymph nodes following single epicutaneous sensitization. Further, depletion of eosinophils results in enhancement of the induced Th1/Th2 immune responses, whereas IL-5-induced hypereosinophilia suppresses these responses. Mechanistically, primed eosinophils cause a reduction in the numbers and activation status of dermal dendritic cells in draining lymph nodes. Collectively, these results demonstrate that primed eosinophils exert suppressive effects on single epicutaneous sensitization through regulation of dermal dendritic cells. Thus, these findings highlight the critical roles of eosinophils in the pathogenesis of atopic dermatitis with important clinical implications for the prevention of allergen sensitization. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Efficacy of a therapeutic vaccine using mutated β-amyloid sensitized dendritic cells in Alzheimer's mice.

    Science.gov (United States)

    Luo, Zhongqiu; Li, Jialin; Nabar, Neel R; Lin, Xiaoyang; Bai, Ge; Cai, Jianfeng; Zhou, Shu-Feng; Cao, Chuanhai; Wang, Jinhuan

    2012-09-01

    Despite FDA suspension of Elan's AN-1792 amyloid beta (Aβ) vaccine in phase IIb clinical trials, the implications of this study are the guiding principles for contemporary anti-Aβ immunotherapy against Alzheimer's disease (AD). AN-1792 showed promising results with regards to Aβ clearance and cognitive function improvement, but also exhibited an increased risk of Th1 mediated meningoencephalitis. As such, vaccine development has continued with an emphasis on eliciting a notable anti-Aβ antibody titer, while avoiding the unwanted Th1 pro-inflammatory response. Previously, we published the first report of an Aβ sensitized dendritic cell vaccine as a therapeutic treatment for AD in BALB/c mice. Our vaccine elicited an anti-Aβ titer, with indications that a Th1 response was not present. This study is the first to investigate the efficacy and safety of our dendritic cell vaccine for the prevention of AD in transgenic mouse models (PDAPP) for AD. We also used Immunohistochemistry to characterize the involvement of LXR, ABCA1, and CD45 in order to gain insight into the potential mechanisms through which this vaccine may provide benefit. The results indicate that (1) the use of mutant Aβ1-42 sensitized dendritic cell vaccine results in durable antibody production, (2) the vaccine provides significant benefits with regards to cognitive function without the global (Th1) inflammation seen in prior Aβ vaccines, (3) histological studies showed an overall decrease in Aβ burden, with an increase in LXR, ABCA1, and CD45, and (4) the beneficial results of our DC vaccine may be due to the LXR/ABCA1 pathway. In the future, mutant Aβ sensitized dendritic cell vaccines could be an efficacious and safe method for the prevention or treatment of AD that circumvents problems associated with traditional anti-Aβ vaccines.

  6. Driving and Age-Related Macular Degeneration

    OpenAIRE

    Owsley, Cynthia; McGwin, Gerald

    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, and considers directions for future research.

  7. Specific heats of degenerate ideal gases

    OpenAIRE

    Caruso, Francisco; Oguri, Vitor; Silveira, Felipe

    2017-01-01

    From arguments based on Heisenberg's uncertainty principle and Pauli's exclusion principle, the molar specific heats of degenerate ideal gases at low temperatures are estimated, giving rise to values consistent with the Nerst-Planck Principle (third law of Thermodynamics). The Bose-Einstein condensation phenomenon based on the behavior of specific heat of massive and non-relativistic boson gases is also presented.

  8. Ecological transition predictably associated with gene degeneration.

    Science.gov (United States)

    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.

  9. Geometry of non-degenerate Susskind fermions

    International Nuclear Information System (INIS)

    Mitra, P.

    1983-01-01

    The Dirac-Kaehler equation on the lattice is known to describe the degenerate ''flavours'' appering in Susskind's approach to lattice fermions. We study the modification that has to be made in this equation in order to lift the degeneracy and give the flavours arbitrary different masses. (orig.)

  10. Exploring Nonconvex, Crossed and Degenerate Polygons

    Science.gov (United States)

    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…

  11. Degenerate parabolic stochastic partial differential equations

    Czech Academy of Sciences Publication Activity Database

    span class="emphasis">Hofmanová, Martinaspan>

    2013-01-01

    Roč. 123, č. 12 (2013), s. 4294-4336 ISSN 0304-4149 R&D Projects: GA ČR GAP201/10/0752 Institutional support: RVO:67985556 Keywords : kinetic solutions * degenerate stochastic parabolic equations Subject RIV: BA - General Mathematics Impact factor: 1.046, year: 2013 http://library.utia.cas.cz/separaty/2013/SI/hofmanova-0397241.pdf

  12. MR findings of degenerating parenchymal neurocysticercosis

    International Nuclear Information System (INIS)

    Lee, Yul; Chung, Eun A; Yang, Ik; Park, Hae Jung; Chung, Soo Young

    1996-01-01

    To evaluate MR imaging findings of degenerating parenchymal neurocysticercosis and to determine the characteristics which distinguish it from other brain diseases. MR imagings of 19 patients (56 lesions) of degenerating parenchymal neurocysticercosis were retrospectively evaluated, focusing on the size and location of lesions signal intensity patterns of cyst fluid and wall, the extent of the surrounding edema and features of contrast enhancement. Degenerating parenchymal neurocysticercosis was located in gray or subcortical while matter in 89.3% of 56 lesions (50/56) ; most of these (98.2%) were smaller than 2 cm in diameter. Cyst fluid signal was hyperintense relative to CSF on T1 and proton density weighted images (92.9%). A hypointense signal rim of the cyst wall was noted in the lesions on proton density (92.9%) and T2 weighted (98.2%) images, Surrounding edema was mostly mild. Peripheral rim enhancement was noted in all lesions, and this was frequently irregular and lobulated (67.9%) with a focal defect in the enhancing rim(41.1%). Findings which could be helpful in distinguishing degenerating parencymal neurocysticercosis from other brain diseases are as follows : small, superficial lesions ; hyperintense signal of the cyst fluid on T1 and proton density weighted images ; hypointense signal of the cyst wall on proton density and T2 weighted images ; relatively mild extent of surrounding edema, and peripheral rim enhancement which is frequently irregular and lobulated with a focal defect in the enhancing rim

  13. Degenerate conformal theories on higher-genus surfaces

    International Nuclear Information System (INIS)

    Gerasimov, A.A.

    1989-01-01

    Two-dimensional degenerate field theories on higher-genus surfaces are investigated. Objects are built on the space of moduli, whose linear combinations are hypothetically conformal blocks in degenerate theories

  14. MR imaging of central nervous system white matter tract degeneration (Wallerian degeneration)

    International Nuclear Information System (INIS)

    Kuhn, M.J.; Johnson, K.A.; Davis, K.R.

    1987-01-01

    Wallerian degeneration is readily demonstrated by MR imaging. Twenty-one patients with MR signal abnormalities in various central nervous system (CNS) white matter tracts were evaluated with regard to (1) nature of signal abnormality, (2) MR anatomy of the involved tract, and (3) primary pathology (e.g., infarct, tumor, hemorrhage). Most examples of wallerian degeneration result in a thin, continuous band of long T1, long T2 signal abnormality conforming to the known anatomic pathway of a CNS axonal tract. Old, large cortical infarcts have the greatest propensity to show subsequent white-matter tract degeneration. Corticospinal tract degeneration is the type most readily visualized, often seen extending completely from the cerebral cortex through the medulla

  15. Ethanol Exposure Causes Muscle Degeneration in Zebrafish

    Directory of Open Access Journals (Sweden)

    Elizabeth C. Coffey

    2018-03-01

    Full Text Available 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.

  16. CTLA-4 blockade during dendritic cell based booster vaccination influences dendritic cell survival and CTL expansion

    DEFF Research Database (Denmark)

    Pedersen, Anders E; Ronchese, Franca

    2007-01-01

    Dendritic cells (DCs) are potent antigen-presenting cells and critical for the priming of CD8+ T cells. Therefore the use of these cells as adjuvant cells has been tested in a large number of experimental and clinical vaccination studies, in particular cancer vaccine studies. A number of protocols...

  17. Nanofibrous nonwovens based on dendritic-linear-dendritic poly(ethylene glycol) hybrids

    DEFF Research Database (Denmark)

    Kikionis, Stefanos; Ioannou, Efstathia; Andren, Oliver C.J.

    2017-01-01

    unsuccessful. Nevertheless, when these DLD hybrids were blended with an array of different biodegradable polymers as entanglement enhancers, nanofibrous nonwovens were successfully prepared by electrospinning. The pseudogeneration degree of the DLDs, the nature of the co-electrospun polymer and the solvent...... nanofibers. Such dendritic nanofibrous scaffolds can be promising materials for biomedical applications due to their biocompatibility, biodegradability, multifunctionality, and advanced structural architecture....

  18. Calcium channel blockers inhibit retinal degeneration in the retinal-degeneration-B mutant of Drosophila.

    Science.gov (United States)

    Sahly, I; Bar Nachum, S; Suss-Toby, E; Rom, A; Peretz, A; Kleiman, J; Byk, T; Selinger, Z; Minke, B

    1992-01-01

    Light accelerates degeneration of photoreceptor cells of the retinal degeneration B (rdgB) mutant of Drosophila. During early stages of degeneration, light stimuli evoke spikes from photoreceptors of the mutant fly; no spikes can be recorded from photoreceptors of the wild-type fly. Production of spike potentials from mutant photoreceptors was blocked by diltiazem, verapamil hydrochloride, and cadmium. Little, if any, effect of the (-)-cis isomer or (+)-cis isomer of diltiazem on the light response was seen. Further, the (+)-cis isomer was approximately 50 times more effective than the (-)-cis isomer in blocking the Ca2+ spikes, indicating that diltiazem action on the rdgB eye is mediated by means of blocking voltage-sensitive Ca2+ channels, rather than by blocking the light-sensitive channels. Application of the Ca(2+)-channel blockers (+)-cis-diltiazem and verapamil hydrochloride to the eyes of rdgB flies over a 7-day period largely inhibited light-dependent degeneration of the photoreceptor cells. Pulse labeling with [32P]phosphate showed much greater incorporation into eye proteins of [32P]phosphate in rdgB flies than in wild-type flies. Retarding the light-induced photoreceptor degeneration in the mutant by Ca(2+)-channel blockers, thus, suggests that toxic increase in intracellular Ca2+ by means of voltage-gated Ca2+ channels, possibly secondary to excessive phosphorylation, leads to photoreceptor degeneration in the rdgB mutant. Images PMID:1309615

  19. Degenerate r-Stirling Numbers and r-Bell Polynomials

    Science.gov (United States)

    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.

  20. Fine structure of synapses on dendritic spines

    Directory of Open Access Journals (Sweden)

    Michael eFrotscher

    2014-09-01

    Full Text Available Camillo Golgi’s Reazione Nera led to the discovery of dendritic spines, small appendages originating from dendritic shafts. With the advent of electron microscopy (EM they were identified as sites of synaptic contact. Later it was found that changes in synaptic strength were associated with changes in the shape of dendritic spines. While live-cell imaging was advantageous in monitoring the time course of such changes in spine structure, EM is still the best method for the simultaneous visualization of all cellular components, including actual synaptic contacts, at high resolution. Immunogold labeling for EM reveals the precise localization of molecules in relation to synaptic structures. Previous EM studies of spines and synapses were performed in tissue subjected to aldehyde fixation and dehydration in ethanol, which is associated with protein denaturation and tissue shrinkage. It has remained an issue to what extent fine structural details are preserved when subjecting the tissue to these procedures. In the present review, we report recent studies on the fine structure of spines and synapses using high-pressure freezing (HPF, which avoids protein denaturation by aldehydes and results in an excellent preservation of ultrastructural detail. In these studies, HPF was used to monitor subtle fine-structural changes in spine shape associated with chemically induced long-term potentiation (cLTP at identified hippocampal mossy fiber synapses. Changes in spine shape result from reorganization of the actin cytoskeleton. We report that cLTP was associated with decreased immunogold labeling for phosphorylated cofilin (p-cofilin, an actin-depolymerizing protein. Phosphorylation of cofilin renders it unable to depolymerize F-actin, which stabilizes the actin cytoskeleton. Decreased levels of p-cofilin, in turn, suggest increased actin turnover, possibly underlying the changes in spine shape associated with cLTP. The findings reviewed here establish HPF as

  1. Dendritic cells during Epstein Barr virus infection

    Directory of Open Access Journals (Sweden)

    Christian eMunz

    2014-06-01

    Full Text Available Epstein Barr virus (EBV causes persistent infection in more than 90% of the human adult population and is associated with 2% of all tumors in humans. This -herpesvirus infects primarily human B and epithelial cells, but has been reported to be sensed by dendritic cells (DCs during primary infection. These activated DCs are thought to contribute to innate restriction of EBV infection and initiate EBV specific adaptive immune responses via cross-priming. The respective evidence and their potential importance for EBV specific vaccine development will be discussed in this review.

  2. Gliadin fragments promote migration of dendritic cells

    Czech Academy of Sciences Publication Activity Database

    Chládková, Barbara; Kamanová, Jana; Palová-Jelínková, Lenka; Cinová, Jana; Šebo, Peter; Tučková, Ludmila

    2011-01-01

    Roč. 15, č. 4 (2011), 938-948 ISSN 1582-1838 R&D Projects: GA ČR GA310/07/0414; GA ČR GD310/08/H077; GA ČR GA310/08/0447; GA AV ČR IAA500200801; GA AV ČR IAA500200914 Institutional research plan: CEZ:AV0Z50200510 Keywords : celiac disease * gliadin * dendritic cell Subject RIV: EC - Immunology Impact factor: 4.125, year: 2011

  3. Barriers in the brain : resolving dendritic spine morphology and compartmentalization

    NARCIS (Netherlands)

    Adrian, Max; Kusters, Remy; Wierenga, Corette J; Storm, Cornelis; Hoogenraad, Casper C; Kapitein, Lukas C

    2014-01-01

    Dendritic spines are micron-sized protrusions that harbor the majority of excitatory synapses in the central nervous system. The head of the spine is connected to the dendritic shaft by a 50-400 nm thin membrane tube, called the spine neck, which has been hypothesized to confine biochemical and

  4. Dendrites Enable a Robust Mechanism for Neuronal Stimulus Selectivity.

    Science.gov (United States)

    Cazé, Romain D; Jarvis, Sarah; Foust, Amanda J; Schultz, Simon R

    2017-09-01

    Hearing, vision, touch: underlying all of these senses is stimulus selectivity, a robust information processing operation in which cortical neurons respond more to some stimuli than to others. Previous models assume that these neurons receive the highest weighted input from an ensemble encoding the preferred stimulus, but dendrites enable other possibilities. Nonlinear dendritic processing can produce stimulus selectivity based on the spatial distribution of synapses, even if the total preferred stimulus weight does not exceed that of nonpreferred stimuli. Using a multi-subunit nonlinear model, we demonstrate that stimulus selectivity can arise from the spatial distribution of synapses. We propose this as a general mechanism for information processing by neurons possessing dendritic trees. Moreover, we show that this implementation of stimulus selectivity increases the neuron's robustness to synaptic and dendritic failure. Importantly, our model can maintain stimulus selectivity for a larger range of loss of synapses or dendrites than an equivalent linear model. We then use a layer 2/3 biophysical neuron model to show that our implementation is consistent with two recent experimental observations: (1) one can observe a mixture of selectivities in dendrites that can differ from the somatic selectivity, and (2) hyperpolarization can broaden somatic tuning without affecting dendritic tuning. Our model predicts that an initially nonselective neuron can become selective when depolarized. In addition to motivating new experiments, the model's increased robustness to synapses and dendrites loss provides a starting point for fault-resistant neuromorphic chip development.

  5. Modelling dendritic ecological networks in space: An integrated network perspective

    Science.gov (United States)

    Erin E. Peterson; Jay M. Ver Hoef; Dan J. Isaak; Jeffrey A. Falke; Marie-Josee Fortin; Chris E. Jordan; Kristina McNyset; Pascal Monestiez; Aaron S. Ruesch; Aritra Sengupta; Nicholas Som; E. Ashley Steel; David M. Theobald; Christian E. Torgersen; Seth J. Wenger

    2013-01-01

    Dendritic ecological networks (DENs) are a unique form of ecological networks that exhibit a dendritic network topology (e.g. stream and cave networks or plant architecture). DENs have a dual spatial representation; as points within the network and as points in geographical space. Consequently, some analytical methods used to quantify relationships in other types of...

  6. Dendritic Spines in Depression: What We Learned from Animal Models

    OpenAIRE

    Qiao, Hui; Li, Ming-Xing; Xu, Chang; Chen, Hui-Bin; An, Shu-Cheng; Ma, Xin-Ming

    2016-01-01

    Depression, a severe psychiatric disorder, has been studied for decades, but the underlying mechanisms still remain largely unknown. Depression is closely associated with alterations in dendritic spine morphology and spine density. Therefore, understanding dendritic spines is vital for uncovering the mechanisms underlying depression. Several chronic stress models, including chronic restraint stress (CRS), chronic unpredictable mild stress (CUMS), and chronic social defeat stress (CSDS), have ...

  7. Immune monitoring using mRNA-transfected dendritic cells

    DEFF Research Database (Denmark)

    Borch, Troels Holz; Svane, Inge Marie; Met, Özcan

    2016-01-01

    Dendritic cells are known to be the most potent antigen presenting cell in the immune system and are used as cellular adjuvants in therapeutic anticancer vaccines using various tumor-associated antigens or their derivatives. One way of loading antigen into the dendritic cells is by m......RNA electroporation, ensuring presentation of antigen through major histocompatibility complex I and potentially activating T cells, enabling them to kill the tumor cells. Despite extensive research in the field, only one dendritic cell-based vaccine has been approved. There is therefore a great need to elucidate...... and understand the immunological impact of dendritic cell vaccination in order to improve clinical benefit. In this chapter, we describe a method for performing immune monitoring using peripheral blood mononuclear cells and autologous dendritic cells transfected with tumor-associated antigen-encoding mRNA....

  8. Statins for age-related macular degeneration.

    Science.gov (United States)

    Gehlbach, Peter; Li, Tianjing; Hatef, Elham

    2015-02-11

    Age-related macular degeneration (AMD) is a progressive late onset disorder of the macula affecting central vision. Age-related macular degeneration is the leading cause of blindness in people over 65 years in industrialized countries. Recent epidemiologic, genetic, and pathological evidence has shown AMD shares a number of risk factors with atherosclerosis, leading to the hypothesis that statins may exert protective effects in AMD. The objective of this review was to examine the effectiveness of statins compared with other treatments, no treatment, or placebo in delaying the onset and progression of AMD. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2014, Issue 6), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to June 2014), EMBASE (January 1980 to June 2014), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to June 2014), PubMed (January 1946 to June 2014), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov), and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 5 June 2014. We included randomized controlled trials (RCTs) that compared statins with other treatments, no treatment, or placebo in participants who were either susceptible to or diagnosed as having early stages of AMD. We used standard methodological procedures expected by The Cochrane Collaboration. Two authors independently evaluated the search results against the selection criteria, abstracted data, and assessed risk of bias. We did not perform meta-analysis due to heterogeneity in the interventions and outcomes among the included studies. Two RCTs with 144 total participants met the selection criteria

  9. Dendritic Connectivity, Heterogeneity, and Scaling in Urban Stormwater Networks: Implications for Socio-Hydrology

    Science.gov (United States)

    Mejia, A.; Jovanovic, T.; Hale, R. L.; Gironas, J. A.

    2017-12-01

    Urban stormwater networks (USNs) are unique dendritic (tree-like) structures that combine both artificial (e.g., swales and pipes) and natural (e.g., streams and wetlands) components. They are central to stream ecosystem structure and function in urban watersheds. The emphasis of conventional stormwater management, however, has been on localized, temporal impacts (e.g., changes to hydrographs at discrete locations), and the performance of individual stormwater control measures. This is the case even though control measures are implemented to prevent impacts on the USN. We develop a modeling approach to retrospectively study hydrological fluxes and states in USNs and apply the model to an urban watershed in Scottsdale, Arizona, USA. Using outputs from the model, we analyze over space and time the network properties of dendritic connectivity, heterogeneity, and scaling. Results show that as the network growth over time, due to increasing urbanization, it tends to become more homogenous in terms of topological features but increasingly heterogeneous in terms of dynamic features. We further use the modeling results to address socio-hydrological implications for USNs. We find that the adoption over time of evolving management strategies (e.g., widespread implementation of vegetated swales and retention ponds versus pipes) may be locally beneficial to the USN but benefits may not propagate systematically through the network. The latter can be reinforced by sudden, perhaps unintended, changes to the overall dendritic connectivity.

  10. Low-Dose Cyclophosphamide Synergizes with Dendritic Cell-Based Immunotherapy in Antitumor Activity

    Directory of Open Access Journals (Sweden)

    Joris D. Veltman

    2010-01-01

    Full Text Available Clinical immunotherapy trials like dendritic cell-based vaccinations are hampered by the tumor's offensive repertoire that suppresses the incoming effector cells. Regulatory T cells are instrumental in suppressing the function of cytotoxic T cells. We studied the effect of low-dose cyclophosphamide on the suppressive function of regulatory T cells and investigated if the success rate of dendritic cell immunotherapy could be improved. For this, mesothelioma tumor-bearing mice were treated with dendritic cell-based immunotherapy alone or in combination with low-dose of cyclophosphamide. Proportions of regulatory T cells and the cytotoxic T cell functions at different stages of disease were analyzed. We found that low-dose cyclophosphamide induced beneficial immunomodulatory effects by preventing the induction of Tregs, and as a consequence, cytotoxic T cell function was no longer affected. Addition of cyclophosphamide improved immunotherapy leading to an increased median and overall survival. Future studies are needed to address the usefulness of this combination treatment for mesothelioma patients.

  11. Large and Small Dendritic Spines Serve Different Interacting Functions in Hippocampal Synaptic Plasticity and Homeostasis

    Directory of Open Access Journals (Sweden)

    Joshua J. W. Paulin

    2016-01-01

    Full Text Available The laying down of memory requires strong stimulation resulting in specific changes in synaptic strength and corresponding changes in size of dendritic spines. Strong stimuli can also be pathological, causing a homeostatic response, depressing and shrinking the synapse to prevent damage from too much Ca2+ influx. But do all types of dendritic spines serve both of these apparently opposite functions? Using confocal microscopy in organotypic slices from mice expressing green fluorescent protein in hippocampal neurones, the size of individual spines along sections of dendrite has been tracked in response to application of tetraethylammonium. This strong stimulus would be expected to cause both a protective homeostatic response and long-term potentiation. We report separation of these functions, with spines of different sizes reacting differently to the same strong stimulus. The immediate shrinkage of large spines suggests a homeostatic protective response during the period of potential danger. In CA1, long-lasting growth of small spines subsequently occurs consolidating long-term potentiation but only after the large spines return to their original size. In contrast, small spines do not change in dentate gyrus where potentiation does not occur. The separation in time of these changes allows clear functional differentiation of spines of different sizes.

  12. Activity-Dependent Exocytosis of Lysosomes Regulates the Structural Plasticity of Dendritic Spines.

    Science.gov (United States)

    Padamsey, Zahid; McGuinness, Lindsay; Bardo, Scott J; Reinhart, Marcia; Tong, Rudi; Hedegaard, Anne; Hart, Michael L; Emptage, Nigel J

    2017-01-04

    Lysosomes have traditionally been viewed as degradative organelles, although a growing body of evidence suggests that they can function as Ca 2+ stores. Here we examined the function of these stores in hippocampal pyramidal neurons. We found that back-propagating action potentials (bpAPs) could elicit Ca 2+ release from lysosomes in the dendrites. This Ca 2+ release triggered the fusion of lysosomes with the plasma membrane, resulting in the release of Cathepsin B. Cathepsin B increased the activity of matrix metalloproteinase 9 (MMP-9), an enzyme involved in extracellular matrix (ECM) remodelling and synaptic plasticity. Inhibition of either lysosomal Ca 2+ signaling or Cathepsin B release prevented the maintenance of dendritic spine growth induced by Hebbian activity. This impairment could be rescued by exogenous application of active MMP-9. Our findings suggest that activity-dependent exocytosis of Cathepsin B from lysosomes regulates the long-term structural plasticity of dendritic spines by triggering MMP-9 activation and ECM remodelling. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  13. Responsive linear-dendritic block copolymers.

    Science.gov (United States)

    Blasco, Eva; Piñol, Milagros; Oriol, Luis

    2014-06-01

    The combination of dendritic and linear polymeric structures in the same macromolecule opens up new possibilities for the design of block copolymers and for applications of functional polymers that have self-assembly properties. There are three main strategies for the synthesis of linear-dendritic block copolymers (LDBCs) and, in particular, the emergence of click chemistry has made the coupling of preformed blocks one of the most efficient ways of obtaining libraries of LDBCs. In these materials, the periphery of the dendron can be precisely functionalised to obtain functional LDBCs with self-assembly properties of interest in different technological areas. The incorporation of stimuli-responsive moieties gives rise to smart materials that are generally processed as self-assemblies of amphiphilic LDBCs with a morphology that can be controlled by an external stimulus. Particular emphasis is placed on light-responsive LDBCs. Furthermore, a brief review of the biomedical or materials science applications of LDBCs is presented. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Analyzing dendritic growth in a population of immature neurons in the adult dentate gyrus using laminar quantification of disjointed dendrites

    Directory of Open Access Journals (Sweden)

    Shira eRosenzweig

    2011-03-01

    Full Text Available In the dentate gyrus of the hippocampus, new granule neurons are continuously produced throughout adult life. A prerequisite for the successful synaptic integration of these neurons is the sprouting and extension of dendrites into the molecular layer of the dentate gyrus. Thus, studies aimed at investigating the developmental stages of adult neurogenesis often use dendritic growth as an important indicator of neuronal health and maturity. Based on the known topography of the dentate gyrus, characterized by distinct laminar arrangement of granule neurons and their extensions, we have developed a new method for analysis of dendritic growth in immature adult-born granule neurons. The method is comprised of laminar quantification of cell bodies, primary, secondary and tertiary dendrites separately and independently from each other. In contrast to most existing methods, laminar quantification of dendrites does not require the use of exogenous markers and does not involve arbitrary selection of individual neurons. The new method relies on immonuhistochemical detection of endogenous markers such as doublecortin to perform a comprehensive analysis of a sub-population of immature neurons. Disjointed, orphan dendrites that often appear in the thin histological sections are taken into account. Using several experimental groups of rats and mice, we demonstrate here the suitable techniques for quantifying neurons and dendrites, and explain how the ratios between the quantified values can be used in a comparative analysis to indicate variations in dendritic growth and complexity.

  15. Automated design of degenerate codon libraries.

    Science.gov (United States)

    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.

  16. Atomic rate coefficients in a degenerate plasma

    Science.gov (United States)

    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.

  17. K-causality and degenerate spacetimes

    Science.gov (United States)

    Dowker, H. F.; Garcia, R. S.; Surya, S.

    2000-11-01

    The causal relation K+ was introduced by Sorkin and Woolgar to extend the standard causal analysis of C2 spacetimes to those that are only C0. Most of their results also hold true in the case of metrics with degeneracies which are C0 but vanish at isolated points. In this paper we seek to examine K+ explicitly in the case of topology-changing `Morse histories' which contain degeneracies. We first demonstrate some interesting features of this relation in globally Lorentzian spacetimes. In particular, we show that K+ is robust and the Hawking and Sachs characterization of causal continuity translates into a natural condition in terms of K+. We then examine K+ in topology-changing Morse spacetimes with the degenerate points excised and then for the Morse histories in which the degenerate points are reinstated. We find further characterizations of causal continuity in these cases.

  18. Degenerate RFID Channel Modeling for Positioning Applications

    Directory of Open Access Journals (Sweden)

    A. Povalac

    2012-12-01

    Full Text Available This paper introduces the theory of channel modeling for positioning applications in UHF RFID. It explains basic parameters for channel characterization from both the narrowband and wideband point of view. More details are given about ranging and direction finding. Finally, several positioning scenarios are analyzed with developed channel models. All the described models use a degenerate channel, i.e. combined signal propagation from the transmitter to the tag and from the tag to the receiver.

  19. Degenerate odd Poisson bracket on Grassmann variables

    International Nuclear Information System (INIS)

    Soroka, V.A.

    2000-01-01

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

  20. Immunology of age-related macular degeneration

    Science.gov (United States)

    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

  1. Loss of Dendritic Complexity Precedes Neurodegeneration in a Mouse Model with Disrupted Mitochondrial Distribution in Mature Dendrites

    Directory of Open Access Journals (Sweden)

    Guillermo López-Doménech

    2016-10-01

    Full Text Available Correct mitochondrial distribution is critical for satisfying local energy demands and calcium buffering requirements and supporting key cellular processes. The mitochondrially targeted proteins Miro1 and Miro2 are important components of the mitochondrial transport machinery, but their specific roles in neuronal development, maintenance, and survival remain poorly understood. Using mouse knockout strategies, we demonstrate that Miro1, as opposed to Miro2, is the primary regulator of mitochondrial transport in both axons and dendrites. Miro1 deletion leads to depletion of mitochondria from distal dendrites but not axons, accompanied by a marked reduction in dendritic complexity. Disrupting postnatal mitochondrial distribution in vivo by deleting Miro1 in mature neurons causes a progressive loss of distal dendrites and compromises neuronal survival. Thus, the local availability of mitochondrial mass is critical for generating and sustaining dendritic arbors, and disruption of mitochondrial distribution in mature neurons is associated with neurodegeneration.

  2. Degenerate pressure driven modified nucleus-acoustic waves in degenerate plasmas

    Science.gov (United States)

    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.

  3. Effect of substance P on recovery from laser-induced retinal degeneration.

    Science.gov (United States)

    Hong, Hyun Sook; Kim, Suna; Nam, Seungwoo; Um, Jihyun; Kim, Yeong Hoon; Son, Youngsook

    2015-01-01

    Retinal degeneration is caused by neovascularization and persistent inflammation in the retinal pigment epithelium (RPE) and choroid, and causes serious eye disease including age-related macular degeneration (AMD). Thus, inhibiting inflammation and neovascularization may be a primary approach to protect the retina from degeneration. The purpose of this study was to determine whether substance P (SP), which can suppress inflammation and mobilize stem cells, can protect the RPE from degeneration. The effect of SP was evaluated by analyzing systemic inflammation, cell survival, and neovascularization within the argon laser-injured retina of mice. At 1 week postinjury, the SP-treated group had lower tumor necrosis factor-alpha and higher interleukin-10 serum concentrations, and a more intact retinal structure compared to the vehicle-treated group. In mice administered SP repeatedly for 4 weeks, the retinal structure appeared normal and showed sparse neovascularization, whereas the vehicle-treated group showed severe retinal destruction and dense neovascularization. Moreover, the efficacy of SP was identical to that of mesenchymal stem cells that were transplanted into the vitreous after retinal injury. This study highlights the potential for the endogenous neuropeptide SP as a treatment for retinal damage to prevent conditions such as AMD. © 2015 by the Wound Healing Society.

  4. Characterization of cytochrome c as marker for retinal cell degeneration by uv/vis spectroscopic imaging

    Science.gov (United States)

    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.

