WorldWideScience

Sample records for complexes potentiate neurodegenerative

  1. Sulforaphane as a Potential Protective Phytochemical against Neurodegenerative Diseases

    Directory of Open Access Journals (Sweden)

    Andrea Tarozzi

    2013-01-01

    Full Text Available A wide variety of acute and chronic neurodegenerative diseases, including ischemic/traumatic brain injury, Alzheimer’s disease, and Parkinson's disease, share common characteristics such as oxidative stress, misfolded proteins, excitotoxicity, inflammation, and neuronal loss. As no drugs are available to prevent the progression of these neurological disorders, intervention strategies using phytochemicals have been proposed as an alternative form of treatment. Among phytochemicals, isothiocyanate sulforaphane, derived from the hydrolysis of the glucosinolate glucoraphanin mainly present in Brassica vegetables, has demonstrated neuroprotective effects in several in vitro and in vivo studies. In particular, evidence suggests that sulforaphane beneficial effects could be mainly ascribed to its peculiar ability to activate the Nrf2/ARE pathway. Therefore, sulforaphane appears to be a promising compound with neuroprotective properties that may play an important role in preventing neurodegeneration.

  2. The potential of microRNAs as biofluid markers of neurodegenerative diseases – a systematic review

    DEFF Research Database (Denmark)

    Danborg, Pia B; Simonsen, Anja H; Waldemar, Gunhild

    2014-01-01

    monitoring. This systematic review clarifies biomarker potential of miRNAs detected in biofluids of neurodegenerative disease patients. Thirty-three and ten miRNAs displayed significant expression between patients with multiple sclerosis and Alzheimer's disease, respectively, compared to healthy controls...

  3. Therapeutic potential of systemic brain rejuvenation strategies for neurodegenerative disease [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Alana M. Horowitz

    2017-08-01

    Full Text Available Neurodegenerative diseases are a devastating group of conditions that cause progressive loss of neuronal integrity, affecting cognitive and motor functioning in an ever-increasing number of older individuals. Attempts to slow neurodegenerative disease advancement have met with little success in the clinic; however, a new therapeutic approach may stem from classic interventions, such as caloric restriction, exercise, and parabiosis. For decades, researchers have reported that these systemic-level manipulations can promote major functional changes that extend organismal lifespan and healthspan. Only recently, however, have the functional effects of these interventions on the brain begun to be appreciated at a molecular and cellular level. The potential to counteract the effects of aging in the brain, in effect rejuvenating the aged brain, could offer broad therapeutic potential to combat dementia-related neurodegenerative disease in the elderly. In particular, results from heterochronic parabiosis and young plasma administration studies indicate that pro-aging and rejuvenating factors exist in the circulation that can independently promote or reverse age-related phenotypes. The recent demonstration that human umbilical cord blood similarly functions to rejuvenate the aged brain further advances this work to clinical translation. In this review, we focus on these blood-based rejuvenation strategies and their capacity to delay age-related molecular and functional decline in the aging brain. We discuss new findings that extend the beneficial effects of young blood to neurodegenerative disease models. Lastly, we explore the translational potential of blood-based interventions, highlighting current clinical trials aimed at addressing therapeutic applications for the treatment of dementia-related neurodegenerative disease in humans.

  4. Potential application of lithium in Parkinson’s and other neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Carol A Lazzara

    2015-10-01

    Full Text Available Lithium, the long-standing hallmark treatment for bipolar disorder, has recently been identified as a potential neuroprotective agent in neurodegeneration. Here we focus on introducing numerous in vitro and in vivo studies that have shown lithium treatment to be efficacious in reducing oxidative stress and inflammation, increasing autophagy, inhibiting apoptosis, and decreasing the accumulation of α-synulcein, with an emphasis on Parkinson’s disease. A number of biological pathways have been shown to be involved in causing these neuroprotective effects. The inhibition of GSK-3β has been the mechanism most studied; however, other modes of action include the regulation of apoptotic proteins and glutamate excitotoxicity as well as down-regulation of Calpain-1. This review provides a framework of the neuroprotective effects of lithium in neurodegenerative diseases and the putative mechanisms by which lithium provides the protection. Lithium-only treatment may not be a suitable therapeutic option for neurodegenerative diseases due to inconsistent efficacy and potential side-effects, however, the use of low dose lithium in combination with other potential or existing therapeutic compounds may be a promising approach to reduce symptoms and disease progression in neurodegenerative diseases.

  5. AMPD2 regulates GTP synthesis and is mutated in a potentially treatable neurodegenerative brainstem disorder.

    Science.gov (United States)

    Akizu, Naiara; Cantagrel, Vincent; Schroth, Jana; Cai, Na; Vaux, Keith; McCloskey, Douglas; Naviaux, Robert K; Van Vleet, Jeremy; Fenstermaker, Ali G; Silhavy, Jennifer L; Scheliga, Judith S; Toyama, Keiko; Morisaki, Hiroko; Sonmez, Fatma M; Celep, Figen; Oraby, Azza; Zaki, Maha S; Al-Baradie, Raidah; Faqeih, Eissa A; Saleh, Mohammed A M; Spencer, Emily; Rosti, Rasim Ozgur; Scott, Eric; Nickerson, Elizabeth; Gabriel, Stacey; Morisaki, Takayuki; Holmes, Edward W; Gleeson, Joseph G

    2013-08-01

    Purine biosynthesis and metabolism, conserved in all living organisms, is essential for cellular energy homeostasis and nucleic acid synthesis. The de novo synthesis of purine precursors is under tight negative feedback regulation mediated by adenosine and guanine nucleotides. We describe a distinct early-onset neurodegenerative condition resulting from mutations in the adenosine monophosphate deaminase 2 gene (AMPD2). Patients have characteristic brain imaging features of pontocerebellar hypoplasia (PCH) due to loss of brainstem and cerebellar parenchyma. We found that AMPD2 plays an evolutionary conserved role in the maintenance of cellular guanine nucleotide pools by regulating the feedback inhibition of adenosine derivatives on de novo purine synthesis. AMPD2 deficiency results in defective GTP-dependent initiation of protein translation, which can be rescued by administration of purine precursors. These data suggest AMPD2-related PCH as a potentially treatable early-onset neurodegenerative disease. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. AMPD2 Regulates GTP Synthesis and is Mutated in a Potentially-Treatable Neurodegenerative Brainstem Disorder

    Science.gov (United States)

    Akizu, Naiara; Cantagrel, Vincent; Schroth, Jana; Cai, Na; Vaux, Keith; McCloskey, Douglas; Naviaux, Robert K.; Vleet, Jeremy Van; Fenstermaker, Ali G.; Silhavy, Jennifer L.; Scheliga, Judith S.; Toyama, Keiko; Morisaki, Hiroko; Sonmez, Fatma Mujgan; Celep, Figen; Oraby, Azza; Zaki, Maha S.; Al-Baradie, Raidah; Faqeih, Eissa; Saleh, Mohammad; Spencer, Emily; Rosti, Rasim Ozgur; Scott, Eric; Nickerson, Elizabeth; Gabriel, Stacey; Morisaki, Takayuki; Holmes, Edward W.; Gleeson, Joseph G.

    2013-01-01

    Purine biosynthesis and metabolism, conserved in all living organisms, is essential for cellular energy homeostasis and nucleic acids synthesis. The de novo synthesis of purine precursors is under tight negative feedback regulation mediated by adenosine and guanine nucleotides. We describe a new distinct early-onset neurodegenerative condition resulting from mutations in the adenosine monophosphate deaminase 2 gene (AMPD2). Patients have characteristic brain imaging features of pontocerebellar hypoplasia (PCH), due to loss of brainstem and cerebellar parenchyma. We found that AMPD2 plays an evolutionary conserved role in the maintenance of cellular guanine nucleotide pools by regulating the feedback inhibition of adenosine derivatives on de novo purine synthesis. AMPD2 deficiency results in defective GTP-dependent initiation of protein translation, which can be rescued by administration of purine precursors. These data suggest AMPD2-related PCH as a new, potentially treatable early-onset neurodegenerative disease. PMID:23911318

  7. Therapeutic potential of α7 nicotinic receptor agonists to regulate neuroinflammation in neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Laura Foucault-Fruchard

    2017-01-01

    Full Text Available Neurodegenerative diseases, such as Alzheimer's, Parkinson's and Huntington's diseases, are all characterized by a component of innate immunity called neuroinflammation. Neuronal loss and neuroinflammation are two phenomena closely linked. Hence, the neuroinflammation is a relevant target for the management of the neurodegenerative diseases given that, to date, there is no treatment to stop neuronal loss. Several studies have investigated the potential effects of activators of alpha 7 nicotinic acetylcholine receptors in animal models of neurodegenerative diseases. These receptors are widely distributed in the central nervous system. After activation, they seem to mediate the cholinergic anti-inflammatory pathway in the brain. This anti-inflammatory pathway, first described in periphery, regulates activation of microglial cells considered as the resident macrophage population of the central nervous system. In this article, we shortly review the agonists of the alpha 7 nicotinic acetylcholine receptors that have been evaluated in vivo and we focused on the selective positive allosteric modulators of these receptors. These compounds represent a key element to enhance receptor activity only in the presence of the endogenous agonist.

  8. Glutamate and Neurodegenerative Disease

    Science.gov (United States)

    Schaeffer, Eric; Duplantier, Allen

    As the main excitatory neurotransmitter in the mammalian central nervous system, glutamate is critically involved in most aspects of CNS function. Given this critical role, it is not surprising that glutamatergic dysfunction is associated with many CNS disorders. In this chapter, we review the literature that links aberrant glutamate neurotransmission with CNS pathology, with a focus on neurodegenerative diseases. The biology and pharmacology of the various glutamate receptor families are discussed, along with data which links these receptors with neurodegenerative conditions. In addition, we review progress that has been made in developing small molecule modulators of glutamate receptors and transporters, and describe how these compounds have helped us understand the complex pharmacology of glutamate in normal CNS function, as well as their potential for the treatment of neurodegenerative diseases.

  9. Maximizing the Potential of Longitudinal Cohorts for Research in Neurodegenerative Diseases: A Community Perspective

    Directory of Open Access Journals (Sweden)

    Catherine J. Moody

    2017-08-01

    Full Text Available Despite a wealth of activity across the globe in the area of longitudinal population cohorts, surprisingly little information is available on the natural biomedical history of a number of age-related neurodegenerative diseases (ND, and the scope for intervention studies based on these cohorts is only just beginning to be explored. The Joint Programming Initiative on Neurodegenerative Disease Research (JPND recently developed a novel funding mechanism to rapidly mobilize scientists to address these issues from a broad, international community perspective. Ten expert Working Groups, bringing together a diverse range of community members and covering a wide ND landscape [Alzheimer's, Parkinson's, frontotemporal degeneration, amyotrophic lateral sclerosis (ALS, Lewy-body and vascular dementia] were formed to discuss and propose potential approaches to better exploiting and coordinating cohort studies. The purpose of this work is to highlight the novel funding process along with a broad overview of the guidelines and recommendations generated by the ten groups, which include investigations into multiple methodologies such as cognition/functional assessment, biomarkers and biobanking, imaging, health and social outcomes, and pre-symptomatic ND. All of these were published in reports that are now publicly available online.

  10. The causative role and therapeutic potential of the kynurenine pathway in neurodegenerative disease.

    Science.gov (United States)

    Amaral, Marta; Outeiro, Tiago F; Scrutton, Nigel S; Giorgini, Flaviano

    2013-06-01

    Metabolites of the kynurenine pathway (KP), which arise from the degradation of tryptophan, have been studied in detail for over a century and garnered the interest of the neuroscience community in the late 1970s and early 1980s with work uncovering the neuromodulatory potential of this pathway. Much research in the following decades has found that perturbations in the levels of KP metabolites likely contribute to the pathogenesis of several neurodegenerative diseases. More recently, it has become apparent that targeting KP enzymes, in particular kynurenine 3-monooxygenase (KMO), may hold substantial therapeutic potential for these disorders. Here we provide an overview of the KP, the neuroactive properties of KP metabolites and their role in neurodegeneration. We also discuss KMO as a therapeutic target for these disorders, and our recent resolution of the crystallographic structure of KMO, which will permit the development of new and improved KMO inhibitors which may ultimately expedite clinical application of these compounds.

  11. Potential importance of B cells in aging and aging-associated neurodegenerative diseases.

    Science.gov (United States)

    Biragyn, Arya; Aliseychik, Maria; Rogaev, Evgeny

    2017-04-01

    Our understanding of B cells as merely antibody producers is slowly changing. Alone or in concert with antibody, they control outcomes of seemingly different diseases such as cancer, rheumatoid arthritis, diabetes, and multiple sclerosis. While their role in activation of effector immune cells is beneficial in cancer but bad in autoimmune diseases, their immunosuppressive and regulatory subsets (Bregs) inhibit autoimmune and anticancer responses. These pathogenic and suppressive functions are not static and appear to be regulated by the nature and strength of inflammation. Although aging increases inflammation and changes the composition and function of B cells, surprisingly, little is known whether the change affects aging-associated neurodegenerative disease, such as Alzheimer's disease (AD). Here, by analyzing B cells in cancer and autoimmune and neuroinflammatory diseases, we elucidate their potential importance in AD and other aging-associated neuroinflammatory diseases.

  12. A knowledge-driven interaction analysis reveals potential neurodegenerative mechanism of multiple sclerosis susceptibility.

    Science.gov (United States)

    Bush, W S; McCauley, J L; DeJager, P L; Dudek, S M; Hafler, D A; Gibson, R A; Matthews, P M; Kappos, L; Naegelin, Y; Polman, C H; Hauser, S L; Oksenberg, J; Haines, J L; Ritchie, M D

    2011-07-01

    Gene-gene interactions are proposed as an important component of the genetic architecture of complex diseases, and are just beginning to be evaluated in the context of genome-wide association studies (GWAS). In addition to detecting epistasis, a benefit to interaction analysis is that it also increases power to detect weak main effects. We conducted a knowledge-driven interaction analysis of a GWAS of 931 multiple sclerosis (MS) trios to discover gene-gene interactions within established biological contexts. We identify heterogeneous signals, including a gene-gene interaction between CHRM3 (muscarinic cholinergic receptor 3) and MYLK (myosin light-chain kinase) (joint P=0.0002), an interaction between two phospholipase C-β isoforms, PLCβ1 and PLCβ4 (joint P=0.0098), and a modest interaction between ACTN1 (actinin alpha 1) and MYH9 (myosin heavy chain 9) (joint P=0.0326), all localized to calcium-signaled cytoskeletal regulation. Furthermore, we discover a main effect (joint P=5.2E-5) previously unidentified by single-locus analysis within another related gene, SCIN (scinderin), a calcium-binding cytoskeleton regulatory protein. This work illustrates that knowledge-driven interaction analysis of GWAS data is a feasible approach to identify new genetic effects. The results of this study are among the first gene-gene interactions and non-immune susceptibility loci for MS. Further, the implicated genes cluster within inter-related biological mechanisms that suggest a neurodegenerative component to MS.

  13. Neurodegenerative Dementia

    International Nuclear Information System (INIS)

    Allard, Michelle

    2006-01-01

    Full text: With increasing life expectancy across the world, the number of elderly people at risk of developing dementia is growing rapidly. Thus, progressive neurodegenerative disorders such as dementia represent a growing public health concern. These diseases are characterized by a progressive loss in most of the cognitive functions. The promise, possibly in a near future, of disease-modifying therapies has made the characterization of the early stages of dementia a topic of major interest. The assessment of these early stages is a challenge for neuroimaging studies. In order to conceive prevention trials; it is of major outcome to fully understand the mechanisms of the cognitive system impairment and its evolution, with a particular reference to the symptomatic pre-dementia stage, when subjects just begin to depart from normality. In this article we review recent progress in neuroimaging, and their potentiality for increasing a diagnostic accuracy. (author)

  14. Therapeutic Role and Drug Delivery Potential of Neuroinflammation as a Target in Neurodegenerative Disorders.

    Science.gov (United States)

    Singh, Abhijeet; Chokriwal, Ankit; Sharma, Madan Mohan; Jain, Devendra; Saxena, Juhi; Stephen, Bjorn John

    2017-08-16

    Neuroinflammation, the condition associated with the hyperactivity of immune cells within the CNS (central nervous system), has recently been linked to a host range of neurodegenerative disorders. Targeting neuroinflammation could be of prime importance as recent research highlights the beneficial aspects associated with modulating the inflammatory mediators associated with the CNS. One of the main obstructions in neuroinflammatory treatments is the hindrance posed by the blood-brain barrier for the delivery of drugs. Hence, research has focused on novel modes of transport for drugs to cross the barrier through drug delivery and nanotechnology approaches. In this Review, we highlight the therapeutic advancement made in the field of neurodegenerative disorders by focusing on the effect neuroinflammation treatment has on these conditions.