  5. Antithymocyte Globulin Induces a Tolerogenic Phenotype in Human Dendritic Cells

    Directory of Open Access Journals (Sweden)

    Tobias Roider

    2016-12-01

    Full Text Available Antithymocyte globulin (ATG is used in the prevention of graft-versus-host disease during allogeneic hematopoietic stem cell transplantation. It is generally accepted that ATG mediates its immunosuppressive effect primarily via depletion of T cells. Here, we analyzed the impact of ATG-Fresenius (now Grafalon® on human monocyte-derived dendritic cells (DC. ATG induced a semi-mature phenotype in DC with significantly reduced expression of CD14, increased expression of HLA-DR, and intermediate expression of CD54, CD80, CD83, and CD86. ATG-DC showed an increase in IL-10 secretion but no IL-12 production. In line with this tolerogenic phenotype, ATG caused a significant induction of indoleamine 2,3-dioxygenase expression and a concomitant increase in levels of tryptophan metabolites in the supernatants of DC. Further, ATG-DC did not induce the proliferation of allogeneic T cells in a mixed lymphocyte reaction but actively suppressed the T cell proliferation induced by mature DC. These data suggest that besides its well-known effect on T cells, ATG modulates the phenotype of DC in a tolerogenic way, which might constitute an essential part of its immunosuppressive action in vivo.

  6. Different protein of Echinococcus granulosus stimulates dendritic induced immune response.

    Science.gov (United States)

    Wang, Yana; Wang, Qiang; Lv, Shiyu; Zhang, Shengxiang

    2015-06-01

    Cystic echinococcosis is a chronic infectious disease that results from a host/parasite interaction. Vaccination with ferritin derived from Echinococcus granulosus is a potential preventative treatment. To understand whether ferritin is capable of inducing a host immune response, we investigated the response of dendritic cells (DCs) to both recombinant ferritin protein and the hydatid fluid (HF) of E. granulosus. We evaluated the immunomodulatory potential of these antigens by performing, immunocytochemistry, electron microscopy and in vivo imaging of monocyte-derived murine DCs. During antigen stimulation of DCs, ferritin cause DCs maturation and induced higher levels of surface marker expression and activated T-cell proliferation and migration. On contrary, HF failed to induce surface marker expression and to stimulate T-cell proliferation. In response to HF, DCs produced interleukin-6 (IL-6), but no IL-12 and IL-10. DCs stimulated with ferritin produced high levels of cytokines. Overall, HF appears to induce host immunosuppression in order to ensure parasite survival via inhibits DC maturation and promotes Th2-dependent secretion of cytokines. Although ferritin also promoted DC maturation and cytokine release, it also activates CD4+T-cell proliferation, but regard of the mechanism of the Eg.ferritin induce host to eradicate E. granulosus were not clear.

  7. T cell motility as modulator of interactions with dendritic cells

    Directory of Open Access Journals (Sweden)

    Jens Volker Stein

    2015-11-01

    Full Text Available It is well established that the balance of costimulatory and inhibitory signals during interactions with dendritic cells (DCs determines T cell transition from a naïve to an activated or tolerant/anergic status. While many of these molecular interactions are well reproduced in reductionist in vitro assays, the highly dynamic motility of naïve T cells in lymphoid tissue acts as an additional lever to fine-tune their activation threshold. T cell detachment from DCs providing suboptimal stimulation allows them to search for DCs with higher levels of stimulatory signals, while storing a transient memory of short encounters. In turn, adhesion of weakly reactive T cells to DCs presenting pMHC with low affinity is prevented by lipid mediators. Finally, controlled recruitment of CD8+ T cells to cognate DC – CD4+ T cell clusters shapes memory T cell formation and the quality of the immune response. Dynamic physiological lymphocyte motility therefore constitutes a mechanism to mitigate low avidity T cell activation and to improve the search for optimal DCs, while contributing to peripheral tolerance induction in the absence of inflammation.

  8. Glial loss of the metallo β-lactamase domain containing protein, SWIP-10, induces age- and glutamate-signaling dependent, dopamine neuron degeneration.

    Directory of Open Access Journals (Sweden)

    Chelsea L Gibson

    2018-03-01

    Full Text Available Across phylogeny, glutamate (Glu signaling plays a critical role in regulating neural excitability, thus supporting many complex behaviors. Perturbed synaptic and extrasynaptic Glu homeostasis in the human brain has been implicated in multiple neuropsychiatric and neurodegenerative disorders including Parkinson's disease, where theories suggest that excitotoxic insults may accelerate a naturally occurring process of dopamine (DA neuron degeneration. In C. elegans, mutation of the glial expressed gene, swip-10, results in Glu-dependent DA neuron hyperexcitation that leads to elevated DA release, triggering DA signaling-dependent motor paralysis. Here, we demonstrate that swip-10 mutations induce premature and progressive DA neuron degeneration, with light and electron microscopy studies demonstrating the presence of dystrophic dendritic processes, as well as shrunken and/or missing cell soma. As with paralysis, DA neuron degeneration in swip-10 mutants is rescued by glial-specific, but not DA neuron-specific expression of wildtype swip-10, consistent with a cell non-autonomous mechanism. Genetic studies implicate the vesicular Glu transporter VGLU-3 and the cystine/Glu exchanger homolog AAT-1 as potential sources of Glu signaling supporting DA neuron degeneration. Degeneration can be significantly suppressed by mutations in the Ca2+ permeable Glu receptors, nmr-2 and glr-1, in genes that support intracellular Ca2+ signaling and Ca2+-dependent proteolysis, as well as genes involved in apoptotic cell death. Our studies suggest that Glu stimulation of nematode DA neurons in early larval stages, without the protective actions of SWIP-10, contributes to insults that ultimately drive DA neuron degeneration. The swip-10 model may provide an efficient platform for the identification of molecular mechanisms that enhance risk for Parkinson's disease and/or the identification of agents that can limit neurodegenerative disease progression.

  9. Low-intensity pulsed ultrasound (LIPUS) and pulsed electromagnetic field (PEMF) treatments affect degeneration of cultured articular cartilage explants

    NARCIS (Netherlands)

    Tan, Lijun; Ren, Yijin; van Kooten, Theo G.; Grijpma, Dirk W.; Kuijer, Roelof

    PURPOSE: Articular cartilage has some capacity for self-repair. Clinically used low-intensity pulsed ultrasound (LIPUS) and pulsed electromagnetic field (PEMF) treatments were compared in their potency to prevent degeneration using an explant model of porcine cartilage. METHODS: Explants of porcine

  10. Low-intensity pulsed ultrasound (LIPUS) and pulsed electromagnetic field (PEMF) treatments affect degeneration of cultured articular cartilage explants

    NARCIS (Netherlands)

    Tan, Lijun; Tan, Lijun; Ren, Yijin; van Kooten, Theo G.; Grijpma, Dirk W.; Kuijer, Roel

    2015-01-01

    Purpose: Articular cartilage has some capacity for self-repair. Clinically used low-intensity pulsed ultrasound (LIPUS) and pulsed electromagnetic field (PEMF) treatments were compared in their potency to prevent degeneration using an explant model of porcine cartilage. Methods: Explants of porcine

  11. The role of free-radical processes in the pathogenesis of age-related macular degeneration. Review

    Directory of Open Access Journals (Sweden)

    A. V. Kolesnikov

    2012-01-01

    Full Text Available the modern ideas of the role of free radical processes in the pathogenesis of age-related macular degeneration (AMD are consid- ered. Data of large randomized clinical trials on application of antioxidants for prevention and therapy AMD are provided. Possibility of the differential application of antioxidants depending on the genetic status of patients is discussed.

  12. Mathematical foundations of the dendritic growth models.

    Science.gov (United States)

    Villacorta, José A; Castro, Jorge; Negredo, Pilar; Avendaño, Carlos

    2007-11-01

    At present two growth models describe successfully the distribution of size and topological complexity in populations of dendritic trees with considerable accuracy and simplicity, the BE model (Van Pelt et al. in J. Comp. Neurol. 387:325-340, 1997) and the S model (Van Pelt and Verwer in Bull. Math. Biol. 48:197-211, 1986). This paper discusses the mathematical basis of these models and analyzes quantitatively the relationship between the BE model and the S model assumed in the literature by developing a new explicit equation describing the BES model (a dendritic growth model integrating the features of both preceding models; Van Pelt et al. in J. Comp. Neurol. 387:325-340, 1997). In numerous studies it is implicitly presupposed that the S model is conditionally linked to the BE model (Granato and Van Pelt in Brain Res. Dev. Brain Res. 142:223-227, 2003; Uylings and Van Pelt in Network 13:397-414, 2002; Van Pelt, Dityatev and Uylings in J. Comp. Neurol. 387:325-340, 1997; Van Pelt and Schierwagen in Math. Biosci. 188:147-155, 2004; Van Pelt and Uylings in Network. 13:261-281, 2002; Van Pelt, Van Ooyen and Uylings in Modeling Dendritic Geometry and the Development of Nerve Connections, pp 179, 2000). In this paper we prove the non-exactness of this assumption, quantify involved errors and determine the conditions under which the BE and S models can be separately used instead of the BES model, which is more exact but considerably more difficult to apply. This study leads to a novel expression describing the BE model in an analytical closed form, much more efficient than the traditional iterative equation (Van Pelt et al. in J. Comp. Neurol. 387:325-340, 1997) in many neuronal classes. Finally we propose a new algorithm in order to obtain the values of the parameters of the BE model when this growth model is matched to experimental data, and discuss its advantages and improvements over the more commonly used procedures.

  13. Dendritic cells in Barrett's esophagus and esophageal adenocarcinoma.

    Science.gov (United States)

    Bobryshev, Yuri V; Tran, Dinh; Killingsworth, Murray C; Buckland, Michael; Lord, Reginald V N

    2009-01-01

    Like other premalignant conditions that develop in the presence of chronic inflammation, the development and progression of Barrett's esophagus is associated with the development of an immune response, but how this immune response is regulated is poorly understood. A comprehensive literature search failed to find any report of the presence of dendritic cells in Barrett's intestinal metaplasia and esophageal adenocarcinoma and this prompted our study. We used immunohistochemical staining and electron microscopy to examine whether dendritic cells are present in Barrett's esophagus and esophageal adenocarcinoma. Immunohistochemical staining with CD83, a specific marker for dendritic cells, was performed on paraffin-embedded sections of Barrett's intestinal metaplasia (IM, n = 12), dysplasia (n = 11) and adenocarcinoma (n = 14). CD83+ cells were identified in the lamina propria surrounding intestinal type glands in Barrett's IM, dysplasia, and cancer tissues. Computerized quantitative analysis showed that the numbers of dendritic cells were significantly higher in cancer tissues. Double immunostaining with CD83, CD20, and CD3, and electron microscopy demonstrated that dendritic cells are present in Barrett's esophagus and form clusters with T cells and B cells directly within the lamina propria. These findings demonstrate that dendritic cells are present in Barrett's tissues, with a significant increase in density in adenocarcinoma compared to benign Barrett's esophagus. Dendritic cells may have a role in the pathogenesis and immunotherapy treatment of Barrett's esophagus and adenocarcinoma.

  14. Statistical Physics of Neural Systems with Nonadditive Dendritic Coupling

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    David Breuer

    2014-03-01

    Full Text Available How neurons process their inputs crucially determines the dynamics of biological and artificial neural networks. In such neural and neural-like systems, synaptic input is typically considered to be merely transmitted linearly or sublinearly by the dendritic compartments. Yet, single-neuron experiments report pronounced supralinear dendritic summation of sufficiently synchronous and spatially close-by inputs. Here, we provide a statistical physics approach to study the impact of such nonadditive dendritic processing on single-neuron responses and the performance of associative-memory tasks in artificial neural networks. First, we compute the effect of random input to a neuron incorporating nonlinear dendrites. This approach is independent of the details of the neuronal dynamics. Second, we use those results to study the impact of dendritic nonlinearities on the network dynamics in a paradigmatic model for associative memory, both numerically and analytically. We find that dendritic nonlinearities maintain network convergence and increase the robustness of memory performance against noise. Interestingly, an intermediate number of dendritic branches is optimal for memory functionality.

  15. Adolescent cocaine exposure simplifies orbitofrontal cortical dendritic arbors

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    Lauren M DePoy

    2014-10-01

    Full Text Available Cocaine and amphetamine remodel dendritic spines within discrete cortico-limbic brain structures including the orbitofrontal cortex (oPFC. Whether dendrite structure is similarly affected, and whether pre-existing cellular characteristics influence behavioral vulnerabilities to drugs of abuse, remain unclear. Animal models provide an ideal venue to address these issues because neurobehavioral phenotypes can be defined both before, and following, drug exposure. We exposed mice to cocaine from postnatal days 31-35, corresponding to early adolescence, using a dosing protocol that causes impairments in an instrumental reversal task in adulthood. We then imaged and reconstructed excitatory neurons in deep-layer oPFC. Prior cocaine exposure shortened and simplified arbors, particularly in the basal region. Next, we imaged and reconstructed orbital neurons in a developmental-genetic model of cocaine vulnerability – the p190rhogap+/- mouse. p190RhoGAP is an actin cytoskeleton regulatory protein that stabilizes dendrites and dendritic spines, and p190rhogap+/- mice develop rapid and robust locomotor activation in response to cocaine. Despite this, oPFC dendritic arbors were intact in drug-naïve p190rhogap+/- mice. Together, these findings provide evidence that adolescent cocaine exposure has long-term effects on dendrite structure in the oPFC, and they suggest that cocaine-induced modifications in dendrite structure may contribute to the behavioral effects of cocaine more so than pre-existing structural abnormalities in this cell population.

  16. Radiation therapy for macular degeneration: technical considerations and preliminary results

    International Nuclear Information System (INIS)

    Brady, Luther W.; Freire, Jorge E.; Longton, Wallace A.; Miyamoto, Curtis T.; Augsburger, James J.; Brown, Gary C.; Micaily, Bizhan; Sagerman, Robert H.

    1997-01-01

    Purpose: This study was undertaken to assess the toxicity and possible benefits from the administration of low-dose external-beam irradiation for Age-Related Macular Degeneration (ARMD). The premise of the treatment is that radiation induces regression and/or promotes inactivation of the subretinal neo-vasculature, resulting in reabsorption of fluid and blood thus reducing the risk for further leakage or bleeding, as well as subretinal fibrosis. Clinically, the beneficial effect could be translated into stabilization of visual acuity and prevention of progression of the wet type of ARMD with the possibility for some visual improvement. Methods and Materials: Allegheny University Hospitals, Hahnemann, Department of Radiation Oncology, treated 278 patients prospectively beginning in January 1995 with low-dose irradiation for wet-type macular degeneration. Two hundred forty-nine patients were treated with a total dose of 14.40 Gy in eight fractions of 1.80 Gy over 10-13 elapsed days, and 27 patients with 20 Gy at 2 Gy per fraction over 12-15 days. The first two patients were treated to a total dose of 10.00 Gy in five fractions of 2.00 Gy. Patients were evaluated at 2-3 weeks and 2-3 months. A percentage (36.7%) of the patients had previously received laser treatments in the study eye, 21.9% once, 5% twice, 9.7% three or more. Subjective visual acuity and toxicity data was collected on all patients. Results: At 2-3 weeks after treatment 195 patients (70%) retained their visual acuity without change, 68 patients (24.5%) stated they had improved vision, and 15 patients (4.8%) stated their vision continued to decrease. Two to 3 months after treatment, 183 patients (65.8%) had no change in their vision. 75 patients (27%) patients had an improvement in their vision, and 20 patients (7.2%) had a decrease in visual acuity. Transient acute reactions occurred in 14 of the 278 patients treated. Conclusion: Our observations in this group of 278 patients support the conclusion

  17. External radiotherapy in macular degeneration: technique and preliminary subjective response

    International Nuclear Information System (INIS)

    Freire, Jorge; Longton, Wallace A.; Miyamoto, Curtis T.; Brady, Luther W.; Augsburger, James; Brown, Gary; Micaily, Bizhan; Unda, Ricardo

    1996-01-01

    Purpose: This study attempted to assess the toxicity and possible preliminary benefits from the administration of low-dose external beam irradiation for age-related macular degeneration (ARMD). The premise of the treatment is that radiation induces regression and/or promotes inactivation of the subretinal neovasculature which would result in reabsorption of fluid and blood. This would reduce the risk for further leakage or bleeding, as well as subretinal fibrosis. Consequently, the beneficial effect could be translated into stabilization of visual acuity and prevention of progression of the wet ARMD with the possibility for slight improvement. Methods and Materials: Allegheny University Department of Radiation Oncology treated 41 patients prospectively from January through October 1995 with low-dose irradiation for wet-type macular degeneration. A total of 39 patients were treated with a total dose of 14.4 Gy in eight fractions of 1.8 Gy/fraction over 10-13 elapsed days. The first two patients were treated with a total dose of 10 Gy in fivefractions of 2 Gy. Patients were evaluated at 2-3 weeks and 2-3 months. Some of the patients (36.7%) had laser treatments in the study eye: 21.9% (9) once, 5% (2) twice, 9.7% (4) thrice or more. Subjective visual acuity and toxicity data were collected on all patients. Results: At 2-3 weeks after treatment 29 patients (70%) retained their visual acuity without change, 10 (24.5%) stated they had improved vision, and 2 (4.8%) stated their vision continued to decrease. At 2-3 months after treatment, 27 patients (65.8%) had no change in their vision, 11 (27%) had an improvement in their vision, and 3 (7.2%) had a decrease in visual acuity. Six patients of 41 in the treated group had acute transient side effects. Conclusion: Our observations in this group of 41 patients support the conclusion that many patients will have improved or stable vision after treatment with low-dose irradiation for age-related wet-type macular degeneration

  18. Human disc degeneration is associated with increased MMP 7 expression.

    Science.gov (United States)

    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.

  19. Tear film proteome in age-related macular degeneration.

    Science.gov (United States)

    Winiarczyk, Mateusz; Kaarniranta, Kai; Winiarczyk, Stanisław; Adaszek, Łukasz; Winiarczyk, Dagmara; Mackiewicz, Jerzy

    2018-06-01

    Age-related macular degeneration (AMD) is the main reason for blindness in elderly people in the developed countries. Current screening protocols have limitations in detecting the early signs of retinal degeneration. Therefore, it would be desirable to find novel biomarkers for early detection of AMD. Development of novel biomarkers would help in the prevention, diagnostics, and treatment of AMD. Proteomic analysis of tear film has shown promise in this research area. If an optimal set of biomarkers could be obtained from accessible body fluids, it would represent a reliable way to monitor disease progression and response to novel therapies. Tear films were collected on Schirmer strips from a total of 22 patients (8 with wet AMD, 6 with dry AMD, and 8 control individuals). 2D electrophoresis was used to separate tear film proteins prior to their identification with matrix-assisted laser desorption/ionization time of flight spectrometer (MALDI-TOF/TOF) and matching with functional databases. A total of 342 proteins were identified. Most of them were previously described in various proteomic studies concerning AMD. Shootin-1, histatin-3, fidgetin-like protein 1, SRC kinase signaling inhibitor, Graves disease carrier protein, actin cytoplasmic 1, prolactin-inducible protein 1, and protein S100-A7A were upregulated in the tear film samples isolated from AMD patients and were not previously linked with this disease in any proteomic analysis. The upregulated proteins supplement our current knowledge of AMD pathogenesis, providing evidence that certain specific proteins are expressed into the tear film in AMD. As far we are aware, this is the first study to have undertaken a comprehensive in-depth analysis of the human tear film proteome in AMD patients.

  20. Dendritic Polyglycerol Sulfate for Therapy and Diagnostics

    Directory of Open Access Journals (Sweden)

    Nadine Rades

    2018-05-01

    Full Text Available Dendritic polyglycerol sulfate (dPGS has originally been investigated as an anticoagulant to potentially substitute for the natural glycosaminoglycan heparin. Compared to unfractionated heparin, dPGS possesses lower anticoagulant activity but a much higher anticomplementary effect. Since coagulation, complement activation, and inflammation are often present in the pathophysiology of numerous diseases, dPGS polymers with both anticoagulant and anticomplementary activities represent promising candidates for the development of polymeric drugs of nanosized architecture. In this review, we describe the nanomedical applications of dPGS based on its anti-inflammatory activity. Furthermore, the application of dPGS as a carrier molecule for diagnostic molecules and therapeutic drugs is reviewed, based on the ability to target tumors and localize in tumor cells. Finally, the application of dPGS for inhibition of virus infections is described.

  1. Platinum dendritic nanoparticles with magnetic behavior

    Energy Technology Data Exchange (ETDEWEB)

    Li, Wenxian, E-mail: wl240@uowmail.edu.au [Institute for Superconducting and Electronic Materials, University of Wollongong, NSW 2522 (Australia); Solar Energy Technologies, School of Computing, Engineering, and Mathematics, University of Western Sydney, Penrith NSW 2751 (Australia); Sun, Ziqi; Nevirkovets, Ivan P.; Dou, Shi-Xue [Institute for Superconducting and Electronic Materials, University of Wollongong, NSW 2522 (Australia); Tian, Dongliang [Key Laboratory of Bio-Inspired Smart Interfacial Science and Technology of the Ministry of Education, School of Chemistry and the Environment, Beihang University, Beijing 100191 (China)

    2014-07-21

    Magnetic nanoparticles have attracted increasing attention for biomedical applications in magnetic resonance imaging, high frequency magnetic field hyperthermia therapies, and magnetic-field-gradient-targeted drug delivery. In this study, three-dimensional (3D) platinum nanostructures with large surface area that features magnetic behavior have been demonstrated. The well-developed 3D nanodendrites consist of plentiful interconnected nano-arms ∼4 nm in size. The magnetic behavior of the 3D dendritic Pt nanoparticles is contributed by the localization of surface electrons due to strongly bonded oxygen/Pluronic F127 and the local magnetic moment induced by oxygen vacancies on the neighboring Pt and O atoms. The magnetization of the nanoparticles exhibits a mixed paramagnetic and ferromagnetic state, originating from the core and surface, respectively. The 3D nanodendrite structure is suitable for surface modification and high amounts of drug loading if the transition temperature was enhanced to room temperature properly.

  2. Towards deep learning with segregated dendrites.

    Science.gov (United States)

    Guerguiev, Jordan; Lillicrap, Timothy P; Richards, Blake A

    2017-12-05

    Deep learning has led to significant advances in artificial intelligence, in part, by adopting strategies motivated by neurophysiology. However, it is unclear whether deep learning could occur in the real brain. Here, we show that a deep learning algorithm that utilizes multi-compartment neurons might help us to understand how the neocortex optimizes cost functions. Like neocortical pyramidal neurons, neurons in our model receive sensory information and higher-order feedback in electrotonically segregated compartments. Thanks to this segregation, neurons in different layers of the network can coordinate synaptic weight updates. As a result, the network learns to categorize images better than a single layer network. Furthermore, we show that our algorithm takes advantage of multilayer architectures to identify useful higher-order representations-the hallmark of deep learning. This work demonstrates that deep learning can be achieved using segregated dendritic compartments, which may help to explain the morphology of neocortical pyramidal neurons.

  3. Harnessing dendritic cells in inflammatory skin diseases.

    Science.gov (United States)

    Chu, Chung-Ching; Di Meglio, Paola; Nestle, Frank O

    2011-02-01

    The skin immune system harbors a complex network of dendritic cells (DCs). Recent studies highlight a diverse functional specialization of skin DC subsets. In addition to generating cellular and humoral immunity against pathogens, skin DCs are involved in tolerogenic mechanisms to ensure the maintenance of immune homeostasis, as well as in pathogenesis of chronic inflammation in the skin when excessive immune responses are initiated and unrestrained. Harnessing DCs by directly targeting DC-derived molecules or selectively modulate DC subsets is a convincing strategy to tackle inflammatory skin diseases. In this review we discuss recent advances underlining the functional specialization of skin DCs and discuss the potential implication for future DC-based therapeutic strategies. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. Harnessing Dendritic Cells for Tumor Antigen Presentation

    Energy Technology Data Exchange (ETDEWEB)

    Nierkens, Stefan [Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Geert Grooteplein 28, Nijmegen 6525 GA (Netherlands); Janssen, Edith M., E-mail: edith.janssen@cchmc.org [Division of Molecular Immunology, Cincinnati Children' s Hospital Research Foundation, University of Cincinnati College of Medicine, 3333 Burnet Avenue, Cincinnati, OH 45229 (United States)

    2011-04-26

    Dendritic cells (DC) are professional antigen presenting cells that are crucial for the induction of anti-tumor T cell responses. As a consequence, research has focused on the harnessing of DCs for therapeutic interventions. Although current strategies employing ex vivo-generated and tumor-antigen loaded DCs have been proven feasible, there are still many obstacles to overcome in order to improve clinical trial successes and offset the cost and complexity of customized cell therapy. This review focuses on one of these obstacles and a pivotal step for the priming of tumor-specific CD8{sup +} and CD4{sup +} T cells; the in vitro loading of DCs with tumor antigens.

  5. Efficient estimation of diffusion during dendritic solidification

    Science.gov (United States)

    Yeum, K. S.; Poirier, D. R.; Laxmanan, V.

    1989-01-01

    A very efficient finite difference method has been developed to estimate the solute redistribution during solidification with diffusion in the solid. This method is validated by comparing the computed results with the results of an analytical solution derived by Kobayashi (1988) for the assumptions of a constant diffusion coefficient, a constant equilibrium partition ratio, and a parabolic rate of the advancement of the solid/liquid interface. The flexibility of the method is demonstrated by applying it to the dendritic solidification of a Pb-15 wt pct Sn alloy, for which the equilibrium partition ratio and diffusion coefficient vary substantially during solidification. The fraction eutectic at the end of solidification is also obtained by estimating the fraction solid, in greater resolution, where the concentration of solute in the interdendritic liquid reaches the eutectic composition of the alloy.

  6. Induction of RNA interference in dendritic cells.

    Science.gov (United States)

    Li, Mu; Qian, Hua; Ichim, Thomas E; Ge, Wei-Wen; Popov, Igor A; Rycerz, Katarzyna; Neu, John; White, David; Zhong, Robert; Min, Wei-Ping

    2004-01-01

    Dendritic cells (DC) reside at the center of the immunological universe, possessing the ability both to stimulate and inhibit various types of responses. Tolerogenic/regulatory DC with therapeutic properties can be generated through various means of manipulations in vitro and in vivo. Here we describe several attractive strategies for manipulation of DC using the novel technique of RNA interference (RNAi). Additionally, we overview some of our data regarding yet undescribed characteristics of RNAi in DC such as specific transfection strategies, persistence of gene silencing, and multi-gene silencing. The advantages of using RNAi for DC genetic manipulation gives rise to the promise of generating tailor-made DC that can be used effectively to treat a variety of immunologically mediated diseases.

  7. Platinum dendritic nanoparticles with magnetic behavior

    International Nuclear Information System (INIS)

    Li, Wenxian; Sun, Ziqi; Nevirkovets, Ivan P.; Dou, Shi-Xue; Tian, Dongliang

    2014-01-01

    Magnetic nanoparticles have attracted increasing attention for biomedical applications in magnetic resonance imaging, high frequency magnetic field hyperthermia therapies, and magnetic-field-gradient-targeted drug delivery. In this study, three-dimensional (3D) platinum nanostructures with large surface area that features magnetic behavior have been demonstrated. The well-developed 3D nanodendrites consist of plentiful interconnected nano-arms ∼4 nm in size. The magnetic behavior of the 3D dendritic Pt nanoparticles is contributed by the localization of surface electrons due to strongly bonded oxygen/Pluronic F127 and the local magnetic moment induced by oxygen vacancies on the neighboring Pt and O atoms. The magnetization of the nanoparticles exhibits a mixed paramagnetic and ferromagnetic state, originating from the core and surface, respectively. The 3D nanodendrite structure is suitable for surface modification and high amounts of drug loading if the transition temperature was enhanced to room temperature properly.

  8. Location matters: the endoplasmic reticulum and protein trafficking in dendrites

    Directory of Open Access Journals (Sweden)

    Omar A Ramírez

    2011-01-01

    Full Text Available Neurons are highly polarized, but the trafficking mechanisms that operate in these cells and the topological organization of their secretory organelles are still poorly understood. Particularly incipient is our knowledge of the role of the neuronal endoplasmic reticulum. Here we review the current understanding of the endoplasmic reticulum in neurons, its structure, composition, dendritic distribution and dynamics. We also focus on the trafficking of proteins through the dendritic endoplasmic reticulum, emphasizing the relevance of transport, retention, assembly of multi-subunit protein complexes and export. We additionally discuss the roles of the dendritic endoplasmic reticulum in synaptic plasticity.

  9. Photoinduced electron transfer between the dendritic zinc phthalocyanines and anthraquinone

    Science.gov (United States)

    Chen, Kuizhi; Wen, Junri; Liu, Jiangsheng; Chen, Zhenzhen; Pan, Sujuan; Huang, Zheng; Peng, Yiru

    2015-03-01

    The intermolecular electron transfer between the novel dendritic zinc (II) phthalocyanines (G1-DPcB and G2-DPcB) and anthraquinone (AQ) was studied by steady-state fluorescence and UV/Vis absorption spectroscopic methods. The effect of dendron generation on intermolecular electron transfer was investigated. The results showed that the fluorescence emission of these dendritic phthalocyanines could be greatly quenched by AQ upon excitation at 610 nm. The Stern- Volmer constant (KSV) of electron transfer was decreased with increasing the dendron generations. Our study suggested that these novel dendritic phthalocyanines were effective new electron donors and transmission complexes and could be used as a potential artifical photosysthesis system.

  10. Dendritic cells in chronic myelomonocytic leukaemia.

    Science.gov (United States)

    Vuckovic, S; Fearnley, D B; Gunningham, S; Spearing, R L; Patton, W N; Hart, D N

    1999-06-01

    Blood dendritic cells (DC) differentiate in vitro via two separate pathways: either directly from blood DC precursors (DCp) or from CD14+ monocytes. In chronic myelomonocytic leukaemia (CMML) abnormal bone marrow precursors contribute to blood monocyte development but DC development has not been studied previously. Monocytes comprised 60% of blood MNC in 15 CMML patients studied, compared with 20% in 16 age-matched controls. The increase in blood monocytes was accompanied by a reciprocal decrease in mean blood DC percentage (from 0.42% of MNC in normal individuals to 0.16% of MNC in CMML patients). Absolute blood DC numbers showed a minimal (non-significant) reduction from 9.8 x 10(6)/l in normal individuals to 7.5 x 10(6)/l in CMML patients. The CD14(low) WCD16+ monocyte subpopulation was not found in CMML patients. After culture in GM-CSF/IL-4, CMML CD14+ monocytes acquired the phenotype of immature monocyte derived DC (Mo-DC) with similar yields to normal blood Mo-DC generation. Addition of TNF-alpha or LPS induced both normal and CMML Mo-DC to express prominent dendritic processes, the CMRF44+ and CD83+ antigens and high levels of HLA-DR, CD80 and CD86. Treatment either with TNF-alpha or LPS increased the allostimulatory activity of normal Mo-DC, but had little effect on the allostimulatory activity of CMML Mo-DC, perhaps reflecting the underlying neoplastic changes in monocyte precursors. We conclude that the blood DC numbers are relatively unaffected in CMML, suggesting discrete regulation of monocyte and DC production.