  15. Gap junctions and hemichannels composed of connexins: potential therapeutic targets for neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Hideyuki eTakeuchi

    2014-09-01

    Full Text Available Microglia are macrophage-like resident immune cells that contribute to the maintenance of homeostasis in the central nervous system (CNS. Abnormal activation of microglia can cause damage in the CNS, and accumulation of activated microglia is a characteristic pathological observation in neurologic conditions such as trauma, stroke, inflammation, epilepsy, and neurodegenerative diseases. Activated microglia secrete high levels of glutamate, which damages CNS cells and has been implicated as a major cause of neurodegeneration in these conditions. Glutamate-receptor blockers and microglia inhibitors (e.g. minocycline have been examined as therapeutic candidates for several neurodegenerative diseases; however, these compounds exerted little therapeutic benefit because they either perturbed physiological glutamate signals or suppressed the actions of protective microglia. The ideal therapeutic approach would hamper the deleterious roles of activated microglia without diminishing their protective effects. We recently found that abnormally activated microglia secrete glutamate via gap-junction hemichannels on the cell surface. Moreover, administration of gap-junction inhibitors significantly suppressed excessive microglial glutamate release and improved disease symptoms in animal models of neurologic conditions such as stroke, multiple sclerosis, amyotrophic lateral sclerosis, and Alzheimer’s disease. Recent evidence also suggests that neuronal and glial communication via gap junctions amplifies neuroinflammation and neurodegeneration. Elucidation of the precise pathologic roles of gap junctions and hemichannels may lead to a novel therapeutic strategies that can slow and halt the progression of neurodegenerative diseases.

  16. A knowledge-driven interaction analysis reveals potential neurodegenerative mechanism of multiple sclerosis susceptibility

    NARCIS (Netherlands)

    Bush, W.S.; McCauley, J.L.; DeJager, P.L.; Dudek, S.M.; Hafler, D.A.; Gibson, R.A.; Matthews, P.M.; Kappos, L.; Naegelin, Y.; Polman, C.H.; Hauser, S.L.; Oksenberg, J.; Haines, J.L.; Ritchie, M.D.

    2011-01-01

    Gene-gene interactions are proposed as an important component of the genetic architecture of complex diseases, and are just beginning to be evaluated in the context of genome-wide association studies (GWAS). In addition to detecting epistasis, a benefit to interaction analysis is that it also

  17. Cyanotoxins at low doses induce apoptosis and inflammatory effects in murine brain cells: Potential implications for neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Larissa Takser

    Full Text Available Cyanotoxins have been shown to be highly toxic for mammalian cells, including brain cells. However, little is known about their effect on inflammatory pathways. This study investigated whether mammalian brain and immune cells can be a target of certain cyanotoxins, at doses approximating those in the guideline levels for drinking water, either alone or in mixtures. We examined the effects on cellular viability, apoptosis and inflammation signalling of several toxins on murine macrophage-like RAW264.7, microglial BV-2 and neuroblastoma N2a cell lines. We tested cylindrospermopsin (CYN, microcystin-LR (MC-LR, and anatoxin-a (ATX-a, individually as well as their mixture. In addition, we studied the neurotoxins β-N-methylamino-l-alanine (BMAA and its isomer 2,4-diaminobutyric acid (DAB, as well as the mixture of both. Cellular viability was determined by the MTT assay. Apoptosis induction was assessed by measuring the activation of caspases 3/7. Cell death and inflammation are the hallmarks of neurodegenerative diseases. Thus, our final step was to quantify the expression of a major proinflammatory cytokine TNF-α by ELISA. Our results show that CYN, MC-LR and ATX-a, but not BMAA and DAB, at low doses, especially when present in a mixture at threefold less concentrations than individual compounds are 3–15 times more potent at inducing apoptosis and inflammation. Our results suggest that common cyanotoxins at low doses have a potential to induce inflammation and apoptosis in immune and brain cells. Further research of the neuroinflammatory effects of these compounds in vivo is needed to improve safety limit levels for cyanotoxins in drinking water and food. Keywords: Cyanotoxins, Low doses, Apoptosis, Inflammation, Brain cells, Neurodegenerative diseases

  18. Theory of complex potential scattering

    International Nuclear Information System (INIS)

    Kok, L.P.; Haeringen, H.v.

    1981-01-01

    We study the effect of the addition of a complex potential lambdaV/sub sep/ to an arbitrary Schroedinger operator H = H 0 +V on the singularities of the S matrix, as a function of lambda. Here V/sub sep/ is a separable interaction, and lambda is a complex coupling parameter. The paths of these singularities are determined to a great extent by certain saddle points in the momentum (or energy) plane. We explain certain critical phenomena recently reported in the literature. Associated with these saddles are branch-type singularities in the complex lambda plane, which are dynamical in origin. Some examples are discussed in detail

  19. New hydroxypyridinone iron-chelators as potential anti-neurodegenerative drugs.

    Science.gov (United States)

    Arduino, Daniela; Silva, Daniel; Cardoso, Sandra M; Chaves, Silvia; Oliveira, Catarina R; Santos, M Amelia

    2008-05-01

    The neuroprotective action of a set of new hydroxypyridinone-based (3,4-HP) compounds (A, B and C), which are iron chelators extra-functionalized with a propargylamino group for potential MAO-B inhibition, was evaluated after cell treatment with MPP+ (an in vivo inducer of parkinsonism) and Abeta(1-40) and/or Abeta(1-42) peptides. Our results show that all these compounds improved cell viability in cells treated with MPP+ and Abeta(1-40) peptide or Abeta(1-42) peptide. In order to evaluate the cellular mechanisms underlying the activity of these compounds, we studied their protective role in caspase activation. All compounds tested were able to prevent MPP+ and Brefeldin A induced caspase-2 activation. They also showed quite effective in the inhibition of caspase-4 and caspase-3 activity, an effector caspase in the apoptotic process. Finally, detection of apoptotic-like cell death after cell exposure to MPP+ was also performed by TUNEL assay. Our results demonstrated that all tested compounds prevented DNA fragmentation by decreasing TUNEL positive cells. A, B and C were more effective than DFP (a 3,4-HP iron-chelating agent in clinical use) in MPP+ induced cell death. Therefore, these results evidenced a neuroprotective and antiapoptotic role for the compounds studied.

  20. Potential Therapeutic Effects of Curcumin, the Anti-inflammatory Agent, Against Neurodegenerative, Cardiovascular, Pulmonary, Metabolic, Autoimmune and Neoplastic Diseases

    Science.gov (United States)

    Aggarwal, Bharat B.; Harikumar, Kuzhuvelil B.

    2009-01-01

    Although safe in most cases, ancient treatments are ignored because neither their active component nor their molecular targets are well defined. This is not the case, however, with curcumin, a yellow-pigment substance and component of turmeric (Curcuma longa), which was identified more than a century ago. For centuries it has been known that turmeric exhibits anti-inflammatory activity, but extensive research performed within the past two decades has shown that the this activity of turmeric is due to curcumin, a diferuloylmethane. This agent has been shown to regulate numerous transcription factors, cytokines, protein kinases, adhesion molecules, redox status and enzymes that have been linked to inflammation. The process of inflammation has been shown to play a major role in most chronic illnesses, including neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. In the current review, we provide evidence for the potential role of curcumin in the prevention and treatment of various pro-inflammatory chronic diseases. These features, combined with the pharmacological safety and negligible cost, render curcumin an attractive agent to explore further. PMID:18662800

  1. Cyanotoxins at low doses induce apoptosis and inflammatory effects in murine brain cells: Potential implications for neurodegenerative diseases.

    Science.gov (United States)

    Takser, Larissa; Benachour, Nora; Husk, Barry; Cabana, Hubert; Gris, Denis

    2016-01-01

    Cyanotoxins have been shown to be highly toxic for mammalian cells, including brain cells. However, little is known about their effect on inflammatory pathways. This study investigated whether mammalian brain and immune cells can be a target of certain cyanotoxins, at doses approximating those in the guideline levels for drinking water, either alone or in mixtures. We examined the effects on cellular viability, apoptosis and inflammation signalling of several toxins on murine macrophage-like RAW264.7, microglial BV-2 and neuroblastoma N2a cell lines. We tested cylindrospermopsin (CYN), microcystin-LR (MC-LR), and anatoxin-a (ATX-a), individually as well as their mixture. In addition, we studied the neurotoxins β- N -methylamino-l-alanine (BMAA) and its isomer 2,4-diaminobutyric acid (DAB), as well as the mixture of both. Cellular viability was determined by the MTT assay. Apoptosis induction was assessed by measuring the activation of caspases 3/7. Cell death and inflammation are the hallmarks of neurodegenerative diseases. Thus, our final step was to quantify the expression of a major proinflammatory cytokine TNF-α by ELISA. Our results show that CYN, MC-LR and ATX-a, but not BMAA and DAB, at low doses, especially when present in a mixture at threefold less concentrations than individual compounds are 3-15 times more potent at inducing apoptosis and inflammation. Our results suggest that common cyanotoxins at low doses have a potential to induce inflammation and apoptosis in immune and brain cells. Further research of the neuroinflammatory effects of these compounds in vivo is needed to improve safety limit levels for cyanotoxins in drinking water and food.

  2. Curcumin and neurodegenerative diseases

    Science.gov (United States)

    Monroy, Adriana; Lithgow, Gordon J.; Alavez, Silvestre

    2013-01-01

    Over the last ten years curcumin has been reported to be effective against a wide variety of diseases and is characterized as having anti-carcinogenic, hepatoprotective, thrombosuppressive, cardioprotective, anti-arthritic, and anti-infectious properties. Recent studies performed in both vertebrate and invertebrate models have been conducted to determine whether curcumin was also neuroprotective. The efficacy of curcumin in several pre-clinical trials for neurodegenerative diseases has created considerable excitement mainly due to its lack of toxicity and low cost. This suggests that curcumin could be a worthy candidate for nutraceutical intervention. Since aging is a common risk factor for neurodegenerative diseases, it is possible that some compounds that target aging mechanisms could also prevent these kinds of diseases. One potential mechanism to explain several of the general health benefits associated with curcumin is that it may prevent aging-associated changes in cellular proteins that lead to protein insolubility and aggregation. This loss in protein homeostasis is associated with several age-related diseases. Recently, curcumin has been found to help maintain protein homeostasis and extend lifespan in the model invertebrate Caenorhabditis elegans. Here, we review the evidence from several animal models that curcumin improves healthspan by preventing or delaying the onset of various neurodegenerative diseases. PMID:23303664

  3. Potential contribution of the neurodegenerative disorders risk loci to cognitive performance in an elderly male gout population.

    Science.gov (United States)

    Han, Lin; Jia, Zhaotong; Cao, Chunwei; Liu, Zhen; Liu, Fuqiang; Wang, Lin; Ren, Wei; Sun, Mingxia; Wang, Baoping; Li, Changgui; Chen, Li

    2017-09-01

    Cognitive impairment has been described in elderly subjects with high normal concentrations of serum uric acid. However, it remains unclear if gout confers an increased poorer cognition than those in individuals with asymptomatic hyperuricemia. The present study aimed at evaluating cognitive function in patients suffering from gout in an elderly male population, and further investigating the genetic contributions to the risk of cognitive function.This study examined the cognitive function as assessed by Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) in 205 male gout patients and 204 controls. The genetic basis of these cognitive measures was evaluated by genome-wide association study (GWAS) data in 102 male gout patients. Furthermore, 7 loci associated with cognition in GWAS were studied for correlation with gout in 1179 male gout patients and 1848 healthy male controls.Compared with controls, gout patients had significantly lower MoCA scores [22.78 ± 3.01 vs 23.42 ± 2.95, P = .023, adjusted by age, body mass index (BMI), education, and emotional disorder]. GWAS revealed 7 single-nucleotide polymorphisms (SNPs) associations with MoCA test at a level of conventional genome-wide significance (P gout in further analysis (all P > .05).Elderly male subjects with gout exhibit accelerated decline in cognition performance. Several neurodegenerative disorders risk loci were identified for genetic contributors to cognitive performance in our Chinese elderly male gout population. Larger prospective studies of the cognitive performance and genetic analysis in gout subjects are recommended.

  4. Progranulin in neurodegenerative disease.

    Science.gov (United States)

    Petkau, Terri L; Leavitt, Blair R

    2014-07-01

    Loss-of-function mutations in the progranulin gene are a common cause of familial frontotemporal dementia (FTD). The purpose of this review is to summarize the role of progranulin in health and disease, because the field is now poised to begin examining therapeutics that alter endogenous progranulin levels. We first review the clinical and neuropathological phenotype of FTD patients carrying mutations in the progranulin gene, which suggests that progranulin-mediated neurodegeneration is multifactorial and influenced by other genetic and/or environmental factors. We then examine evidence for the role of progranulin in the brain with a focus on mouse model systems. A better understanding of the complexity of progranulin biology in the brain will help guide the development of progranulin-modulating therapies for neurodegenerative disease. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Potential contribution of the neurodegenerative disorders risk loci to cognitive performance in an elderly male gout population

    Science.gov (United States)

    Han, Lin; Jia, Zhaotong; Cao, Chunwei; Liu, Zhen; Liu, Fuqiang; Wang, Lin; Ren, Wei; Sun, Mingxia; Wang, Baoping; Li, Changgui; Chen, Li

    2017-01-01

    Abstract Cognitive impairment has been described in elderly subjects with high normal concentrations of serum uric acid. However, it remains unclear if gout confers an increased poorer cognition than those in individuals with asymptomatic hyperuricemia. The present study aimed at evaluating cognitive function in patients suffering from gout in an elderly male population, and further investigating the genetic contributions to the risk of cognitive function. This study examined the cognitive function as assessed by Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) in 205 male gout patients and 204 controls. The genetic basis of these cognitive measures was evaluated by genome-wide association study (GWAS) data in 102 male gout patients. Furthermore, 7 loci associated with cognition in GWAS were studied for correlation with gout in 1179 male gout patients and 1848 healthy male controls. Compared with controls, gout patients had significantly lower MoCA scores [22.78 ± 3.01 vs 23.42 ± 2.95, P = .023, adjusted by age, body mass index (BMI), education, and emotional disorder]. GWAS revealed 7 single-nucleotide polymorphisms (SNPs) associations with MoCA test at a level of conventional genome-wide significance (P gene (Padjusted = 4.2 × 10−9, Padjusted = 4.7 × 10–9) at 14q22. The next best signal was in RELN gene (rs155333, Padjusted = 1.3 × 10–8) at 7q22, while the other variants at rs17458357 (Padjusted = 3.98 × 10–8), rs2572683 (Padjusted = 8.9 × 10–8), rs12555895 (Padjusted = 2.6 × 10–8), and rs3764030 (Padjusted = 9.4 × 10–8) were also statistically significant. The 7 SNPs were not associated with gout in further analysis (all P > .05). Elderly male subjects with gout exhibit accelerated decline in cognition performance. Several neurodegenerative disorders risk loci were identified for genetic contributors to cognitive performance in our

  6. Autophagy and neurodegenerative disorders

    Institute of Scientific and Technical Information of China (English)

    Evangelia Kesidou; Roza Lagoudaki; Olga Touloumi; Kyriaki-Nefeli Poulatsidou; Constantina Simeonidou

    2013-01-01

    Accumulation of aberrant proteins and inclusion bodies are hallmarks in most neurodegenerative diseases. Consequently, these aggregates within neurons lead to toxic effects, overproduction of reactive oxygen species and oxidative stress. Autophagy is a significant intracel ular mechanism that removes damaged organelles and misfolded proteins in order to maintain cel homeostasis. Excessive or insufficient autophagic activity in neurons leads to altered homeostasis and influences their survival rate, causing neurodegeneration. The review article provides an update of the role of autophagic process in representative chronic and acute neurodegenerative disorders.