  11. Dendritic Kv3.3 potassium channels in cerebellar purkinje cells regulate generation and spatial dynamics of dendritic Ca2+ spikes.

    Science.gov (United States)

    Zagha, Edward; Manita, Satoshi; Ross, William N; Rudy, Bernardo

    2010-06-01

    Purkinje cell dendrites are excitable structures with intrinsic and synaptic conductances contributing to the generation and propagation of electrical activity. Voltage-gated potassium channel subunit Kv3.3 is expressed in the distal dendrites of Purkinje cells. However, the functional relevance of this dendritic distribution is not understood. Moreover, mutations in Kv3.3 cause movement disorders in mice and cerebellar atrophy and ataxia in humans, emphasizing the importance of understanding the role of these channels. In this study, we explore functional implications of this dendritic channel expression and compare Purkinje cell dendritic excitability in wild-type and Kv3.3 knockout mice. We demonstrate enhanced excitability of Purkinje cell dendrites in Kv3.3 knockout mice, despite normal resting membrane properties. Combined data from local application pharmacology, voltage clamp analysis of ionic currents, and assessment of dendritic Ca(2+) spike threshold in Purkinje cells suggest a role for Kv3.3 channels in opposing Ca(2+) spike initiation. To study the physiological relevance of altered dendritic excitability, we measured [Ca(2+)](i) changes throughout the dendritic tree in response to climbing fiber activation. Ca(2+) signals were specifically enhanced in distal dendrites of Kv3.3 knockout Purkinje cells, suggesting a role for dendritic Kv3.3 channels in regulating propagation of electrical activity and Ca(2+) influx in distal dendrites. These findings characterize unique roles of Kv3.3 channels in dendrites, with implications for synaptic integration, plasticity, and human disease.

  12. βIII Spectrin Is Necessary for Formation of the Constricted Neck of Dendritic Spines and Regulation of Synaptic Activity in Neurons.

    Science.gov (United States)

    Efimova, Nadia; Korobova, Farida; Stankewich, Michael C; Moberly, Andrew H; Stolz, Donna B; Wang, Junling; Kashina, Anna; Ma, Minghong; Svitkina, Tatyana

    2017-07-05

    Dendritic spines are postsynaptic structures in neurons often having a mushroom-like shape. Physiological significance and cytoskeletal mechanisms that maintain this shape are poorly understood. The spectrin-based membrane skeleton maintains the biconcave shape of erythrocytes, but whether spectrins also determine the shape of nonerythroid cells is less clear. We show that βIII spectrin in hippocampal and cortical neurons from rodent embryos of both sexes is distributed throughout the somatodendritic compartment but is particularly enriched in the neck and base of dendritic spines and largely absent from spine heads. Electron microscopy revealed that βIII spectrin forms a detergent-resistant cytoskeletal network at these sites. Knockdown of βIII spectrin results in a significant decrease in the density of dendritic spines. Surprisingly, the density of presynaptic terminals is not affected by βIII spectrin knockdown. However, instead of making normal spiny synapses, the presynaptic structures in βIII spectrin-depleted neurons make shaft synapses that exhibit increased amplitudes of miniature EPSCs indicative of excessive postsynaptic excitation. Thus, βIII spectrin is necessary for formation of the constricted shape of the spine neck, which in turn controls communication between the synapse and the parent dendrite to prevent excessive excitation. Notably, mutations of SPTNB2 encoding βIII spectrin are associated with neurodegenerative syndromes, spinocerebellar ataxia Type 5, and spectrin-associated autosomal recessive cerebellar ataxia Type 1, but molecular mechanisms linking βIII spectrin functions to neuronal pathologies remain unresolved. Our data suggest that spinocerebellar ataxia Type 5 and spectrin-associated autosomal recessive cerebellar ataxia Type 1 pathology likely arises from poorly controlled synaptic activity that leads to excitotoxicity and neurodegeneration. SIGNIFICANCE STATEMENT Dendritic spines are small protrusions from neuronal

  13. Intacs for early pellucid marginal degeneration.

    Science.gov (United States)

    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.

  14. Genome instability: Linking ageing and brain degeneration.

    Science.gov (United States)

    Barzilai, Ari; Schumacher, Björn; Shiloh, Yosef

    2017-01-01

    Ageing is a multifactorial process affected by cumulative physiological changes resulting from stochastic processes combined with genetic factors, which together alter metabolic homeostasis. Genetic variation in maintenance of genome stability is emerging as an important determinant of ageing pace. Genome instability is also closely associated with a broad spectrum of conditions involving brain degeneration. Similarities and differences can be found between ageing-associated decline of brain functionality and the detrimental effect of genome instability on brain functionality and development. This review discusses these similarities and differences and highlights cell classes whose role in these processes might have been underestimated-glia and microglia. Copyright © 2016. Published by Elsevier B.V.

  15. Degenerate stars. XII - Recognition of hot nondegenerates

    Science.gov (United States)

    Greenstein, J. L.

    1980-12-01

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

  16. Aneutronic fusion in a degenerate plasma

    International Nuclear Information System (INIS)

    Son, S.; Fisch, N.J.

    2004-01-01

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

  17. Aneutronic Fusion in a Degenerate Plasma

    International Nuclear Information System (INIS)

    Son, S.; Fisch, N.J.

    2004-01-01

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

  18. Heme oxygenase-1 modulates degeneration of the intervertebral disc after puncture in Bach 1 deficient mice.

    Science.gov (United States)

    Ohta, Ryo; Tanaka, Nobuhiro; Nakanishi, Kazuyoshi; Kamei, Naosuke; Nakamae, Toshio; Izumi, Bunichiro; Fujioka, Yuki; Ochi, Mitsuo

    2012-09-01

    Intervertebral disc degeneration is considered to be a major feature of low back pain. Furthermore, oxidative stress has been shown to be an important factor in degenerative diseases such as osteoarthritis and is considered a cause of intervertebral disc degeneration. The purpose of this study was to clarify the correlation between oxidative stress and intervertebral disc degeneration using Broad complex-Tramtrack-Bric-a-brac and cap'n'collar homology 1 deficient (Bach 1-/-) mice which highly express heme oxygenase-1 (HO-1). HO-1 protects cells from oxidative stress. Caudal discs of 12-week-old and 1-year-old mice were evaluated as age-related models. Each group and period, 5 mice (a total of 20 mice, a total of 20 discs) were evaluated as age-related model. C9-C10 caudal discs in 12-week-old Bach 1-/- and wild-type mice were punctured using a 29-gauge needle as annulus puncture model. Each group and period, 5 mice (a total of 60 mice, a total of 60 discs) were evaluated. The progress of disc degeneration was evaluated at pre-puncture, 1, 2, 4, 8 and 12 weeks post-puncture. Radiographic, histologic and immunohistologic analysis were performed to compare between Bach 1-/- and wild-type mice. In the age-related model, there were no significant differences between Bach 1-/- and wild-type mice radiologically and histologically. However, in the annulus puncture model, histological scoring revealed significant difference at 8 and 12 weeks post-puncture. The number of HO-1 positive cells was significantly greater in Bach 1-/- mice at every period. The apoptosis rate was significantly lower at 1 and 2 weeks post-puncture in Bach 1-/- mice. Oxidative stress prevention may avoid the degenerative process of the intervertebral disc after puncture, reducing the number of apoptosis cells. High HO-1 expression may also inhibit oxidative stress and delay the process of intervertebral disc degeneration.

  19. The influence of refractive error and lattice degeneration on the incidence of retinal detachment.

    Science.gov (United States)

    Burton, T C

    1989-01-01

    This study indicates the feasibility of stratifying the general population into various risk pools for retinal detachment depending on a person's age, refractive status, and the presence of lattice degeneration. At first impression the risks seem at variance with the fine clinical studies of Byer, who has shown a very low detachment rate in the population with lattice degeneration. In all likelihood the vast majority of his patients were emmetropic or mildly myopic, so that very few would be expected to develop detachments during their entire lifetimes, let along during intervals of only 10 to 20 years. This study shows the futility of following, or treating prophylactically, young emmetropic individuals with lattice degeneration. Assuming that prophylaxis is actually effective, one would have to treat 1000 emmetropic lattice patients in the 30 to 39 year age group to prevent a single detachment over a 10-year period. Lattice patients with low to moderate degrees of myopia tend to develop detachments between 40 and 60 years of age caused by premature posterior vitreous separation and tractional tears. Clearly prophylaxis for this group is not warranted, since only 5% to 10% of these individuals will experience detachments in their lifetimes. On the other hand this study has verified the previous suspicions that persons with myopia exceeding -5.0 D accompanied by lattice degeneration have an extraordinarily high risk of detachment during their lifetimes. Detachments in this group tend to cluster in the second, third, and fourth decades, are typically caused by atrophic holes, are slowly progressive, and are often simultaneously bilateral. Enhanced vigilance is certainly appropriate during this time and perhaps consideration should be given to prophylactically treating this group. This would be no small task, since within a population of 1 million persons there would be about 1150 aged 10 to 39 years with myopia exceeding -5.0 D and lattice degeneration. Only 4

  20. MRI and MR tractography in bilateral hypertrophic olivary degeneration

    Directory of Open Access Journals (Sweden)

    Debraj Sen

    2014-01-01

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

  1. MRI and MR tractography in bilateral hypertrophic olivary degeneration.

    Science.gov (United States)

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

    2014-10-01

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

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

    OpenAIRE

    Mathew, David J.; Sarma, Saurabh Kumar; Basaiawmoit, Jennifer V.

    2016-01-01

    Lattice degeneration of the retina is not infrequently encountered on a dilated retinal examination and many of them do not need any intervention. We report a case of atypical lattice degeneration variant with peripheral retinal detachment. An asymptomatic 35-year-old lady with minimal refractive error was found to have extensive lattice degeneration, peripheral retinal detachment and fibrotic changes peripherally with elevation of retinal vessels on dilated retinal examination. There were al...

  3. MRI and MR tractography in bilateral hypertrophic olivary degeneration

    International Nuclear Information System (INIS)

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

    2014-01-01

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

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

    Science.gov (United States)

    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.

  5. Facile fabrication of dendritic silver structures and their surface ...

    Indian Academy of Sciences (India)

    have high sensitivity to surface enhanced Raman spectroscopy response. ... of interfaces and molecularly thin-films. SERS is a ... face plasmon polaritons, while the second is attributed ... 2.2 Fabrication and characterization of dendritic.

  6. Simulation of dendritic growth of magnesium alloys with fluid flow

    Directory of Open Access Journals (Sweden)

    Meng-wu Wu

    2017-11-01

    Full Text Available Fluid flow has a significant impact on the microstructure evolution of alloys during solidification. Based on the previous work relating simulation of the dendritic growth of magnesium alloys with hcp (hexagonal close-packed structure, an extension was made to the formerly established CA (cellular automaton model with the purpose of studying the effect of fluid flow on the dendritic growth of magnesium alloys. The modified projection method was used to solve the transport equations of flow field. By coupling the flow field with the solute field, simulation results of equiaxed and columnar dendritic growth of magnesium alloys with fluid flow were achieved. The simulated results were quantitatively compared with those without fluid flow. Moreover, a comparison was also made between the present work and previous works conducted by others. It can be concluded that a deep understanding of the dendritic growth of magnesium alloys with fluid flow can be obtained by applying the present numerical model.

  7. CD163 positive subsets of blood dendritic cells

    DEFF Research Database (Denmark)

    Maniecki, Maciej Bogdan; Møller, Holger Jon; Moestrup, Søren Kragh

    2006-01-01

    CD163 and CD91 are scavenging receptors with highly increased expression during the differentiation of monocytes into the anti-inflammatory macrophage phenotype. In addition, CD91 is expressed in monocyte-derived dendritic cells (MoDCs), where the receptor is suggested to be important...... for internalization of CD91-targeted antigens to be presented on the dendritic cell surface for T-cell stimulation. Despite their overlap in functionality, the expression of CD91 and CD163 has never been compared and the expression of CD163 in the monocyte-dendritic cell lineage is not yet characterized. CD163...... expression in dendritic cells (DCs) was investigated using multicolor flow cytometry in peripheral blood from 31 healthy donors and 15 HIV-1 patients in addition to umbilical cord blood from 5 newborn infants. Total RNA was isolated from MACS purified DCs and CD163 mRNA was determined with real-time reverse...

  8. Breast Cancer Vaccines Based on Dendritic Cells and the Chemokines

    National Research Council Canada - National Science Library

    Mule, James

    1998-01-01

    The major objective of this project is to establish a new modality for the treatment of breast cancer that employs the combination of chemokine gene-modified fibroblasts with breast tumor-pulsed dendritic cells (DC...

  9. CD56 marks human dendritic cell subsets with cytotoxic potential

    NARCIS (Netherlands)

    Roothans, D.; Smits, E.; Lion, E.; Tel, J.; Anguille, S.

    2013-01-01

    Human plasmacytoid and myeloid dendritic cells (DCs), when appropriately stimulated, can express the archetypal natural killer (NK)-cell surface marker CD56. In addition to classical DC functions, CD56(+) DCs are endowed with an unconventional cytotoxic capacity.

  10. Supramolecular Dendriphores: Anionic Organometallic Phosphors Embedded in Polycationic Dendritic Species

    NARCIS (Netherlands)

    McDonald, A.R.; Mores, D.; de Mello-Donega, C.; van Walree, C.A.; Klein Gebbink, R.J.M.; Lutz, M.; Spek, A.L.; Meijerink, A.; van Klink, G.P.M.; van Koten, G.

    2009-01-01

    Heteroleptic iridium(III) organometallic complexes have been functionalized with sulfate tethers. These systems have been thoroughly characterized spectroscopically. Subsequently these iridium(III) complexes were reacted with polyionic dendritic materials yielding iridium(III) organometallic

  11. Supramolecular effects in dendritic systems containing photoactive groups

    Directory of Open Access Journals (Sweden)

    GIANLUCA CAMILLO AZZELLINI

    2000-03-01

    Full Text Available In this article are described dendritic structures containing photoactive groups at the surface or in the core. The observed supramolecular effects can be attributed to the nature of the photoactive group and their location in the dendritic architecture. The peripheric azobenzene groups in these dendrimeric compounds can be regarded as single residues that retain the spectroscopic and photochemical properties of free azobenzene moiety. The E and Z forms of higher generation dendrimer, functionalized with azobenzene groups, show different host ability towards eosin dye, suggesting the possibility of using such dendrimer in photocontrolled host-guest systems. The photophysical properties of many dendritic-bipyridine ruthenium complexes have been investigated. Particularly in aerated medium more intense emission and a longer excited-state lifetime are observed as compared to the parent unsubstituted bipyridine ruthenium complexes. These differences can be attributed to a shielding effect towards dioxygen quenching originated by the dendritic branches.

  12. Breast Cancer Vaccines Based on Dendritic Cells and the Chemokines

    National Research Council Canada - National Science Library

    Mule, James

    1997-01-01

    The major objective of this project is to establish a new modality for the treatment of breast cancer that employs the combination of chemokine gene modified fibroblasts with breast tumor pulsed dendritic cells (DC...

  13. Molecule Matters-Dendritic Architecture-A Clever Route to ...

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 12; Issue 1. Molecule Matters - Dendritic Architecture - A Clever Route to Monodispersed Macromolecules. N Jayaraman. Feature Article Volume 12 Issue 1 January 2007 pp 60-66 ...

  14. Many-Body Green Function of Degenerate Systems

    International Nuclear Information System (INIS)

    Brouder, Christian; Panati, Gianluca; Stoltz, Gabriel

    2009-01-01

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

  15. The prognosis of retinal detachment due to lattice degeneration.

    Science.gov (United States)

    Benson, W E; Morse, P H

    1978-09-01

    In a series of 553 consecutive retinal detachments, 29% (120) were due to lattice degeneration. Forty-five percent of these were due to atrophic holes in the lattice degeneration and 55% were due to tears caused by traction posterior to or at the end of a patch of lattice. In phakic patients, retinal detachments due to atrophic holes were most common in young myopes. Detachments due to traction tears were seen in older, less myopic patients. The incidence of massive periretinal proliferation was less (5%) in detachments due to lattice degeneration than in detachments not due to lattice degeneration (6.5%).

  16. Dendritic biomimicry: microenvironmental hydrogen-bonding effects on tryptophan fluorescence.

    Science.gov (United States)

    Koenig, S; Müller, L; Smith, D K

    2001-03-02

    Two series of dendritically modified tryptophan derivatives have been synthesised and their emission spectra measured in a range of different solvents. This paper presents the syntheses of these novel dendritic structures and discusses their emission spectra in terms of both solvent and dendritic effects. In the first series of dendrimers, the NH group of the indole ring is available for hydrogen bonding, whilst in the second series, the indole NH group has been converted to NMe. Direct comparison of the emission wavelengths of analogous NH and NMe derivatives indicates the importance of the Kamlet-Taft solvent beta3 parameter, which reflects the ability of the solvent to accept a hydrogen bond from the NH group, an effect not possible for the NMe series of dendrimers. For the NH dendrimers, the attachment of a dendritic shell to the tryptophan subunit leads to a red shift in emission wavelength. This dendritic effect only operates in non-hydrogen-bonding solvents. For the NMe dendrimers, however, the attachment of a dendritic shell has no effect on the emission spectra of the indole ring. This proves the importance of hydrogen bonding between the branched shell and the indole NH group in causing the dendritic effect. This is the first time a dendritic effect has been unambiguously assigned to individual hydrogen-bonding interactions and indicates that such intramolecular interactions are important in dendrimers, just as they are in proteins. Furthermore, this paper sheds light on the use of tryptophan residues as a probe of the microenvironment within proteins--in particular, it stresses the importance of hydrogen bonds formed by the indole NH group.

  17. A portrait of a sucker using landscape genetics: how colonization and life history undermine the idealized dendritic metapopulation.

    Science.gov (United States)

    Salisbury, Sarah J; McCracken, Gregory R; Keefe, Donald; Perry, Robert; Ruzzante, Daniel E

    2016-09-01

    Dendritic metapopulations have been attributed unique properties by in silico studies, including an elevated genetic diversity relative to a panmictic population of equal total size. These predictions have not been rigorously tested in nature, nor has there been full consideration of the interacting effects among contemporary landscape features, colonization history and life history traits of the target species. We tested for the effects of dendritic structure as well as the relative importance of life history, environmental barriers and historical colonization on the neutral genetic structure of a longnose sucker (Catostomus catostomus) metapopulation in the Kogaluk watershed of northern Labrador, Canada. Samples were collected from eight lakes, genotyped with 17 microsatellites, and aged using opercula. Lakes varied in differentiation, historical and contemporary connectivity, and life history traits. Isolation by distance was detected only by removing two highly genetically differentiated lakes, suggesting a lack of migration-drift equilibrium and the lingering influence of historical factors on genetic structure. Bayesian analyses supported colonization via the Kogaluk's headwaters. The historical concentration of genetic diversity in headwaters inferred by this result was supported by high historical and contemporary effective sizes of the headwater lake, T-Bone. Alternatively, reduced allelic richness in headwaters confirmed the dendritic structure's influence on gene flow, but this did not translate to an elevated metapopulation effective size. A lack of equilibrium and upstream migration may have dampened the effects of dendritic structure. We suggest that interacting historical and contemporary factors prevent the achievement of the idealized traits of a dendritic metapopulation in nature. © 2016 John Wiley & Sons Ltd.

  18. Getting superstring amplitudes by degenerating Riemann surfaces

    International Nuclear Information System (INIS)

    Matone, Marco; Volpato, Roberto

    2010-01-01

    We explicitly show how the chiral superstring amplitudes can be obtained through factorisation of the higher genus chiral measure induced by suitable degenerations of Riemann surfaces. This powerful tool also allows to derive, at any genera, consistency relations involving the amplitudes and the measure. A key point concerns the choice of the local coordinate at the node on degenerate Riemann surfaces that greatly simplifies the computations. As a first application, starting from recent ansaetze for the chiral measure up to genus five, we compute the chiral two-point function for massless Neveu-Schwarz states at genus two, three and four. For genus higher than three, these computations include some new corrections to the conjectural formulae appeared so far in the literature. After GSO projection, the two-point function vanishes at genus two and three, as expected from space-time supersymmetry arguments, but not at genus four. This suggests that the ansatz for the superstring measure should be corrected for genus higher than four.

  19. Metabolic anatomy of paraneoplastic cerebellar degeneration

    International Nuclear Information System (INIS)

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

    1988-01-01

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

  20. Progranulin in frontotemporal lobar degeneration and neuroinflammation

    Directory of Open Access Journals (Sweden)

    Hutton Michael L

    2007-02-01

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

  1. Observable consequences of partially degenerate leptogenesis

    CERN Document Server

    Ellis, Jonathan Richard; Yanagida, T; Ellis, John; Raidal, Martti

    2002-01-01

    In the context of the seesaw mechanism, it is natural that the large solar and atmospheric neutrino mixing angles originate separately from large 2 by 2 mixings in the neutrino and charged-lepton sectors, respectively, and large mixing in the neutrino couplings is in turn more plausible if two of the heavy singlet neutrinos are nearly degenerate. We study the phenomenology of this scenario, calculating leptogenesis by solving numerically the set of coupled Boltzmann equations for out-of-equilibrium heavy singlet neutrino decays in the minimal supersymmetric seesaw model. The near-degenerate neutrinos may weigh < 10^8 GeV, avoiding the cosmological gravitino problem. This scenario predicts that Br(mu to e gamma) should be strongly suppressed, because of the small singlet neutrino masses, whilst Br(tau to mu gamma) may be large enough to be observable in B-factory or LHC experiments. If the light neutrino masses are hierarchical, we predict that the neutrinoless double-beta decay parameter m_{ee} is approxim...

  2. MR imaging findings of hypertrophic olivary degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Do Joong; Jeon, Pyung; Kim, Dong Ik [Yonsei Univ. College of Medicine, Seoul (Korea, Republic of)

    1997-06-01

    To describe the magnetic resonance (MR) imaging findings of hypertrophic olivary degeneration (HOD) MR images of seven patients with HOD were retrospectively reviewed. Two were women and five were men, and they were aged between 48 and 65 (mean 58) years. Imaging examinations were performed with a 1.5-T unit, and the findings were used to evaluate the size and signal intensity of olivary lesions. The time interval from hemorrhagic ictus to MR imaging was between two and 30 months. Follow-up examinations were performed in two patients. All four patients with hemorrhages involving the central tegmental tract in the pons or midbrain showed ipsilateral HOD. Among these four, bilateral HOD was seen in one patient with hemorrhage involving the bilateral central tegmental tract, and in another with tegmental hemorrhage extending to the ipsilateral superior cerebellar peduncle. One patient with cerebellar hemorrhage involving the dentate nucleus had contralateral HOD. Two patients with multiple hemorrhages involving both the pons and cerebellum showed bilateral HOD. Axial MR images showed mild enlargement of the involved olivary mucleus, with high signal intensity on both proton density and T2 weighted images. There was no apparent enhancement on postcontrast T1-weighted images. MR imaging can clearly distinguish secondary olivary degeneration from underlying pathology involving the central tegmental tract in the pons or midbrain and cerebellum. These olivary abnormalities should not, however, be mistaken for primary medullary lesions.

  3. Vitreous in lattice degeneration of retina.

    Science.gov (United States)

    Foos, R Y; Simons, K B

    1984-05-01

    A localized pocket of missing vitreous invariably overlies lattice degeneration of the retina. Subjects with lattice also have a higher rate of rhegmatogenous retinal detachment, which is usually a complication of retinal tears. The latter are in turn a result of alterations in the central vitreous--that is, synchysis senilis leading to posterior vitreous detachment. In order to determine if there is either an association or a deleterious interaction between the local and central lesions of the vitreous in eyes with lattice, a comparison was made in autopsy eyes with and without lattice the degree of synchysis and rate of vitreous detachment. Results show no association between the local and central vitreous lesions, indicating that a higher rate of vitreous detachment is not the basis for the higher rate of retinal detachment in eyes with lattice. Also, there was no suggestion of deleterious interaction between the local and central vitreous lesions, either through vitreodonesis as a basis for precocious vitreous detachment, or through a greater degree of synchysis as a basis for interconnection of local and central lacunae (which could extend the localized retinal detachment in eyes with holes in lattice degeneration).

  4. MR imaging findings of hypertrophic olivary degeneration

    International Nuclear Information System (INIS)

    Kim, Do Joong; Jeon, Pyung; Kim, Dong Ik

    1997-01-01

    To describe the magnetic resonance (MR) imaging findings of hypertrophic olivary degeneration (HOD) MR images of seven patients with HOD were retrospectively reviewed. Two were women and five were men, and they were aged between 48 and 65 (mean 58) years. Imaging examinations were performed with a 1.5-T unit, and the findings were used to evaluate the size and signal intensity of olivary lesions. The time interval from hemorrhagic ictus to MR imaging was between two and 30 months. Follow-up examinations were performed in two patients. All four patients with hemorrhages involving the central tegmental tract in the pons or midbrain showed ipsilateral HOD. Among these four, bilateral HOD was seen in one patient with hemorrhage involving the bilateral central tegmental tract, and in another with tegmental hemorrhage extending to the ipsilateral superior cerebellar peduncle. One patient with cerebellar hemorrhage involving the dentate nucleus had contralateral HOD. Two patients with multiple hemorrhages involving both the pons and cerebellum showed bilateral HOD. Axial MR images showed mild enlargement of the involved olivary mucleus, with high signal intensity on both proton density and T2 weighted images. There was no apparent enhancement on postcontrast T1-weighted images. MR imaging can clearly distinguish secondary olivary degeneration from underlying pathology involving the central tegmental tract in the pons or midbrain and cerebellum. These olivary abnormalities should not, however, be mistaken for primary medullary lesions

  5. Hyaline cartilage degenerates after autologous osteochondral transplantation.

    Science.gov (United States)

    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.

  6. The unfolded protein response is required for dendrite morphogenesis

    Science.gov (United States)

    Wei, Xing; Howell, Audrey S; Dong, Xintong; Taylor, Caitlin A; Cooper, Roshni C; Zhang, Jianqi; Zou, Wei; Sherwood, David R; Shen, Kang

    2015-01-01

    Precise patterning of dendritic fields is essential for the formation and function of neuronal circuits. During development, dendrites acquire their morphology by exuberant branching. How neurons cope with the increased load of protein production required for this rapid growth is poorly understood. Here we show that the physiological unfolded protein response (UPR) is induced in the highly branched Caenorhabditis elegans sensory neuron PVD during dendrite morphogenesis. Perturbation of the IRE1 arm of the UPR pathway causes loss of dendritic branches, a phenotype that can be rescued by overexpression of the ER chaperone HSP-4 (a homolog of mammalian BiP/ grp78). Surprisingly, a single transmembrane leucine-rich repeat protein, DMA-1, plays a major role in the induction of the UPR and the dendritic phenotype in the UPR mutants. These findings reveal a significant role for the physiological UPR in the maintenance of ER homeostasis during morphogenesis of large dendritic arbors. DOI: http://dx.doi.org/10.7554/eLife.06963.001 PMID:26052671

  7. Dendritic cells recognize tumor-specific glycosylation of carcinoembryonic antigen on colorectal cancer cells through dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin

    NARCIS (Netherlands)

    van Gisbergen, Klaas P. J. M.; Aarnoudse, Corlien A.; Meijer, Gerrit A.; Geijtenbeek, Teunis B. H.; van Kooyk, Yvette

    2005-01-01

    Dendritic cells play a pivotal role in the induction of antitumor immune responses. Immature dendritic cells are located intratumorally within colorectal cancer and intimately interact with tumor cells, whereas mature dendritic cells are present peripheral to the tumor. The majority of colorectal

  8. Age-Related Macular Degeneration: Pathogenesis, Genetic Background, and the Role of Nutritional Supplements

    Directory of Open Access Journals (Sweden)

    Marilita M. Moschos

    2014-01-01

    Full Text Available Age-related macular degeneration (ARMD is the leading cause of severe vision loss and blindness worldwide, mainly affecting people over 65 years old. Dry and wet ARDM are the main types of the disease, which seem to have a multifactorial background. The aim of this review is to summarize the mechanisms of ARMD pathogenesis and exhibit the role of diet and nutritional supplements in the onset and progression of the disease. Environmental factors, such as smoking, alcohol, and, diet appear to interact with mutations in nuclear and mitochondrial DNA, contributing to the pathogenesis of ARMD. Inflammatory mediators and oxidative stress, induced by the daily exposure of retina to high pressure of oxygen and light radiation, have been also associated with ARMD lesions. Other than medical and surgical therapies, nutritional supplements hold a significant role in the prevention and treatment of ARMD, eliminating the progression of macular degeneration.

  9. Equine dendritic cells generated with horse serum have enhanced functionality in comparison to dendritic cells generated with fetal bovine serum

    OpenAIRE

    Ziegler, Anja; Everett, Helen; Hamza, Eman; Garbani, Mattia; Gerber, Vinzenz; Marti, Eliane; Steinbach, Falko

    2016-01-01

    BACKGROUND: Dendritic cells are professional antigen-presenting cells that play an essential role in the initiation and modulation of T cell responses. They have been studied widely for their potential clinical applications, but for clinical use to be successful, alternatives to xenogeneic substances like fetal bovine serum (FBS) in cell culture need to be found. Protocols for the generation of dendritic cells ex vivo from monocytes are well established for several species, including hor...

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

    Science.gov (United States)

    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.

  11. PARP inhibitors protect against sex- and AAG-dependent alkylation-induced neural degeneration.

    Science.gov (United States)

    Allocca, Mariacarmela; Corrigan, Joshua J; Fake, Kimberly R; Calvo, Jennifer A; Samson, Leona D

    2017-09-15

    Alkylating agents are commonly used to treat cancer. Although base excision repair (BER) is a major pathway for repairing DNA alkylation damage, under certain conditions, the initiation of BER produces toxic repair intermediates that damage healthy tissues. The initiation of BER by the alkyladenine DNA glycosylase (AAG, a.k.a. MPG) can mediate alkylation-induced cytotoxicity in specific cells in the retina and cerebellum of male mice. Cytotoxicity in both wild-type and Aag -transgenic ( AagTg ) mice is abrogated in the absence of Poly(ADP-ribose) polymerase-1 (PARP1). Here, we tested whether PARP inhibitors can also prevent alkylation-induced retinal and cerebellar degeneration in male and female WT and AagTg mice. Importantly, we found that WT mice display sex-dependent alkylation-induced retinal damage (but not cerebellar damage), with WT males being more sensitive than females. Accordingly, estradiol treatment protects males against alkylation-induced retinal degeneration. In AagTg male and female mice, the alkylation-induced tissue damage in both the retina and cerebellum is exacerbated and the sex difference in the retina is abolished. PARP inhibitors, much like Parp1 gene deletion, protect against alkylation-induced AAG-dependent neuronal degeneration in WT and AagTg mice, regardless of the gender, but their efficacy in preventing alkylation-induced neuronal degeneration depends on PARP inhibitor characteristics and doses. The recent surge in the use of PARP inhibitors in combination with cancer chemotherapeutic alkylating agents might represent a powerful tool for obtaining increased therapeutic efficacy while avoiding the collateral effects of alkylating agents in healthy tissues.