  7. Coenzyme Q10 effects in neurodegenerative disease

    Directory of Open Access Journals (Sweden)

    Meredith Spindler

    2009-11-01

    Full Text Available Meredith Spindler1, M Flint Beal1,2, Claire Henchcliffe1,21Department of Neurology, 2Department of Neuroscience, Weill Medical College of Cornell University, New York, NY, USAAbstract: Coenzyme Q10 (CoQ10 is an essential cofactor in the mitochondrial respiratory chain, and as a dietary supplement it has recently gained attention for its potential role in the treatment of neurodegenerative disease. Evidence for mitochondrial dysfunction in neurodegenerative disorders derives from animal models, studies of mitochondria from patients, identification of genetic defects in patients with neurodegenerative disease, and measurements of markers of oxidative stress. Studies of in vitro models of neuronal toxicity and animal models of neurodegenerative disorders have demonstrated potential neuroprotective effects of CoQ10. With this data in mind, several clinical trials of CoQ10 have been performed in Parkinson’s disease and atypical Parkinson’s syndromes, Huntington’s disease, Alzheimer disease, Friedreich’s ataxia, and amyotrophic lateral sclerosis, with equivocal findings. CoQ10 is widely available in multiple formulations and is very well tolerated with minimal adverse effects, making it an attractive potential therapy. Phase III trials of high-dose CoQ10 in large sample sizes are needed to further ascertain the effects of CoQ10 in neurodegenerative diseases.Keywords: coenzyme Q10, neurodegenerative disease, Parkinson’s disease, Huntington’s disease, mitochondrial dysfunction

  8. Aquatherapy for neurodegenerative disorders.

    Science.gov (United States)

    Plecash, Alyson R; Leavitt, Blair R

    2014-01-01

    Aquatherapy is used for rehabilitation and exercise; water provides a challenging, yet safe exercise environment for many special populations. We have reviewed the use of aquatherapy programs in four neurodegenerative disorders: Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, and Huntington's disease. Results support the use of aquatherapy in Parkinson's disease and multiple sclerosis, however further evidence is required to make specific recommendations in all of the aforementioned disorders.

  9. Complex dynamical invariants for two-dimensional complex potentials

    Indian Academy of Sciences (India)

    Abstract. Complex dynamical invariants are searched out for two-dimensional complex poten- tials using rationalization method within the framework of an extended complex phase space characterized by x = x1 + ip3, y = x2 + ip4, px = p1 + ix3, py = p2 + ix4. It is found that the cubic oscillator and shifted harmonic oscillator ...

  10. Complex trajectories in a classical periodic potential

    International Nuclear Information System (INIS)

    Anderson, Alexander G; Bender, Carl M

    2012-01-01

    This paper examines the complex trajectories of a classical particle in the potential V(x) = −cos (x). Almost all the trajectories describe a particle that hops from one well to another in an erratic fashion. However, it is shown analytically that there are two special classes of trajectories x(t) determined only by the energy of the particle and not by the initial position of the particle. The first class consists of periodic trajectories; that is, trajectories that return to their initial position x(0) after some real time T. The second class consists of trajectories for which there exists a real time T such that x(t + T) = x(t) ± 2π. These two classes of classical trajectories are analogous to valence and conduction bands in quantum mechanics, where the quantum particle either remains localized or else tunnels resonantly (conducts) through a crystal lattice. These two special types of trajectories are associated with sets of energies of measure 0. For other energies, it is shown that for long times the average velocity of the particle becomes a fractal-like function of energy. (paper)

  11. Complex trajectories in a classical periodic potential

    Science.gov (United States)

    Anderson, Alexander G.; Bender, Carl M.

    2012-11-01

    This paper examines the complex trajectories of a classical particle in the potential V(x) = -cos (x). Almost all the trajectories describe a particle that hops from one well to another in an erratic fashion. However, it is shown analytically that there are two special classes of trajectories x(t) determined only by the energy of the particle and not by the initial position of the particle. The first class consists of periodic trajectories; that is, trajectories that return to their initial position x(0) after some real time T. The second class consists of trajectories for which there exists a real time T such that x(t + T) = x(t) ± 2π. These two classes of classical trajectories are analogous to valence and conduction bands in quantum mechanics, where the quantum particle either remains localized or else tunnels resonantly (conducts) through a crystal lattice. These two special types of trajectories are associated with sets of energies of measure 0. For other energies, it is shown that for long times the average velocity of the particle becomes a fractal-like function of energy.

  12. Neuroprotective effects of the anti-cancer drug sunitinib in models of HIV neurotoxicity suggests potential for the treatment of neurodegenerative disorders.

    Science.gov (United States)

    Wrasidlo, Wolf; Crews, Leslie A; Tsigelny, Igor F; Stocking, Emily; Kouznetsova, Valentina L; Price, Diana; Paulino, Amy; Gonzales, Tania; Overk, Cassia R; Patrick, Christina; Rockenstein, Edward; Masliah, Eliezer

    2014-12-01

    Anti-retrovirals have improved and extended the life expectancy of patients with HIV. However, as this population ages, the prevalence of cognitive changes is increasing. Aberrant activation of kinases, such as receptor tyrosine kinases (RTKs) and cyclin-dependent kinase 5 (CDK5), play a role in the mechanisms of HIV neurotoxicity. Inhibitors of CDK5, such as roscovitine, have neuroprotective effects; however, CNS penetration is low. Interestingly, tyrosine kinase inhibitors (TKIs) display some CDK inhibitory activity and ability to cross the blood-brain barrier. We screened a small group of known TKIs for a candidate with additional CDK5 inhibitory activity and tested the efficacy of the candidate in in vitro and in vivo models of HIV-gp120 neurotoxicity. Among 12 different compounds, sunitinib inhibited CDK5 with an IC50 of 4.2 μM. In silico analysis revealed that, similarly to roscovitine, sunitinib fitted 6 of 10 features of the CDK5 pharmacophore. In a cell-based model, sunitinib reduced CDK5 phosphorylation (pCDK5), calpain-dependent p35/p25 conversion and protected neuronal cells from the toxic effects of gp120. In glial fibrillary acidic protein-gp120 transgenic (tg) mice, sunitinib reduced levels of pCDK5, p35/p25 and phosphorylated tau protein, along with amelioration of the neurodegenerative pathology. Compounds such as sunitinib with dual kinase inhibitory activity could ameliorate the cognitive impairment associated with chronic HIV infection of the CNS. Moreover, repositioning existing low MW compounds holds promise for the treatment of patients with neurodegenerative disorders. © 2014 The British Pharmacological Society.

  13. Performance Potential at one Complex, Specific Site

    DEFF Research Database (Denmark)

    Laursen, Bjørn

    2015-01-01

    disciplines: performance, drama, dance and music. Complex rules of “borders” between audience and actors/performers appeared to be present and active during this long happening. Different narrative genres were active simultaneously during the experimental session. A lot of complex and surprising phenomena...... and combinations of spatial, dramaturgical, narrative and interactive challenges, which appear to be of special interest for the kind of experiences an audience might gather in a site like this, originally created with totally different intentions. Or was it?...

  14. Remarks on the Schroedinger operator with singular complex potentials

    International Nuclear Information System (INIS)

    Brezis, Haim; Kato, Tosio

    1979-01-01

    To describe this method in a simple case Section 2 begin with real valued potentials. The main results in Section 2 are essentially known. In Section 3 the case of complex potentials is exposed. Schroedinger operators with complex potentials have been studied by Nelson. This results were extended. Here more general singularities are exposed

  15. Synthesis of dithiotherdithiols, potential technetium complexing agents

    International Nuclear Information System (INIS)

    Alagui, A.; Apparu, M.; Vidal, M.; Pasqualini, R.

    1991-01-01

    The following dithioetherdithiols: 2.10-dimethyl-4.8-dithiaundecane-2.10-dithiol (1), 5-butyl-3.7-dithianonane-1.9-dithiol (2) and 4.4,6.6-tetramethyl-3.7-dithianonane-1.9-dithiol (3) have been synthesized. These compounds are very attractive as potential precursors of technetiated radiopharmaceuticals. While the syntheses of compounds (1) and (2) have been achieved satisfactorily, that of (3) unfortunately could not be effected: the reaction of ethanedithiol (or of its monobenzylated or monobenzoylated derivatives) with 2.4-dimethylpentane-2.4-diol leads mostly to cyclization or fragmentation products [fr

  16. Level crossings in complex two-dimensional potentials

    Indian Academy of Sciences (India)

    Two-dimensional P T -symmetric quantum-mechanical systems with the complex cubic potential 12 = 2 + 2 + 2 and the complex Hénon–Heiles potential HH = 2 + 2 + (2 − 3/3) are investigated. Using numerical and perturbative methods, energy spectra are obtained to high levels. Although both ...

  17. Poles of the S matrix for a complex potential

    International Nuclear Information System (INIS)

    Dabrowski, J.

    1996-01-01

    Trajectories of S matrix poles in complex k plane are presented for a complex square well potential. A simple rule is given for predicting the effect of an absorptive potential on the location of these poles. copyright 1996 The American Physical Society

  18. DNA damage in neurodegenerative diseases

    Energy Technology Data Exchange (ETDEWEB)

    Coppedè, Fabio, E-mail: fabio.coppede@med.unipi.it; Migliore, Lucia, E-mail: lucia.migliore@med.unipi.it

    2015-06-15

    Highlights: • Oxidative DNA damage is one of the earliest detectable events in the neurodegenerative process. • The mitochondrial DNA is more vulnerable to oxidative attack than the nuclear DNA. • Cytogenetic damage has been largely documented in Alzheimer's disease patients. • The question of whether DNA damage is cause or consequence of neurodegeneration is still open. • Increasing evidence links DNA damage and repair with epigenetic phenomena. - Abstract: Following the observation of increased oxidative DNA damage in nuclear and mitochondrial DNA extracted from post-mortem brain regions of patients affected by neurodegenerative diseases, the last years of the previous century and the first decade of the present one have been largely dedicated to the search of markers of DNA damage in neuronal samples and peripheral tissues of patients in early, intermediate or late stages of neurodegeneration. Those studies allowed to demonstrate that oxidative DNA damage is one of the earliest detectable events in neurodegeneration, but also revealed cytogenetic damage in neurodegenerative conditions, such as for example a tendency towards chromosome 21 malsegregation in Alzheimer's disease. As it happens for many neurodegenerative risk factors the question of whether DNA damage is cause or consequence of the neurodegenerative process is still open, and probably both is true. The research interest in markers of oxidative stress was shifted, in recent years, towards the search of epigenetic biomarkers of neurodegenerative disorders, following the accumulating evidence of a substantial contribution of epigenetic mechanisms to learning, memory processes, behavioural disorders and neurodegeneration. Increasing evidence is however linking DNA damage and repair with epigenetic phenomena, thereby opening the way to a very attractive and timely research topic in neurodegenerative diseases. We will address those issues in the context of Alzheimer's disease

  19. DNA damage in neurodegenerative diseases

    International Nuclear Information System (INIS)

    Coppedè, Fabio; Migliore, Lucia

    2015-01-01

    Highlights: • Oxidative DNA damage is one of the earliest detectable events in the neurodegenerative process. • The mitochondrial DNA is more vulnerable to oxidative attack than the nuclear DNA. • Cytogenetic damage has been largely documented in Alzheimer's disease patients. • The question of whether DNA damage is cause or consequence of neurodegeneration is still open. • Increasing evidence links DNA damage and repair with epigenetic phenomena. - Abstract: Following the observation of increased oxidative DNA damage in nuclear and mitochondrial DNA extracted from post-mortem brain regions of patients affected by neurodegenerative diseases, the last years of the previous century and the first decade of the present one have been largely dedicated to the search of markers of DNA damage in neuronal samples and peripheral tissues of patients in early, intermediate or late stages of neurodegeneration. Those studies allowed to demonstrate that oxidative DNA damage is one of the earliest detectable events in neurodegeneration, but also revealed cytogenetic damage in neurodegenerative conditions, such as for example a tendency towards chromosome 21 malsegregation in Alzheimer's disease. As it happens for many neurodegenerative risk factors the question of whether DNA damage is cause or consequence of the neurodegenerative process is still open, and probably both is true. The research interest in markers of oxidative stress was shifted, in recent years, towards the search of epigenetic biomarkers of neurodegenerative disorders, following the accumulating evidence of a substantial contribution of epigenetic mechanisms to learning, memory processes, behavioural disorders and neurodegeneration. Increasing evidence is however linking DNA damage and repair with epigenetic phenomena, thereby opening the way to a very attractive and timely research topic in neurodegenerative diseases. We will address those issues in the context of Alzheimer's disease

  20. Convergent molecular defects underpin diverse neurodegenerative diseases.

    Science.gov (United States)

    Tofaris, George K; Buckley, Noel J

    2018-02-19

    In our ageing population, neurodegenerative disorders carry an enormous personal, societal and economic burden. Although neurodegenerative diseases are often thought of as clinicopathological entities, increasing evidence suggests a considerable overlap in the molecular underpinnings of their pathogenesis. Such overlapping biological processes include the handling of misfolded proteins, defective organelle trafficking, RNA processing, synaptic health and neuroinflammation. Collectively but in different proportions, these biological processes in neurons or non-neuronal cells lead to regionally distinct patterns of neuronal vulnerability and progression of pathology that could explain the disease symptomology. With the advent of patient-derived cellular models and novel genetic manipulation tools, we are now able to interrogate this commonality despite the cellular complexity of the brain in order to develop novel therapeutic strategies to prevent or arrest neurodegeneration. Here, we describe broadly these concepts and their relevance across neurodegenerative diseases. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  1. Oxidative stress treatment for clinical trials in neurodegenerative diseases.

    Science.gov (United States)

    Ienco, Elena Caldarazzo; LoGerfo, Annalisa; Carlesi, Cecilia; Orsucci, Daniele; Ricci, Giulia; Mancuso, Michelangelo; Siciliano, Gabriele

    2011-01-01

    Oxidative stress is a metabolic condition arising from imbalance between the production of potentially reactive oxygen species and the scavenging activities. Mitochondria are the main providers but also the main scavengers of cell oxidative stress. The role of mitochondrial dysfunction and oxidative stress in the pathogenesis of neurodegenerative diseases is well documented. Therefore, therapeutic approaches targeting mitochondrial dysfunction and oxidative damage hold great promise in neurodegenerative diseases. Despite this evidence, human experience with antioxidant neuroprotectants has generally been negative with regards to the clinical progress of disease, with unclear results in biochemical assays. Here we review the antioxidant approaches performed so far in neurodegenerative diseases and the future challenges in modern medicine.

  2. Aptamer and its applications in neurodegenerative diseases.

    Science.gov (United States)

    Qu, Jing; Yu, Shuqing; Zheng, Yuan; Zheng, Yan; Yang, Hui; Zhang, Jianliang

    2017-02-01

    Aptamers are small single-stranded DNA or RNA oligonucleotide fragments or small peptides, which can bind to targets by high affinity and specificity. Because aptamers are specific, non-immunogenic and non-toxic, they are ideal materials for clinical applications. Neurodegenerative disorders are ravaging the lives of patients. Even though the mechanism of these diseases is still elusive, they are mainly characterized by the accumulation of misfolded proteins in the central nervous system. So it is essential to develop potential measures to slow down or prevent the onset of these diseases. With the advancements of the technologies, aptamers have opened up new areas in this research field. Aptamers could bind with these related target proteins to interrupt their accumulation, subsequently blocking or preventing the process of neurodegenerative diseases. This review presents recent advances in the aptamer generation and its merits and limitations, with emphasis on its applications in neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, transmissible spongiform encephalopathy, Huntington's disease and multiple sclerosis.

  3. The uranium potential of the Bushveld igneous complex

    International Nuclear Information System (INIS)

    Andreoli, M.A.G.; Hart, R.J.; Brynard, H.J.; Camisani-Calzolari, F.A.G.M.

    1987-06-01

    A review of published literature supported by field observations on the uranium potential of the Bushveld Complex indicates that this geological region may host deposits with reserves in the range of a few thousand tons U 3 O 8 . The possibility that the Bushveld Complex or its cover rocks hosts, or has ever hosted in the past, giant uranium deposits such as those of Olympic Dam, Key Lake, Jabiluka or Rossing is considered to be unlikely. The potential for volcanogenic, caldera-type deposits in the Rooiberg Felsites remains at present untested. Recommendations for research currently sponsored by the AEC at the University of Pretoria are presented

  4. Lack of miRNA misregulation at early pathological stages in Drosophila neurodegenerative disease models

    Directory of Open Access Journals (Sweden)

    Anita eReinhardt

    2012-10-01

    Full Text Available Late onset neurodegenerative diseases represent a major public health concern as the population in many countries ages. Both frequent diseases such as Alzheimer disease (AD, 14% incidence for 80-84 year old Europeans or Parkinson disease (PD, 1.4% prevalence for > 55 years old share, with other low-incidence neurodegenerative pathologies such as spinocerebellar ataxias (SCAs, 0.01% prevalence and frontotemporal lobar degeneration (FTLD, 0.02% prevalence, a lack of efficient treatment in spite of important research efforts. Besides significant progress, studies with animal models have revealed unexpected complexities in the degenerative process, emphasizing a need to better understand the underlying pathological mechanisms. Recently, microRNAs, a class of small regulatory non-coding RNAs, have been implicated in some neurodegenerative diseases. The current data supporting a role of miRNAs in PD, tauopathies, dominant ataxias and FTLD will first be discussed to emphasize the different levels of the pathological processes which may be affected by miRNAs. To investigate a potential involvement of miRNA dysregulation in the early stages of these neurodegenerative diseases we have used Drosophila models for 7 diseases (PD, 3 FTLD, 3 dominant ataxias that recapitulate many features of the human diseases. We performed deep sequencing of head small RNAs after 3 days of pathological protein expression in the fly head neurons. We found no evidence for a statistically significant difference in miRNA expression in this early stage of the pathological process. In addition, we could not identify small non coding CAG repeat RNAs (sCAG in polyQ disease models. Thus our data suggest that transcriptional deregulation of miRNAs or sCAG is unlikely to play a significant role in the initial stages of neurodegenerative diseases.

  5. Molecular diagnostics of neurodegenerative disorders

    Directory of Open Access Journals (Sweden)

    Megha eAgrawal

    2015-09-01

    Full Text Available Molecular diagnostics provide a powerful method to detect and diagnose various neurological diseases such as Alzheimer’s and Parkinson’s disease. The confirmation of such diagnosis allows early detection and subsequent medical counseling that help specific patients to undergo clinically important drug trials. This provides a medical pathway to have better insight of neurogenesis and eventual cure of the neurodegenerative diseases. In this short review, we present recent advances in molecular diagnostics especially biomarkers and imaging spectroscopy for neurological diseases. We describe advances made in Alzheimer’s disease, Parkinson’s disease, Amyotrophic lateral sclerosis and Huntington’s disease, and finally present a perspective on the future directions to provide a framework for further developments and refinements of molecular diagnostics to combat neurodegenerative disorders.

  6. Molecular diagnostics of neurodegenerative disorders.

    Science.gov (United States)

    Agrawal, Megha; Biswas, Abhijit

    2015-01-01

    Molecular diagnostics provide a powerful method to detect and diagnose various neurological diseases such as Alzheimer's and Parkinson's disease. The confirmation of such diagnosis allows early detection and subsequent medical counseling that help specific patients to undergo clinically important drug trials. This provides a medical pathway to have better insight of neurogenesis and eventual cure of the neurodegenerative diseases. In this short review, we present recent advances in molecular diagnostics especially biomarkers and imaging spectroscopy for neurological diseases. We describe advances made in Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD), and finally present a perspective on the future directions to provide a framework for further developments and refinements of molecular diagnostics to combat neurodegenerative disorders.

  7. Essential Tremor: A Neurodegenerative Disease?

    Directory of Open Access Journals (Sweden)

    Julian Benito-Leon

    2014-07-01

    Full Text Available Background: Essential tremor (ET is one of the most common neurological disorders among adults, and is the most common of the many tremor disorders. It has classically been viewed as a benign monosymptomatic condition, yet over the past decade, a growing body of evidence indicates that ET is a progressive condition that is clinically heterogeneous, as it may be associated with a spectrum of clinical features, with both motor and non‐motor elements. In this review, I will describe the most significant emerging milestones in research which, when taken together, suggest that ET is a neurodegenerative condition.Methods: A PubMed search conducted in June 2014 crossing the terms “essential tremor” (ET and “neurodegenerative” yielded 122 entries, 20 of which included the term “neurodegenerative” in the article title. This was supplemented by articles in the author's files that pertained to this topic.Results/Discussion: There is an open and active dialogue in the medical community as to whether ET is a neurodegenerative disease, with considerable evidence in favor of this. Specifically, ET is a progressive disorder of aging associated with neuronal loss (reduction in Purkinje cells as well as other post‐mortem changes that occur in traditional neurodegenerative disorders. Along with this, advanced neuroimaging techniques are now demonstrating distinct structural changes, several of which are consistent with neuronal loss, in patients with ET. However, further longitudinal clinical and neuroimaging longitudinal studies to assess progression are required.

  8. Post-prior equivalence for transfer reactions with complex potentials

    Science.gov (United States)

    Lei, Jin; Moro, Antonio M.

    2018-01-01

    In this paper, we address the problem of the post-prior equivalence in the calculation of inclusive breakup and transfer cross sections. For that, we employ the model proposed by Ichimura et al. [Phys. Rev. C 32, 431 (1985), 10.1103/PhysRevC.32.431], conveniently generalized to include the part of the cross section corresponding the transfer to bound states. We pay particular attention to the case in which the unobserved particle is left in a bound state of the residual nucleus, in which case the theory prescribes the use of a complex potential, responsible for the spreading width of the populated single-particle states. We see that the introduction of this complex potential gives rise to an additional term in the prior cross-section formula, not present in the usual case of real binding potentials. The equivalence is numerically tested for the 58Ni(d ,p X ) reaction.

  9. Neuroimaging Biomarkers of Neurodegenerative Diseases and Dementia

    OpenAIRE

    Risacher, Shannon L.; Saykin, Andrew J.

    2013-01-01

    Neurodegenerative disorders leading to dementia are common diseases that affect many older and some young adults. Neuroimaging methods are important tools for assessing and monitoring pathological brain changes associated with progressive neurodegenerative conditions. In this review, the authors describe key findings from neuroimaging studies (magnetic resonance imaging and radionucleotide imaging) in neurodegenerative disorders, including Alzheimer’s disease (AD) and prodromal stages, famili...

  10. Potential Trace Metal–Organic Complexation in the Atmosphere

    Directory of Open Access Journals (Sweden)

    Hiroshi Okochi

    2002-01-01

    Full Text Available It is possible that metal–organic complexation enhances the uptake of gaseous organic compounds and the solubility of metals in aerosols and atmospheric water. We investigated potential atmospheric organic ligands and the enhanced uptake of hydroxy-, oxo-, and dicarboxylic acids as well as dicarbonyls into atmospheric aqueous aerosol. We examined complexation with transition metals (iron, manganese, nickel, copper, zinc and lead on the basis of available references and our experimental data. Humic-like substances are most likely ligands in the atmosphere, although this is a poorly characterized material. A number of polycarboxylic acids and hydroxy forms (e.g., citric and tartronic acids effectively complex metals such as copper in atmospheric aerosols. The simple equilibrium model calculations show that the effect of the complexation on the gas–aqueous phase partition of gaseous atmospheric ligands is quite small for the ligands with the high physical Henry’s law constants, e.g., dicarboxylic acids represented by oxalic acid, even if they have high affinity with metal ions. The lower Henry’s law constants of the α-dicarbonyls, such as glyoxal and methylglyoxal, mean that the complexation could lead to profound increases in their partition into the aqueous phase. Despite quantum mechanical arguments for copper–glyoxal complexes, experiments showed no evidence of complexation between either hydrated or unhydrated α-dicarbonyls and the cupric ion. By contrast the β-dicarbonyl, malondialdehyde, has properties that would allow it to partition into atmospheric water via the complexation with metal ions under some conditions.

  11. Determinantal method for complex angular momenta in potential scattering

    Energy Technology Data Exchange (ETDEWEB)

    Lee, B. W. [University of Pennsylvania, Philadelphia, PA (United States)

    1963-01-15

    In this paper I would like do describe a formulation of the complex angular momenta in potential scattering based on the Lippmann-Schwinger integral equation rather than on the Schrödinger differential equation. This is intended as a preliminary to the paper by SAWYER on the Regge poles and high energy limits in field theory (Bethe-Salpeter amplitudes), where the integral formulation is definitely more advantageous than the differential formulation.

  12. Unsteady subsonic and supersonic potential aerodynamics for complex configurations

    Science.gov (United States)

    Morino, L.; Tseng, K.

    1977-01-01

    A recently developed general theory for unsteady compressible potential fluid dynamics for complex-configuration aircraft is reviewed. The method is based on a combination of the following techniques: Green's function method (to transform the differential equation into an integral differential-delay equation), finite element method (to transform the equation into a set of differential-delay equations in time), and the Laplace transform method (to transform the differential-delay equations into algebraic equations).

  13. [Retinal imaging of the macula and optic disc in neurodegenerative diseases].

    Science.gov (United States)

    Turski, G N; Schmitz-Valckenberg, S; Holz, F G; Finger, R P

    2017-02-01

    Due to current demographic trends, the prevalence of mild cognitive impairment and dementia is expected to increase considerably. For potential new therapies it is important to identify patients at risk as early as possible. Currently, there is no population-based screening. Therefore, identification of biomarkers that will help screen the population at risk is urgently needed. Thus, a literature review on retinal pathology in neurodegenerative diseases was performed. PubMed was searched for studies published up to August 2016 using the following keywords: "mild cognitive impairment", "dementia", "eye", "ocular biomarkers", "OCT" and "OCT angiography". Relevant publications were selected and summarized qualitatively. Multiple studies using noninvasive in vivo optical coherence tomography (OCT) imaging showed nonspecific retinal pathological changes in patients with neurodegenerative diseases such as mild cognitive impairment, Alzheimer's and Parkinson's disease. Pathological changes in macular volume, optic nerve fiber layer thickness and the ganglion cell complex were observed. However, based on available evidence, no ocular biomarkers for neurodegeneration which could be integrated in routine clinical diagnostics have been identified. The potential use of OCT in the early diagnostic workup and monitoring of progression of neurodegenerative diseases needs to be further explored in longitudinal studies with large cohorts.

  14. Strategic directions of personnel potential forming of a building complex

    Directory of Open Access Journals (Sweden)

    Simonova Marina

    2016-01-01

    Full Text Available The analysis of directions of strategic approach forming of labor potential management of a building complex is carried out in this paper. On the basis of this analysis the system of actions for strategy forming divided into consecutive stages is offered. The development of the personnel forecast is a strategic planning basis. One of personnel forecast variants is the correlation of needs estimates in personnel of a building complex with available allowances. On the basis of the personnel forecast strategic analysis it is possible to compose working programs for the stated goals of implementation. Operational assessment of personnel requirements of a building complex is proved to be combined with strategic objectives. Some assessment approaches to qualitative and quantitative need for specialists of a building complex are offered. The fact that high-quality labor power supply system of a building complex with should be based on industry development forecast and increase in construction products competitiveness is revealed in the article. Strategic management priority will allow to react immediately to the current situation changes, to introduce amendments both into tactical, and operational management.

  15. Motor Phenotype in Neurodegenerative Disorders: Gait and Balance Platform Study Design Protocol for the Ontario Neurodegenerative Research Initiative (ONDRI).

    Science.gov (United States)

    Montero-Odasso, Manuel; Pieruccini-Faria, Frederico; Bartha, Robert; Black, Sandra E; Finger, Elizabeth; Freedman, Morris; Greenberg, Barry; Grimes, David A; Hegele, Robert A; Hudson, Christopher; Kleinstiver, Peter W; Lang, Anthony E; Masellis, Mario; McLaughlin, Paula M; Munoz, Douglas P; Strother, Stephen; Swartz, Richard H; Symons, Sean; Tartaglia, Maria Carmela; Zinman, Lorne; Strong, Michael J; McIlroy, William

    2017-01-01

    The association of cognitive and motor impairments in Alzheimer's disease and other neurodegenerative diseases is thought to be related to damage in the common brain networks shared by cognitive and cortical motor control processes. These common brain networks play a pivotal role in selecting movements and postural synergies that meet an individual's needs. Pathology in this "highest level" of motor control produces abnormalities of gait and posture referred to as highest-level gait disorders. Impairments in cognition and mobility, including falls, are present in almost all neurodegenerative diseases, suggesting common mechanisms that still need to be unraveled. To identify motor-cognitive profiles across neurodegenerative diseases in a large cohort of patients. Cohort study that includes up to 500 participants, followed every year for three years, across five neurodegenerative disease groups: Alzheimer's disease/mild cognitive impairment, frontotemporal degeneration, vascular cognitive impairment, amyotrophic lateral sclerosis, and Parkinson's disease. Gait and balance will be assessed using accelerometers and electronic walkways, evaluated at different levels of cognitive and sensory complexity, using the dual-task paradigm. Comparison of cognitive and motor performances across neurodegenerative groups will allow the identification of motor-cognitive phenotypes through the standardized evaluation of gait and balance characteristics. As part of the Ontario Neurodegenerative Research Initiative (ONDRI), the gait and balance platform aims to identify motor-cognitive profiles across neurodegenerative diseases. Gait assessment, particularly while dual-tasking, will help dissect the cognitive and motor contribution in mobility and cognitive decline, progression to dementia syndromes, and future adverse outcomes including falls and mortality.

  16. Heat shock protein 90 in neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Rodina Anna

    2010-06-01

    Full Text Available Abstract Hsp90 is a molecular chaperone with important roles in regulating pathogenic transformation. In addition to its well-characterized functions in malignancy, recent evidence from several laboratories suggests a role for Hsp90 in maintaining the functional stability of neuronal proteins of aberrant capacity, whether mutated or over-activated, allowing and sustaining the accumulation of toxic aggregates. In addition, Hsp90 regulates the activity of the transcription factor heat shock factor-1 (HSF-1, the master regulator of the heat shock response, mechanism that cells use for protection when exposed to conditions of stress. These biological functions therefore propose Hsp90 inhibition as a dual therapeutic modality in neurodegenerative diseases. First, by suppressing aberrant neuronal activity, Hsp90 inhibitors may ameliorate protein aggregation and its associated toxicity. Second, by activation of HSF-1 and the subsequent induction of heat shock proteins, such as Hsp70, Hsp90 inhibitors may redirect neuronal aggregate formation, and protect against protein toxicity. This mini-review will summarize our current knowledge on Hsp90 in neurodegeneration and will focus on the potential beneficial application of Hsp90 inhibitors in neurodegenerative diseases.

  17. Chameleon sequences in neurodegenerative diseases

    International Nuclear Information System (INIS)

    Bahramali, Golnaz; Goliaei, Bahram; Minuchehr, Zarrin; Salari, Ali

    2016-01-01

    Chameleon sequences can adopt either alpha helix sheet or a coil conformation. Defining chameleon sequences in PDB (Protein Data Bank) may yield to an insight on defining peptides and proteins responsible in neurodegeneration. In this research, we benefitted from the large PDB and performed a sequence analysis on Chameleons, where we developed an algorithm to extract peptide segments with identical sequences, but different structures. In order to find new chameleon sequences, we extracted a set of 8315 non-redundant protein sequences from the PDB with an identity less than 25%. Our data was classified to “helix to strand (HE)”, “helix to coil (HC)” and “strand to coil (CE)” alterations. We also analyzed the occurrence of singlet and doublet amino acids and the solvent accessibility in the chameleon sequences; we then sorted out the proteins with the most number of chameleon sequences and named them Chameleon Flexible Proteins (CFPs) in our dataset. Our data revealed that Gly, Val, Ile, Tyr and Phe, are the major amino acids in Chameleons. We also found that there are proteins such as Insulin Degrading Enzyme IDE and GTP-binding nuclear protein Ran (RAN) with the most number of chameleons (640 and 405 respectively). These proteins have known roles in neurodegenerative diseases. Therefore it can be inferred that other CFP's can serve as key proteins in neurodegeneration, and a study on them can shed light on curing and preventing neurodegenerative diseases.