  12. Deciphering dendritic cell heterogenity in immunity

    Directory of Open Access Journals (Sweden)

    Michaël eChopin

    2012-02-01

    Full Text Available Dendritic cells (DCs are specialized antigen presenting cells that are exquisitely adapted to sense pathogens and induce the development of adaptive immune responses. They form a complex network of phenotypically and functionally distinct subsets. Within this network, individual DC subsets display highly specific roles in local immunosurveillance, migration and antigen presentation. This division of labor amongst DCs offers great potential to tune the immune response by harnessing subset-specific attributes of DCs in the clinical setting. Until recently, our understanding of DC subsets has been limited and paralleled by poor clinical translation and efficacy. We have now begun to unravel how different DC subsets develop within a complex multilayered system. These finding open up exciting possibilities for targeted manipulation of DC subsets. Furthermore, ground-breaking developments overcoming a major translational obstacle – identification of similar DC populations in mouse and man – now set the stage for significant advances in the field. Here we explore the determinants that underpin cellular and transcriptional heterogeneity within the DC network, how these influence DC distribution and localization at steady-state, and the capacity of DCs to present antigens via direct or cross-presentation during pathogen infection.

  13. Epigenetic regulation of axon and dendrite growth

    Directory of Open Access Journals (Sweden)

    Ephraim F Trakhtenberg

    2012-03-01

    Full Text Available Neuroregenerative therapies for central nervous system (CNS injury, neurodegenerative disease, or stroke require axons of damaged neurons to grow and reinnervate their targets. However, mature mammalian CNS neurons do not regenerate their axons, limiting recovery in these diseases (Yiu and He, 2006. CNS’ regenerative failure may be attributable to the development of an inhibitory CNS environment by glial-associated inhibitory molecules (Yiu and He, 2006, and by various cell-autonomous factors (Sun and He, 2010. Intrinsic axon growth ability also declines developmentally (Li et al., 1995; Goldberg et al., 2002; Bouslama-Oueghlani et al., 2003; Blackmore and Letourneau, 2006 and is dependent on transcription (Moore et al., 2009. Although neurons’ intrinsic capacity for axon growth may depend in part on the panoply of expressed transcription factors (Moore and Goldberg, 2011, epigenetic factors such as the accessibility of DNA and organization of chromatin are required for downstream genes to be transcribed. Thus a potential approach to overcoming regenerative failure focuses on the epigenetic mechanisms regulating regenerative gene expression in the CNS. Here we review molecular mechanisms regulating the epigenetic state of DNA through chromatin modifications, their implications for regulating axon and dendrite growth, and important new directions for this field of study.

  14. Isolation of Human Skin Dendritic Cell Subsets.

    Science.gov (United States)

    Gunawan, Merry; Jardine, Laura; Haniffa, Muzlifah

    2016-01-01

    Dendritic cells (DCs) are specialized leukocytes with antigen-processing and antigen-presenting functions. DCs can be divided into distinct subsets by anatomical location, phenotype and function. In human, the two most accessible tissues to study leukocytes are peripheral blood and skin. DCs are rare in human peripheral blood (skin covering an average total surface area of 1.8 m(2) has approximately tenfold more DCs than the average 5 L of total blood volume (Wang et al., J Invest Dermatol 134:965-974, 2014). DCs migrate spontaneously from skin explants cultured ex vivo, which provide an easy method of cell isolation (Larsen et al., J Exp Med 172:1483-1493, 1990; Lenz et al., J Clin Invest 92:2587-2596, 1993; Nestle et al., J Immunol 151:6535-6545, 1993). These factors led to the extensive use of skin DCs as the "prototype" migratory DCs in human studies. In this chapter, we detail the protocols to isolate DCs and resident macrophages from human skin. We also provide a multiparameter flow cytometry gating strategy to identify human skin DCs and to distinguish them from macrophages.

  15. Crosstalk between T lymphocytes and dendritic cells.

    Science.gov (United States)

    Hivroz, Claire; Chemin, Karine; Tourret, Marie; Bohineust, Armelle

    2012-01-01

    Dendritic cells (DCs) are professional antigen-presenting cells (APCs) with the unique property of inducing priming and differentiation of naïve CD4+ and CD8+ T cells into helper and cytotoxic effectors. Their efficiency is due to their unique ability to process antigen, express costimulatory molecules, secrete cytokines, and migrate to tissues or lymphoid organs to prime T cells. DCs also play an important role in T-cell peripheral tolerance. There is ample evidence that the DC ability to present antigens is regulated by CD4+ helper T cells. Indeed, interactions between surface receptors and ligands expressed respectively by T cells and DCs, as well as T-cell-derived cytokines modify DC functions. This T-cell-induced modification of DCs has been called "education" or "licensing." This intimate crosstalk between DCs and T lymphocytes is key in establishing appropriate adaptive immune responses. It requires cognate interactions between T lymphocytes and DCs, which are organized in time and space by structures called immunological synapses. Here we discuss the particular aspects of immunological synapses formed between T cells and DCs and the role these organized interactions have in T-cell-DC crosstalk.

  16. Dendritic Cells—Importance in Allergy—

    Directory of Open Access Journals (Sweden)

    Setsuya Aiba

    2007-01-01

    Full Text Available In this review we discuss the role of dendritic cells (DC in the pathogenesis of allergic contact hypersensitivity (ACH and atopic disorders, such as asthma and atopic eczema. In ACH patients, DC recognize the invasion of simple chemicals such as haptens, and trigger antigen-specific T cell responses leading to the characteristic histological and clinical changes such as spongiosis and papulovesicular eruptions. During atopic disorders, it is well known that the Th2-deviated immune response plays a crucial role in their pathogenesis. DC provide T cells with antigen and costimulatory signals (signals 1 and 2, respectively, as well as with a polarizing signal (signal 3. When studying ACH, it is important to understand how simple chemicals induce the activation of DC and their migration to the draining lymph nodes where they supply signals 1 and 2 to naïve T cells. The mechanisms by which DC induce the Th2-deviated immune response, namely via the Th2-deviated signal 3, are central topics in the pathogenesis of atopic disorders.

  17. The role of dendritic cells in cancer

    DEFF Research Database (Denmark)

    Hansen, Morten; Andersen, Mads Hald

    2017-01-01

    Though present in low numbers, dendritic cells (DCs) are recognized as major players in the control of cancer by adaptive immunity. The roles of cytotoxic CD8+ T-cells and Th1 helper CD4+ T-cells are well-documented in murine models of cancer and associated with a profound prognostic impact when...... infiltrating human tumors, but less information is known about how these T-cells gain access to the tumor or how they are primed to become tumor-specific. Here, we highlight recent findings that demonstrate a vital role of CD103+ DCs, which have been shown to be experts in cross-priming and the induction...... of anti-tumor immunity. We also focus on two different mediators that impair the function of tumor-associated DCs: prostaglandin E2 and β-catenin. Both of these mediators seem to be important for the exclusion of T-cells in the tumor microenvironment and may represent key pathways to target in optimized...

  18. A dam for retrograde axonal degeneration in multiple sclerosis?

    NARCIS (Netherlands)

    Balk, L.J.; Twisk, J.W.R.; Steenwijk, M.D.; Daams, M.; Tewarie, P.; Killestein, J.; Uitdehaag, B.M.J.; Polman, C.H.; Petzold, A.F.S.

    2014-01-01

    Objective: Trans-synaptic axonal degeneration is a mechanism by which neurodegeneration can spread from a sick to a healthy neuron in the central nervous system. This study investigated to what extent trans-synaptic axonal degeneration takes place within the visual pathway in multiple sclerosis

  19. New treatment strategies for canine intervertebral disc degeneration

    NARCIS (Netherlands)

    Smolders, L.A.

    2013-01-01

    Degeneration of the intervertebral disc (IVD) is a common problem in dogs and humans. IVD degeneration can lead to herniation of the IVD with subsequent compression of neural structures and various clinical signs, including back pain. Current treatment of IVD disease is conservative or surgical.

  20. Lattice degeneration of the retina and retinal detachment.

    Science.gov (United States)

    Semes, L P

    1992-01-01

    Lattice retinal degeneration is considered the most significant peripheral retinal disorder potentially predisposing to retinal breaks and retinal detachment. Lattice degeneration affects the vitreous and inner retinal layers with secondary changes as deep as the retinal pigment epithelium and perhaps the choriocapillaris. Variations in clinical appearance are the rule; geographically, lattice lesions favor the vertical meridians between the equator and the ora serrata. Lattice degeneration begins early in life and has been reported in sequential generations of the same family. Along with its customary bilateral occurrence, lattice shares other characteristics of a dystrophy. The association between the vitreous and retina in lattice lesions may be responsible for the majority of lattice-induced retinal detachments. The tumultuous event of posterior vitreous separation in the presence of abnormally strong vitreoretinal adherence is the trigger for a retinal tear that, in turn, may lead to retinal detachment. Although retinal holes in young patients with lattice degeneration may play a role in the evolution of retinal detachment, the clinical course of lattice degeneration seems to be one of dormancy rather than of progressive change. This discussion outlines the pathophysiology of lattice retinal degeneration and the relationship of pathophysiology to clinical presentation. The epidemiology of lattice degeneration is summarized, as are the possible precursors to retinal detachment. A clinical characterization of the natural history of lattice degeneration is offered, and interventions for complications are described. To conclude, management strategies from a primary-care standpoint are reviewed.

  1. Prevalence of age-related macular degeneration in elderly Caucasians

    DEFF Research Database (Denmark)

    Erke, Maja G; Bertelsen, Geir; Peto, Tunde

    2012-01-01

    To describe the sex- and age-specific prevalence of drusen, geographic atrophy, and neovascular age-related macular degeneration (AMD).......To describe the sex- and age-specific prevalence of drusen, geographic atrophy, and neovascular age-related macular degeneration (AMD)....

  2. Negative electroretinograms in pericentral pigmentary retinal degeneration.

    Science.gov (United States)

    Hotta, Kazuki; Kondo, Mineo; Nakamura, Makoto; Hotta, Junko; Terasaki, Hiroko; Miyake, Yozo; Hida, Tetsuo

    2006-01-01

    The clinical presentation and electrophysiological findings are described of three consecutive cases with pericentral pigmentary retinal degeneration. The responses to bright flashes after dark adaptation showed negative waveform shape in all cases. Rod responses were strongly reduced compared with cone responses. Cone electroretinograms elicited by long-duration stimuli showed greater loss of the on-response than the off-response. The ratio of the on-response amplitude to off-response amplitude of these patients (0.52 +/- 0.12; mean +/- SD, n = 6) was significantly smaller than that of normal subject (0.83 +/- 0.21; mean +/- SD, n = 8) (Mann-Whitney U-test, P retinal function, especially in transmission between photoreceptors and depolarizing bipolar cells.

  3. Tidal effects in twin-degenerate binaries

    International Nuclear Information System (INIS)

    Campbell, C.G.

    1984-01-01

    The tidal velocity field is calculated for an initially non-rotating low mass white dwarf secondary in a twin-degenerate binary. These motions are used to find the tidal torque on the secondary, to first order in the orbital frequency, and an expression is derived for the synchronization time. For a lobe-filling secondary the synchronization time has a weak dependence on the mass and luminosity of the star, and for the binary G61-29 is found to be of the same order as the estimated lifetime of the system. It is emphasized, however, that tidal excitation of non-radial oscillatory modes in the secondary may significantly shorten the synchronization time. (author)

  4. A COMPUTATIONAL MODEL OF MOTOR NEURON DEGENERATION

    Science.gov (United States)

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

    2014-01-01

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

  5. A computational model of motor neuron degeneration.

    Science.gov (United States)

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

    2014-08-20

    To explore the link between bioenergetics and motor neuron degeneration, we used a computational model in which detailed morphology and ion conductance are paired with intracellular ATP production and consumption. We found that reduced ATP availability increases the metabolic cost of a single action potential and disrupts K+/Na+ homeostasis, resulting in a chronic depolarization. The magnitude of the ATP shortage at which this ionic instability occurs depends on the morphology and intrinsic conductance characteristic of the neuron. If ATP shortage is confined to the distal part of the axon, the ensuing local ionic instability eventually spreads to the whole neuron and involves fasciculation-like spiking events. A shortage of ATP also causes a rise in intracellular calcium. Our modeling work supports the notion that mitochondrial dysfunction can account for salient features of the paralytic disorder amyotrophic lateral sclerosis, including motor neuron hyperexcitability, fasciculation, and differential vulnerability of motor neuron subpopulations. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Degenerate R-S perturbation theory

    Science.gov (United States)

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

    1973-01-01

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

  7. Nearly degenerate neutrinos, supersymmetry and radiative corrections

    International Nuclear Information System (INIS)

    Casas, J.A.; Espinosa, J.R.; Ibarra, A.; Navarro, I.

    2000-01-01

    If neutrinos are to play a relevant cosmological role, they must be essentially degenerate with a mass matrix of the bimaximal mixing type. We study this scenario in the MSSM framework, finding that if neutrino masses are produced by a see-saw mechanism, the radiative corrections give rise to mass splittings and mixing angles that can accommodate the atmospheric and the (large angle MSW) solar neutrino oscillations. This provides a natural origin for the Δm 2 sol 2 atm hierarchy. On the other hand, the vacuum oscillation solution to the solar neutrino problem is always excluded. We discuss also in the SUSY scenario other possible effects of radiative corrections involving the new neutrino Yukawa couplings, including implications for triviality limits on the Majorana mass, the infrared fixed point value of the top Yukawa coupling, and gauge coupling and bottom-tau unification

  8. Progression of Fatty Muscle Degeneration in Atraumatic Rotator Cuff Tears.

    Science.gov (United States)

    Hebert-Davies, Jonah; Teefey, Sharlene A; Steger-May, Karen; Chamberlain, Aaron M; Middleton, William; Robinson, Kathryn; Yamaguchi, Ken; Keener, Jay D

    2017-05-17

    The purpose of this prospective study was to examine the progression of fatty muscle degeneration over time in asymptomatic shoulders with degenerative rotator cuff tears. Subjects with an asymptomatic rotator cuff tear in 1 shoulder and pain due to rotator cuff disease in the contralateral shoulder were enrolled in a prospective cohort. Subjects were followed annually with shoulder ultrasonography, which evaluated tear size, location, and fatty muscle degeneration. Tears that were either full-thickness at enrollment or progressed to a full-thickness defect during follow-up were examined. A minimum follow-up of 2 years was necessary for eligibility. One hundred and fifty-six shoulders with full-thickness rotator cuff tears were potentially eligible. Seventy shoulders had measurable fatty muscle degeneration of at least 1 rotator cuff muscle at some time point. Patients with fatty muscle degeneration in the shoulder were older than those without degeneration (mean, 65.8 years [95% confidence interval (CI), 64.0 to 67.6 years] compared with 61.0 years [95% CI, 59.1 to 62.9 years]; p tears at baseline was larger in shoulders with degeneration than in shoulders that did not develop degeneration (13 and 10 mm wide, respectively, and 13 and 10 mm long; p Tears with fatty muscle degeneration were more likely to have enlarged during follow-up than were tears that never developed muscle degeneration (79% compared with 58%; odds ratio, 2.64 [95% CI, 1.29 to 5.39]; p muscle degeneration occurred more frequently in shoulders with tears that had enlarged (43%; 45 of 105) than in shoulders with tears that had not enlarged (20%; 10 of 51; p tears with enlargement and progression of muscle degeneration were more likely to extend into the anterior supraspinatus than were those without progression (53% and 17%, respectively; p tear size (p = 0.56). The median time from tear enlargement to progression of fatty muscle degeneration was 1.0 year (range, -2.0 to 6.9 years) for the

  9. Formation of Degenerate Band Gaps in Layered Systems

    Directory of Open Access Journals (Sweden)

    Alexey P. Vinogradov

    2012-06-01

    Full Text Available 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.

  10. [Lattice degeneration of the peripheral retina: ultrastructural study].

    Science.gov (United States)

    Bec, P; Malecaze, F; Arne, J L; Mathis, A

    1985-01-01

    The ultrastructural study of a case of snail track degeneration shows the presence of lipid inclusions in both the glial and the macrophage cells in every layer of the retina, and the existence of intraretinal fibers different from collagen fibers appearing to be glial filaments similar to those found in astrocytic gliomes and to the Rosenthal fibers observed in senile nervous cells. Other features were thinning of the retina and absence of blood vessels in the retina. There are no abnormalities of the vitreo-retinal juncture. All the lesions are in agreement with those observed by Daicker [Ophthalmologica, Basel 165: 360-365, 1972; Klin. Mbl. Augenheilk. 172: 581-583, 1978] with some differences, however. They are different from those found in lattice degeneration. They show that snail track degeneration is a specific form of peripheral retinal degeneration which is quite different from lattice degeneration and must not be considered similar.

  11. Mechanism of Inflammation in Age-Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Francesco Parmeggiani

    2012-01-01

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

  12. Dopamine induces soluble α-synuclein oligomers and nigrostriatal degeneration.

    Science.gov (United States)

    Mor, Danielle E; Tsika, Elpida; Mazzulli, Joseph R; Gould, Neal S; Kim, Hanna; Daniels, Malcolm J; Doshi, Shachee; Gupta, Preetika; Grossman, Jennifer L; Tan, Victor X; Kalb, Robert G; Caldwell, Kim A; Caldwell, Guy A; Wolfe, John H; Ischiropoulos, Harry

    2017-11-01

    Parkinson's disease (PD) is defined by the loss of dopaminergic neurons in the substantia nigra and the formation of Lewy body inclusions containing aggregated α-synuclein. Efforts to explain dopamine neuron vulnerability are hindered by the lack of dopaminergic cell death in α-synuclein transgenic mice. To address this, we manipulated both dopamine levels and α-synuclein expression. Nigrally targeted expression of mutant tyrosine hydroxylase with enhanced catalytic activity increased dopamine levels without damaging neurons in non-transgenic mice. In contrast, raising dopamine levels in mice expressing human A53T mutant α-synuclein induced progressive nigrostriatal degeneration and reduced locomotion. Dopamine elevation in A53T mice increased levels of potentially toxic α-synuclein oligomers, resulting in conformationally and functionally modified species. Moreover, in genetically tractable Caenorhabditis elegans models, expression of α-synuclein mutated at the site of interaction with dopamine prevented dopamine-induced toxicity. These data suggest that a unique mechanism links two cardinal features of PD: dopaminergic cell death and α-synuclein aggregation.

  13. Mechanism of Inflammation in Age-Related Macular Degeneration

    Science.gov (United States)

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

    2012-01-01

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

  14. Automatic age-related macular degeneration detection and staging

    Science.gov (United States)

    van Grinsven, Mark J. J. P.; Lechanteur, Yara T. E.; van de Ven, Johannes P. H.; van Ginneken, Bram; Theelen, Thomas; Sánchez, Clara I.

    2013-03-01

    Age-related macular degeneration (AMD) is a degenerative disorder of the central part of the retina, which mainly affects older people and leads to permanent loss of vision in advanced stages of the disease. AMD grading of non-advanced AMD patients allows risk assessment for the development of advanced AMD and enables timely treatment of patients, to prevent vision loss. AMD grading is currently performed manually on color fundus images, which is time consuming and expensive. In this paper, we propose a supervised classification method to distinguish patients at high risk to develop advanced AMD from low risk patients and provide an exact AMD stage determination. The method is based on the analysis of the number and size of drusen on color fundus images, as drusen are the early characteristics of AMD. An automatic drusen detection algorithm is used to detect all drusen. A weighted histogram of the detected drusen is constructed to summarize the drusen extension and size and fed into a random forest classifier in order to separate low risk from high risk patients and to allow exact AMD stage determination. Experiments showed that the proposed method achieved similar performance as human observers in distinguishing low risk from high risk AMD patients, obtaining areas under the Receiver Operating Characteristic curve of 0.929 and 0.934. A weighted kappa agreement of 0.641 and 0.622 versus two observers were obtained for AMD stage evaluation. Our method allows for quick and reliable AMD staging at low costs.

  15. Recent developments in age-related macular degeneration: a review

    Science.gov (United States)

    Al-Zamil, Waseem M; Yassin, Sanaa A

    2017-01-01

    Background Visual impairment in elderly people is a considerable health problem that significantly affects quality of life of millions worldwide. The magnitude of this issue is becoming more evident with an aging population and an increasing number of older individuals. Objective The objective of this article was to review the clinical and pathological aspects of age-related macular degeneration (AMD), diagnostic tools, and therapeutic modalities presently available or underway for both atrophic and wet forms of the disease. Methods An online review of the PubMed database was performed, searching for the key words. The search was limited to articles published since 1980 to date. Results Several risk factors have been linked to AMD, such as age (>60 years), lifestyle (smoking and diet), and family history. Although the pathogenesis of AMD remains unclear, genetic factors have been implicated in the condition. Treatment for atrophic AMD is mainly close observation, coupled with nutritional supplements such as zinc and antioxidants, whereas treatment of wet AMD is based on targeting choroidal neovascular membranes. Conclusion Identification of modifiable risk factors would improve the possibilities of preventing the progression of AMD. The role of anti-vascular endothelial growth factor (anti-VEGF) agents has transformed the therapeutic approach of the potentially blinding disease “wet AMD” into a more favorable outcome. PMID:28860733

  16. Human intestinal dendritic cells as controllers of mucosal immunity

    Directory of Open Access Journals (Sweden)

    David Bernardo

    2013-06-01

    Full Text Available Dendritic cells are the most potent, professional antigen-presenting cells in the body; following antigen presentation they control the type (proinflammatory/regulatory of immune response that will take place, as well as its location. Given their high plasticity and maturation ability in response to local danger signals derived from innate immunity, dendritic cells are key actors in the connection between innate immunity and adaptive immunity responses. In the gut dendritic cells control immune tolerance mechanisms against food and/or commensal flora antigens, and are also capable of initiating an active immune response in the presence of invading pathogens. Dendritic cells are thus highly efficient in controlling the delicate balance between tolerance and immunity in an environment so rich in antigens as the gut, and any factor involving these cells may impact their function, ultimately leading to the development of bowel conditions such as celiac disease or inflammatory bowel disease. In this review we shall summarize our understanding of human intestinal dendritic cells, their ability to express and induce migration markers, the various environmental factors modulating their properties, their subsets in the gut, and the problems entailed by their study, including identification strategies, differences between humans and murine models, and phenotypical variations along the gastrointestinal tract.

  17. Location-dependent excitatory synaptic interactions in pyramidal neuron dendrites.

    Directory of Open Access Journals (Sweden)

    Bardia F Behabadi

    Full Text Available Neocortical pyramidal neurons (PNs receive thousands of excitatory synaptic contacts on their basal dendrites. Some act as classical driver inputs while others are thought to modulate PN responses based on sensory or behavioral context, but the biophysical mechanisms that mediate classical-contextual interactions in these dendrites remain poorly understood. We hypothesized that if two excitatory pathways bias their synaptic projections towards proximal vs. distal ends of the basal branches, the very different local spike thresholds and attenuation factors for inputs near and far from the soma might provide the basis for a classical-contextual functional asymmetry. Supporting this possibility, we found both in compartmental models and electrophysiological recordings in brain slices that the responses of basal dendrites to spatially separated inputs are indeed strongly asymmetric. Distal excitation lowers the local spike threshold for more proximal inputs, while having little effect on peak responses at the soma. In contrast, proximal excitation lowers the threshold, but also substantially increases the gain of distally-driven responses. Our findings support the view that PN basal dendrites possess significant analog computing capabilities, and suggest that the diverse forms of nonlinear response modulation seen in the neocortex, including uni-modal, cross-modal, and attentional effects, could depend in part on pathway-specific biases in the spatial distribution of excitatory synaptic contacts onto PN basal dendritic arbors.

  18. A dendrite-suppressing composite ion conductor from aramid nanofibres.

    Science.gov (United States)

    Tung, Siu-On; Ho, Szushen; Yang, Ming; Zhang, Ruilin; Kotov, Nicholas A

    2015-01-27

    Dendrite growth threatens the safety of batteries by piercing the ion-transporting separators between the cathode and anode. Finding a dendrite-suppressing material that combines high modulus and high ionic conductance has long been considered a major technological and materials science challenge. Here we demonstrate that these properties can be attained in a composite made from Kevlar-derived aramid nanofibres assembled in a layer-by-layer manner with poly(ethylene oxide). Importantly, the porosity of the membranes is smaller than the growth area of the dendrites so that aramid nanofibres eliminate 'weak links' where the dendrites pierce the membranes. The aramid nanofibre network suppresses poly(ethylene oxide) crystallization detrimental for ion transport, giving a composite that exhibits high modulus, ionic conductivity, flexibility, ion flux rates and thermal stability. Successful suppression of hard copper dendrites by the composite ion conductor at extreme discharge conditions is demonstrated, thereby providing a new approach for the materials engineering of solid ion conductors.

  19. eGFP expression under the Uchl1 promoter labels corticospinal motor neurons and a subpopulation of degeneration resistant spinal motor neurons in ALS mouse models

    Science.gov (United States)

    Yasvoina, Marina V.

    Current understanding of basic cellular and molecular mechanisms for motor neuron vulnerability during motor neuron disease initiation and progression is incomplete. The complex cytoarchitecture and cellular heterogeneity of the cortex and spinal cord greatly impedes our ability to visualize, isolate, and study specific neuron populations in both healthy and diseased states. We generated a novel reporter line, the Uchl1-eGFP mouse, in which cortical and spinal components of motor neuron circuitry are genetically labeled with eGFP under the Uchl1 promoter. A series of cellular and anatomical analyses combined with retrograde labeling, molecular marker expression, and electrophysiology were employed to determine identity of eGFP expressing cells in the motor cortex and the spinal cord of novel Uchl1-eGFP reporter mice. We conclude that eGFP is expressed in corticospinal motor neurons (CSMN) in the motor cortex and a subset of S-type alpha and gamma spinal motor neurons (SMN) in the spinal cord. hSOD1G93A and Alsin-/- mice, mouse models for amyotrophic lateral sclerosis (ALS), were bred to Uchl1-eGFP reporter mouse line to investigate the pathophysiology and underlying mechanisms of CSMN degeneration in vivo. Evidence suggests early and progressive degeneration of CSMN and SMN in the hSOD1G93A transgenic mice. We show an early increase of autophagosome formation in the apical dendrites of vulnerable CSMN in hSOD1G93A-UeGFP mice, which is localized to the apical dendrites. In addition, labeling S-type alpha and gamma SMN in the hSOD1G93A-UeGFP mice provide a unique opportunity to study basis of their resistance to degeneration. Mice lacking alsin show moderate clinical phenotype and mild CSMN axon degeneration in the spinal cord, which suggests vulnerability of CSMN. Therefore, we investigated the CSMN cellular and axon defects in aged Alsin-/- mice bred to Uchl1-eGFP reporter mouse line. We show that while CSMN are preserved and lack signs of degeneration, CSMN axons

  20. Noise tolerant dendritic lattice associative memories

    Science.gov (United States)

    Ritter, Gerhard X.; Schmalz, Mark S.; Hayden, Eric; Tucker, Marc

    2011-09-01

    Linear classifiers based on computation over the real numbers R (e.g., with operations of addition and multiplication) denoted by (R, +, x), have been represented extensively in the literature of pattern recognition. However, a different approach to pattern classification involves the use of addition, maximum, and minimum operations over the reals in the algebra (R, +, maximum, minimum) These pattern classifiers, based on lattice algebra, have been shown to exhibit superior information storage capacity, fast training and short convergence times, high pattern classification accuracy, and low computational cost. Such attributes are not always found, for example, in classical neural nets based on the linear inner product. In a special type of lattice associative memory (LAM), called a dendritic LAM or DLAM, it is possible to achieve noise-tolerant pattern classification by varying the design of noise or error acceptance bounds. This paper presents theory and algorithmic approaches for the computation of noise-tolerant lattice associative memories (LAMs) under a variety of input constraints. Of particular interest are the classification of nonergodic data in noise regimes with time-varying statistics. DLAMs, which are a specialization of LAMs derived from concepts of biological neural networks, have successfully been applied to pattern classification from hyperspectral remote sensing data, as well as spatial object recognition from digital imagery. The authors' recent research in the development of DLAMs is overviewed, with experimental results that show utility for a wide variety of pattern classification applications. Performance results are presented in terms of measured computational cost, noise tolerance, classification accuracy, and throughput for a variety of input data and noise levels.

  1. Molecular imaging of serotonin degeneration in mild cognitive impairment.

    Science.gov (United States)

    Smith, Gwenn S; Barrett, Frederick S; Joo, Jin Hui; Nassery, Najlla; Savonenko, Alena; Sodums, Devin J; Marano, Christopher M; Munro, Cynthia A; Brandt, Jason; Kraut, Michael A; Zhou, Yun; Wong, Dean F; Workman, Clifford I

    2017-09-01

    Neuropathological and neuroimaging studies have consistently demonstrated degeneration of monoamine systems, especially the serotonin system, in normal aging and Alzheimer's disease. The evidence for degeneration of the serotonin system in mild cognitive impairment is limited. Thus, the goal of the present study was to measure the serotonin transporter in vivo in mild cognitive impairment and healthy controls. The serotonin transporter is a selective marker of serotonin terminals and of the integrity of serotonin projections to cortical, subcortical and limbic regions and is found in high concentrations in the serotonergic cell bodies of origin of these projections (raphe nuclei). Twenty-eight participants with mild cognitive impairment (age 66.6±6.9, 16 males) and 28 healthy, cognitively normal, demographically matched controls (age 66.2±7.1, 15 males) underwent magnetic resonance imaging for measurement of grey matter volumes and high-resolution positron emission tomography with well-established radiotracers for the serotonin transporter and regional cerebral blood flow. Beta-amyloid imaging was performed to evaluate, in combination with the neuropsychological testing, the likelihood of subsequent cognitive decline in the participants with mild cognitive impairment. The following hypotheses were tested: 1) the serotonin transporter would be lower in mild cognitive impairment compared to controls in cortical and limbic regions, 2) in mild cognitive impairment relative to controls, the serotonin transporter would be lower to a greater extent and observed in a more widespread pattern than lower grey matter volumes or lower regional cerebral blood flow and 3) lower cortical and limbic serotonin transporters would be correlated with greater deficits in auditory-verbal and visual-spatial memory in mild cognitive impairment, not in controls. Reduced serotonin transporter availability was observed in mild cognitive impairment compared to controls in cortical and limbic

  2. Transplantation of retinal pigment epithelial cells - a possible future treatment for age-related macular degeneration

    DEFF Research Database (Denmark)

    Wiencke, Anne Katrine

    2001-01-01

    ophthalmology, age-related macular degeneration, transplantation, retinal pigment epithelial cells, treatment......ophthalmology, age-related macular degeneration, transplantation, retinal pigment epithelial cells, treatment...

  3. Transplantation of retinal pigment epithelial cells - a possible future treatment for age-related macular degeneration

    DEFF Research Database (Denmark)

    Wiencke, Anne Katrine

    2001-01-01

    ophthalmology, age-related macular degeneration, retinal pigment epithelial cells, transplantation, treatment......ophthalmology, age-related macular degeneration, retinal pigment epithelial cells, transplantation, treatment...