  18. Chameleon sequences in neurodegenerative diseases.

    Science.gov (United States)

    Bahramali, Golnaz; Goliaei, Bahram; Minuchehr, Zarrin; Salari, Ali

    2016-03-25

    Chameleon sequences can adopt either alpha helix sheet or a coil conformation. Defining chameleon sequences in PDB (Protein Data Bank) may yield to an insight on defining peptides and proteins responsible in neurodegeneration. In this research, we benefitted from the large PDB and performed a sequence analysis on Chameleons, where we developed an algorithm to extract peptide segments with identical sequences, but different structures. In order to find new chameleon sequences, we extracted a set of 8315 non-redundant protein sequences from the PDB with an identity less than 25%. Our data was classified to "helix to strand (HE)", "helix to coil (HC)" and "strand to coil (CE)" alterations. We also analyzed the occurrence of singlet and doublet amino acids and the solvent accessibility in the chameleon sequences; we then sorted out the proteins with the most number of chameleon sequences and named them Chameleon Flexible Proteins (CFPs) in our dataset. Our data revealed that Gly, Val, Ile, Tyr and Phe, are the major amino acids in Chameleons. We also found that there are proteins such as Insulin Degrading Enzyme IDE and GTP-binding nuclear protein Ran (RAN) with the most number of chameleons (640 and 405 respectively). These proteins have known roles in neurodegenerative diseases. Therefore it can be inferred that other CFP's can serve as key proteins in neurodegeneration, and a study on them can shed light on curing and preventing neurodegenerative diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Tau imaging in neurodegenerative diseases

    Energy Technology Data Exchange (ETDEWEB)

    Dani, M.; Edison, P. [Imperial College London, Neurology Imaging Unit, Division of Neuroscience, London (United Kingdom); Brooks, D.J. [Imperial College London, Neurology Imaging Unit, Division of Neuroscience, London (United Kingdom); Aarhus University, Institute of Clinical Medicine, Aarhus (Denmark)

    2016-06-15

    Aggregated tau protein is a major neuropathological substrate central to the pathophysiology of neurodegenerative diseases such as Alzheimer's disease (AD), frontotemporal dementia, progressive supranuclear palsy, corticobasal degeneration and chronic traumatic encephalopathy. In AD, it has been shown that the density of hyperphosphorylated tau tangles correlates closely with neuronal dysfunction and cell death, unlike β-amyloid. Until now, diagnostic and pathologic information about tau deposition has only been available from invasive techniques such as brain biopsy or autopsy. The recent development of selective in-vivo tau PET imaging ligands including [{sup 18}F]THK523, [{sup 18}F]THK5117, [{sup 18}F]THK5105 and [{sup 18}F]THK5351, [{sup 18}F]AV1451(T807) and [{sup 11}C]PBB3 has provided information about the role of tau in the early phases of neurodegenerative diseases, and provided support for diagnosis, prognosis, and imaging biomarkers to track disease progression. Moreover, the spatial and longitudinal relationship of tau distribution compared with β - amyloid and other pathologies in these diseases can be mapped. In this review, we discuss the role of aggregated tau in tauopathies, the challenges posed in developing selective tau ligands as biomarkers, the state of development in tau tracers, and the new clinical information that has been uncovered, as well as the opportunities for improving diagnosis and designing clinical trials in the future. (orig.)

  20. Chameleon sequences in neurodegenerative diseases

    Energy Technology Data Exchange (ETDEWEB)

    Bahramali, Golnaz [Institute of Biochemistry and Biophysics, University of Tehran, Tehran (Iran, Islamic Republic of); Goliaei, Bahram, E-mail: goliaei@ut.ac.ir [Institute of Biochemistry and Biophysics, University of Tehran, Tehran (Iran, Islamic Republic of); Minuchehr, Zarrin, E-mail: minuchehr@nigeb.ac.ir [Department of Systems Biotechnology, National Institute of Genetic Engineering and Biotechnology, (NIGEB), Tehran (Iran, Islamic Republic of); Salari, Ali [Department of Systems Biotechnology, National Institute of Genetic Engineering and Biotechnology, (NIGEB), Tehran (Iran, Islamic Republic of)

    2016-03-25

    Chameleon sequences can adopt either alpha helix sheet or a coil conformation. Defining chameleon sequences in PDB (Protein Data Bank) may yield to an insight on defining peptides and proteins responsible in neurodegeneration. In this research, we benefitted from the large PDB and performed a sequence analysis on Chameleons, where we developed an algorithm to extract peptide segments with identical sequences, but different structures. In order to find new chameleon sequences, we extracted a set of 8315 non-redundant protein sequences from the PDB with an identity less than 25%. Our data was classified to “helix to strand (HE)”, “helix to coil (HC)” and “strand to coil (CE)” alterations. We also analyzed the occurrence of singlet and doublet amino acids and the solvent accessibility in the chameleon sequences; we then sorted out the proteins with the most number of chameleon sequences and named them Chameleon Flexible Proteins (CFPs) in our dataset. Our data revealed that Gly, Val, Ile, Tyr and Phe, are the major amino acids in Chameleons. We also found that there are proteins such as Insulin Degrading Enzyme IDE and GTP-binding nuclear protein Ran (RAN) with the most number of chameleons (640 and 405 respectively). These proteins have known roles in neurodegenerative diseases. Therefore it can be inferred that other CFP's can serve as key proteins in neurodegeneration, and a study on them can shed light on curing and preventing neurodegenerative diseases.

  1. Ketogenic Diet in Neuromuscular and Neurodegenerative Diseases

    Science.gov (United States)

    Damiani, Ernesto; Bosco, Gerardo

    2014-01-01

    An increasing number of data demonstrate the utility of ketogenic diets in a variety of metabolic diseases as obesity, metabolic syndrome, and diabetes. In regard to neurological disorders, ketogenic diet is recognized as an effective treatment for pharmacoresistant epilepsy but emerging data suggests that ketogenic diet could be also useful in amyotrophic lateral sclerosis, Alzheimer, Parkinson's disease, and some mitochondriopathies. Although these diseases have different pathogenesis and features, there are some common mechanisms that could explain the effects of ketogenic diets. These mechanisms are to provide an efficient source of energy for the treatment of certain types of neurodegenerative diseases characterized by focal brain hypometabolism; to decrease the oxidative damage associated with various kinds of metabolic stress; to increase the mitochondrial biogenesis pathways; and to take advantage of the capacity of ketones to bypass the defect in complex I activity implicated in some neurological diseases. These mechanisms will be discussed in this review. PMID:25101284

  2. The uranium potential of the Bushveld Complex, South Africa

    International Nuclear Information System (INIS)

    Simpson, P.R.

    1986-04-01

    This paper presents a summary on much of the existing geochemical data on the siliceous components of the Bushveld Complex (i.e., the felsites, granophyres and granites) with a view to establishing the U potential of the district. Although very few U analyses are actually available, sophisticated normalised data plots are utilized to estimate the probable U contents of the rock types. The members of the siliceous suite exhibit a gradual chemical evolution through time and illustrates that the most evolved members of the suite probably contained the highest primary U contents. It is emphasized that most known Bushveld Sn and F occurrences, with which U is likely to be associated, and most of the recognized radiometric anomalies in the complex, are concentrated along major lineaments. In this respect the Murchison and Franspoort directions are considered to be particularly important. In conclusion the argument follows that the potential for undiscovered hydrothermal U ores in the Bushveld Complex is high, and that five factors will probably control the location of such deposits. These factors include: 1. Sn, F and LIL-enriched source granite; 2. High post-emplacement heat production to promote the development of post-emplacement mineralizing systems; 3. A tectonically unstable source region with major fracture zones; 4. Suitable trap environments in the granites and their country rocks; 5. A source of fluids from aquifers in the granite aureole

  3. Therapeutic potential of Mediator complex subunits in metabolic diseases.

    Science.gov (United States)

    Ranjan, Amol; Ansari, Suraiya A

    2018-01-01

    The multisubunit Mediator is an evolutionary conserved transcriptional coregulatory complex in eukaryotes. It is needed for the transcriptional regulation of gene expression in general as well as in a gene specific manner. Mediator complex subunits interact with different transcription factors as well as components of RNA Pol II transcription initiation complex and in doing so act as a bridge between gene specific transcription factors and general Pol II transcription machinery. Specific interaction of various Mediator subunits with nuclear receptors (NRs) and other transcription factors involved in metabolism has been reported in different studies. Evidences indicate that ligand-activated NRs recruit Mediator complex for RNA Pol II-dependent gene transcription. These NRs have been explored as therapeutic targets in different metabolic diseases; however, they show side-effects as targets due to their overlapping involvement in different signaling pathways. Here we discuss the interaction of various Mediator subunits with transcription factors involved in metabolism and whether specific interaction of these transcription factors with Mediator subunits could be potentially utilized as therapeutic strategy in a variety of metabolic diseases. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  4. Complex-potential description of the damped harmonic oscillator

    International Nuclear Information System (INIS)

    Exner, P.

    1981-01-01

    Multidimensional damped harmonic oscillator is treated by means of a non-selfadjoint Hamiltonian with complex potential. The latter is chosen as V(x)=xx(A-iW)x with positive matrices A, W, By a perturbation-theory argument, the corresponding Hamiltonian H=-1/2Δ+V with the natural domain is shown to be closed and such that Vsub(t)=exp(-iHt) is a continuous contractive semigroup. Explicit integral-operator form of Vsub(t) is found by use of Lie-Trotter formula [ru

  5. Role of sigma-1 receptors in neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Linda Nguyen

    2015-01-01

    Full Text Available Neurodegenerative diseases with distinct genetic etiologies and pathological phenotypes appear to share common mechanisms of neuronal cellular dysfunction, including excitotoxicity, calcium dysregulation, oxidative damage, ER stress and mitochondrial dysfunction. Glial cells, including microglia and astrocytes, play an increasingly recognized role in both the promotion and prevention of neurodegeneration. Sigma receptors, particularly the sigma-1 receptor subtype, which are expressed in both neurons and glia of multiple regions within the central nervous system, are a unique class of intracellular proteins that can modulate many biological mechanisms associated with neurodegeneration. These receptors therefore represent compelling putative targets for pharmacologically treating neurodegenerative disorders. In this review, we provide an overview of the biological mechanisms frequently associated with neurodegeneration, and discuss how sigma-1 receptors may alter these mechanisms to preserve or restore neuronal function. In addition, we speculate on their therapeutic potential in the treatment of various neurodegenerative disorders.

  6. Sleep disturbance in mental health problems and neurodegenerative disease

    Directory of Open Access Journals (Sweden)

    Anderson KN

    2013-05-01

    Full Text Available Kirstie N Anderson1 Andrew J Bradley2,3 1Department of Neurology, Newcastle Upon Tyne Hospitals NHS Trust, Newcastle Upon Tyne, UK; 2Eli Lilly and Company Limited, Lilly House, Basingstoke, UK; 3Institute of Neuroscience, Newcastle University, Newcastle Upon Tyne, UK Abstract: Sleep has been described as being of the brain, by the brain, and for the brain. This fundamental neurobiological behavior is controlled by homeostatic and circadian (24-hour processes and is vital for normal brain function. This review will outline the normal sleep–wake cycle, the changes that occur during aging, and the specific patterns of sleep disturbance that occur in association with both mental health disorders and neurodegenerative disorders. The role of primary sleep disorders such as insomnia, obstructive sleep apnea, and REM sleep behavior disorder as potential causes or risk factors for particular mental health or neurodegenerative problems will also be discussed. Keywords: sleep, mental health, neurodegenerative disorders, cognition

  7. Role of Ionizing Radiation in Neurodegenerative Diseases

    Directory of Open Access Journals (Sweden)

    Neel K. Sharma

    2018-05-01

    Full Text Available Ionizing radiation (IR from terrestrial sources is continually an unprotected peril to human beings. However, the medical radiation and global radiation background are main contributors to human exposure and causes of radiation sickness. At high-dose exposures acute radiation sickness occurs, whereas chronic effects may persist for a number of years. Radiation can increase many circulatory, age related and neurodegenerative diseases. Neurodegenerative diseases occur a long time after exposure to radiation, as demonstrated in atomic bomb survivors, and are still controversial. This review discuss the role of IR in neurodegenerative diseases and proposes an association between neurodegenerative diseases and exposure to IR.

  8. Role of Ionizing Radiation in Neurodegenerative Diseases

    Science.gov (United States)

    Sharma, Neel K.; Sharma, Rupali; Mathur, Deepali; Sharad, Shashwat; Minhas, Gillipsie; Bhatia, Kulsajan; Anand, Akshay; Ghosh, Sanchita P.

    2018-01-01

    Ionizing radiation (IR) from terrestrial sources is continually an unprotected peril to human beings. However, the medical radiation and global radiation background are main contributors to human exposure and causes of radiation sickness. At high-dose exposures acute radiation sickness occurs, whereas chronic effects may persist for a number of years. Radiation can increase many circulatory, age related and neurodegenerative diseases. Neurodegenerative diseases occur a long time after exposure to radiation, as demonstrated in atomic bomb survivors, and are still controversial. This review discuss the role of IR in neurodegenerative diseases and proposes an association between neurodegenerative diseases and exposure to IR. PMID:29867445

  9. Complex periodic potentials with a finite number of band gaps

    International Nuclear Information System (INIS)

    Khare, Avinash; Sukhatme, Uday

    2006-01-01

    We obtain several new results for the complex generalized associated Lame potential V(x)=a(a+1)m sn 2 (y,m)+b(b+1)m sn 2 (y+K(m),m)+f(f+1)m sn 2 (y+K(m)+iK ' (m),m)+g(g+1)m sn 2 (y+iK ' (m),m), where y≡x-K(m)/2-iK ' (m)/2, sn(y,m) is the Jacobi elliptic function with modulus parameter m, and there are four real parameters a,b,f,g. First, we derive two new duality relations which, when coupled with a previously obtained duality relation, permit us to relate the band edge eigenstates of the 24 potentials obtained by permutations of the parameters a,b,f,g. Second, we pose and answer the question: how many independent potentials are there with a finite number 'a' of band gaps when a,b,f,g are integers and a≥b≥f≥g≥0? For these potentials, we clarify the nature of the band edge eigenfunctions. We also obtain several analytic results when at least one of the four parameters is a half-integer. As a by-product, we also obtain new solutions of Heun's differential equation

  10. Transgenic nonhuman primates for neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Chan Anthony WS

    2004-06-01

    Full Text Available Abstract Animal models that represent human diseases constitute an important tool in understanding the pathogenesis of the diseases, and in developing effective therapies. Neurodegenerative diseases are complex disorders involving neuropathologic and psychiatric alterations. Although transgenic and knock-in mouse models of Alzheimer's disease, (AD, Parkinson's disease (PD and Huntington's disease (HD have been created, limited representation in clinical aspects has been recognized and the rodent models lack true neurodegeneration. Chemical induction of HD and PD in nonhuman primates (NHP has been reported, however, the role of intrinsic genetic factors in the development of the diseases is indeterminable. Nonhuman primates closely parallel humans with regard to genetic, neuroanatomic, and cognitive/behavioral characteristics. Accordingly, the development of NHP models for neurodegenerative diseases holds greater promise for success in the discovery of diagnoses, treatments, and cures than approaches using other animal species. Therefore, a transgenic NHP carrying a mutant gene similar to that of patients will help to clarify our understanding of disease onset and progression. Additionally, monitoring disease onset and development in the transgenic NHP by high resolution brain imaging technology such as MRI, and behavioral and cognitive testing can all be carried out simultaneously in the NHP but not in other animal models. Moreover, because of the similarity in motor repertoire between NHPs and humans, it will also be possible to compare the neurologic syndrome observed in the NHP model to that in patients. Understanding the correlation between genetic defects and physiologic changes (e.g. oxidative damage will lead to a better understanding of disease progression and the development of patient treatments, medications and preventive approaches for high risk individuals. The impact of the transgenic NHP model in understanding the role which

  11. Absorption dynamics and delay time in complex potentials

    Science.gov (United States)

    Villavicencio, Jorge; Romo, Roberto; Hernández-Maldonado, Alberto

    2018-05-01

    The dynamics of absorption is analyzed by using an exactly solvable model that deals with an analytical solution to Schrödinger’s equation for cutoff initial plane waves incident on a complex absorbing potential. A dynamical absorption coefficient which allows us to explore the dynamical loss of particles from the transient to the stationary regime is derived. We find that the absorption process is characterized by the emission of a series of damped periodic pulses in time domain, associated with damped Rabi-type oscillations with a characteristic frequency, ω = (E + ε)/ℏ, where E is the energy of the incident waves and ‑ε is energy of the quasidiscrete state of the system induced by the absorptive part of the Hamiltonian; the width γ of this resonance governs the amplitude of the pulses. The resemblance of the time-dependent absorption coefficient with a real decay process is discussed, in particular the transition from exponential to nonexponential regimes, a well-known feature of quantum decay. We have also analyzed the effect of the absorptive part of the potential on the dynamical delay time, which behaves differently from the one observed in attractive real delta potentials, exhibiting two regimes: time advance and time delay.

  12. Peroxisome proliferator-activated receptors (PPARs) as therapeutic target in neurodegenerative disorders

    International Nuclear Information System (INIS)

    Agarwal, Swati; Yadav, Anuradha; Chaturvedi, Rajnish Kumar

    2017-01-01

    Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors and they serve to be a promising therapeutic target for several neurodegenerative disorders, which includes Parkinson disease, Alzheimer's disease, Huntington disease and Amyotrophic Lateral Sclerosis. PPARs play an important role in the downregulation of mitochondrial dysfunction, proteasomal dysfunction, oxidative stress, and neuroinflammation, which are the major causes of the pathogenesis of neurodegenerative disorders. In this review, we discuss about the role of PPARs as therapeutic targets in neurodegenerative disorders. Several experimental approaches suggest potential application of PPAR agonist as well as antagonist in the treatment of neurodegenerative disorders. Several epidemiological studies found that the regular usage of PPAR activating non-steroidal anti-inflammatory drugs is effective in decreasing the progression of neurodegenerative diseases including PD and AD. We also reviewed the neuroprotective effects of PPAR agonists and associated mechanism of action in several neurodegenerative disorders both in vitro as well as in vivo animal models. - Highlights: • Peroxisome -activated receptors (PPARs) serve to be a promising therapeutic target for several neurodegenerative disorders. • PPAR agonist as well as provides neuroprotection in vitro as well as in vivo animal models of neurodegenerative disorders. • PPAR activating anti-inflammatory drugs use is effective in decreasing progression of neurodegenerative diseases.

  13. Nanobiomaterials' applications in neurodegenerative diseases.

    Science.gov (United States)

    Silva Adaya, Daniela; Aguirre-Cruz, Lucinda; Guevara, Jorge; Ortiz-Islas, Emma

    2017-02-01

    The blood-brain barrier is the interface between the blood and brain, impeding the passage of most circulating cells and molecules, protecting the latter from foreign substances, and maintaining central nervous system homeostasis. However, its restrictive nature constitutes an obstacle, preventing therapeutic drugs from entering the brain. Usually, a large systemic dose is required to achieve pharmacological therapeutic levels in the brain, leading to adverse effects in the body. As a consequence, various strategies are being developed to enhance the amount and concentration of therapeutic compounds in the brain. One such tool is nanotechnology, in which nanostructures that are 1-100 nm are designed to deliver drugs to the brain. In this review, we examine many nanotechnology-based approaches to the treatment of neurodegenerative diseases. The review begins with a brief history of nanotechnology, followed by a discussion of its definition, the properties of most reported nanomaterials, their biocompatibility, the mechanisms of cell-material interactions, and the current status of nanotechnology in treating Alzheimer's, Parkinson's diseases, and amyotrophic lateral sclerosis. Of all strategies to deliver drug to the brain that are used in nanotechnology, drug release systems are the most frequently reported.

  14. One-dimensional crystal with a complex periodic potential

    International Nuclear Information System (INIS)

    Boyd, John K.

    2001-01-01

    A one-dimensional crystal model is constructed with a complex periodic potential. A wave function solution for the crystal model is derived without relying on Bloch functions. The new wave function solution of this model is shown to correspond to the solution for the probability amplitude of a two-level system. The energy discriminant is evaluated using an analytic formula derived from the probability amplitude solution, and based on an expansion parameter related to the energy and potential amplitude. From the wave function energy discriminant the crystal band structure is derived and related to standard energy bands and gaps. It is also shown that several of the properties of the two-level system apply to the one-dimensional crystal model. The two-level system solution which evolves in time is shown to manifest as a spatial configuration of the one-dimensional crystal model. The sensitivity of the wave function probability density is interpreted in the context of the new solution. The spatial configuration of the wave function, and the appearance of a long wavelength in the wave function probability density is explained in terms of the properties of Bessel functions

  15. [Caregivers of people with neurodegenerative diseases: from help to delegation].

    Science.gov (United States)

    Delzescaux, Sabine; Blondel, Frédéric

    2015-01-01

    Being a caregiver is difficult, even more so when it comes to helping people with a neurodegenerative disease. These caregivers, either family members or close friends, are confronted with an unexpected delegation which can prove to be highly complex as the pitfalls can indeed be significant. Moreover, the support the caregivers can provide depends on the support they can get for themselves. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  16. The Role of Copper in Neurodegenerative Disease

    Science.gov (United States)

    Rose, Francis M.

    My research concerns the fundamental atomistic mechanisms of neurodegenerative diseases and the methodologies by which they may be discerned. This thesis consists of three primary parts. The introductory material is the raison d'etre for this work and a critical overview of the specific physics, mathematics and algorithms used in this research. The methods are presented along with specific details in order to facilitate future replication and enhancement. With the groundwork of mechanisms and methods out of the way, we then explore a nouveau atomistic mechanism describing the onset of Parkinson's disease, a disease that has been closely linked to misfolded metalloproteins. Further exploration of neurodegeneration takes place in the following chapter, where a remedial approach to Alzheimer's disease via a simulated chelation of a metalloprotein is undertaken. Altogether, the methods and techniques applied here allow for simulated exploration of both the atomistic mechanisms of neurodegeneration and their potential remediation strategies. The beginning portion of the research efforts explore protein misfolding dynamics in the presence a copper ion. Misfolding of the human alpha-synuclein (aS) protein has been implicated as a central constituent in neurodegenerative disease. In Parkinson's disease (PD) in particular, aS is thought to be the causative participant when found concentrated into neuritic plaques. Here we propose a scenario involving the metal ion Cu2+ as the protein misfolding initiator of fibrillized aS, the chief component of neuritic plaques. From experimental results we know these misfolded proteins have a rich beta--sheet signature, a marker that we reproduce with our simulated model. This model identifies a process of structural modifications to a natively unfolded alpha-synuclein resulting in a partially folded intermediate with a well defined nucleation site. It serves as a precursor to the fully misfolded protein. Understanding the nucleation

  17. Drosophila as an In Vivo Model for Human Neurodegenerative Disease

    Science.gov (United States)

    McGurk, Leeanne; Berson, Amit; Bonini, Nancy M.

    2015-01-01

    With the increase in the ageing population, neurodegenerative disease is devastating to families and poses a huge burden on society. The brain and spinal cord are extraordinarily complex: they consist of a highly organized network of neuronal and support cells that communicate in a highly specialized manner. One approach to tackling problems of such complexity is to address the scientific questions in simpler, yet analogous, systems. The fruit fly, Drosophila melanogaster, has been proven tremendously valuable as a model organism, enabling many major discoveries in neuroscientific disease research. The plethora of genetic tools available in Drosophila allows for exquisite targeted manipulation of the genome. Due to its relatively short lifespan, complex questions of brain function can be addressed more rapidly than in other model organisms, such as the mouse. Here we discuss features of the fly as a model for human neurodegenerative disease. There are many distinct fly models for a range of neurodegenerative diseases; we focus on select studies from models of polyglutamine disease and amyotrophic lateral sclerosis that illustrate the type and range of insights that can be gleaned. In discussion of these models, we underscore strengths of the fly in providing understanding into mechanisms and pathways, as a foundation for translational and therapeutic research. PMID:26447127

  18. Neurodegenerative Disorders Treatment: The MicroRNA Role.

    Science.gov (United States)

    Ridolfi, Barbara; Abdel-Haq, Hanin

    2017-01-01

    Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease and prion disease are not timely and effectively treated using conventional therapies. This emphasizes the need for alternative therapeutic approaches. In this respect, gene-based therapies have been adopted as potentially feasible alternative therapies, where the microRNA (miRNA) approach has experienced a great explosion in recent years. Because miRNAs have been shown to be implicated in the pathogenesis of several diseases including neurodegenerative diseases, they are intensely studied as candidates for diagnostic and prognostic biomarkers, as predictors of drug response and as therapeutic agents. In this review, we evaluate the feasibility of both direct and indirect miRNA mimics and inhibitors toward the regulation of neurodegenerative-related genes both in vivo and in vitro models, highlight the advantages and drawbacks associated with miRNA-based therapy, and summarize the relevant techniques and approaches attempted to deliver miRNAs to the central nervous system for therapeutic purposes, with particular regard to the exosomes. Additionally, we describe a new approach that holds great promise for the treatment of a wide range of diseases including neurodegenerative disorders. This approach is based on addressing the incorporation of miRNAs into exosomes to increase the quantity and quality of miRNA packed and delivered to the central nervous system and other sites of action. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  19. Potential of Kalemegdan complex as a tourist attraction of Belgrade

    Directory of Open Access Journals (Sweden)

    Tatović Nevena

    2014-01-01

    Full Text Available As the site of tumultuous cultural and historic events, Belgrade is one of the most popular tourist destinations in the region visited by a growing number of both national and international tourists. Kalemegdan complex, which is, as a rule, an indispensable point of tourist visits, holds a special place among tourist attractions of the city. At the same time, there is a general opinion that Kalemegdan is also the most important element of the overall attraction potential for tourism development in Belgrade, which is otherwise relatively modest compared to other European capitals. In this paper, an attempt has been made to assess the tourist value of Kalemegdan by using the combined qualitative and quantitative method. In contrast to the usual surveys of international tourists whose views do not necessarily reflect the 'attractiveness' and even less the fair value of attraction, the authors have opted for expert opinion in several profiles relevant to the case study. Tourism experts, travel guides, landscape architects, architects and environmentalists assessed the value of Kalemegdan as a tourist attraction, expressed through several distinctive indicators. Average values for each set of indicators, obtained by combining these marks, have led to the conclusion that the Kalemegdan Park with Belgrade Fortress has a relatively high tourism value in the level of national importance. The research has also showed the need for additional activities aimed at improving presentation and interpretation of the Belgrade's famous tourist attractions.

  20. Transmission of Neurodegenerative Disorders Through Blood Transfusion

    DEFF Research Database (Denmark)

    Edgren, Gustaf; Hjalgrim, Henrik; Rostgaard, Klaus

    2016-01-01

    BACKGROUND: The aggregation of misfolded proteins in the brain occurs in several neurodegenerative disorders. Aberrant protein aggregation is inducible in rodents and primates by intracerebral inoculation. Possible transfusion transmission of neurodegenerative diseases has important public health...... implications. OBJECTIVE: To investigate possible transfusion transmission of neurodegenerative disorders. DESIGN: Retrospective cohort study. SETTING: Nationwide registers of transfusions in Sweden and Denmark. PARTICIPANTS: 1 465 845 patients who received transfusions between 1968 and 2012. MEASUREMENTS.......9% received a transfusion from a donor diagnosed with one of the studied neurodegenerative diseases. No evidence of transmission of any of these diseases was found, regardless of approach. The hazard ratio for dementia in recipients of blood from donors with dementia versus recipients of blood from healthy...

  1. The aging brain and neurodegenerative disorders

    International Nuclear Information System (INIS)

    Braffman, B.H.; Trojanowski, J.Q.; Atlas, S.W.

    1991-01-01

    Both the aging brain and neurodegenerative disorders are characterized by a lack of vital endurance of affected neurons resulting in their premature death. Neuronal shrinkage or atrophy and death are normal and inevitable aspects of normal or successful aging; this is unexpected, excessive, and premature in neurodegenerative disorders. These histologic changes result in the neuroimaging findings of focal and/or diffuse atrophy with consequent enlargement of cerebrospinal fluid (CSF) spaces. The aging brain and neurodegenerative disorders share other magnetic resonance (MR) changes, i.e., markedly hypointense extrapyramidal nuclei and hyperintense white matter foci. The sequelae of senescent vascular changes result in additional characteristic features of the aging brain. This paper presents the MR and neuropathologic manifestations of both the normal aging brain and the brain affected by neurodegenerative disorders

  2. The emergence of designed multiple ligands for neurodegenerative disorders.

    Science.gov (United States)

    Geldenhuys, Werner J; Youdim, Moussa B H; Carroll, Richard T; Van der Schyf, Cornelis J

    2011-09-01

    The incidence of neurodegenerative diseases has seen a constant increase in the global population, and is likely to be the result of extended life expectancy brought about by better health care. Despite this increase in the incidence of neurodegenerative diseases, there has been a dearth in the introduction of new disease-modifying therapies that are approved to prevent or delay the onset of these diseases, or reverse the degenerative processes in brain. Mounting evidence in the peer-reviewed literature shows that the etiopathology of these diseases is extremely complex and heterogeneous, resulting in significant comorbidity and therefore unlikely to be mitigated by any drug acting on a single pathway or target. A recent trend in drug design and discovery is the rational design or serendipitous discovery of novel drug entities with the ability to address multiple drug targets that form part of the complex pathophysiology of a particular disease state. In this review we discuss the rationale for developing such multifunctional drugs (also called designed multiple ligands or DMLs), and why these drug candidates seem to offer better outcomes in many cases compared to single-targeted drugs in pre-clinical studies for neurodegenerative diseases such as Alzheimer's and Parkinson's disease. Examples are drawn from the literature of drug candidates that have already reached the market, some unsuccessful attempts, and others that are still in the drug development pipeline. Copyright © 2011. Published by Elsevier Ltd.

  3. Progranulin: at the interface of neurodegenerative and metabolic diseases.

    Science.gov (United States)

    Nguyen, Andrew D; Nguyen, Thi A; Martens, Lauren Herl; Mitic, Laura L; Farese, Robert V

    2013-12-01

    Progranulin is a widely expressed, cysteine-rich, secreted glycoprotein originally discovered for its growth factor-like properties. Its subsequent identification as a causative gene for frontotemporal dementia (FTD), a devastating early-onset neurodegenerative disease, has catalyzed a surge of new discoveries about progranulin function in the brain. More recently, progranulin was recognized as an adipokine involved in diet-induced obesity and insulin resistance, revealing its metabolic function. We review here progranulin biology in both neurodegenerative and metabolic diseases. In particular, we highlight the growth factor-like, trophic, and anti-inflammatory properties of progranulin as potential unifying themes in these seemingly divergent conditions. We also discuss potential therapeutic options for raising progranulin levels to treat progranulin-deficient FTD, as well as the possible consequences of such treatment. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Advances in epigenetics and epigenomics for neurodegenerative diseases.

    Science.gov (United States)

    Qureshi, Irfan A; Mehler, Mark F

    2011-10-01

    In the post-genomic era, epigenetic factors-literally those that are "over" or "above" genetic ones and responsible for controlling the expression and function of genes-have emerged as important mediators of development and aging; gene-gene and gene-environmental interactions; and the pathophysiology of complex disease states. Here, we provide a brief overview of the major epigenetic mechanisms (ie, DNA methylation, histone modifications and chromatin remodeling, and non-coding RNA regulation). We highlight the nearly ubiquitous profiles of epigenetic dysregulation that have been found in Alzheimer's and other neurodegenerative diseases. We also review innovative methods and technologies that enable the characterization of individual epigenetic modifications and more widespread epigenomic states at high resolution. We conclude that, together with complementary genetic, genomic, and related approaches, interrogating epigenetic and epigenomic profiles in neurodegenerative diseases represent important and increasingly practical strategies for advancing our understanding of and the diagnosis and treatment of these disorders.

  5. Disordered APP metabolism and neurovasculature in trauma and aging: Combined risks for chronic neurodegenerative disorders.