  4. Current knowledge and trends in age-related macular degeneration: today's and future treatments.

    Science.gov (United States)

    Velez-Montoya, Raul; Oliver, Scott C N; Olson, Jeffrey L; Fine, Stuart L; Mandava, Naresh; Quiroz-Mercado, Hugo

    2013-09-01

    To address the most dynamic and current issues concerning today's treatment options and promising research efforts regarding treatment for age-related macular degeneration. This review is aimed to serve as a practical reference for more in-depth reviews on the subject. An online review of the database PubMed and Ovid were performed, searching for the key words age-related macular degeneration, AMD, VEGF, treatment, PDT, steroids, bevacizumab, ranibizumab, VEGF-trap, radiation, combined therapy, as well as their compound phrases. The search was limited to articles published since 1985. All returned articles were carefully screened, and their references were manually reviewed for additional relevant data. The web page www.clinicaltrials.gov was also accessed in search of relevant research trials. A total of 363 articles were reviewed, including 64 additional articles extracted from the references. At the end, only 160 references were included in this review. Treatment for age-related macular degeneration is a very dynamic research field. While current treatments are mainly aimed at blocking vascular endothelial growth factor, future treatments seek to prevent vision loss because of scarring. Promising efforts have been made to address the dry form of the disease, which has lacked effective treatment.

  5. Progress toward the maintenance and repair of degenerating retinal circuitry.

    Science.gov (United States)

    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.

  6. Age related macular degeneration and visual disability.

    Science.gov (United States)

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

    2011-02-01

    Age-related macular degeneration (AMD) is the leading cause of central blindness or low vision among the elderly in industrialized countries. AMD is caused by a combination of genetic and environmental factors. Among modifiable environmental risk factors, cigarette smoking has been associated with both the dry and wet forms of AMD and may increase the likelihood of worsening pre-existing AMD. Despite advances, the treatment of AMD has limitations and affected patients are often referred for low vision rehabilitation to help them cope with their remaining eyesight. The characteristic visual impairment for both forms of AMD is loss of central vision (central scotoma). This loss results in severe difficulties with reading that may be only partly compensated by magnifying glasses or screen-projection devices. The loss of central vision associated with the disease has a profound impact on patient quality of life. With progressive central visual loss, patients lose their ability to perform the more complex activities of daily living. Common vision aids include low vision filters, magnifiers, telescopes and electronic aids. Low vision rehabilitation (LVR) is a new subspecialty emerging from the traditional fields of ophthalmology, optometry, occupational therapy, and sociology, with an ever-increasing impact on the usual concepts of research, education, and services for visually impaired patients. Relatively few ophthalmologists practise LVR and fewer still routinely use prismatic image relocation (IR) in AMD patients. IR is a method of stabilizing oculomotor functions with the purpose of promoting better function of preferred retinal loci (PRLs). The aim of vision rehabilitation therapy consists in the achievement of techniques designed to improve PRL usage. The use of PRLs to compensate for diseased foveae has offered hope to these patients in regaining some function. However, in a recently published meta-analysis, prism spectacles were found to be unlikely to be of

  7. Orchestration of transplantation tolerance by regulatory dendritic cell therapy or in-situ targeting of dendritic cells.

    Science.gov (United States)

    Morelli, Adrian E; Thomson, Angus W

    2014-08-01

    Extensive research in murine transplant models over the past two decades has convincingly demonstrated the ability of regulatory dendritic cells (DCregs) to promote long-term allograft survival. We review important considerations regarding the source of therapeutic DCregs (donor or recipient) and their mode of action, in-situ targeting of DCregs, and optimal therapeutic regimens to promote DCreg function. Recent studies have defined protocols and mechanisms whereby ex-vivo-generated DCregs of donor or recipient origin subvert allogeneic T-cell responses and promote long-term organ transplant survival. Particular interest has focused on how donor antigen is acquired, processed and presented by autologous dendritic cells, on the stability of DCregs, and on in-situ targeting of dendritic cells to promote their tolerogenic function. New evidence of the therapeutic efficacy of DCregs in a clinically relevant nonhuman primate organ transplant model and production of clinical grade DCregs support early evaluation of DCreg therapy in human graft recipients. We discuss strategies currently used to promote dendritic cell tolerogenicity, including DCreg therapy and in-situ targeting of dendritic cells, with a view to improved understanding of underlying mechanisms and identification of the most promising strategies for therapeutic application.

  8. Dendritic protein synthesis in the normal and diseased brain

    Science.gov (United States)

    Swanger, Sharon A.; Bassell, Gary J.

    2015-01-01

    Synaptic activity is a spatially-limited process that requires a precise, yet dynamic, complement of proteins within the synaptic micro-domain. The maintenance and regulation of these synaptic proteins is regulated, in part, by local mRNA translation in dendrites. Protein synthesis within the postsynaptic compartment allows neurons tight spatial and temporal control of synaptic protein expression, which is critical for proper functioning of synapses and neural circuits. In this review, we discuss the identity of proteins synthesized within dendrites, the receptor-mediated mechanisms regulating their synthesis, and the possible roles for these locally synthesized proteins. We also explore how our current understanding of dendritic protein synthesis in the hippocampus can be applied to new brain regions and to understanding the pathological mechanisms underlying varied neurological diseases. PMID:23262237

  9. A Model of Dendritic Cell Therapy for Melanoma

    Directory of Open Access Journals (Sweden)

    Ami eRadunskaya

    2013-03-01

    Full Text Available Dendritic cells are a promising immunotherapy tool for boosting an individual's antigen specific immune response to cancer. We develop a mathematical model using differential and delay-differential equations to describe the interactions between dendritic cells, effector-immune cells and tumor cells. We account for the trafficking of immune cells between lymph, blood, and tumor compartments. Our model reflects experimental results both for dendritic-cell trafficking and for immune suppression of tumor growth in mice. In addition, in silico experiments suggest more effective immunotherapy treatment protocols can be achieved by modifying dose location and schedule. A sensitivity analysis of the model reveals which patient-specific parameters have the greatest impact on treatment efficacy.

  10. Immunity and Tolerance Induced by Intestinal Mucosal Dendritic Cells

    Directory of Open Access Journals (Sweden)

    Julio Aliberti

    2016-01-01

    Full Text Available Dendritic cells present in the digestive tract are constantly exposed to environmental antigens, commensal flora, and invading pathogens. Under steady-state conditions, these cells have high tolerogenic potential, triggering differentiation of regulatory T cells to protect the host from unwanted proinflammatory immune responses to innocuous antigens or commensals. On the other hand, these cells must discriminate between commensal flora and invading pathogens and mount powerful immune response against pathogens. A potential result of unbalanced tolerogenic versus proinflammatory responses mediated by dendritic cells is associated with chronic inflammatory conditions, such as Crohn’s disease, ulcerative colitis, food allergies, and celiac disease. Herein, we review the dendritic cell population involved in mediating tolerance and immunity in mucosal surfaces, the progress in unveiling their development in vivo, and factors that can influence their functions.

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

    Directory of Open Access Journals (Sweden)

    Khetani Radhika S

    2006-05-01

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

  12. Overview of clinical trials for dry age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Wen-Sheng Cheng

    2017-01-01

    Full Text Available The overall goal of treating age-related macular degeneration (AMD is to target the underlying cause of the disease and prevent, or at least slow down, the loss of vision, which requires the preservation of the choroid, retinal pigment epithelium (RPE, and photoreceptors. At present, there is no proven drug treatment for dry AMD; however, the cessation of smoking and treatments based on the age-related eye diseases study vitamin formula combined with a healthy diet are considered the only options for slowing disease progression. A number of pharmaceutical agents are currently under evaluation for the treatment of dry AMD using strategies such as reduction RPE and photoreceptor loss, neuroprotection, visual cycle modulators, suppression of inflammation, prevention of oxidative damage, and choroidal perfusion enhancers. The hope is that some of these therapies will achieve significant improvement to current management and prevent future loss of vision in this devastating eye condition.

  13. A Novel Forward Genetic Screen for Identifying Mutations Affecting Larval Neuronal Dendrite Development in Drosophila melanogaster

    OpenAIRE

    Medina, Paul Mark B.; Swick, Lance L.; Andersen, Ryan; Blalock, Zachary; Brenman, Jay E.

    2006-01-01

    Vertebrate and invertebrate dendrites are information-processing compartments that can be found on both central and peripheral neurons. Elucidating the molecular underpinnings of information processing in the nervous system ultimately requires an understanding of the genetic pathways that regulate dendrite formation and maintenance. Despite the importance of dendrite development, few forward genetic approaches have been used to analyze the latest stages of dendrite development, including the ...

  14. Blastic plasmacytoid dendritic cell neoplasm with absolute monocytosis at presentation

    Directory of Open Access Journals (Sweden)

    Jaworski JM

    2015-02-01

    Full Text Available Joseph M Jaworski,1,2 Vanlila K Swami,1 Rebecca C Heintzelman,1 Carrie A Cusack,3 Christina L Chung,3 Jeremy Peck,3 Matthew Fanelli,3 Micheal Styler,4 Sanaa Rizk,4 J Steve Hou1 1Department of Pathology and Laboratory Medicine, Hahnemann University Hospital/Drexel University College of Medicine, Philadelphia, PA, USA; 2Department of Pathology, Mercy Fitzgerald Hospital, Darby, PA, USA; 3Department of Dermatology, Hahnemann University Hospital/Drexel University College of Medicine, Philadelphia, PA, USA; 4Department of Hematology/Oncology, Hahnemann University Hospital/Drexel University College of Medicine, Philadelphia, PA, USA Abstract: Blastic plasmacytoid dendritic cell neoplasm is an uncommon malignancy derived from precursors of plasmacytoid dendritic cells. Nearly all patients present initially with cutaneous manifestations, with many having extracutaneous disease additionally. While response to chemotherapy initially is effective, relapse occurs in most, with a leukemic phase ultimately developing. The prognosis is dismal. While most of the clinical and pathologic features are well described, the association and possible prognostic significance between peripheral blood absolute monocytosis (>1.0 K/µL and blastic plasmacytoid dendritic cell neoplasm have not been reported. We report a case of a 68-year-old man who presented with a rash for 4–5 months. On physical examination, there were multiple, dull-pink, indurated plaques on the trunk and extremities. Complete blood count revealed thrombocytopenia, absolute monocytosis of 1.7 K/µL, and a negative flow cytometry study. Biopsy of an abdominal lesion revealed typical features of blastic plasmacytoid dendritic cell neoplasm. Patients having both hematologic and nonhematologic malignancies have an increased incidence of absolute monocytosis. Recent studies examining Hodgkin and non-Hodgkin lymphoma patients have suggested that this is a negative prognostic factor. The association between

  15. Distinguishing linear vs. nonlinear integration in CA1 radial oblique dendrites: it’s about time

    Directory of Open Access Journals (Sweden)

    José Francisco eGómez González

    2011-11-01

    Full Text Available It was recently shown that multiple excitatory inputs to CA1 pyramidal neuron dendrites must be activated nearly simultaneously to generate local dendritic spikes and superlinear responses at the soma; even slight input desynchronization prevented local spike initiation (Gasparini, 2006;Losonczy, 2006. This led to the conjecture that CA1 pyramidal neurons may only express their nonlinear integrative capabilities during the highly synchronized sharp waves and ripples that occur during slow wave sleep and resting/consummatory behavior, whereas during active exploration and REM sleep (theta rhythm, inadequate synchronization of excitation would lead CA1 pyramidal cells to function as essentially linear devices. Using a detailed single neuron model, we replicated the experimentally observed synchronization effect for brief inputs mimicking single synaptic release events. When synapses were driven instead by double pulses, more representative of the bursty inputs that occur in vivo, we found that the tolerance for input desynchronization was increased by more than an order of magnitude. The effect depended mainly on paired pulse facilitation of NMDA receptor-mediated responses at Schaffer collateral synapses. Our results suggest that CA1 pyramidal cells could function as nonlinear integrative units in all major hippocampal states.

  16. Localized thermonuclear runaways and volcanoes on degenerate dwarf stars

    Energy Technology Data Exchange (ETDEWEB)

    Shara, M.M.

    1982-10-15

    Practically all studies to date of thermonuclear runaways on degenerate dwarf stars in binary systems have considered only spherically symmetric eruptions. We emphasize that even slightly non-spherically symmetric accretion leads to transverse temperature gradients in the dwarfs' accreted envelopes. Over a rather broad range of parameter space, thermalization time scales in accreted envelopes are much longer than thermonuclear runaway time scales. Thus localized thermonuclear runaways (i.e., runaways much smaller than the host degenerate star) rather than spherically symmetric global eruptions are likely to occur on many degenerate dwarfs. Localized runaways are more likely to occur on more massive and/or hotter dwarfs.

  17. Cystic adventitial degeneration: ectopic ganglia from adjacent joint capsules.

    Science.gov (United States)

    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.

  18. Acquired Nonpigmented Vitreous Cyst Associated With Lattice Degeneration.

    Science.gov (United States)

    Lu, Jing; Mai, Guiying; Liu, Ruyuan; Luo, Yan; Lu, Lin

    2017-10-01

    A 63-year-old male presented with a round-shaped floater and visual obscuration in the right eye. Clinical evaluation showed a nonpigmented vitreous cyst connected to a lattice degeneration by a stalk. Immunostaining of the vitreous cyst obtained from vitrectomy showed its origin of retinal neuroepithelium. The cyst was formed by continuous vitreous traction, which might tear up the disrupted retina at the area of lattice degeneration. This report added the lattice degeneration to the list of causes for the acquired vitreous cyst. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:856-858.]. Copyright 2017, SLACK Incorporated.

  19. [Clinical features and prognosis of retinal lattice degeneration].

    Science.gov (United States)

    Guo, X R

    1990-07-01

    110 cases (110 eyes) of retinal lattice degeneration were clinically observed and followed up for 3-8 years. Most lesions were located in the superotemporal quadrant, band-shaped, and parallel to the ora serrata. 80.9% of the lesions presented various degrees of pigmentation, 67.1% yellowish white spots, and 83.6% white lines. 32.9% of the eyes developed retinal holes. Most lattice degenerations were accompanied by vitreous degeneration and vitreoretinal traction. The disease progressed only slowly, though in a few cases it tended to expand.

  20. Involvement of dendritic cells in allograft rejection new implications of dendritic cell-endothelial cell interactions.

    Science.gov (United States)

    Schlichting, C L; Schareck, W D; Kofler, S; Weis, M

    2007-04-01

    For almost half a century immunologists have tried to tear down the MHC barrier, which separates two unrelated individuals during transplantation. Latest experimental data suggest that a breakthrough in vitro is imminent. Dendritic cells (DCs), which activate naïve allo-reactive T-cells (TCs), play a central role in the establishment of allo-antigen-specific immunity. Allograft solid organ rejection is initiated at the foreign endothelial cell (EC) layer, which forms an immunogenic barrier for migrating DCs. Thus, DC/EC interactions might play a crucial role in antigen-specific allograft rejection. Organ rejection is mediated by host allo-reactive TCs, which are activated by donor DCs (direct activation) or host DCs (indirect activation). Direct allo-antigen presentation by regulatory dendritic cells (DCreg) can play an instructive role towards tolerance induction. Several groups established that, DCregs, if transplanted beforehand, enter host thymus, spleen, or bone marrow where they might eventually establish allo-antigen-specific tolerance. A fundamental aspect of DC function is migration throughout the entire organism. After solid organ transplantation, host DCs bind to ECs, invade allograft tissues, and finally transmigrate into lymphoid vessels and secondary lymphoid organs, where they present allo-antigens to naïve host TCs. Recent data suggest that in vitro manipulated DCregs may mediate allo-transplantation tolerance induction. However, the fundamental mechanisms on how such DCregs cause host TCs in the periphery towards tolerance remain unclear. One very promising experimental concept is the simultaneous manipulation of DC direct and indirect TC activation/suppression, towards donor antigen-specific allo-transplantation tolerance. The allo-antigen-specific long-term tolerance induction mediated by DCreg pre-transplantation (with simultaneous short-term immunosuppression) has become reproducible in the laboratory animal setting. Despite the shortcomings

  1. Prophylactic effects of sulforaphane on depression-like behavior and dendritic changes in mice after inflammation.

    Science.gov (United States)

    Zhang, Ji-Chun; Yao, Wei; Dong, Chao; Yang, Chun; Ren, Qian; Ma, Min; Han, Mei; Wu, Jin; Ushida, Yusuke; Suganuma, Hiroyuki; Hashimoto, Kenji

    2017-01-01

    Inflammation plays a role in the pathophysiology of depression. Sulforaphane (SFN), an isothiocyanate compound derived from broccoli, is a potent activator of the NF-E2-related factor-2 (Nrf2), which plays a role in inflammation. In this study, we examined whether the prevention effects of SFN in lipopolysaccharide (LPS) induced depression-like behavior in mice. Pretreatment with SFN significantly blocked an increase in the serum tumor necrosis factor-α (TNF-α) level and an increase in microglial activation of brain regions after a single administration of LPS (0.5 mg/kg). Furthermore, SFN significantly potentiated increased serum levels of IL-10 after LPS administration. In the tail-suspension test and forced swimming test, SFN significantly attenuated an increase of the immobility time after LPS administration. In addition, SFN significantly recovered to control levels for LPS-induced alterations in the proteins such as brain-derived neurotrophic factor, postsynaptic density protein 95 and AMPA receptor 1 (GluA1) and dendritic spine density in the brain regions. Finally, dietary intake of 0.1% glucoraphanin (a glucosinolate precursor of SFN) food during the juvenile and adolescence could prevent the onset of LPS-induced depression-like behaviors and dendritic spine changes in the brain regions at adulthood. In conclusion, these findings suggest that dietary intake of SFN-rich broccoli sprout has prophylactic effects on inflammation-related depressive symptoms. Therefore, supplementation of SFN-rich broccoli sprout could be prophylactic vegetable to prevent or minimize the relapse by inflammation in the remission state of depressed patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Domain shape instabilities and dendrite domain growth in uniaxial ferroelectrics

    Science.gov (United States)

    Shur, Vladimir Ya.; Akhmatkhanov, Andrey R.

    2018-01-01

    The effects of domain wall shape instabilities and the formation of nanodomains in front of moving walls obtained in various uniaxial ferroelectrics are discussed. Special attention is paid to the formation of self-assembled nanoscale and dendrite domain structures under highly non-equilibrium switching conditions. All obtained results are considered in the framework of the unified kinetic approach to domain structure evolution based on the analogy with first-order phase transformation. This article is part of the theme issue `From atomistic interfaces to dendritic patterns'.

  3. Neuron array with plastic synapses and programmable dendrites.

    Science.gov (United States)

    Ramakrishnan, Shubha; Wunderlich, Richard; Hasler, Jennifer; George, Suma

    2013-10-01

    We describe a novel neuromorphic chip architecture that models neurons for efficient computation. Traditional architectures of neuron array chips consist of large scale systems that are interfaced with AER for implementing intra- or inter-chip connectivity. We present a chip that uses AER for inter-chip communication but uses fast, reconfigurable FPGA-style routing with local memory for intra-chip connectivity. We model neurons with biologically realistic channel models, synapses and dendrites. This chip is suitable for small-scale network simulations and can also be used for sequence detection, utilizing directional selectivity properties of dendrites, ultimately for use in word recognition.

  4. Electrical and Structural Characterization of Web Dendrite Crystals

    Science.gov (United States)

    Schwuttke, G. H.; Koliwad, K.; Dumas, K. A.

    1985-01-01

    Minority carrier lifetime distributions in silicon web dendrites are measured. Emphasis is placed on measuring areal homogeneity of lifetime, show its dependency on structural defects, and its unique change during hot processing. The internal gettering action of defect layers present in web crystals and their relation to minority carrier lifetime distributions is discussed. Minority carrier lifetime maps of web dendrites obtained before and after high temperature heat treatment are compared to similar maps obtained from 100 mm diameter Czochralski silicon wafers. Such maps indicate similar or superior areal homogeneity of minority carrier lifetime in webs.

  5. Modelling dendritic ecological networks in space: anintegrated network perspective

    Science.gov (United States)

    Peterson, Erin E.; Ver Hoef, Jay M.; Isaak, Dan J.; Falke, Jeffrey A.; Fortin, Marie-Josée; Jordon, Chris E.; McNyset, Kristina; Monestiez, Pascal; Ruesch, Aaron S.; Sengupta, Aritra; Som, Nicholas; Steel, E. Ashley; Theobald, David M.; Torgersen, Christian E.; Wenger, Seth J.

    2013-01-01

    Dendritic ecological networks (DENs) are a unique form of ecological networks that exhibit a dendritic network topology (e.g. stream and cave networks or plant architecture). DENs have a dual spatial representation; as points within the network and as points in geographical space. Consequently, some analytical methods used to quantify relationships in other types of ecological networks, or in 2-D space, may be inadequate for studying the influence of structure and connectivity on ecological processes within DENs. We propose a conceptual taxonomy of network analysis methods that account for DEN characteristics to varying degrees and provide a synthesis of the different approaches within

  6. Clinical application of dendritic cells in cancer vaccination therapy

    DEFF Research Database (Denmark)

    Svane, Inge Marie; Soot, Mette Line; Buus, Søren

    2003-01-01

    During the last decade use of dendritic cells (DC) has moved from murine and in vitro studies to clinical trials as adjuvant in cancer immunotherapy. Here they function as delivery vehicles for exogenous tumor antigens, promoting an efficient antigen presentation. The development of protocols...... for large-scale generation of dendritic cells for clinical applications has made possible phase I/II studies designed to analyze the toxicity, feasibility and efficacy of this approach. In clinical trials, DC-based vaccination of patients with advanced cancer has in many cases led to immunity...

  7. File list: InP.Bld.05.AllAg.Dendritic_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  8. File list: Unc.Bld.50.AllAg.Dendritic_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  9. File list: InP.Bld.10.AllAg.Dendritic_Cells [Chip-atlas[Archive

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  10. File list: Unc.Bld.20.AllAg.Dendritic_Cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  11. Dendrobium nobile Lindl alkaloid, a novel autophagy inducer, protects against axonal degeneration induced by Aβ25-35 in hippocampus neurons in vitro.

    Science.gov (United States)

    Li, Li-Sheng; Lu, Yan-Liu; Nie, Jing; Xu, Yun-Yan; Zhang, Wei; Yang, Wen-Jin; Gong, Qi-Hai; Lu, Yuan-Fu; Lu, Yang; Shi, Jing-Shan

    2017-04-01

    Axonal degeneration is a pathological symbol in the early stage of Alzheimer's disease (AD), which can be triggered by amyloid-β (Aβ) peptide deposition. Growing evidence indicates that deficit of autophagy eventually leads to the axonal degeneration. Our previous studies have shown that Dendrobium nobile Lindl alkaloid (DNLA) had protective effect on neuron impairment in vivo and in vitro; however, the underlying mechanisms is still unclear. We exposed cultured hippocampus neurons to Aβ 25-35 to investigate the effect of DNLA in vitro. Axonal degeneration was evaluated by immunofluorescence staining and MTT assay. Neurons overexpressing GFP-LC3B were used to measure the formation of autophagosome. Autophagosome-lysosome fusion, the lysosomal pH, and cathepsin activity were assessed to reflect autophagy process. Proteins of interest were analyzed by Western blot. DNLA pretreatment significantly inhibited axonal degeneration induced by Aβ 25-35 peptide in vitro. Further studies revealed DNLA treatment increased autophagic flux through promoting formation and degradation of autophagosome in hippocampus neurons. Moreover, enhancement of autophagic flux was responsible for the protective effects of DNLA on axonal degeneration. DNLA prevents Aβ 25-35 -induced axonal degeneration via activation of autophagy process and could be a novel therapeutic target. © 2017 John Wiley & Sons Ltd.

  12. A Gemini snapshot survey for double degenerates

    Science.gov (United States)

    Kilic, Mukremin; Brown, Warren R.; Gianninas, A.; Curd, Brandon; Bell, Keaton J.; Allende Prieto, Carlos

    2017-11-01

    We present the results from a Gemini snapshot radial-velocity survey of 44 low-mass white-dwarf candidates selected from the Sloan Digital Sky Survey (SDSS) spectroscopy. To find sub-hour orbital period binary systems, our time-series spectroscopy had cadences of 2-8 min over a period of 20-30 min. Through follow-up observations at Gemini and the MMT, we identify four double-degenerate binary systems with periods ranging from 53 min to 7 h. The shortest period system, SDSS J123549.88+154319.3, was recently identified as a sub-hour period detached binary by Breedt and collaborators. Here, we refine the orbital and physical parameters of this system. High-speed and time-domain survey photometry observations do not reveal eclipses or other photometric effects in any of our targets. We compare the period distribution of these four systems with the orbital period distribution of known double white dwarfs; the median period decreases from 0.64 to 0.24 d for M = 0.3-0.5 M⊙ to M < 0.3 M⊙ white dwarfs. However, we do not find a statistically significant correlation between the orbital period and white-dwarf mass.

  13. Correlations in a partially degenerate electron plasma

    Energy Technology Data Exchange (ETDEWEB)

    Chihara, Junzo [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

    1998-03-01

    The density-functional theory proves that an ion-electron mixture can be treated as a one-component liquid interacting only via a pairwise interaction in the evaluation of the ion-ion radial distribution function (RDF), and provides a set of integral equations: one is an integral equation for the ion-ion RDF and another for an effective ion-ion interaction, which depends on the ion-ion RDF. This formulation gives a set of integral equation to calculate plasma structures with combined use of the electron-electron correlations in a partially degenerate electron plasma. Therefore, it is important for this purpose to determine the electron-electron correlations at a arbitrary temperature. Here, they are calculated by the quantal version of the hypernetted chain (HNC) equation. On the basis of the jellium-vacancy model, the ionic and electronic structures of rubidium are calculated for the range from liquid metal to plasma states by increasing the temperature at the fixed density using the electron-correlation results. (author)

  14. Radiation therapy: age-related macular degeneration.

    Science.gov (United States)

    Mendez, Carlos A Medina; Ehlers, Justis P

    2013-01-01

    Age-related macular degeneration (AMD) is the leading cause of severe irreversible vision loss in patients over the age of 50 years in the developed world. Neovascular AMD (NVAMD) is responsible for 90% of the cases with severe visual loss. In the last decade, the treatment paradigm for NVAMD has been transformed by the advent of anti-vascular endothelial growth factor therapy. Despite the excellent results of anti-vascular endothelial growth factor therapy, frequent injections remain a necessity for most patients. The burden of these frequent visits as well as the cumulative risks of indefinite intravitreal injections demand continued pursuit of more enduring therapy that provides similar functional results. Radiotherapy has been studied for two decades as a potential therapy for NVAMD. Because of its antiangiogenic properties, radiation therapy remains a promising potential adjunctive resource for the treatment of choroidal neovascularization secondary to NVAMD. This review considers the past, present and future of radiation as a treatment or combination treatment of NVAMD. Copyright © 2013 S. Karger AG, Basel.

  15. Animal models of age related macular degeneration

    Science.gov (United States)

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

    2013-01-01

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

  16. Radiotherapy in age-related macula degeneration

    International Nuclear Information System (INIS)

    Gripp, Stephan; Stammen, Johannes; Petersen, Claudia; Hartmann, Axel; Willers, Reinhart; Althaus, Christoph

    2002-01-01

    Purpose: To ascertain the benefit from radiotherapy in age-related macula degeneration in a single-arm longitudinal study. Methods and Materials: From 1997 to 1998, 39 patients with occult and 33 patients with classic choroidal neovascularization (CNV) were irradiated with 16 Gy. Fluorescein angiography and measurements of visual acuity were performed before and 3, 6, and 12 months after irradiation. Results: Complete follow-up data for 1 year were available from 69 patients. The mean patient age was 72 years (range 49-92). Vision decreased in 43, was stable in 18, and improved in 8 cases. The mean vision deteriorated significantly (p=0.02, Wilcoxon test), particularly within the first 3 months. Patients with occult CNV did significantly better than did those with classic CNV (p=0.03). The proportion of patients retaining vision ≥0.2 fell from 65% to 42% (p <0.01), for classic and occult CNV from 50% to 23%, and for occult CNV from 77% to 56% (p<0.02), respectively. CNV size increased in 30 patients and was stable in 38. Neither age (p=0.17) nor gender (p=0.21, chi-square test) influenced prognosis. Four patients reported transitional complaints. Conclusion: Low-dose fractionated radiotherapy with 16 Gy is well tolerated. However, vision and reading ability were not preserved in most patients

  17. Coulomb Logarithm in Nonideal and Degenerate Plasmas

    Science.gov (United States)

    Filippov, A. V.; Starostin, A. N.; Gryaznov, V. K.

    2018-03-01

    Various methods for determining the Coulomb logarithm in the kinetic theory of transport and various variants of the choice of the plasma screening constant, taking into account and disregarding the contribution of the ion component and the boundary value of the electron wavevector are considered. The correlation of ions is taken into account using the Ornstein-Zernike integral equation in the hypernetted-chain approximation. It is found that the effect of ion correlation in a nondegenerate plasma is weak, while in a degenerate plasma, this effect must be taken into account when screening is determined by the electron component alone. The calculated values of the electrical conductivity of a hydrogen plasma are compared with the values determined experimentally in the megabar pressure range. It is shown that the values of the Coulomb logarithm can indeed be smaller than unity. Special experiments are proposed for a more exact determination of the Coulomb logarithm in a magnetic field for extremely high pressures, for which electron scattering by ions prevails.

  18. Double Degenerates among DA white dwarfs

    International Nuclear Information System (INIS)

    Bragaglia, A.; Greggio, L.; Renzini, A.; D'odorico, S.

    1990-01-01

    The results of a spectroscopic survey of catalog white dwarfs in search of radial velocity variations indicative of a binary motion are reported. In a sample of 54 DA white dwarfs, one Double Degenerate (DD) system with a period of 1.15 days (the shortest period DD system yet discovered) is found. Two other excellent and two good DD candidates, and two white dwarf + red dwarf pairs were also found. If all the candidates should be confirmed, this would indicate a frequency of about 13 percent of interacting binaries in an unbiased sample of evolved stars, with a DD frequency of about 10 percent. These results suggest fairly large values for the common-envelope parameter alpha, implying that a source of energy other than orbital may be required to eject the envelope during common-envelope events. Finally, in combination with previous evidence our result implies that DDs with WD components of the DA variety are unlikely to be the precursors of Type I supernovae, but DDs with non-DA components remain very attractive candidates. 20 refs

  19. CERKL knockdown causes retinal degeneration in zebrafish.

    Directory of Open Access Journals (Sweden)

    Marina Riera

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

  20. Magnonic triply-degenerate nodal points

    Science.gov (United States)

    Owerre, S. A.