    Science.gov (United States)

    Ikonomovic, Milos D; Mi, Zhiping; Abrahamson, Eric E

    2017-03-01

    Traumatic brain injury (TBI), advanced age, and cerebral vascular disease are factors conferring increased risk for late onset Alzheimer's disease (AD). These conditions are also related pathologically through multiple interacting mechanisms. The hallmark pathology of AD consists of pathological aggregates of amyloid-β (Aβ) peptides and tau proteins. These molecules are also involved in neuropathology of several other chronic neurodegenerative diseases, and are under intense investigation in the aftermath of TBI as potential contributors to the risk for developing AD and chronic traumatic encephalopathy (CTE). The pathology of TBI is complex and dependent on injury severity, age-at-injury, and length of time between injury and neuropathological evaluation. In addition, the mechanisms influencing pathology and recovery after TBI likely involve genetic/epigenetic factors as well as additional disorders or comorbid states related to age and central and peripheral vascular health. In this regard, dysfunction of the aging neurovascular system could be an important link between TBI and chronic neurodegenerative diseases, either as a precipitating event or related to accumulation of AD-like pathology which is amplified in the context of aging. Thus with advanced age and vascular dysfunction, TBI can trigger self-propagating cycles of neuronal injury, pathological protein aggregation, and synaptic loss resulting in chronic neurodegenerative disease. In this review we discuss evidence supporting TBI and aging as dual, interacting risk factors for AD, and the role of Aβ and cerebral vascular dysfunction in this relationship. Evidence is discussed that Aβ is involved in cyto- and synapto-toxicity after severe TBI, and that its chronic effects are potentiated by aging and impaired cerebral vascular function. From a therapeutic perspective, we emphasize that in the fields of TBI- and aging-related neurodegeneration protective strategies should include preservation of

  6. Effective potentials from complex simulations: a potential-matching algorithm and remarks on coarse-grained potentials

    International Nuclear Information System (INIS)

    Toth, Gergely

    2007-01-01

    The projection of complex interactions onto simple distance-dependent or angle-dependent classical mechanical functions is a long-standing theoretical challenge in the field of computational sciences concerning biomolecules, colloids, aggregates and simple systems as well. The construction of an effective potential may be based on theoretical assumptions, on the application of fitting procedures on experimental data and on the simplification of complex molecular simulations. Recently, a force-matching method was elaborated to project the data of Car-Parrinello ab initio molecular dynamics simulations onto two-particle classical interactions (Izvekov et al 2004 J. Chem. Phys. 120 10896). We have developed a potential-matching algorithm as a practical analogue of this force-matching method. The algorithm requires a large number of configurations (particle positions) and a single value of the potential energy for each configuration. We show the details of the algorithm and the test calculations on simple systems. The test calculation on water showed an example in which a similar structure was obtained for qualitatively different pair interactions. The application of the algorithm on reverse Monte Carlo configurations was tried as well. We detected inconsistencies in a part of our calculations. We found that the coarse graining of potentials cannot be performed perfectly both for the structural and the thermodynamic data. For example, if one applies an inverse method with an input of the pair-correlation function, it provides energetics data for the configurations uniquely. These energetics data can be different from the desired ones obtained by all atom simulations, as occurred in the testing of our potential-matching method

  7. Health benefits of methylxanthines in neurodegenerative diseases.

    Science.gov (United States)

    Oñatibia-Astibia, Ainhoa; Franco, Rafael; Martínez-Pinilla, Eva

    2017-06-01

    Methylxanthines (MTXs) are consumed by almost everybody in almost every area of the world. Caffeine, theophylline and theobromine are the most well-known members of this family of compounds; they are present, inter alia, in coffee, tea, cacao, yerba mate and cola drinks. MTXs are readily absorbed in the gastrointestinal tract and are able to penetrate into the central nervous system, where they exert significant psychostimulant actions, which are more evident in acute intake. Coffee has been paradigmatic, as its use was forbidden in many diseases, however, this negative view has radically changed; evidence shows that MTXs display health benefits in diseases involving cell death in the nervous system. This paper reviews data that appraise the preventive and even therapeutic potential of MTXs in a variety of neurodegenerative diseases. Future perspectives include the use of MTXs to advance the understanding the pathophysiology of, inter alia, Alzheimer's disease (AD) and Parkinson's disease (PD), and the use of the methylxanthine chemical moiety as a basis for the development of new and more efficacious drugs. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Mapping Neurodegenerative Disease Onset and Progression.

    Science.gov (United States)

    Seeley, William W

    2017-08-01

    Brain networks have been of long-standing interest to neurodegeneration researchers, including but not limited to investigators focusing on conventional prion diseases, which are known to propagate along neural pathways. Tools for human network mapping, however, remained inadequate, limiting our understanding of human brain network architecture and preventing clinical research applications. Until recently, neuropathological studies were the only viable approach to mapping disease onset and progression in humans but required large autopsy cohorts and laborious methods for whole-brain sectioning and staining. Despite important advantages, postmortem studies cannot address in vivo, physiological, or longitudinal questions and have limited potential to explore early-stage disease except for the most common disorders. Emerging in vivo network-based neuroimaging strategies have begun to address these issues, providing data that complement the neuropathological tradition. Overall, findings to date highlight several fundamental principles of neurodegenerative disease anatomy and pathogenesis, as well as some enduring mysteries. These principles and mysteries provide a road map for future research. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

  9. Complexity: a potential paradigm for a health promotion discipline.

    Science.gov (United States)

    Tremblay, Marie-Claude; Richard, Lucie

    2014-06-01

    Health promotion underpins a distancing from narrow, simplifying health approaches associated with the biomedical model. However, it has not yet succeeded in formally establishing its theoretical, epistemological and methodological foundations on a single paradigm. The complexity paradigm, which it has yet to broach head-on, might provide it with a disciplinary matrix in line with its implicit stances and basic values. This article seeks to establish complexity's relevance as a paradigm that can contribute to the development of a health promotion discipline. The relevance of complexity is justified primarily by its matching with several implicit epistemological and methodological/theoretical stances found in the cardinal concepts and principles of health promotion. The transcendence of ontological realism and determinism as well as receptiveness in respect of the reflexivity that complexity encompasses are congruent with the values of social justice, participation, empowerment and the concept of positive health that the field promotes. Moreover, from a methodological and theoretical standpoint, complexity assumes a holistic, contextual and transdisciplinary approach, toward which health promotion is tending through its emphasis on ecology and interdisciplinary action. In a quest to illustrate our position, developmental evaluation is presented as an example of practice stemming from a complexity paradigm that can be useful in the evaluation of health promotion initiatives. In short, we argue that it would be advantageous for health promotion to integrate this paradigm, which would provide it with a formal framework appropriate to its purposes and concerns.

  10. [Investigation of Genetic Aetiology in Neurodegenerative Ataxias: Recommendations from the Group of Neurogenetics of Centro Hospitalar São João, Portugal].

    Science.gov (United States)

    Gomes, Tiago; Guimaraes, Joana; Leão, Miguel

    2017-06-30

    In recent decades, a long and increasing list of monogenic neurodegenerative ataxias has been identified, allowing for better characterization of the pathophysiology, phenotype and prognosis of this heterogeneous group of disorders, while also revealing potential new therapeutic targets. However, the heterogeneity and complexity of the genotype-phenotype relationships and the high costs of molecular genetics often make it difficult for clinicians to decide on a molecular investigation based on an unbiased rational plan. Clinical history is essential to guide the diagnostic workup, but often the phenotype does not hold enough specificity to allow for predicting the genotype. The Group of Neurogenetics of the Centro Hospitalar São João, a multidisciplinary team of neurologists and geneticists with special interest in neurogenetic disorders, devised consensus recommendations for the investigation of the genetic aetiology of neurodegenerative ataxias in clinical practice, based on international consensus documents (currently containing potentially outdated information) and published scientific evidence on this topic. At the time these recommendations were written, there were around 10 well described autosomal recessive loci and more than 27 autosomal dominant loci for neurodegenerative ataxias. This document covers, in a pragmatic way, the rational process used for the genetic diagnosis of neurodegenerative ataxias, with specific recommendations for the various groups of these heterogeneous diseases, per the Portuguese reality.

  11. Investigation of Genetic Aetiology in Neurodegenerative Ataxias: Recommendations from the Group of Neurogenetics of Centro Hospitalar São João, Portugal

    Directory of Open Access Journals (Sweden)

    Tiago Gomes

    2017-06-01

    Full Text Available In recent decades, a long and increasing list of monogenic neurodegenerative ataxias has been identified, allowing for better characterization of the pathophysiology, phenotype and prognosis of this heterogeneous group of disorders, while also revealing potential new therapeutic targets. However, the heterogeneity and complexity of the genotype-phenotype relationships and the high costs of molecular genetics often make it difficult for clinicians to decide on a molecular investigation based on an unbiased rational plan. Clinical history is essential to guide the diagnostic workup, but often the phenotype does not hold enough specificity to allow for predicting the genotype. The Group of Neurogenetics of the Centro Hospitalar São João, a multidisciplinary team of neurologists and geneticists with special interest in neurogenetic disorders, devised consensus recommendations for the investigation of the genetic aetiology of neurodegenerative ataxias in clinical practice, based on international consensus documents (currently containing potentially outdated information and published scientific evidence on this topic. At the time these recommendations were written, there were around 10 well described autosomal recessive loci and more than 27 autosomal dominant loci for neurodegenerative ataxias. This document covers, in a pragmatic way, the rational process used for the genetic diagnosis of neurodegenerative ataxias, with specific recommendations for the various groups of these heterogeneous diseases, per the Portuguese reality.

  12. Select estrogens within the complex formulation of conjugated equine estrogens (Premarin® are protective against neurodegenerative insults: implications for a composition of estrogen therapy to promote neuronal function and prevent Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Brinton Roberta

    2006-03-01

    Full Text Available Abstract Background Results of the Women's Health Initiative Memory Study (WHIMS raised concerns regarding the timing and formulation of hormone interventions. Conjugated equine estrogens (CEE, used as the estrogen therapy in the WHIMS trial, is a complex formulation containing multiple estrogens, including several not secreted by human ovaries, as well as other biologically active steroids. Although the full spectrum of estrogenic components present in CEE has not yet been resolved, 10 estrogens have been identified. In the present study, we sought to determine which estrogenic components, at concentrations commensurate with their plasma levels achieved following a single oral dose of 0.625 mg CEE (the dose used in the WHIMS trial in women, are neuroprotective and whether combinations of those neuroprotective estrogens provide added benefit. Further, we sought, through computer-aided modeling analyses, to investigate the potential correlation of the molecular mechanisms that conferred estrogen neuroprotection with estrogen interactions with the estrogen receptor (ER. Results Cultured basal forebrain neurons were exposed to either β-amyloid25–35 or excitotoxic glutamate with or without pretreatment with estrogens followed by neuroprotection analyses. Three indicators of neuroprotection that rely on different aspects of neuronal damage and viability, LDH release, intracellular ATP level and MTT formazan formation, were used to assess neuroprotective efficacy. Results of these analyses indicate that the estrogens, 17α-estradiol, 17β-estradiol, equilin, 17α-dihydroequilin, equilinen, 17α-dihydroequilenin, 17β-dihydroequilenin, and Δ8,9-dehydroestrone were each significantly neuroprotective in reducing neuronal plasma membrane damage induced by glutamate excitotoxicity. Of these estrogens, 17β-estradiol and Δ8,9-dehydroestrone were effective in protecting neurons against β-amyloid25–35-induced intracellular ATP decline

  13. Redox Potentials of Ligands and Complexes – a DFT Approach

    African Journals Online (AJOL)

    NICO

    A review of the limited literature concerned with theoretical ways to predict experimentally measured redox potentials of ligands and ... electrode surface, over-potentials and high solvent resistance, ... A correlation coefficient of 0.969 in the linear relation with ... of E0' were performed in two steps, i.e. calculation of the free.

  14. Complex products and systems: potential from using lay out platforms

    NARCIS (Netherlands)

    Halman, Johannes I.M.; Hofer, Adrian P.

    2004-01-01

    In their quest to manage the complexity of offering greater product variety, firms in many industries are considering platform-based development of product families. Key in this approach is the sharing of components, modules, and other assets across a family of products. Current research indicates

  15. Complex products and Systems: Potential from using layout platforms

    NARCIS (Netherlands)

    Hofer, A.P.; Halman, J.I.M.

    2004-01-01

    In their quest to manage the complexity of offering greater product variety, firms in many industries are considering platform-based development of product families. Key in this approach is the sharing of components, modules, and other assets across a family of products. Current research indicates

  16. Nutraceutical Potential of Phenolics from ′Brava′ and ′Mansa′ Extra-Virgin Olive Oils on the Inhibition of Enzymes Associated to Neurodegenerative Disorders in Comparison with Those of ′Picual′ and ′Cornicabra′

    Directory of Open Access Journals (Sweden)

    María Figueiredo-González

    2018-03-01

    Full Text Available The increasing interest in the Mediterranean diet is based on the protective effects against several diseases, including neurodegenerative disorders. Polyphenol-rich functional foods have been proposed to be unique supplementary and nutraceutical treatments for these disorders. Extra-virgin olive oils (EVOOs obtained from ′Brava′ and ′Mansa′, varieties recently identified from Galicia (northwestern Spain, were selected for in vitro screening to evaluate their capacity to inhibit key enzymes involved in Alzheimer′s disease (AD (acetylcholinesterase (AChE, butyrylcholinesterase (BuChE and 5-lipoxygenase (5-LOX, major depressive disorder (MDD and Parkinson′s disease (PD (monoamine oxidases: hMAO-A and hMAO-B respectively. ′Brava′ oil exhibited the best inhibitory activity against all enzymes, when they are compared to ′Mansa′ oil: BuChE (IC50 = 245 ± 5 and 591 ± 23 mg·mL−1, 5-LOX (IC50 = 45 ± 7 and 106 ± 14 mg·mL−1, hMAO-A (IC50 = 30 ± 1 and 72 ± 10 mg·mL−1 and hMAO-B (IC50 = 191 ± 8 and 208 ± 14 mg·mL−1, respectively. The inhibitory capacity of the phenolic extracts could be associated with the content of secoiridoids, lignans and phenolic acids.

  17. Maxillofacial trauma: managing potentially dangerous and disfiguring complex injuries [digest].

    Science.gov (United States)

    Das, Devjani; Salazar, Lea; Zaurova, Milana

    2017-04-22

    Patients with maxillofacial trauma require a careful evaluation due to the anatomical proximity of the maxillofacial region to the head and neck. Facial injuries can range from soft-tissue lacerations and nondisplaced nasal fractures to severe, complex fractures, eye injuries, and possible brain injury. Though the Advanced Trauma Life Support (ATLS) guidelines provide a framework for the management of trauma patients, they do not provide a detailed reference for many subtle or complex facial injuries. This issue adds a more comprehensive and systematic approach to the secondary survey of the maxillofacial area and emergency department management of injuries to the face. In addition to an overall review of maxillofacial trauma pathophysiology, associated injuries, and physical examination, this review will also discuss relevant imaging, treatment, and disposition plans. [Points & Pearls is a digest of Emergency Medicine Practice].

  18. Excitatory amino acid neurotoxicity and neurodegenerative disease.

    Science.gov (United States)

    Meldrum, B; Garthwaite, J

    1990-09-01

    The progress over the last 30 years in defining the role of excitatory amino acids in normal physiological function and in the abnormal neuronal activity of epilepsy has been reviewed in earlier articles in this series. In the last five years it has become clear that excitatory amino acids also play a role in a wide range of neurodegenerative processes. The evidence is clearest where the degenerative process is acute, but is more controversial for slow degenerative processes. In this article Brian Meldrum and John Garthwaite review in vivo and in vitro studies of the cytotoxicity of amino acids and summarize the contribution of such toxicity to acute and chronic neurodegenerative disorders.

  19. Olfactory memory impairment in neurodegenerative diseases.

    Science.gov (United States)

    Bahuleyan, Biju; Singh, Satendra

    2012-10-01

    Olfactory disorders are noted in a majority of neurodegenerative diseases, but they are often misjudged and are rarely rated in the clinical setting. Severe changes in the olfactory tests are observed in Parkinson's disease. Olfactory deficits are an early feature in Alzheimer's disease and they worsen with the disease progression. Alterations in the olfactory function are also noted after severe head injuries, temporal lobe epilepsy, multiple sclerosis, and migraine. The purpose of the present review was to discuss the available scientific knowledge on the olfactory memory and to relate its impairment with neurodegenerative diseases.