    2017-12-01

    We generalize the concept of triply-degenerate nodal points to non-collinear antiferromagnets. Here, we introduce this concept to insulating quantum antiferromagnets on the decorated honeycomb lattice, with spin-1 bosonic quasiparticle excitations known as magnons. We demonstrate the existence of magnonic surface states with constant energy contours that form pairs of magnonic arcs connecting the surface projection of the magnonic triple nodal points. The quasiparticle excitations near the triple nodal points represent three-component bosons beyond that of magnonic Dirac, Weyl, and nodal-line cases. They can be regarded as a direct reflection of the intrinsic spin carried by magnons. Furthermore, we show that the magnonic triple nodal points can split into magnonic Weyl points, as the system transits from a non-collinear spin structure to a non-coplanar one with a non-zero scalar spin chirality. Our results not only apply to insulating antiferromagnets, but also provide a platform to seek for triple nodal points in metallic antiferromagnets.

  1. [The age-related macular degeneration as a vascular disease/part of systemic vasculopathy: contributions to its pathogenesis].

    Science.gov (United States)

    Fischer, Tamás

    2015-03-01

    The wall of blood vessels including those in choroids may be harmed by several repeated and/or prolonged mechanical, physical, chemical, microbiological, immunologic, and genetic impacts (risk factors), which may trigger a protracted response, the so-called host defense response. As a consequence, pathological changes resulting in vascular injury (e. g. atherosclerosis, age-related macular degeneration) may be evolved. Risk factors can also act directly on the endothelium through an increased production of reactive oxygen species promoting an endothelial activation, which leads to endothelial dysfunction, the onset of vascular disease. Thus, endothelial dysfunction is a link between the harmful stimulus and vascular injury; any kind of harmful stimuli may trigger the defensive chain that results in inflammation that may lead to vascular injury. It has been shown that even early age-related macular degeneration is associated with the presence of diffuse arterial disease and patients with early age-related macular degeneration demonstrate signs of systemic and retinal vascular alterations. Chronic inflammation, a feature of AMD, is tightly linked to diseases associated with ED: AMD is accompanied by a general inflammatory response, in the form of complement system activation, similar to that observed in degenerative vascular diseases such as atherosclerosis. All these facts indicate that age-related macular degeneration may be a vascular disease (or part of a systemic vasculopathy). This recognition could have therapeutic implications because restoration of endothelial dysfunction may prevent the development or improve vascular disease resulting in prevention or improvement of age-related macular degeneration as well.

  2. Complement inhibitors for age-related macular degeneration.

    Science.gov (United States)

    Williams, Michael A; McKay, Gareth J; Chakravarthy, Usha

    2014-01-15

    Given the relatively high prevalence of age-related macular degeneration (AMD) and the increased incidence of AMD as populations age, the results of trials of novel treatments are awaited with much anticipation. The complement cascade describes a series of proteolytic reactions occurring throughout the body that generate proteins with a variety of roles including the initiation and promotion of immune reactions against foreign materials or micro-organisms. The complement cascade is normally tightly regulated, but much evidence implicates complement overactivity in AMD and so it is a logical therapeutic target in the treatment of AMD. To assess the effects and safety of complement inhibitors in the prevention or treatment of advanced AMD. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2013, Issue 11), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to November 2013), EMBASE (January 1980 to November 2013), Allied and Complementary Medicine Database (AMED) (January 1985 to November 2013), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to November 2013), OpenGrey (System for Information on Grey Literature in Europe) (www.opengrey.eu/), Web of Science Conference Proceedings Citation Index - Science (CPCI-S) (January 1990 to November 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 21 November 2013. We also performed handsearching of proceedings, from 2012 onwards, of meetings and conferences of specific professional organisations. We planned to include randomised controlled trials (RCTs) with

  3. Determination of source terms in a degenerate parabolic equation

    International Nuclear Information System (INIS)

    Cannarsa, P; Tort, J; Yamamoto, M

    2010-01-01

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

  4. The degenerate-internal-states approximation for cold collisions

    NARCIS (Netherlands)

    Maan, A.C.; Tiesinga, E.; Stoof, H.T.C.; Verhaar, B.J.

    1990-01-01

    The Degenerate-Internal-States approximation as well as its first-order correction are shown to provide a convenient method for calculating elastic and inelastic collision amplitudes for low temperature atomic scattering.

  5. Magnetism and magnetostriction in a degenerate rigid band

    International Nuclear Information System (INIS)

    Kulakowski, K.; Barbara, B.

    1990-09-01

    We investigate the influence of the spin-orbit coupling on the magnetic and magnetoelastic phenomena in ferromagnetic band systems. The description is within the Stoner model of a degenerate rigid band, for temperature T = O. (author). 14 refs

  6. Relativistic degenerate electron plasma in an intense magnetic field

    International Nuclear Information System (INIS)

    Delsante, A.E.; Frankel, N.E.

    1978-01-01

    The dielectric response function for a dense, ultra-degenerate relativistic electron plasma in an intense uniform magnetic field is presented. Dispersion relations for plasma oscillations parallel and perpendicular to the magnetic field are obtained

  7. Arbitrary electron acoustic waves in degenerate dense plasmas

    Science.gov (United States)

    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.

  8. An imbedding theorem and its applications in degenerate elliptic equations

    International Nuclear Information System (INIS)

    Duong Minh Duc.

    1988-06-01

    We improve the Rellich-Kondrachov theorem and apply it to study strongly degenerate and singular elliptic equations. We obtain the maximum principle, Harnacks's inequality and global regularity for solutions of those equations. (author). 11 refs

  9. Traumatic brain injury causes an FK506-sensitive loss and an overgrowth of dendritic spines in rat forebrain.

    Science.gov (United States)

    Campbell, John N; Register, David; Churn, Severn B

    2012-01-20

    Traumatic brain injury (TBI) causes both an acute loss of tissue and a progressive injury through reactive processes such as excitotoxicity and inflammation. These processes may worsen neural dysfunction by altering neuronal circuitry beyond the focally-damaged tissue. One means of circuit alteration may involve dendritic spines, micron-sized protuberances of dendritic membrane that support most of the excitatory synapses in the brain. This study used a modified Golgi-Cox technique to track changes in spine density on the proximal dendrites of principal cells in rat forebrain regions. Spine density was assessed at 1 h, 24 h, and 1 week after a lateral fluid percussion TBI of moderate severity. At 1 h after TBI, no changes in spine density were observed in any of the brain regions examined. By 24 h after TBI, however, spine density had decreased in ipsilateral neocortex in layer II and III and dorsal dentate gyrus (dDG). This apparent loss of spines was prevented by a single, post-injury administration of the calcineurin inhibitor FK506. These results, together with those of a companion study, indicate an FK506-sensitive mechanism of dendritic spine loss in the TBI model. Furthermore, by 1 week after TBI, spine density had increased substantially above control levels, bilaterally in CA1 and CA3 and ipsilaterally in dDG. The apparent overgrowth of spines in CA1 is of particular interest, as it may explain previous reports of abnormal and potentially epileptogenic activity in this brain region.

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

    OpenAIRE

    Phillip David Fletcher; Laura eDowney; Pirada eWitoonpanich; Jason eWarren

    2013-01-01

    Musicophilia, or abnormal craving for music, is a poorly understood phenomenon that has been associated in particular with focal degeneration of the temporal lobes. Here we addressed the brain basis of musicophilia using voxel-based morphometry (VBM) on MR volumetric brain images in a retrospectively ascertained cohort of patients meeting clinical consensus criteria for frontotemporal lobar degeneration: of 37 cases ascertained, 12 had musicophilia and 25 did not exhibit the phenomenon. The s...

  11. Degenerated uterine leiomyomas mimicking malignant bilateral ovarian surface epithelial tumors

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Yi Boem Ha; Lee, Hae Kyung; Lee, Min Hee; Choi, Seo Youn; Chung, Soo Ho [Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon (Korea, Republic of)

    2017-07-15

    Uterine leiomyomas are the most common benign uterine neoplasms. Undegenerated uterine leiomyomas are easily recognizable by the typical imaging findings on radiologic studies. However, degenerated fibroids can have unusual and variable appearances. The atypical appearances due to degenerative changes may cause confusion in diagnosis of leiomyomas. In this article, we report a case of a patient with extensive cystic and myxoid degeneration of uterine leiomyoma, mimicking malignant bilateral ovarian surface epithelial tumors.

  12. Electromagnetic solitons in degenerate relativistic electron–positron plasma

    International Nuclear Information System (INIS)

    Berezhiani, V I; Shatashvili, N L; Tsintsadze, N L

    2015-01-01

    The existence of soliton-like electromagnetic (EM) distributions in a fully degenerate electron–positron plasma is studied applying relativistic hydrodynamic and Maxwell equations. For a circularly polarized wave it is found that the soliton solutions exist both in relativistic as well as nonrelativistic degenerate plasmas. Plasma density in the region of soliton pulse localization is reduced considerably. The possibility of plasma cavitation is also shown. (invited comment)

  13. SINGLE-DEGENERATE TYPE Ia SUPERNOVAE ARE PREFERENTIALLY OVERLUMINOUS

    International Nuclear Information System (INIS)

    Fisher, Robert; Jumper, Kevin

    2015-01-01

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

  14. Death Receptor 6 Promotes Wallerian Degeneration in Peripheral Axons.

    Science.gov (United States)

    Gamage, Kanchana K; Cheng, Irene; Park, Rachel E; Karim, Mardeen S; Edamura, Kazusa; Hughes, Christopher; Spano, Anthony J; Erisir, Alev; Deppmann, Christopher D

    2017-03-20

    Axon degeneration during development is required to sculpt a functional nervous system and is also a hallmark of pathological insult, such as injury [1, 2]. Despite similar morphological characteristics, very little overlap in molecular mechanisms has been reported between pathological and developmental degeneration [3-5]. In the peripheral nervous system (PNS), developmental axon pruning relies on receptor-mediated extrinsic degeneration mechanisms to determine which axons are maintained or degenerated [5-7]. Receptors have not been implicated in Wallerian axon degeneration; instead, axon autonomous, intrinsic mechanisms are thought to be the primary driver for this type of axon disintegration [8-10]. Here we survey the role of neuronally expressed, paralogous tumor necrosis factor receptor super family (TNFRSF) members in Wallerian degeneration. We find that an orphan receptor, death receptor 6 (DR6), is required to drive axon degeneration after axotomy in sympathetic and sensory neurons cultured in microfluidic devices. We sought to validate these in vitro findings in vivo using a transected sciatic nerve model. Consistent with the in vitro findings, DR6 -/- animals displayed preserved axons up to 4 weeks after injury. In contrast to phenotypes observed in Wld s and Sarm1 -/- mice, preserved axons in DR6 -/- animals display profound myelin remodeling. This indicates that deterioration of axons and myelin after axotomy are mechanistically distinct processes. Finally, we find that JNK signaling after injury requires DR6, suggesting a link between this novel extrinsic pathway and the axon autonomous, intrinsic pathways that have become established for Wallerian degeneration. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Natural history of seminiferous tubule degeneration in Klinefelter syndrome

    DEFF Research Database (Denmark)

    Aksglaede, Lise; Wikström, Anne M; Rajpert-De Meyts, Ewa

    2006-01-01

    Klinefelter syndrome (47,XXY) is characterized by small, firm testis, gynaecomastia, azoospermia and hypergonadotropic hypogonadism. Degeneration of the seminiferous tubules in 47,XXY males is a well-described phenomenon. It begins in the fetus, progresses through infancy and accelerates dramatic......Klinefelter syndrome (47,XXY) is characterized by small, firm testis, gynaecomastia, azoospermia and hypergonadotropic hypogonadism. Degeneration of the seminiferous tubules in 47,XXY males is a well-described phenomenon. It begins in the fetus, progresses through infancy and accelerates...

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

    Science.gov (United States)

    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.

  17. Phonon emission in a degenerate semiconductor at low lattice temperatures

    International Nuclear Information System (INIS)

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

    2015-01-01

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

  18. Posterior Lattice Degeneration Characterized by Spectral Domain Optical Tomography

    OpenAIRE

    Manjunath, Varsha; Taha, Mohammed; Fujimoto, James G.; Duker, Jay S.

    2011-01-01

    PURPOSE: To utilize high-resolution spectral domain optical coherence tomography (SD-OCT) in the characterization of retinal and vitreal morphological changes overlying posterior lattice degeneration. METHODS: A cross-sectional, retrospective analysis was performed on 13 eyes of 13 nonconsecutive subjects with posterior lattice degeneration seen at the New England Eye Center, Tufts Medical Center between October 2009 and January 2010. SD-OCT images taken through the region of latti...

  19. The prevalence of sacroiliac joint degeneration in asymptomatic adults.

    Science.gov (United States)

    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.

  20. Risk of retinal detachment in patients with lattice degeneration.

    Science.gov (United States)

    Sasaki, K; Ideta, H; Yonemoto, J; Tanaka, S; Hirose, A; Oka, C

    1998-01-01

    To determine the risk of retinal detachment in patients with lattice degeneration of the retina, we statistically analyzed the incidence of retinal detachment in these patients. The data of hospital patients with retinal detachment associated with lattice degeneration in Kumamoto Prefecture, Japan, in 1990 were collected. The prevalence of lattice degeneration in Kumamoto was reported to be 9.5% in 1980. Based on population data from the 1990 census, the cumulative incidence of retinal detachment associated with lattice degeneration was calculated in this study. Among 1,840,000 residents in Kumamoto, there were 110 patients with retinal detachment associated with lattice degeneration; 72 with detachment resulting from tractional tears (tears), and 38 with detachment from atrophic holes. The cumulative incidence of retinal detachment from atrophic holes was 1.5% at the age of 40 years; from tears it was 3.6% at the age of 80 years. The cumulative incidence of detachment from both atrophic holes and tears was 5.3% at the age of 80 years. The results of this study are useful for clarifying the natural course of lattice degeneration.

  1. Posterior lattice degeneration characterized by spectral domain optical coherence tomography.

    Science.gov (United States)

    Manjunath, Varsha; Taha, Mohammed; Fujimoto, James G; Duker, Jay S

    2011-03-01

    The purpose of this study was to use high-resolution spectral domain optical coherence tomography in the characterization of retinal and vitreal morphological changes overlying posterior lattice degeneration. A cross-sectional retrospective analysis was performed on 13 eyes of 13 nonconsecutive subjects with posterior lattice degeneration seen at the New England Eye Center, Tufts Medical Center between October 2009 and January 2010. Spectral domain optical coherence tomography images taken through the region of lattice degeneration were qualitatively analyzed. Four characteristic changes of the retina and vitreous were seen in the 13 eyes with lattice degeneration: 1) anterior/posterior U-shaped vitreous traction; 2) retinal breaks; 3) focal retinal thinning; and 4) vitreous membrane formation. The morphologic appearance of vitreous traction and retinal breaks were found to be consistent with previous histologic reports. It is possible to image posterior lattice degeneration in many eyes using spectral domain optical coherence tomography and to visualize the spectrum of retinal and vitreous changes throughout the area of lattice degeneration.

  2. Modulation of cytokine production profiles in splenic dendritic cells ...

    African Journals Online (AJOL)

    We examined the role of splenic dendritic cells in immune response to Toxoplasma gondii infection in SAG1 (P30+) transgenic mice by investigating the kinetics of intracellular cytokines expression of IL-4, IL-10, IL-12 and IFN-γ by intracellular cytokine staining (ICS) using flow cytometry, and compared the results to those of ...

  3. The effects of renal transplantation on circulating dendritic cells

    NARCIS (Netherlands)

    D.A. Hesselink (Dennis); L.M.B. Vaessen (Leonard); W.C.J. Hop (Wim); W. Schoordijk-Verschoor (Wenda); J.N.M. IJzermans (Jan); C.C. Baan (Carla); W. Weimar (Willem)

    2005-01-01

    textabstractThe effects of immunosuppressive agents on T cell function have been well characterized but virtually nothing is known about the effects of renal transplantation on human dendritic cells (DCs). With the use of flow cytometry, we studied the kinetics of myeloid and plasmacytoid DCs in

  4. Circulating dendritic cells in pediatric patients with nephrotic syndrome

    African Journals Online (AJOL)

    Background: Dendritic cells (DCs) represent one of the most extensively studied topics in immunology, because of their central role in the induction and regulation of adaptive immunity, and because of their therapeutic potential for manipulating immune responses. Objectives: To evaluate circulating DC levels in pediatric ...

  5. Unimpaired dendritic cell functions in MVP/LRP knockout mice.

    NARCIS (Netherlands)

    Mossink, MH; Groot, de J.; Zon, van A; Franzel-Luiten, E; Schoester, M.; Scheffer, G.L.; Sonneveld, P.; Scheper, R.J.; Wiemer, EA

    2003-01-01

    Dendritic cells (DCs) act as mobile sentinels of the immune system. By stimulating T lymphocytes, DCs are pivotal for the initiation of both T- and B-cell-mediated immune responses. Recently, ribonucleoprotein particles (vaults) were found to be involved in the development and/or function of human

  6. Dendritic cell-tumor cell hybrids and immunotherapy

    DEFF Research Database (Denmark)

    Cathelin, Dominique; Nicolas, Alexandra; Bouchot, André

    2011-01-01

    Dendritic cells (DC) are professional antigen-presenting cells currently being used as a cellular adjuvant in cancer immunotherapy strategies. Unfortunately, DC-based vaccines have not demonstrated spectacular clinical results. DC loading with tumor antigens and DC differentiation and activation...

  7. Search for a solute-drag effect in dendritic solidification

    International Nuclear Information System (INIS)

    Eckler, K.; Herlach, D.M.; Aziz, M.J.

    1994-01-01

    The authors report the results of an indirect experimental test for the solute-drag effect in alloy solidification by fitting the data of Eckler et.al. for Ni-B dendrite tip velocities vs undercooling to models in several ways. The unknown equilibrium partition coefficient, k e , was varied as a fitting parameter. When they combine the dendrite growth model of Boettinger et al. with the Continuous Growth Model (CGM) of Aziz and Kaplan with solute drag, they cannot fit the data for any value of k e . When they combine dendrite growth theory with the CGM without solute drag, they obtain a reasonable fit to the data for k e = 4 x 10 -6 . When they combine dendrite growth theory with a new partial-solute-drag interpolation between the with-solute-drag and the without-solute-drag versions of the CGM, they obtain a still better fit to the data for k e = 2.8 x 10 - 4. This result points out the possibility of partial solute-drag during solidification and the importance of an independent determination of k e in order to distinguish between models

  8. Genetically engineered dendritic cell-based cancer vaccines

    Czech Academy of Sciences Publication Activity Database

    Bubeník, Jan

    2001-01-01

    Roč. 18, č. 3 (2001), s. 475-478 ISSN 1019-6439 R&D Projects: GA MZd NC5526 Keywords : dendritic cell s * tumour vaccines Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.330, year: 2001

  9. Tumor-Mediated Suppression of Dendritic Cell Vaccines

    National Research Council Canada - National Science Library

    Akporiaye, Emmanuel

    2004-01-01

    .... One of these factors is Transforming Growth Factor-beta (TGF-beta). TGF-beta is produced in large quantities by different types of cancer including breast cancer and inhibits the actions of several immune cells including dendritic cells (DC...

  10. Genetically modified dendritic cell-based cancer vaccines

    Czech Academy of Sciences Publication Activity Database

    Bubeník, Jan

    2001-01-01

    Roč. 47, č. 5 (2001), s. 153-155 ISSN 0015-5500 R&D Projects: GA MZd NC5526 Keywords : dendritic cell s * cancer vaccines Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.519, year: 2001

  11. Fractal analysis of electrolytically-deposited palladium hydride dendrites

    International Nuclear Information System (INIS)

    Bursill, L.A.; Julin, Peng; Xudong, Fan.

    1990-01-01

    The fractal scaling characteristics of the surface profile of electrolytically-deposited palladium hydride dendritic structures have been obtained using conventional and high resolution transmission electron microscopy. The results are in remarkable agreement with the modified diffusion-limited aggregation model. 19 refs., 3 tabs., 13 figs

  12. Utilizing dendritic scaffold for feasible formation of naphthalene ...

    Indian Academy of Sciences (India)

    the effect of dendritic scaffolds on the feasibility of naphthalene excimer formation has not been reported in the literature. Here, we report synthesis and photophysical study of naphthalene functionalized zero and first genera- tion PAMAM dendrimers in order to understand the mechanism of excimer formation in the system.

  13. Cryotherapy in Dendritic Keratitis. | Mpyet | Nigerian Journal of ...

    African Journals Online (AJOL)

    This study evaluates the effectiveness of cryotherapy in the treatment of Dendritic Keratitis where antiviral agents are not available. The result show some improvement in visual acuity while one patient has a drop in vision. The extent of corneal scarring appears to depend on the duration of the disease and extent of stroma ...

  14. Dendritic Spines in Depression: What We Learned from Animal Models

    Directory of Open Access Journals (Sweden)

    Hui Qiao

    2016-01-01

    Full Text Available Depression, a severe psychiatric disorder, has been studied for decades, but the underlying mechanisms still remain largely unknown. Depression is closely associated with alterations in dendritic spine morphology and spine density. Therefore, understanding dendritic spines is vital for uncovering the mechanisms underlying depression. Several chronic stress models, including chronic restraint stress (CRS, chronic unpredictable mild stress (CUMS, and chronic social defeat stress (CSDS, have been used to recapitulate depression-like behaviors in rodents and study the underlying mechanisms. In comparison with CRS, CUMS overcomes the stress habituation and has been widely used to model depression-like behaviors. CSDS is one of the most frequently used models for depression, but it is limited to the study of male mice. Generally, chronic stress causes dendritic atrophy and spine loss in the neurons of the hippocampus and prefrontal cortex. Meanwhile, neurons of the amygdala and nucleus accumbens exhibit an increase in spine density. These alterations induced by chronic stress are often accompanied by depression-like behaviors. However, the underlying mechanisms are poorly understood. This review summarizes our current understanding of the chronic stress-induced remodeling of dendritic spines in the hippocampus, prefrontal cortex, orbitofrontal cortex, amygdala, and nucleus accumbens and also discusses the putative underlying mechanisms.

  15. Identification of human tissue cross-presenting dendritic cells

    OpenAIRE

    Haniffa, Muzlifah; Collin, Matthew; Ginhoux, Florent

    2013-01-01

    Dendritic cells (DCs) are a heterogeneous group of functionally specialized antigen-presenting cells. We recently characterized the human tissue cross-presenting DCs and aligned the human and mouse DC subsets. Our findings will facilitate the translation of murine DC studies to the human setting and aid the design of DC-based vaccine strategies for infection and cancer immunotherapy.

  16. Blastic Plasmacytoid Dendritic Cell Leukemia in a Black Malian

    African Journals Online (AJOL)

    2017-06-28

    Jun 28, 2017 ... BPDCN in Mali. KEYWORDS: Acute Leukemia, black african, dendritic cell, Mali ... myeloid neoplasm by the 2008 world health organization classification of .... There are many standardized treatment regimens, and many protocols with ... leukemia chemotherapy regimen[7,11] or chronic leukemia treatment ...

  17. Characteristics of the Dendrite Growth in the Electrochemical Alane Production Process

    Directory of Open Access Journals (Sweden)

    Park Hyun-Kyu

    2016-01-01

    Full Text Available The electrochemical alane production process was proposed for a feasible production of alane. The operation of process was difficult because of short circuit by a dendrite growth in the reactor. Therefore, characteristics of the dendrite growth in the process were investigated. We conducted the electrochemical alane production process using Teflon block for inhibition of the dendrite growth. The obtained dendrite was characterized by XRD, SEM and ICP-AES. It was concluded that the dendrite growth was attributed to a melting and agglomeration of Al fine particles existed in the solution.

  18. Differential charge-transfer cross sections for systems with energetically degenerate or near-degenerate channels

    International Nuclear Information System (INIS)

    Nguyen, H.; Bredy, R.; Camp, H.A.; DePaola, B.D.; Awata, T.

    2004-01-01

    Resolution plays a vital role in spectroscopic studies. In the usual recoil-ion momentum spectroscopy (RIMS), Q-value resolution is relied upon to distinguish between different collision channels: The better the Q-value resolution, the better one is able to resolve energetically similar channels. Although traditional COLTRIMS greatly improves Q-value resolution by cooling the target and thus greatly reducing the initial target momentum spread, the resolution of the technique is still limited by target temperature. However, with the recent development in RIMS, namely, magneto-optical trap recoil ion momentum spectroscopy (MOTRIMS) superior recoil ion momentum resolution as well as charge transfer measurements with laser excited targets have become possible. Through MOTRIMS, methods for the measurements of target excited state fraction and kinematically complete relative charge transfer cross sections have been developed, even for some systems having energetically degenerate or nearly degenerate channels. In the present work, the systems of interest having energy degeneracies or near degeneracies are Rb + , K + , and Li + colliding with trapped Rb(5l), where l=s and p

  19. Frontotemporal Lobar Degeneration and microRNAs

    Directory of Open Access Journals (Sweden)

    Paola ePiscopo

    2016-02-01

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

  20. Evidence-based analysis of prophylactic treatment of asymptomatic retinal breaks and lattice degeneration.

    Science.gov (United States)

    Wilkinson, C P

    2000-01-01

    To assess the quality of information in the literature regarding the benefits of prophylactic treatment of asymptomatic retinal tears and lattice degeneration. Asymptomatic retinal breaks occur in approximately 7% of patients over age 40, and lattice degeneration is present in approximately 8% of the general population. Because retinal breaks cause retinal detachment and lattice degeneration is associated with approximately 30% of retinal detachments, prophylactic treatment of these lesions has sometimes been recommended. A panel of vitreoretinal experts performed a literature review of all publications regarding prevention of retinal detachment that have been published in English. These articles were then used to prepare recommendations for patient care in an American Academy of Ophthalmology Preferred Practice Pattern (PPP). Each recommendation was rated according to: (1) its importance in the care process and (2) the strength of evidence supporting the given recommendation. Most recommendations were rated as A (most important to patient care). Only a single publication was graded as I (providing strong evidence in support of a recommendation), and this was not a prospective trial. Of the few publications rated as II (substantial evidence), most were studies documenting a lack of treatment benefit. Because of an absence of level I and level II studies in the literature, level III (consensus of expert opinion) was the basis for most recommendations in the PPP. The current literature regarding prevention of retinal detachment does not provide sufficient information to support strongly prophylactic treatment of lesions other than symptomatic flap tears. Prospective randomized trials of prophylactic therapy are indicated. Eyes highly predisposed to retinal detachment should be considered for such studies.

  1. IL-10 ameliorates TNF-α induced meniscus degeneration in mature meniscal tissue in vitro.

    Science.gov (United States)

    Behrendt, P; Häfelein, K; Preusse-Prange, A; Bayer, A; Seekamp, A; Kurz, B

    2017-05-16

    Joint inflammation causes meniscus degeneration and can exacerbate post-traumatic meniscus injuries by extracellular matrix degradation, cellular de-differentiation and cell death. The aim of this study was to examine whether anti-inflammatory interleukin-10 exerts protective effects in an in vitro model of TNF-α-induced meniscus degeneration. Meniscus tissue was harvested from the knees of adult cows. After 24 h of equilibrium explants were simultaneously treated with bovine TNF-α and IL-10. After an incubation time of 72 h cell death was measured histomorphometrically (nuclear blebbing, NB) and release of glycosaminoglycans (GAG, DMMB assay) and nitric oxide (NO, Griess-reagent) were analysed. Transcription levels (mRNA) of matrix degrading enzymes, collagen type X (COL10A1) and nitric oxide synthetase 2 (NOS2) were measured by quantitative real time PCR. TNF-α-dependent formation of the aggrecanase-specific aggrecan neoepitope NITEGE was visualised by immunostaining. Differences between groups were calculated using a one-way ANOVA with a Bonferroni post hoc test. Administration of IL-10 significantly prevented the TNF-α-related cell death (P .001), release of NO (P .003) and NOS2 expression (P .04). Release of GAG fragments (P .001), NITEGE formation and expression of MMP3 (P .007), -13 (P .02) and ADAMTS4 (P .001) were significantly reduced. The TNF-α-dependent increase in COL10A1 expression was also antagonized by IL-10 (P .02). IL-10 prevented crucial mechanisms of meniscal degeneration induced by a key cytokine of OA, TNF-α. Administration of IL-10 might improve the biological regeneration and provide a treatment approach in degenerative meniscus injuries and in conditions of post-traumatic sports injuries.

  2. Modelling the genetic risk in age-related macular degeneration.

    Directory of Open Access Journals (Sweden)

    Felix Grassmann

    Full Text Available Late-stage age-related macular degeneration (AMD is a common sight-threatening disease of the central retina affecting approximately 1 in 30 Caucasians. Besides age and smoking, genetic variants from several gene loci have reproducibly been associated with this condition and likely explain a large proportion of disease. Here, we developed a genetic risk score (GRS for AMD based on 13 risk variants from eight gene loci. The model exhibited good discriminative accuracy, area-under-curve (AUC of the receiver-operating characteristic of 0.820, which was confirmed in a cross-validation approach. Noteworthy, younger AMD patients aged below 75 had a significantly higher mean GRS (1.87, 95% CI: 1.69-2.05 than patients aged 75 and above (1.45, 95% CI: 1.36-1.54. Based on five equally sized GRS intervals, we present a risk classification with a relative AMD risk of 64.0 (95% CI: 14.11-1131.96 for individuals in the highest category (GRS 3.44-5.18, 0.5% of the general population compared to subjects with the most common genetic background (GRS -0.05-1.70, 40.2% of general population. The highest GRS category identifies AMD patients with a sensitivity of 7.9% and a specificity of 99.9% when compared to the four lower categories. Modeling a general population around 85 years of age, 87.4% of individuals in the highest GRS category would be expected to develop AMD by that age. In contrast, only 2.2% of individuals in the two lowest GRS categories which represent almost 50% of the general population are expected to manifest AMD. Our findings underscore the large proportion of AMD cases explained by genetics particularly for younger AMD patients. The five-category risk classification could be useful for therapeutic stratification or for diagnostic testing purposes once preventive treatment is available.

  3. Nutritional Modulation of Age-Related Macular Degeneration

    Science.gov (United States)

    Weikel, Karen A; Taylor, Allen

    2012-01-01

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

  4. Dendritic development of Drosophila high order visual system neurons is independent of sensory experience

    Directory of Open Access Journals (Sweden)

    Reuter John E

    2003-06-01

    Full Text Available Abstract Background The complex and characteristic structures of dendrites are a crucial part of the neuronal architecture that underlies brain function, and as such, their development has been a focal point of recent research. It is generally believed that dendritic development is controlled by a combination of endogenous genetic mechanisms and activity-dependent mechanisms. Therefore, it is of interest to test the relative contributions of these two types of mechanisms towards the construction of specific dendritic trees. In this study, we make use of the highly complex Vertical System (VS of motion sensing neurons in the lobula plate of the Drosophila visual system to gauge the importance of visual input and synaptic activity to dendritic development. Results We find that the dendrites of VS1 neurons are unchanged in dark-reared flies as compared to control flies raised on a 12 hour light, 12 hour dark cycle. The dendrites of these flies show no differences from control in dendrite complexity, spine number, spine density, or axon complexity. Flies with genetically ablated eyes show a slight but significant reduction in the complexity and overall length of VS1 dendrites, although this effect may be due to a reduction in the overall size of the dendritic field in these flies. Conclusions Overall, our results indicate no role for visual experience in the development of VS dendrites, while spontaneous activity from photoreceptors may play at most a subtle role in the formation of fully complex dendrites in these high-order visual processing neurons.

  5. Variability in millimeter wave scattering properties of dendritic ice crystals

    International Nuclear Information System (INIS)

    Botta, Giovanni; Aydin, Kültegin; Verlinde, Johannes

    2013-01-01

    A detailed electromagnetic scattering model for ice crystals is necessary for calculating radar reflectivity from cloud resolving model output in any radar simulator. The radar reflectivity depends on the backscattering cross sections and size distributions of particles in the radar resolution volume. The backscattering cross section depends on the size, mass and distribution of mass within the crystal. Most of the available electromagnetic scattering data for ice hydrometeors rely on simple ice crystal types and a single mass–dimensional relationship for a given type. However, a literature survey reveals that the mass–dimensional relationships for dendrites cover a relatively broad region in the mass–dimensional plane. This variability of mass and mass distribution of dendritic ice crystals cause significant variability in their backscattering cross sections, more than 10 dB for all sizes (0.5–5 mm maximum dimension) and exceeding 20 dB for the larger ones at X-, Ka-, and W-band frequencies. Realistic particle size distributions are used to calculate radar reflectivity and ice water content (IWC) for three mass–dimensional relationships. The uncertainty in the IWC for a given reflectivity spans an order of magnitude in value at all three frequencies because of variations in the unknown mass–dimensional relationship and particle size distribution. The sensitivity to the particle size distribution is reduced through the use of dual frequency reflectivity ratios, e.g., Ka- and W-band frequencies, together with the reflectivity at one of the frequencies for estimating IWC. -- Highlights: • Millimeter wave backscattering characteristics of dendritic crystals are modeled. • Natural variability of dendrite shapes leads to large variability in their mass. • Dendrite mass variability causes large backscattering cross section variability. • Reflectivity–ice water content relation is sensitive to mass and size distribution. • Dual frequency

  6. Teleophthalmology in preventive medicine

    CERN Document Server

    Michelson, Georg

    2014-01-01

    This book provides an up-to-date overview of the clinical applications, methods, and technologies of teleophthalmology within the field of preventive medicine. The ability of novel methods to detect the initial signs of neurodegenerative diseases on the basis of alterations in the retina is reviewed, and detailed attention is paid to the role of teleophthalmology in screening for vision-threatening diseases such as diabetic retinopathy, glaucoma, and age-related macular degeneration. A major part of the book is devoted to novel imaging methods and the latest information technologies, including advanced mobile communication and Web 2.0 applications in teleophthalmology. In addition, the initial projects of an interdisciplinary cooperation in preventive medicine are described. All of the authors are experienced in the scientific and practical aspects of teleophthalmology, including e-learning, and have produced a book that will meet the needs of all medical care providers interested in using teleophthalmology.

  7. Risk factors of age-related macular degeneration in Argentina

    Directory of Open Access Journals (Sweden)

    María Eugenia Nano

    2013-04-01

    Full Text Available PURPOSES: To assess the risk factors of age-related macular degeneration in Argentina using a case-control study. METHODS: Surveys were used for subjects' antioxidant intake, age/gender, race, body mass index, hypertension, diabetes (and type of treatment, smoking, sunlight exposure, red meat consumption, fish consumption, presence of age-related macular degeneration and family history of age-related macular degeneration. Main effects models for logistic regression and ordinal logistic regression were used to analyze the results. RESULTS: There were 175 cases and 175 controls with a mean age of 75.4 years and 75.5 years, respectively, of whom 236 (67.4% were female. Of the cases with age-related macular degeneration, 159 (45.4% had age-related macular degeneration in their left eyes, 154 (44.0% in their right eyes, and 138 (39.4% in both eyes. Of the cases with age-related macular degeneration in their left eyes, 47.8% had the dry type, 40.3% had the wet type, and the type was unknown for 11.9%. The comparable figures for right eyes were: 51.9%, 34.4%, and 13.7%, respectively. The main effects model was dominated by higher sunlight exposure (OR [odds ratio]: 3.3 and a family history of age-related macular degeneration (OR: 4.3. Other factors included hypertension (OR: 2.1, smoking (OR: 2.2, and being of the Mestizo race, which lowered the risk of age-related macular degeneration (OR: 0.40. Red meat/fish consumption, body mass index, and iris color did not have an effect. Higher age was associated with progression to more severe age-related macular degeneration. CONCLUSION: Sunlight exposure, family history of age-related macular degeneration, and an older age were the significant risk factors. There may be other variables, as the risk was not explained very well by the existing factors. A larger sample may produce different and better results.

  8. DC-SIGN, a C-type lectin on dendritic cells that unveils many aspects of dendritic cell biology

    NARCIS (Netherlands)

    Geijtenbeek, Teunis B. H.; Engering, Anneke; van Kooyk, Yvette

    2002-01-01

    Dendritic cells (DC) are present in essentially every tissue where they operate at the interface of innate and acquired immunity by recognizing pathogens and presenting pathogen-derived peptides to T cells. It is becoming clear that not all C-type lectins on DC serve as antigen receptors recognizing

  9. Structure of stable degeneration of K3 surfaces into pairs of rational elliptic surfaces

    OpenAIRE

    Kimura, Yusuke

    2018-01-01

    F-theory/heterotic duality is formulated in the stable degeneration limit of a K3 fibration on the F-theory side. In this note, we analyze the structure of the stable degeneration limit. We discuss whether stable degeneration exists for pairs of rational elliptic surfaces. We demonstrate that, when two rational elliptic surfaces have an identical complex structure, stable degeneration always exists. We provide an equation that systematically describes the stable degeneration of a K3 surface i...

  10. Equine dendritic cells generated with horse serum have enhanced functionality in comparison to dendritic cells generated with fetal bovine serum.

    Science.gov (United States)

    Ziegler, Anja; Everett, Helen; Hamza, Eman; Garbani, Mattia; Gerber, Vinzenz; Marti, Eliane; Steinbach, Falko

    2016-11-15

    Dendritic cells are professional antigen-presenting cells that play an essential role in the initiation and modulation of T cell responses. They have been studied widely for their potential clinical applications, but for clinical use to be successful, alternatives to xenogeneic substances like fetal bovine serum (FBS) in cell culture need to be found. Protocols for the generation of dendritic cells ex vivo from monocytes are well established for several species, including horses. Currently, the gold standard protocol for generating dendritic cells from monocytes across various species relies upon a combination of GM-CSF and IL-4 added to cell culture medium which is supplemented with FBS. The aim of this study was to substitute FBS with heterologous horse serum. For this purpose, equine monocyte-derived dendritic cells (eqMoDC) were generated in the presence of horse serum or FBS and analysed for the effect on morphology, phenotype and immunological properties. Changes in the expression of phenotypic markers (CD14, CD86, CD206) were assessed during dendritic cell maturation by flow cytometry. To obtain a more complete picture of the eqMoDC differentiation and assess possible differences between FBS- and horse serum-driven cultures, a transcriptomic microarray analysis was performed. Lastly, immature eqMoDC were primed with a primary antigen (ovalbumin) or a recall antigen (tetanus toxoid) and, after maturation, were co-cultured with freshly isolated autologous CD5 + T lymphocytes to assess their T cell stimulatory capacity. The microarray analysis demonstrated that eqMoDC generated with horse serum were indistinguishable from those generated with FBS. However, eqMoDC incubated with horse serum-supplemented medium exhibited a more characteristic dendritic cell morphology during differentiation from monocytes. A significant increase in cell viability was also observed in eqMoDC cultured with horse serum. Furthermore, eqMoDC generated in the presence of horse serum

  11. Orchestration of transplantation tolerance by regulatory dendritic cell therapy or in situ targeting of dendritic cells

    Science.gov (United States)

    Morelli, Adrian E.; Thomson, Angus W.

    2014-01-01

    Purpose of review Extensive research in murine transplant models over the past two decades has convincingly demonstrated the ability of regulatory dendritic cells (DCreg) to promote long-term allograft survival. We review important considerations regarding the source of therapeutic DCreg (donor or recipient) and their mode of action, in situ targeting of DCreg, and optimal therapeutic regimens to promote DCreg function. Recent findings Recent studies have defined protocols and mechanisms whereby ex vivo-generated DCreg of donor or recipient origin subvert allogeneic T cell responses and promote long-term organ transplant survival. Particular interest has focused on how donor antigen (Ag) is acquired, processed and presented by autologous DCs, on the stability of DCreg, and on in situ targeting of DC to promote their tolerogenic function. New evidence of the therapeutic efficacy of DCreg in a clinically-relevant non-human primate organ transplant model and production of clinical grade DCreg support early evaluation of DCreg therapy in human graft recipients. Summary We discuss strategies currently used to promote DC tolerogenicity, including DCreg therapy and in situ targeting of DC, with a view to improved understanding of underlying mechanisms and identification of the most promising strategies for therapeutic application. PMID:24926700

  12. Dysfunction in endoplasmic reticulum-mitochondria crosstalk underlies SIGMAR1 loss of function mediated motor neuron degeneration.

    Science.gov (United States)

    Bernard-Marissal, Nathalie; Médard, Jean-Jacques; Azzedine, Hamid; Chrast, Roman

    2015-04-01

    Mutations in Sigma 1 receptor (SIGMAR1) have been previously identified in patients with amyotrophic lateral sclerosis and disruption of Sigmar1 in mouse leads to locomotor deficits. However, cellular mechanisms underlying motor phenotypes in human and mouse with disturbed SIGMAR1 function have not been described so far. Here we used a combination of in vivo and in vitro approaches to investigate the role of SIGMAR1 in motor neuron biology. Characterization of Sigmar1(-/-) mice revealed that affected animals display locomotor deficits associated with muscle weakness, axonal degeneration and motor neuron loss. Using primary motor neuron cultures, we observed that pharmacological or genetic inactivation of SIGMAR1 led to motor neuron axonal degeneration followed by cell death. Disruption of SIGMAR1 function in motor neurons disturbed endoplasmic reticulum-mitochondria contacts, affected intracellular calcium signalling and was accompanied by activation of endoplasmic reticulum stress and defects in mitochondrial dynamics and transport. These defects were not observed in cultured sensory neurons, highlighting the exacerbated sensitivity of motor neurons to SIGMAR1 function. Interestingly, the inhibition of mitochondrial fission was sufficient to induce mitochondria axonal transport defects as well as axonal degeneration similar to the changes observed after SIGMAR1 inactivation or loss. Intracellular calcium scavenging and endoplasmic reticulum stress inhibition were able to restore mitochondrial function and consequently prevent motor neuron degeneration. These results uncover the cellular mechanisms underlying motor neuron degeneration mediated by loss of SIGMAR1 function and provide therapeutically relevant insight into motor neuronal diseases. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  13. REMOD: a computational tool for remodeling neuronal dendrites

    Directory of Open Access Journals (Sweden)

    Panagiotis Bozelos

    2014-05-01

    Full Text Available In recent years, several modeling studies have indicated that dendritic morphology is a key determinant of how individual neurons acquire a unique signal processing profile. The highly branched dendritic structure that originates from the cell body, explores the surrounding 3D space in a fractal-like manner, until it reaches a certain amount of complexity. Its shape undergoes significant alterations not only in various neuropathological conditions, but in physiological, too. Yet, despite the profound effect that these alterations can have on neuronal function, the causal relationship between structure and function remains largely elusive. The lack of a systematic approach for remodeling neuronal cells and their dendritic trees is a key limitation that contributes to this problem. In this context, we developed a computational tool that allows the remodeling of any type of neurons, given a set of exemplar morphologies. The tool is written in Python and provides a simple GUI that guides the user through various options to manipulate selected neuronal morphologies. It provides the ability to load one or more morphology files (.swc or .hoc and choose specific dendrites to operate one of the following actions: shrink, remove, extend or branch (as shown in Figure 1. The user retains complete control over the extent of each alteration and if a chosen action is not possible due to pre-existing structural constraints, appropriate warnings are produced. Importantly, the tool can also be used to extract morphology statistics for one or multiple morphologies, including features such as the total dendritic length, path length to the root, branch order, diameter tapering, etc. Finally, an experimental utility enables the user to remodel entire dendritic trees based on preloaded statistics from a database of cell-type specific neuronal morphologies. To our knowledge, this is the first tool that allows (a the remodeling of existing –as opposed to the de novo

  14. Cigarette smoke promotes dendritic cell accumulation in COPD; a Lung Tissue Research Consortium study

    Directory of Open Access Journals (Sweden)

    Yi Eunhee S

    2010-04-01

    Full Text Available Abstract Background Abnormal immune responses are believed to be highly relevant in the pathogenesis of chronic obstructive pulmonary disease (COPD. Dendritic cells provide a critical checkpoint for immunity by their capacity to both induce and suppress immunity. Although evident that cigarette smoke, the primary cause of COPD, significantly influences dendritic cell functions, little is known about the roles of dendritic cells in the pathogenesis of COPD. Methods The extent of dendritic cell infiltration in COPD tissue specimens was determined using immunohistochemical localization of CD83+ cells (marker of matured myeloid dendritic cells, and CD1a+ cells (Langerhans cells. The extent of tissue infiltration with Langerhans cells was also determined by the relative expression of the CD207 gene in COPD versus control tissues. To determine mechanisms by which dendritic cells accumulate in COPD, complimentary studies were conducted using monocyte-derived human dendritic cells exposed to cigarette smoke extract (CSE, and dendritic cells extracted from mice chronically exposed to cigarette smoke. Results In human COPD lung tissue, we detected a significant increase in the total number of CD83+ cells, and significantly higher amounts of CD207 mRNA when compared with control tissue. Human monocyte-derived dendritic cells exposed to CSE (0.1-2% exhibited enhanced survival in vitro when compared with control dendritic cells. Murine dendritic cells extracted from mice exposed to cigarette smoke for 4 weeks, also demonstrated enhanced survival compared to dendritic cells extracted from control mice. Acute exposure of human dendritic cells to CSE induced the cellular pro-survival proteins heme-oxygenase-1 (HO-1, and B cell lymphoma leukemia-x(L (Bcl-xL, predominantly through oxidative stress. Although activated human dendritic cells conditioned with CSE expressed diminished migratory CCR7 expression, their migration towards the CCR7 ligand CCL21 was not

  15. Mechanisms of Distal Axonal Degeneration in Peripheral Neuropathies

    Science.gov (United States)

    Cashman, Christopher R.; Höke, Ahmet

    2015-01-01

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

  16. LONGITUDINAL STRUCTURAL CHANGES IN LATE-ONSET RETINAL DEGENERATION.

    Science.gov (United States)

    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.

  17. Deficiency of adaptive immunity does not interfere with Wallerian degeneration.

    Directory of Open Access Journals (Sweden)

    Christopher R Cashman

    Full Text Available Following injury, distal axons undergo the process of Wallerian degeneration, and then cell debris is cleared to create a permissive environment for axon regeneration. The innate and adaptive immune systems are believed to be critical for facilitating the clearance of myelin and axonal debris during this process. However, immunodeficient animal models are regularly used in transplantation studies investigating cell therapies to modulate the degenerative/regenerative response. Given the importance of the immune system in preparing a permissive environment for regeneration by clearing debris, animals lacking, in part or in full, a functional immune system may have an impaired ability to regenerate due to poor myelin clearance, and may, thus, be poor hosts to study modulators of regeneration and degeneration. To study this hypothesis, three different mouse models with impaired adaptive immunity were compared to wild type animals in their ability to degenerate axons and clear myelin debris one week following sciatic nerve transection. Immunofluorescent staining for axons and quantitation of axon density with nerve histomorphometry of the distal stump showed no consistent discrepancy between immunodeficient and wild type animals, suggesting axons tended to degenerate equally between the two groups. Debris clearance was assessed by macrophage density and relative myelin basic protein expression within the denervated nerve stump, and no consistent impairment of debris clearance was found. These data suggested deficiency of the adaptive immune system does not have a substantial effect on axon degeneration one week following axonal injury.

  18. Dendritic thickness: a morphometric parameter to classify mouse retinal ganglion cells

    Directory of Open Access Journals (Sweden)

    L.D. Loopuijt

    2007-10-01

    Full Text Available To study the dendritic morphology of retinal ganglion cells in wild-type mice we intracellularly injected these cells with Lucifer yellow in an in vitro preparation of the retina. Subsequently, quantified values of dendritic thickness, number of branching points and level of stratification of 73 Lucifer yellow-filled ganglion cells were analyzed by statistical methods, resulting in a classification into 9 groups. The variables dendritic thickness, number of branching points per cell and level of stratification were independent of each other. Number of branching points and level of stratification were independent of eccentricity, whereas dendritic thickness was positively dependent (r = 0.37 on it. The frequency distribution of dendritic thickness tended to be multimodal, indicating the presence of at least two cell populations composed of neurons with dendritic diameters either smaller or larger than 1.8 µm ("thin" or "thick" dendrites, respectively. Three cells (4.5% were bistratified, having thick dendrites, and the others (95.5% were monostratified. Using k-means cluster analysis, monostratified cells with either thin or thick dendrites were further subdivided according to level of stratification and number of branching points: cells with thin dendrites were divided into 2 groups with outer stratification (0-40% and 2 groups with inner (50-100% stratification, whereas cells with thick dendrites were divided into one group with outer and 3 groups with inner stratification. We postulate, that one group of cells with thin dendrites resembles cat ß-cells, whereas one group of cells with thick dendrites includes cells that resemble cat a-cells.

  19. Spiny Neurons of Amygdala, Striatum and Cortex Use Dendritic Plateau Potentials to Detect Network UP States

    Directory of Open Access Journals (Sweden)

    Katerina D Oikonomou

    2014-09-01

    Full Text Available Spiny neurons of amygdala, striatum, and cerebral cortex share four interesting features: [1] they are the most abundant cell type within their respective brain area, [2] covered by thousands of thorny protrusions (dendritic spines, [3] possess high levels of dendritic NMDA conductances, and [4] experience sustained somatic depolarizations in vivo and in vitro (UP states. In all spiny neurons of the forebrain, adequate glutamatergic inputs generate dendritic plateau potentials (dendritic UP states characterized by (i fast rise, (ii plateau phase lasting several hundred milliseconds and (iii abrupt decline at the end of the plateau phase. The dendritic plateau potential propagates towards the cell body decrementally to induce a long-lasting (longer than 100 ms, most often 200 – 800 ms steady depolarization (~20 mV amplitude, which resembles a neuronal UP state. Based on voltage-sensitive dye imaging, the plateau depolarization in the soma is precisely time-locked to the regenerative plateau potential taking place in the dendrite. The somatic plateau rises after the onset of the dendritic voltage transient and collapses with the breakdown of the dendritic plateau depolarization. We hypothesize that neuronal UP states in vivo reflect the occurrence of dendritic plateau potentials (dendritic UP states. We propose that the somatic voltage waveform during a neuronal UP state is determined by dendritic plateau potentials. A mammalian spiny neuron uses dendritic plateau potentials to detect and transform coherent network activity into a ubiquitous neuronal UP state. The biophysical properties of dendritic plateau potentials allow neurons to quickly attune to the ongoing network activity, as well as secure the stable amplitudes of successive UP states.

  20. Endothelial cell-derived microparticles induce plasmacytoid dendritic cell maturation: potential implications in inflammatory diseases.

    Science.gov (United States)

    Angelot, Fanny; Seillès, Estelle; Biichlé, Sabeha; Berda, Yael; Gaugler, Béatrice; Plumas, Joel; Chaperot, Laurence; Dignat-George, Françoise; Tiberghien, Pierre; Saas, Philippe; Garnache-Ottou, Francine

    2009-11-01

    Increased circulating endothelial microparticles, resulting from vascular endothelium dysfunction, and plasmacytoid dendritic cell activation are both encountered in common inflammatory disorders. The aim of our study was to determine whether interactions between endothelial microparticles and plasmacytoid dendritic cells could contribute to such pathologies. Microparticles generated from endothelial cell lines, platelets or activated T cells were incubated with human plasmacytoid dendritic cells sorted from healthy donor blood or with monocyte-derived dendritic cells. Dendritic cell maturation was evaluated by flow cytometry, cytokine secretion as well as naive T-cell activation and polarization. Labeled microparticles were also used to study cellular interactions. Endothelial microparticles induced plasmacytoid dendritic cell maturation. In contrast, conventional dendritic cells were resistant to endothelial microparticle-induced maturation. In addition to upregulation of co-stimulatory molecules, endothelial microparticle-matured plasmacytoid dendritic cells secreted inflammatory cytokines (interleukins 6 and 8, but no interferon-alpha) and also induced allogeneic naive CD4(+) T cells to proliferate and to produce type 1 cytokines such as interferon-gamma and tumor necrosis factor-alpha. Endothelial microparticle endocytosis by plasmacytoid dendritic cells appeared to be required for plasmacytoid dendritic cell maturation. Importantly, the ability of endothelial microparticles to induce plasmacytoid dendritic cells to mature was specific as microparticles derived from activated T cells or platelets (the major source of circulating microparticules in healthy subjects) did not induce such plasmacytoid dendritic cell maturation. Our data show that endothelial microparticles specifically induce plasmacytoid dendritic cell maturation and production of inflammatory cytokines. This novel activation pathway may be implicated in various inflammatory disorders and

  1. Rotavirus activates lymphocytes from non-obese diabetic mice by triggering toll-like receptor 7 signaling and interferon production in plasmacytoid dendritic cells.

    Directory of Open Access Journals (Sweden)

    Jessica A Pane

    2014-03-01

    Full Text Available It has been proposed that rotavirus infection promotes the progression of genetically-predisposed children to type 1 diabetes, a chronic autoimmune disease marked by infiltration of activated lymphocytes into pancreatic islets. Non-obese diabetic (NOD mice provide a model for the human disease. Infection of adult NOD mice with rhesus monkey rotavirus (RRV accelerates diabetes onset, without evidence of pancreatic infection. Rather, RRV spreads to the pancreatic and mesenteric lymph nodes where its association with antigen-presenting cells, including dendritic cells, induces cellular maturation. RRV infection increases levels of the class I major histocompatibility complex on B cells and proinflammatory cytokine expression by T cells at these sites. In autoimmunity-resistant mice and human mononuclear cells from blood, rotavirus-exposed plasmacytoid dendritic cells contribute to bystander polyclonal B cell activation through type I interferon expression. Here we tested the hypothesis that rotavirus induces bystander activation of lymphocytes from NOD mice by provoking dendritic cell activation and proinflammatory cytokine secretion. NOD mouse splenocytes were stimulated with rotavirus and assessed for activation by flow cytometry. This stimulation activated antigen-presenting cells and B cells independently of virus strain and replicative ability. Instead, activation depended on virus dose and was prevented by blockade of virus decapsidation, inhibition of endosomal acidification and interference with signaling through Toll-like receptor 7 and the type I interferon receptor. Plasmacytoid dendritic cells were more efficiently activated than conventional dendritic cells by RRV, and contributed to the activation of B and T cells, including islet-autoreactive CD8+ T cells. Thus, a double-stranded RNA virus can induce Toll-like receptor 7 signaling, resulting in lymphocyte activation. Our findings suggest that bystander activation mediated by type I

  2. Monocyte-derived dendritic cells are essential for CD8+ T cell activation and anti-tumor responses after local immunotherapy

    Directory of Open Access Journals (Sweden)

    Sabine eKuhn

    2015-11-01

    Full Text Available Tumors harbor several populations of dendritic cells with the ability to prime tumor-specific T cells. However, these T cells mostly fail to differentiate into armed effectors and are unable to control tumor growth. We have previously shown that treatment with immunostimulatory agents at the tumor site can activate anti-tumor immune responses, and is associated with the appearance of a population of monocyte-derived dendritic cells in the tumor and tumor-draining lymph node. Here we use dendritic cell or monocyte depletion and monocyte transfer to show that these monocyte-derived dendritic cells are critical to the activation of anti-tumor immune responses. Treatment with the immunostimulatory agents Monosodium Urate crystals and Mycobacterium smegmatis induced the accumulation of monocytes in the draining lymph node, their upregulation of CD11c and MHCII, and expression of iNOS, TNFα and IL12p40. Blocking monocyte entry into the lymph node and tumor through neutralization of the chemokine CCL2 or inhibition of Colony Stimulating Factor-1 receptor signaling prevented the generation of monocyte-derived dendritic cells, the infiltration of tumor-specific T cells into the tumor, and anti-tumor responses. In a reciprocal fashion, monocytes transferred into mice depleted of CD11c+ cells were sufficient to rescue CD8+ T cell priming in lymph node and delay tumor growth. Thus monocytes exposed to the appropriate conditions become powerful activators of tumor-specific CD8+ T cells and anti-tumor immunity.

  3. Rotavirus Activates Lymphocytes from Non-Obese Diabetic Mice by Triggering Toll-Like Receptor 7 Signaling and Interferon Production in Plasmacytoid Dendritic Cells

    Science.gov (United States)

    Pane, Jessica A.; Webster, Nicole L.; Coulson, Barbara S.

    2014-01-01

    It has been proposed that rotavirus infection promotes the progression of genetically-predisposed children to type 1 diabetes, a chronic autoimmune disease marked by infiltration of activated lymphocytes into pancreatic islets. Non-obese diabetic (NOD) mice provide a model for the human disease. Infection of adult NOD mice with rhesus monkey rotavirus (RRV) accelerates diabetes onset, without evidence of pancreatic infection. Rather, RRV spreads to the pancreatic and mesenteric lymph nodes where its association with antigen-presenting cells, including dendritic cells, induces cellular maturation. RRV infection increases levels of the class I major histocompatibility complex on B cells and proinflammatory cytokine expression by T cells at these sites. In autoimmunity-resistant mice and human mononuclear cells from blood, rotavirus-exposed plasmacytoid dendritic cells contribute to bystander polyclonal B cell activation through type I interferon expression. Here we tested the hypothesis that rotavirus induces bystander activation of lymphocytes from NOD mice by provoking dendritic cell activation and proinflammatory cytokine secretion. NOD mouse splenocytes were stimulated with rotavirus and assessed for activation by flow cytometry. This stimulation activated antigen-presenting cells and B cells independently of virus strain and replicative ability. Instead, activation depended on virus dose and was prevented by blockade of virus decapsidation, inhibition of endosomal acidification and interference with signaling through Toll-like receptor 7 and the type I interferon receptor. Plasmacytoid dendritic cells were more efficiently activated than conventional dendritic cells by RRV, and contributed to the activation of B and T cells, including islet-autoreactive CD8+ T cells. Thus, a double-stranded RNA virus can induce Toll-like receptor 7 signaling, resulting in lymphocyte activation. Our findings suggest that bystander activation mediated by type I interferon

  4. Dendritic spine pathology in autism: lessons learned from mouse models

    Institute of Scientific and Technical Information of China (English)

    Qiangge Zhang; Dingxi Zhou; Guoping Feng

    2016-01-01

    Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders that affect up to 1.5% of population in the world. Recent large scale genomic studies show that genetic causes of ASD are very heterogeneous. Gene ontology, pathway analysis and animal model studies have revealed several potential converging mechanisms including postsynaptic dysfunction of excitatory synapses. In this review, we focus on the structural and functional specializations of dendritic spines, and describe their defects in ASD. We use Fragile X syndrome, Rett syndrome and Phe-lan-McDermid syndrome, three of the most studied neurodevelopmental disorders with autism features, as examples to demonstrate the significant contribution made by mouse models towards the understanding of monogenic ASD. We envision that the development and application of new technologies to study the function of dendritic spines in valid animal models will eventually lead to innovative treatments for ASD.

  5. Suppressing Lithium Dendrite Growth with a Single-Component Coating.

    Science.gov (United States)

    Liu, Haodong; Zhou, Hongyao; Lee, Byoung-Sun; Xing, Xing; Gonzalez, Matthew; Liu, Ping

    2017-09-13

    A single-component coating was formed on lithium (Li) metal in a lithium iodide/organic carbonate [dimethyl carbonate (DMC) and ethylene carbonate (EC)] electrolyte. LiI chemically reacts with DMC to form lithium methyl carbonate (LMC), which precipitates and forms the chemically homogeneous coating layer on the Li surface. This coating layer is shown to enable dendrite-free Li cycling in a symmetric Li∥Li cell even at a current density of 3 mA cm -2 . Adding EC to DMC modulates the formation of LMC, resulting in a stable coating layer that is essential for long-term Li cycling stability. Furthermore, the coating can enable dendrite-free cycling after being transferred to common LiPF 6 /carbonate electrolytes, which are compatible with metal oxide cathodes.

  6. EphB/syndecan-2 signaling in dendritic spine morphogenesis

    DEFF Research Database (Denmark)

    Ethell, I M; Irie, F; Kalo, M S

    2001-01-01

    We previously reported that the cell surface proteoglycan syndecan-2 can induce dendritic spine formation in hippocampal neurons. We demonstrate here that the EphB2 receptor tyrosine kinase phosphorylates syndecan-2 and that this phosphorylation event is crucial for syndecan-2 clustering and spine...... formation. Syndecan-2 is tyrosine phosphorylated and forms a complex with EphB2 in mouse brain. Dominant-negative inhibition of endogenous EphB receptor activities blocks clustering of endogenous syndecan-2 and normal spine formation in cultured hippocampal neurons. This is the first evidence that Eph...... receptors play a physiological role in dendritic spine morphogenesis. Our observations suggest that spine morphogenesis is triggered by the activation of Eph receptors, which causes tyrosine phosphorylation of target molecules, such as syndecan-2, in presumptive spines....

  7. Blastic plasmacytoid dendritic cell neoplasm: report of two pediatric cases.

    Science.gov (United States)

    Dharmani, Preeti Ashok; Mittal, Neha Manish; Subramanian, P G; Galani, Komal; Badrinath, Yajamanam; Amare, Pratibha; Gujral, Sumeet

    2015-01-01

    Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare subtype of acute leukemia that typically follows a highly aggressive clinical course in adults, whereas experience in children with this disease is very limited. We report cases of two children in whom bone marrow showed infiltration by large atypical monocytoid 'blast-like' cells which on immunophenotyping expressed CD4, CD56, HLA-DR and CD33 while were negative for CD34 other T-cell, B-cell and myeloid markers. The differential diagnoses considered were AML, T/NK-cell leukemia and acute undifferentiated leukemia. Additional markers CD303/BDCA-2 and CD123 which are recently validated plasmacytoid dendritic cell markers were done which helped us clinch the diagnosis of this rare neoplasm. An accurate diagnosis of BPDCN is essential in order to provide prompt treatment. Due to its rarity and only recent recognition as a distinct clinicopathological entity, no standardized therapeutic approach has been established for BPDCN.

  8. Large-area sheet task advanced dendritic web growth development

    Science.gov (United States)

    Duncan, C. S.; Seidensticker, R. G.; Mchugh, J. P.

    1984-01-01

    The thermal models used for analyzing dendritic web growth and calculating the thermal stress were reexamined to establish the validity limits imposed by the assumptions of the models. Also, the effects of thermal conduction through the gas phase were evaluated and found to be small. New growth designs, both static and dynamic, were generated using the modeling results. Residual stress effects in dendritic web were examined. In the laboratory, new techniques for the control of temperature distributions in three dimensions were developed. A new maximum undeformed web width of 5.8 cm was achieved. A 58% increase in growth velocity of 150 micrometers thickness was achieved with dynamic hardware. The area throughput goals for transient growth of 30 and 35 sq cm/min were exceeded.

  9. Numerical model for dendritic solidification of binary alloys

    Science.gov (United States)

    Felicelli, S. D.; Heinrich, J. C.; Poirier, D. R.

    1993-01-01

    A finite element model capable of simulating solidification of binary alloys and the formation of freckles is presented. It uses a single system of equations to deal with the all-liquid region, the dendritic region, and the all-solid region. The dendritic region is treated as an anisotropic porous medium. The algorithm uses the bilinear isoparametric element, with a penalty function approximation and a Petrov-Galerkin formulation. Numerical simulations are shown in which an NH4Cl-H2O mixture and a Pb-Sn alloy melt are cooled. The solidification process is followed in time. Instabilities in the process can be clearly observed and the final compositions obtained.

  10. Synaptic clustering within dendrites: an emerging theory of memory formation

    Science.gov (United States)

    Kastellakis, George; Cai, Denise J.; Mednick, Sara C.; Silva, Alcino J.; Poirazi, Panayiota

    2015-01-01

    It is generally accepted that complex memories are stored in distributed representations throughout the brain, however the mechanisms underlying these representations are not understood. Here, we review recent findings regarding the subcellular mechanisms implicated in memory formation, which provide evidence for a dendrite-centered theory of memory. Plasticity-related phenomena which affect synaptic properties, such as synaptic tagging and capture, synaptic clustering, branch strength potentiation and spinogenesis provide the foundation for a model of memory storage that relies heavily on processes operating at the dendrite level. The emerging picture suggests that clusters of functionally related synapses may serve as key computational and memory storage units in the brain. We discuss both experimental evidence and theoretical models that support this hypothesis and explore its advantages for neuronal function. PMID:25576663

  11. Cystic degeneration of liver malignancies. Study by US and CT

    Energy Technology Data Exchange (ETDEWEB)

    Kumada, Takashi; Nakano, Satoshi; Kitamura, Kimio; Watahiki, Hajime; Takeda, Isao

    1983-03-01

    CT and US were carried out on 81 patients with hepatocellular carcinoma, 20 patients with cholangiocellular carcinoma and 94 patients with metastatic liver cancer. 1) Cystic degeneration was observed in one with hepatocellular carcinoma (1.2%), one with cholangiocellular carcinoma (5.0%) and 12 with metastatic liver cancer (12.8%) by US, but this change was observed in only 5 by CT (1,0,4, respectively). Metastatic liver cancer showed the highest incidence among these tumors. 2) The characteristics of cystic degeneration of the liver tumors were thickened wall and irregularity of the inner surface of the wall. 3) Judging from macroscopic and histopathological findings, liquefactive necrosis in the tumors was shown as ''echoluent'' area. We concluded that cystic degeneration was one of the important findings in metastatic liver cancer and that careful observation by US and CT avoided the confusion with other hepatic cystic diseases.

  12. Quantization with maximally degenerate Poisson brackets: the harmonic oscillator!

    International Nuclear Information System (INIS)

    Nutku, Yavuz

    2003-01-01

    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

  13. An iterative method for selecting degenerate multiplex PCR primers.

    Science.gov (United States)

    Souvenir, Richard; Buhler, Jeremy; Stormo, Gary; Zhang, Weixiong

    2007-01-01

    Single-nucleotide polymorphism (SNP) genotyping is an important molecular genetics process, which can produce results that will be useful in the medical field. Because of inherent complexities in DNA manipulation and analysis, many different methods have been proposed for a standard assay. One of the proposed techniques for performing SNP genotyping requires amplifying regions of DNA surrounding a large number of SNP loci. To automate a portion of this particular method, it is necessary to select a set of primers for the experiment. Selecting these primers can be formulated as the Multiple Degenerate Primer Design (MDPD) problem. The Multiple, Iterative Primer Selector (MIPS) is an iterative beam-search algorithm for MDPD. Theoretical and experimental analyses show that this algorithm performs well compared with the limits of degenerate primer design. Furthermore, MIPS outperforms an existing algorithm that was designed for a related degenerate primer selection problem.

  14. Natural history of seminiferous tubule degeneration in Klinefelter syndrome

    DEFF Research Database (Denmark)

    Aksglaede, Lise; Wikström, Anne M; Rajpert-De Meyts, Ewa

    2006-01-01

    Klinefelter syndrome (47,XXY) is characterized by small, firm testis, gynaecomastia, azoospermia and hypergonadotropic hypogonadism. Degeneration of the seminiferous tubules in 47,XXY males is a well-described phenomenon. It begins in the fetus, progresses through infancy and accelerates dramatic......Klinefelter syndrome (47,XXY) is characterized by small, firm testis, gynaecomastia, azoospermia and hypergonadotropic hypogonadism. Degeneration of the seminiferous tubules in 47,XXY males is a well-described phenomenon. It begins in the fetus, progresses through infancy and accelerates...... summarize current knowledge on the development of the classical endocrinological and histological features of 47,XXY males from fetus to adulthood and review the literature concerning the degeneration of the seminiferous tubules in this syndrome....

  15. Degenerate Fermi gas in a combined harmonic-lattice potential

    International Nuclear Information System (INIS)

    Blakie, P. B.; Bezett, A.; Buonsante, P.

    2007-01-01

    In this paper we derive an analytic approximation to the density of states for atoms in a combined optical lattice and harmonic trap potential as used in current experiments with quantum degenerate gases. We compare this analytic density of states to numerical solutions and demonstrate its validity regime. Our work explicitly considers the role of higher bands and when they are important in quantitative analysis of this system. Applying our density of states to a degenerate Fermi gas, we consider how adiabatic loading from a harmonic trap into the combined harmonic-lattice potential affects the degeneracy temperature. Our results suggest that occupation of excited bands during loading should lead to more favorable conditions for realizing degenerate Fermi gases in optical lattices

  16. Peripheral retinal degenerations and the risk of retinal detachment.

    Science.gov (United States)

    Lewis, Hilel

    2003-07-01

    To review the degenerative diseases of the peripheral retina in relationship with the risk to develop a rhegmatogenous retinal detachment and to present recommendations for use in eyes at increased risk of developing a retinal detachment. Focused literature review and author's clinical experience. Retinal degenerations are common lesions involving the peripheral retina, and most of them are clinically insignificant. Lattice degeneration, degenerative retinoschisis, cystic retinal tufts, and, rarely, zonular traction tufts, can result in a rhegmatogenous retinal detachment. Therefore, these lesions have been considered for prophylactic therapy; however, adequate studies have not been performed to date. Well-designed, prospective, randomized clinical studies are necessary to determine the benefit-risk ratio of prophylactic treatment. In the meantime, the evidence available suggests that most of the peripheral retinal degenerations should not be treated except in rare, high-risk situations.

  17. Plastic deformation of silicon dendritic web ribbons during the growth

    Science.gov (United States)

    Cheng, L. J.; Dumas, K. A.; Su, B. M.; Leipold, M. H.

    1984-01-01

    The distribution of slip dislocations in silicon dendritic web ribbons due to plastic deformation during the cooling phase of the growth was studied. The results show the existence of two distinguishable stress regions across the ribbon formed during the plastic deformation stage, namely, shear stress at the ribbon edges and tensile stress at the middle. In addition, slip dislocations caused by shear stress near the edges appear to originate at the twin plane.

  18. Solute redistribution in dendritic solidification with diffusion in the solid

    Science.gov (United States)

    Ganesan, S.; Poirier, D. R.

    1989-01-01

    An investigation of solute redistribution during dendritic solidification with diffusion in the solid has been performed using numerical techniques. The extent of diffusion is characterized by the instantaneous and average diffusion parameters. These parameters are functions of the diffusion Fourier number, the partition ratio and the fraction solid. Numerical results are presented as an approximate model, which is used to predict the average diffusion parameter and calculate the composition of the interdendritic liquid during solidification.

  19. Prospective Clinical Testing of Regulatory Dendritic Cells in Organ Transplantation

    OpenAIRE

    Thomson, Angus W.; Zahorchak, Alan F.; Ezzelarab, Mohamed B.; Butterfield, Lisa H.; Lakkis, Fadi G.; Metes, Diana M.

    2016-01-01

    Dendritic cells (DC) are rare, professional antigen-presenting cells with ability to induce or regulate alloimmune responses. Regulatory DC (DCreg) with potential to down-modulate acute and chronic inflammatory conditions that occur in organ transplantation can be generated in vitro under a variety of conditions. Here, we provide a rationale for evaluation of DCreg therapy in clinical organ transplantation with the goal of promoting sustained, donor-specific hyporesponsiveness, while lowering...

  20. [Myopia: frequency of lattice degeneration and axial length].

    Science.gov (United States)

    Martín Sánchez, M D; Roldán Pallarés, M

    2001-05-01

    To evaluate the relationship between lattice retinal degeneration and axial length of the eye in different grades of myopia. A sample of 200 eyes from 124 myopic patients was collected by chance. The average age was 34.8 years (20-50 years) and the myopia was between 0.5 and 20 diopters (D). The eyes were grouped according to the degree of refraction defect, the mean axial length of each group (Scan A) and the frequency of lattice retinal degeneration and the relationship between these variables was studied. The possible influence of age on our results was also considered. For the statistical analysis, the SAS 6.07 program with the variance analysis for quantitative variables, and chi(2) test for qualitative variables with a 5% significance were used. A multivariable linear regression model was also adjusted. The highest frequency of lattice retinal degeneration occurred in those myopia patients having more than 15 D, and also in the group of myopia patients between 3 and 6 D, but this did not show statistical significance when compared with the other myopic groups. If the axial length is assessed, a greater frequency of lattice retinal degeneration is also found when the axial length is 25-27 mm and 29-30 mm, which correspond, respectively, to myopias between 3-10 D and more than 15 D. When the multivariable linear regression model was adjusted, the axial length showed the existence of lattice retinal degeneration (beta 0.41 mm; p=0.08) adjusted by the number of diopters (beta 0.38 mm; plattice retinal degeneration was found for myopias with axial eye length between 29-30 mm (more than 15 D), and 25-27 mm (between 3-10 D).

  1. Overview of the Tusas Code for Simulation of Dendritic Solidification

    Energy Technology Data Exchange (ETDEWEB)

    Trainer, Amelia J. [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States); Newman, Christopher Kyle [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Francois, Marianne M. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-01-07

    The aim of this project is to conduct a parametric investigation into the modeling of two dimensional dendrite solidification, using the phase field model. Specifically, we use the Tusas code, which is for coupled heat and phase-field simulation of dendritic solidification. Dendritic solidification, which may occur in the presence of an unstable solidification interface, results in treelike microstructures that often grow perpendicular to the rest of the growth front. The interface may become unstable if the enthalpy of the solid material is less than that of the liquid material, or if the solute is less soluble in solid than it is in liquid, potentially causing a partition [1]. A key motivation behind this research is that a broadened understanding of phase-field formulation and microstructural developments can be utilized for macroscopic simulations of phase change. This may be directly implemented as a part of the Telluride project at Los Alamos National Laboratory (LANL), through which a computational additive manufacturing simulation tool is being developed, ultimately to become part of the Advanced Simulation and Computing Program within the U.S. Department of Energy [2].

  2. Evaluation of two different dendritic cell preparations with BCG reactivity

    Directory of Open Access Journals (Sweden)

    Fol Marek

    2016-01-01

    Full Text Available Dendritic cells (DCs play a key-role in the immune response against intracellular bacterial pathogens, including mycobacteria. Monocyte-derived dendritic cells (MoDCs are considered to behave as inflammatory cell populations. Different immunomagnetic methods (positive and negative can be used to purify monocytes before their in vitro differentiation and their culture behavior can be expected to be different. In this study we evaluated the reactivity of two dendritic cell populations towards the Bacillus Calmette-Guérin (BCG antigen. Monocytes were obtained from the blood of healthy donors, using positive and negative immunomagnetic separation methods. The expression of DC-SIGN, CD86, CD80, HLA-DR and CD40 on MoDCs was estimated by flow cytometry. The level of IL-12p70, IL-10 and TNF-α was measured by ELISA. Neither of the tested methods affected the surface marker expression of DCs. No significant alteration in immunological response, measured by cytokine production, was noted either. After BCG stimulation, the absence of IL-12, but the IL-23 production was observed in both cell preparations. Positive and negative magnetic separation methods are effective techniques to optimize the preparation of monocytes as the source of MoDCs for potential clinical application.

  3. Dextromethorphan Inhibits Activations and Functions in Dendritic Cells

    Directory of Open Access Journals (Sweden)

    Der-Yuan Chen

    2013-01-01

    Full Text Available Dendritic cells (DCs play an important role in connecting innate and adaptive immunity. Thus, DCs have been regarded as a major target for the development of immunomodulators. In this study, we examined the effect of dextromethorphan (DXM, a common cough suppressant with a high safety profile, on the activation and function of DCs. In the presence of DXM, the LPS-induced expression of the costimulatory molecules in murine bone marrow-derived dendritic cells (BMDCs was significantly suppressed. In addition, DXM treatment reduced the production of reactive oxygen species (ROS, proinflammatory cytokines, and chemokines in maturing BMDCs that were activated by LPS. Therefore, DXM abrogated the ability of LPS-stimulated DCs to induce Ag-specific T-cell activation, as determined by their decreased proliferation and IFN-γ secretion in mixed leukocyte cultures. Moreover, the inhibition of LPS-induced MAPK activation and NF-κB translocation may contribute to the suppressive effect of DXM on BMDCs. Remarkably, DXM decreased the LPS-induced surface expression of CD80, CD83, and HLA-DR and the secretion of IL-6 and IL-12 in human monocyte-derived dendritic cells (MDDCs. These findings provide a new insight into the impact of DXM treatment on DCs and suggest that DXM has the potential to be used in treating DC-related acute and chronic diseases.

  4. Anti tumor vaccination with hybrid dendritic-tumour cells

    International Nuclear Information System (INIS)

    Barbuto, Jose Alexandre M.; Neves, Andreia R.; Ensina, Luis Felipe C.; Anselmo, Luciene B.

    2005-01-01

    Dendritic cells are the most potent antigen-presenting cells, and the possibility of their use for cancer vaccination has renewed the interest in this therapeutic modality. Nevertheless, the ideal immunization protocol with these cells has not been described yet. In this paper we describe the preliminary results of a protocol using autologous tumor and allogeneic dendritic hybrid cell vaccination every 6 weeks, for metastatic melanoma and renal cell carcinoma (RCC) patients. Thirty-five patients were enrolled between March 2001 and March 2003. Though all patients included presented with large tumor burdens and progressive diseases, 71% of them experienced stability after vaccination, with durations up to 19 months. Among RCC patients 3/22 (14%) presented objective responses. The median time to progression was 4 months for melanoma and 5.7 months for RCC patients; no significant untoward effects were noted. Furthermore, immune function, as evaluated by cutaneous delayed-type hypersensitivity reactions to recall antigens and by peripheral blood proliferative responses to tumor-specific and nonspecific stimuli, presented a clear tendency to recover in vaccinated patients. These data indicate that dendritic cell-tumor cell hybrid vaccination affects the natural history of advanced cancer and provide support for its study in less advanced patients, who should, more likely, benefit even more from this approach. (author)

  5. Dendritic cell fate is determined by BCL11A

    Science.gov (United States)

    Ippolito, Gregory C.; Dekker, Joseph D.; Wang, Yui-Hsi; Lee, Bum-Kyu; Shaffer, Arthur L.; Lin, Jian; Wall, Jason K.; Lee, Baeck-Seung; Staudt, Louis M.; Liu, Yong-Jun; Iyer, Vishwanath R.; Tucker, Haley O.

    2014-01-01

    The plasmacytoid dendritic cell (pDC) is vital to the coordinated action of innate and adaptive immunity. pDC development has not been unequivocally traced, nor has its transcriptional regulatory network been fully clarified. Here we confirm an essential requirement for the BCL11A transcription factor in fetal pDC development, and demonstrate this lineage-specific requirement in the adult organism. Furthermore, we identify BCL11A gene targets and provide a molecular mechanism for its action in pDC commitment. Embryonic germ-line deletion of Bcl11a revealed an absolute cellular, molecular, and functional absence of pDCs in fetal mice. In adults, deletion of Bcl11a in hematopoietic stem cells resulted in perturbed yet continued generation of progenitors, loss of downstream pDC and B-cell lineages, and persisting myeloid, conventional dendritic, and T-cell lineages. Challenge with virus resulted in a marked reduction of antiviral response in conditionally deleted adults. Genome-wide analyses of BCL11A DNA binding and expression revealed that BCL11A regulates transcription of E2-2 and other pDC differentiation modulators, including ID2 and MTG16. Our results identify BCL11A as an essential, lineage-specific factor that regulates pDC development, supporting a model wherein differentiation into pDCs represents a primed “default” pathway for common dendritic cell progenitors. PMID:24591644

  6. Extended Hellmann-Feynman theorem for degenerate eigenstates

    Science.gov (United States)

    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.

  7. Global Carleman estimates for degenerate parabolic operators with applications

    CERN Document Server

    Cannarsa, P; Vancostenoble, J

    2016-01-01

    Degenerate parabolic operators have received increasing attention in recent years because they are associated with both important theoretical analysis, such as stochastic diffusion processes, and interesting applications to engineering, physics, biology, and economics. This manuscript has been conceived to introduce the reader to global Carleman estimates for a class of parabolic operators which may degenerate at the boundary of the space domain, in the normal direction to the boundary. Such a kind of degeneracy is relevant to study the invariance of a domain with respect to a given stochastic diffusion flow, and appears naturally in climatology models.

  8. Design of the Advanced Virgo non-degenerate recycling cavities

    International Nuclear Information System (INIS)

    Granata, M; Barsuglia, M; Flaminio, R; Freise, A; Hild, S; Marque, J

    2010-01-01

    Advanced Virgo is the project to upgrade the interferometric gravitational wave detector Virgo, and it foresees the implementation of power and signal non-degenerate recycling cavities. Such cavities suppress the build-up of high order modes of the resonating sidebands, with some advantage for the commissioning of the detector and the build-up of the gravitational signal. Here we present the baseline design of the Advanced Virgo non-degenerate recycling cavities, giving some preliminary results of simulations about the tolerances of this design to astigmatism, mirror figure errors and thermal lensing.

  9. Transport in partially degenerate, magnetized plasmas. Pt. 1. Collision operators

    International Nuclear Information System (INIS)

    Brown, S.R.; Haines, M.G.

    1997-01-01

    The quantum Boltzmann collision operator is expanded to yield a degenerate form of the Fokker-Planck collision operator. This is analyzed using Rosenbluth potentials to give a degenerate analogue of the Shkarofsky operator. The distribution function is then expanded about an equilibrium Fermi-Dirac distribution function using a tensor perturbation formulation to give a zeroth-order and a first-order collision operator. These equations are shown to satisfy the relevant conservation equations. It is shown that the distribution function relaxes to a Fermi-Dirac form through electron-electron collisions. (Author)

  10. Wallerian degeneration of the corticospinal tract in the brain stem

    International Nuclear Information System (INIS)

    Uchino, Akira; Onomura, Kentaro; Ohno, Masato

    1989-01-01

    Magnetic resonance imaging (MRI) of wallerian degeneration of the corticospinal tract in the brain stem was studied in 25 patients with chronic supratentorial vascular accidents. In the relatively early stages, at least three months after ictus, increased signal intensities in axial T 2 -weighted images - with or without decreased signal intensities in axial T 1 -weighted images - were observed in the brain stem ipsilaterally. In later stages, at least six months after ictus, shrinkage of the brain stem ipsilaterally - with or without decreased signal intensities - was clearly observed in axial T 1 -weighted images. MRI is therefore regarded a sensitive diagnostic modality for evaluating wallerian degeneration in the brain stem. (author)

  11. Relationship between retinal lattice degeneration and open angle glaucoma.

    Science.gov (United States)

    Rahimi, Mansour

    2005-01-01

    Patients with retinal disorders may develop glaucoma of both a primary and secondary type. Pigment may contribute to trabecular obstruction in some patients with open-angle glaucoma. Lattice degeneration of the retina in its typical form is a sharply demarcated, circumferentially oriented, degenerative process with significant alterations of retinal pigmentation. The association between myopia, open angle glaucoma and pigment dispersion is striking. Therefore, it could be postulated that there is significant prevalence of open angle glaucoma in patients with retinal lattice degeneration, especially in combination with myopia.

  12. Automated imaging dark adaptometer for investigating hereditary retinal degenerations

    Science.gov (United States)

    Azevedo, Dario F. G.; Cideciyan, Artur V.; Regunath, Gopalakrishnan; Jacobson, Samuel G.

    1995-05-01

    We designed and built an automated imaging dark adaptometer (AIDA) to increase accuracy, reliability, versatility and speed of dark adaptation testing in patients with hereditary retinal degenerations. AIDA increases test accuracy by imaging the ocular fundus for precise positioning of bleaching and stimulus lights. It improves test reliability by permitting continuous monitoring of patient fixation. Software control of stimulus presentation provides broad testing versatility without sacrificing speed. AIDA promises to facilitate the measurement of dark adaptation in studies of the pathophysiology of retinal degenerations and in future treatment trials of these diseases.

  13. Maximum principles for boundary-degenerate linear parabolic differential operators

    OpenAIRE

    Feehan, Paul M. N.

    2013-01-01

    We develop weak and strong maximum principles for boundary-degenerate, linear, parabolic, second-order partial differential operators, $Lu := -u_t-\\tr(aD^2u)-\\langle b, Du\\rangle + cu$, with \\emph{partial} Dirichlet boundary conditions. The coefficient, $a(t,x)$, is assumed to vanish along a non-empty open subset, $\\mydirac_0!\\sQ$, called the \\emph{degenerate boundary portion}, of the parabolic boundary, $\\mydirac!\\sQ$, of the domain $\\sQ\\subset\\RR^{d+1}$, while $a(t,x)$ may be non-zero at po...

  14. Vitamin B1-deficient mice show impairment of hippocampus-dependent memory formation and loss of hippocampal neurons and dendritic spines: potential microendophenotypes of Wernicke-Korsakoff syndrome.

    Science.gov (United States)

    Inaba, Hiroyoshi; Kishimoto, Takuya; Oishi, Satoru; Nagata, Kan; Hasegawa, Shunsuke; Watanabe, Tamae; Kida, Satoshi

    2016-12-01

    Patients with severe Wernicke-Korsakoff syndrome (WKS) associated with vitamin B1 (thiamine) deficiency (TD) show enduring impairment of memory formation. The mechanisms of memory impairment induced by TD remain unknown. Here, we show that hippocampal degeneration is a potential microendophenotype (an endophenotype of brain disease at the cellular and synaptic levels) of WKS in pyrithiamine-induced thiamine deficiency (PTD) mice, a rodent model of WKS. PTD mice show deficits in the hippocampus-dependent memory formation, although they show normal hippocampus-independent memory. Similarly with WKS, impairments in memory formation did not recover even at 6 months after treatment with PTD. Importantly, PTD mice exhibit a decrease in neurons in the CA1, CA3, and dentate gyrus (DG) regions of the hippocampus and reduced density of wide dendritic spines in the DG. Our findings suggest that TD induces hippocampal degeneration, including the loss of neurons and spines, thereby leading to enduring impairment of hippocampus-dependent memory formation.

  15. Vitamin B1-deficient mice show impairment of hippocampus-dependent memory formation and loss of hippocampal neurons and dendritic spines: potential microendophenotypes of Wernicke–Korsakoff syndrome

    Science.gov (United States)

    Inaba, Hiroyoshi; Kishimoto, Takuya; Oishi, Satoru; Nagata, Kan; Hasegawa, Shunsuke; Watanabe, Tamae; Kida, Satoshi

    2016-01-01

    Patients with severe Wernicke–Korsakoff syndrome (WKS) associated with vitamin B1 (thiamine) deficiency (TD) show enduring impairment of memory formation. The mechanisms of memory impairment induced by TD remain unknown. Here, we show that hippocampal degeneration is a potential microendophenotype (an endophenotype of brain disease at the cellular and synaptic levels) of WKS in pyrithiamine-induced thiamine deficiency (PTD) mice, a rodent model of WKS. PTD mice show deficits in the hippocampus-dependent memory formation, although they show normal hippocampus-independent memory. Similarly with WKS, impairments in memory formation did not recover even at 6 months after treatment with PTD. Importantly, PTD mice exhibit a decrease in neurons in the CA1, CA3, and dentate gyrus (DG) regions of the hippocampus and reduced density of wide dendritic spines in the DG. Our findings suggest that TD induces hippocampal degeneration, including the loss of neurons and spines, thereby leading to enduring impairment of hippocampus-dependent memory formation. PMID:27576603

  16. Xenopus laevis Retinal Ganglion Cell Dendritic Arbors Develop Independently of Visual Stimulation

    Directory of Open Access Journals (Sweden)

    Barbara Lom

    2004-01-01

    Full Text Available Newly formed neurons must locate their appropriate target cells and then form synaptic connections with these targets in order to establish a functional nervous system. In the vertebrate retina, retinal ganglion cell (RGC dendrites extend from the cell body and form synapses with nearby amacrine and bipolar cells. RGC axons, however, exit the retina and synapse with the dendrites of midbrain neurons in the optic tectum. We examined how visual stimulation influenced Xenopus RGC dendritic arborization. Neuronal activity is known to be an important factor in shaping dendritic and axonal arborization. Thus, we reared tadpoles in dark and light environments then used rhodamine dextran retrograde labeling to identify RGCs in the retina. When we compared RGC dendritic arbors from tadpoles reared in dark and light environments, we found no morphological differences, suggesting that physiological visual activity did not contribute to the morphological development of Xenopus RGC dendritic arbors.

  17. Sarcomeres pattern proprioceptive sensory dendritic endings through Perlecan/UNC-52 in C. elegans

    Science.gov (United States)

    Liang, Xing; Dong, Xintong; Moerman, Donald G.; Shen, Kang; Wang, Xiangming

    2015-01-01

    Sensory dendrites innervate peripheral tissues through cell-cell interactions that are poorly understood. The proprioceptive neuron PVD in C. elegans extends regular terminal dendritic branches between muscle and hypodermis. We found that the PVD branch pattern was instructed by adhesion molecule SAX-7/L1CAM, which formed regularly spaced stripes on the hypodermal cell. The regularity of the SAX-7 pattern originated from the repeated and regularly spaced dense body of the sarcomeres in the muscle. The extracellular proteoglycan, UNC-52/Perlecan, links the dense body to the hemidesmosome on the hypodermal cells, which in turn instructed the SAX-7 stripes and PVD dendrites. Both UNC-52 and hemidesmosome components exhibited highly regular stripes that interdigitated with the SAX-7 stripe and PVD dendrites, reflecting the striking precision of subcellular patterning between muscle, hypodermis and dendrites. Hence, the muscular contractile apparatus provides the instructive cues to pattern proprioceptive dendrites. PMID:25982673

  18. Multiple modes of action potential initiation and propagation in mitral cell primary dendrite

    DEFF Research Database (Denmark)

    Chen, Wei R; Shen, Gongyu Y; Shepherd, Gordon M

    2002-01-01

    recordings with computational modeling to analyze action-potential initiation and propagation in the primary dendrite. In response to depolarizing current injection or distal olfactory nerve input, fast Na(+) action potentials were recorded along the entire length of the primary dendritic trunk. With weak......-to-moderate olfactory nerve input, an action potential was initiated near the soma and then back-propagated into the primary dendrite. As olfactory nerve input increased, the initiation site suddenly shifted to the distal primary dendrite. Multi-compartmental modeling indicated that this abrupt shift of the spike......-initiation site reflected an independent thresholding mechanism in the distal dendrite. When strong olfactory nerve excitation was paired with strong inhibition to the mitral cell basal secondary dendrites, a small fast prepotential was recorded at the soma, which indicated that an action potential was initiated...

  19. Subcellular Location of PKA Controls Striatal Plasticity: Stochastic Simulations in Spiny Dendrites

    Science.gov (United States)

    Oliveira, Rodrigo F.; Kim, MyungSook; Blackwell, Kim T.

    2012-01-01

    Dopamine release in the striatum has been implicated in various forms of reward dependent learning. Dopamine leads to production of cAMP and activation of protein kinase A (PKA), which are involved in striatal synaptic plasticity and learning. PKA and its protein targets are not diffusely located throughout the neuron, but are confined to various subcellular compartments by anchoring molecules such as A-Kinase Anchoring Proteins (AKAPs). Experiments have shown that blocking the interaction of PKA with AKAPs disrupts its subcellular location and prevents LTP in the hippocampus and striatum; however, these experiments have not revealed whether the critical function of anchoring is to locate PKA near the cAMP that activates it or near its targets, such as AMPA receptors located in the post-synaptic density. We have developed a large scale stochastic reaction-diffusion model of signaling pathways in a medium spiny projection neuron dendrite with spines, based on published biochemical measurements, to investigate this question and to evaluate whether dopamine signaling exhibits spatial specificity post-synaptically. The model was stimulated with dopamine pulses mimicking those recorded in response to reward. Simulations show that PKA colocalization with adenylate cyclase, either in the spine head or in the dendrite, leads to greater phosphorylation of DARPP-32 Thr34 and AMPA receptor GluA1 Ser845 than when PKA is anchored away from adenylate cyclase. Simulations further demonstrate that though cAMP exhibits a strong spatial gradient, diffusible DARPP-32 facilitates the spread of PKA activity, suggesting that additional inactivation mechanisms are required to produce spatial specificity of PKA activity. PMID:22346744

  20. Loss of dendritic connectivity in southern California's urban riverscape facilitates decline of an endemic freshwater fish.

    Science.gov (United States)

    Richmond, Jonathan Q; Backlin, Adam R; Galst-Cavalcante, Carey; O'Brien, John W; Fisher, Robert N

    2018-01-01

    Life history adaptations and spatial configuration of metapopulation networks allow certain species to persist in extreme fluctuating environments, yet long-term stability within these systems relies on the maintenance of linkage habitat. Degradation of such linkages in urban riverscapes can disrupt this dynamic in aquatic species, leading to increased extinction debt in local populations experiencing environment-related demographic flux. We used microsatellites and mtDNA to examine the effects of collapsed network structure in the endemic Santa Ana sucker Catostomus santaanae of southern California, a threatened species affected by natural flood-drought cycles, "boom-and-bust" demography, hybridization and presumed artificial transplantation. Our results show a predominance of drift-mediated processes in shaping population structure and that reverse mechanisms for counterbalancing the genetic effects of these phenomena have dissipated with the collapse of dendritic connectivity. We use approximate Bayesian models to support two cases of artificial transplantation and provide evidence that one of the invaded systems better represents the historic processes that maintained genetic variation within watersheds than any remaining drainages where C. santaanae is considered native. We further show that a stable dry gap in the northern range is preventing genetic dilution of pure C. santaanae persisting upstream of a hybrid assemblage involving a non-native sucker and that local accumulation of genetic variation in the same drainage is influenced by position within the network. This work has important implications for declining species that have historically relied on dendritic metapopulation networks to maintain source-sink dynamics in phasic environments, but no longer possess this capacity in urban-converted landscapes. © 2017 John Wiley & Sons Ltd.