  20. Open Science Meets Stem Cells: A New Drug Discovery Approach for Neurodegenerative Disorders.

    Science.gov (United States)

    Han, Chanshuai; Chaineau, Mathilde; Chen, Carol X-Q; Beitel, Lenore K; Durcan, Thomas M

    2018-01-01

    Neurodegenerative diseases are a challenge for drug discovery, as the biological mechanisms are complex and poorly understood, with a paucity of models that faithfully recapitulate these disorders. Recent advances in stem cell technology have provided a paradigm shift, providing researchers with tools to generate human induced pluripotent stem cells (iPSCs) from patient cells. With the potential to generate any human cell type, we can now generate human neurons and develop "first-of-their-kind" disease-relevant assays for small molecule screening. Now that the tools are in place, it is imperative that we accelerate discoveries from the bench to the clinic. Using traditional closed-door research systems raises barriers to discovery, by restricting access to cells, data and other research findings. Thus, a new strategy is required, and the Montreal Neurological Institute (MNI) and its partners are piloting an "Open Science" model. One signature initiative will be that the MNI biorepository will curate and disseminate patient samples in a more accessible manner through open transfer agreements. This feeds into the MNI open drug discovery platform, focused on developing industry-standard assays with iPSC-derived neurons. All cell lines, reagents and assay findings developed in this open fashion will be made available to academia and industry. By removing the obstacles many universities and companies face in distributing patient samples and assay results, our goal is to accelerate translational medical research and the development of new therapies for devastating neurodegenerative disorders.

  1. Open Science Meets Stem Cells: A New Drug Discovery Approach for Neurodegenerative Disorders

    Directory of Open Access Journals (Sweden)

    Chanshuai Han

    2018-02-01

    Full Text Available Neurodegenerative diseases are a challenge for drug discovery, as the biological mechanisms are complex and poorly understood, with a paucity of models that faithfully recapitulate these disorders. Recent advances in stem cell technology have provided a paradigm shift, providing researchers with tools to generate human induced pluripotent stem cells (iPSCs from patient cells. With the potential to generate any human cell type, we can now generate human neurons and develop “first-of-their-kind” disease-relevant assays for small molecule screening. Now that the tools are in place, it is imperative that we accelerate discoveries from the bench to the clinic. Using traditional closed-door research systems raises barriers to discovery, by restricting access to cells, data and other research findings. Thus, a new strategy is required, and the Montreal Neurological Institute (MNI and its partners are piloting an “Open Science” model. One signature initiative will be that the MNI biorepository will curate and disseminate patient samples in a more accessible manner through open transfer agreements. This feeds into the MNI open drug discovery platform, focused on developing industry-standard assays with iPSC-derived neurons. All cell lines, reagents and assay findings developed in this open fashion will be made available to academia and industry. By removing the obstacles many universities and companies face in distributing patient samples and assay results, our goal is to accelerate translational medical research and the development of new therapies for devastating neurodegenerative disorders.

  2. Cell ageing: a flourishing field for neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Dora Brites

    2015-06-01

    Full Text Available Cellular senescence is viewed as an irreversible cell-cycle arrest mechanism involving a complexity of biological progressive processes and the acquisition of diverse cellular phenotypes. Several cell-intrinsic and extrinsic causes (stresses may lead to diverse cellular signaling cascades that include oxidative stress, mitochondrial dysfunction, DNA damage, excessive accumulation of misfolded proteins, impaired microRNA processing and inflammation. Here we review recent advances in the causes and consequences of brain cell ageing, including the senescence of endothelial cells at the central nervous system barriers, as well as of neurons and glial cells. We address what makes ageing an important risk factor for neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and cerebrovascular disease. In particular, we highlight the importance of defects in mitochondrial dynamics, in the cathepsin activity imbalance, in cell-cell communication, in the accumulation of misfolded and unfolded proteins and in the microRNA profiling as having potential impact on cellular ageing processes. Another important aspect is that the absence of specific senescence biomarkers has hampered the characterization of senescent cells in ageing and age-associated diseases. In accordance, the senescence-associated secretory phenotype (SASP or secretome was shown to vary in distinct cell types and upon different stressors, and SASP heterogeneity is believed to create subsets of senenescent cells. In addition to secreted proteins, we then place extracellular vesicles (exosomes and ectosomes as important mediators of intercellular communication with pathophysiological roles in disease spreading, and as emerging targets for therapeutic intervention. We also discuss the application of engineered extracellular vesicles as vehicles for drug delivery. Finally, we summarize current knowledge on methods to rejuvenate senescent cells

  3. Implications of glial nitric oxyde in neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Jose Enrique eYuste

    2015-08-01

    Full Text Available Nitric oxide (NO is a pleiotropic janus-faced molecule synthesized by nitric oxide synthases (NOS which plays a critical role in a number of physiological and pathological processes in humans. The physiological roles of NO depend on its local concentrations, as well as its availability and the nature of downstream target molecules. Its double-edged sword action has been linked to neurodegenerative disorders. Excessive NO production, as the evoked by inflammatory signals, has been identified as one of the major causative reasons for the pathogenesis of several neurodegenerative diseases. Moreover, excessive NO synthesis under neuroinflammation leads to the formation of reactive nitrogen species and neuronal cell death. There is an intimate relation between microglial activation, NO and neuroinflammation in the human brain. The role of NO in neuroinflammation has been defined in animal models where this neurotransmitter can modulate the inflammatory process acting on key regulatory pathways, such as those associated with excitotoxicity processes induced by glutamate accumulation and microglial activation. Activated glia express inducible NOS and produce NO that triggers calcium mobilization from the endoplasmic reticulum, activating the release of vesicular glutamate from astroglial cells resulting in neuronal death. This change in microglia potentially contributes to the increased age-associated susceptibility and neurodegeneration. In the current review, information is provided about the role of NO, glial activation and age-related processes in the central nervous system (CNS that may be helpful in the isolation of new therapeutic targets for aging and neurodegenerative diseases.

  4. Sublethal RNA Oxidation as a Mechanism for Neurodegenerative Disease

    Directory of Open Access Journals (Sweden)

    Mark A. Smith

    2008-05-01

    Full Text Available Although cellular RNA is subjected to the same oxidative insults as DNA and other cellular macromolecules, oxidative damage to RNA has not been a major focus in investigations of the biological consequences of free radical damage. In fact, because it is largely single-stranded and its bases lack the protection of hydrogen bonding and binding by specific proteins, RNA may be more susceptible to oxidative insults than is DNA. Oxidative damage to protein-coding RNA or non-coding RNA will, in turn, potentially cause errors in proteins and/or dysregulation of gene expression. While less lethal than mutations in the genome, such sublethal insults to cells might be associated with underlying mechanisms of several chronic diseases, including neurodegenerative disease. Recently, oxidative RNA damage has been described in several neurodegenerative diseases including Alzheimer disease, Parkinson disease, dementia with Lewy bodies, and prion diseases. Of particular interest, oxidative RNA damage can be demonstrated in vulnerable neurons early in disease, suggesting that RNA oxidation may actively contribute to the onset of the disease. An increasing body of evidence suggests that, mechanistically speaking, the detrimental effects of oxidative RNA damage to protein synthesis are attenuated, at least in part, by the existence of protective mechanisms that prevent the incorporation of the damaged ribonucleotides into the translational machinery. Further investigations aimed at understanding the processing mechanisms related to oxidative RNA damage and its consequences may provide significant insights into the pathogenesis of neurodegenerative and other degenerative diseases and lead to better therapeutic strategies.

  5. Medicinal Plants in Neurodegenerative Diseases: Perspective of Traditional Persian Medicine.

    Science.gov (United States)

    Farzaei, Mohammad Hosein; Shahpiri, Zahra; Mehri, Mohammad Reza; Bahramsoltani, Roodabeh; Rezaei, Mahdi; Raeesdana, Azade; Rahimi, Roja

    2018-01-01

    Neurodegenerative diseases are a progressive loss of structure and/or function of neurons. Weak therapeutic response and progressive nature of the diseases, as well as a wide range of side effects caused by conventional therapeutic approaches make patients seek for complementary and alternative medicine. The aim of the present paper is to discuss the neuropharmacological basis of medicinal plants and their principle phytochemicals which have been used in traditional Persian medicine for different types of neurodegenerative diseases. Medicinal plants introduced in traditional Persian medicine perform beneficial effects in neurodegenerative diseases via various cellular and molecular mechanisms including suppression of apoptosis mediated by an increase in the expression of anti-apoptotic agents (e.g. Bcl-2) as well as a decrease in the expression and activity of proapoptotic proteins (e.g. Bax, caspase 3 and 9). Alleviating inflammatory responses and suppressing the expression and function of pro-inflammatory cytokines like Tumor necrosis factor α and interleukins, as well as improvement in antioxidative performance mediated by superoxide dismutase and catalase, are among other neuroprotective mechanisms of traditional medicinal plants. Modulation of transcription, transduction, intracellular signaling pathways including ERK, p38, and MAPK, with upstream regulatory activity on inflammatory cascades, apoptosis and oxidative stress associated pathways, play an essential role in the preventive and therapeutic potential of the plants in neurodegenerative diseases. Medicinal plants used in traditional Persian medicine along with their related phytochemicals by affecting various neuropharmacological pathways can be considered as future drugs or adjuvant therapies with conventional pharmacotherapeutics; though, further clinical studies are necessary for the confirmation of their safety and efficacy. Copyright© Bentham Science Publishers; For any queries, please email at

  6. Synthesis and structure of copper(II) complexes: Potential cyanide ...

    Indian Academy of Sciences (India)

    easy accessibility to Cu(I), Cu(II) and Cu(III) oxidation states.3,20–38 ... erty to oxidize primary alcohol to aldehyde since they are potential N,O ... Electronic spectra were recorded on a. Shimadzu .... the appropriate temperature 37. ◦. C for 24h.

  7. Potential atmospheric pollution from the Invergordon industrial complex

    Energy Technology Data Exchange (ETDEWEB)

    Neustein, S A; Danby, N P

    1971-11-01

    The main atmospheric pollutants from the Invergordon complex will be fluorine and hydrogen fluoride from the aluminum smelter and sulfur dioxide and hydrocarbons from the oil refinery. Both acute and chronic tree damage is expected. The effects of F and SO/sub 2/ on the trees via the soil is expected to be insignificant. Acute tree damage results from high concentrations of pollutants as a result of meteorological conditions or industrial cleansing failure. Chronic tree damage results from long term low level pollution. Broad leaved trees are not regarded as susceptible to chronic pollution. All the conifers are susceptible. Clean air sampling has begun in order to provide before and after comparison. Foliage samplers will be taken for a radius of 16,000 m. A survey of lichens has been completed. Lichenology may assist in discrimination between F and SO/sub 2/ injuries.

  8. Delta-function potential with a complex coupling

    International Nuclear Information System (INIS)

    Mostafazadeh, Ali

    2006-01-01

    We explore the Hamiltonian operator H = -d 2 /dx 2 + zδ(x), where x element of R, δ(x) is the Dirac delta function and z is an arbitrary complex coupling constant. For a purely imaginary z, H has a spectral singularity at E = -z 2 /4 element of R + . For Re(z) 2 /4. For the case that Re(z) > 0, H has a real, positive, continuous spectrum that is free from spectral singularities. For this latter case, we construct an associated biorthonormal system and use it to perform a perturbative calculation of a positive-definite inner product that renders H self-adjoint. This allows us to address the intriguing question of the nonlocal aspects of the equivalent Hermitian Hamiltonian for the system. In particular, we compute the energy expectation values for various Gaussian wave packets to show that the non-Hermiticity effect diminishes rapidly outside an effective interaction region

  9. Paramagnetic metal complexes as potential relaxation agents for NMR imaging

    International Nuclear Information System (INIS)

    Coroiu, Ilioara; Demco, D. E.; Darabont, Al.; Bogdan, M.

    1997-01-01

    The development of nuclear magnetic resonance (NMR) imaging technique as a clinical diagnostic modality has prompted the need for a new class of pharmaceuticals. These drugs must be administered to a patient in order to enhance the image contrast between the normal and diseased tissue and/or indicate the status of organ function or blood flow. Paramagnetic compounds are presently undergoing extensive evaluation as contrast agents in magnetic resonance imaging (MRI). These agents increase contrast in MRI by differentially localizing in tissue where they increase the relaxation rates of nearby water protons. The longitudinal R 1 and transverse R 2 relaxivities were measured as a function of molar concentrations for some new paramagnetic complexes like the following: dysprosium, erbium and gadolinium citrates, gadolinium methylene diphosphonate, dysprosium and gadolinium iminodiacetate, manganese para-aminobenzoate and copper nicotinate. The available theoretical approaches for quantitative understanding are presented. (authors)

  10. Substituent effect on redox potential of nitrido technetium complexes with Schiff base ligand. Theoretical calculations

    International Nuclear Information System (INIS)

    Takayama, T.; Sekine, T.; Kudo, H.

    2003-01-01

    Theoretical calculations based on the density functional theory (DFT) were performed to understand the effect of substituents on the molecular and electronic structures of technetium nitrido complexes with salen type Schiff base ligands. Optimized structures of these complexes are square pyramidal. The electron density on a Tc atom of the complex with electron withdrawing substituents is lower than that of the complex with electron donating substituents. The HOMO energy is lower in the complex with electron withdrawing substituents than that in the complex with electron donating substituents. The charge on Tc atoms is a good measure that reflects the redox potential of [TcN(L)] complex. (author)

  11. Evaluation of the uranium potential of the Bushveld Complex

    International Nuclear Information System (INIS)

    Cheney, E.S.

    1986-04-01

    The poor quality of the airborne radiometric surveys and the lack of exploration geochemical data in the public domain prevent a satisfactory assessment of the uranium potential of the Bushveld area. Undue reliance must be placed upon fitting models of uranium ore deposits to the geology of the Bushveld area. Although the Bushveld granites have an unusually high background of uranium (20 to 40 ppm), they probably only host small vein-type deposits. The vein at the Albert Silver mine should be investigated as a type example to determine if it is only economic in the narrow interval of supergene enrichment. The Rooiberg Group has considerable potential for caldera-related deposits and for uranium-bearing sulphide deposits (including Olympic Dam-type deposits) in sedimentary interbeds. The Loskop Formation appears to be correlative with the Glentig and lower Swaershoek Formations of the Waterberg area. The Waterberg Group is the logical host to investigate for giant uncomformity/vein-type uranium deposits like those in Canada and Australia. Because the Waterberg consists of four uncomformity-bounded sequences, it is rarely more than 3 km thick; all of the sequences could be younger than 1770 Ma

  12. Complexation Effect on Redox Potential of Iron(III)-Iron(II) Couple: A Simple Potentiometric Experiment

    Science.gov (United States)

    Rizvi, Masood Ahmad; Syed, Raashid Maqsood; Khan, Badruddin

    2011-01-01

    A titration curve with multiple inflection points results when a mixture of two or more reducing agents with sufficiently different reduction potentials are titrated. In this experiment iron(II) complexes are combined into a mixture of reducing agents and are oxidized to the corresponding iron(III) complexes. As all of the complexes involve the…

  13. Engaging stakeholders on complex, and potentially contested, science

    International Nuclear Information System (INIS)

    Holmes, John; Atherton, Elizabeth; Tweed, Cherry

    2014-01-01

    An effective process for engaging stakeholders on the science underpinning radioactive waste disposal will be essential for the successful implementation of geological disposal in the United Kingdom. Of particular importance are those stakeholders representing, and living in, volunteer communities. There have been two major shifts over the last 10-20 years in society's engagement with science which are particularly relevant to the Radioactive Waste Management Directorate's (RWMD) stakeholder engagement: - a shift to a more inclusive approach in which the public have more of a say about science and its uses; - a shift to a more evidence-based approach to societal decision making. Significant challenges to effective communication and confidence building in geological disposal arise from: - the complexities and uncertainties inherent in the relevant science; - the sensitivities and 'high stakes' (locally and nationally) associated with a disposal facility; - the expectation that there will continue to be vocal stakeholders who are fundamentally opposed to geological disposal of radioactive wastes who will focus on any remaining uncertainties as just cause for their position. This abstract summarises the findings of a project to evaluate approaches to engaging with stakeholders on the science underpinning sensitive decisions in sectors other than radioactive waste disposal and to identify elements of good practice which may help RWMD in taking forward the implementation of a geological disposal facility for the United Kingdom's radioactive wastes. Six elements of good practice are listed and discussed below: - Using science appropriately: Taking an inclusive, evidence-based approach in which collaborative inquiry takes a holistic, weight-of-evidence view of the science rather than focusing on items of evidence in isolation, using them to prove or disprove a particular point of view. - Building trust: Ensuring that processes of engagement engender trust, and that trust

  14. Pain in Neurodegenerative Disease : Current Knowledge and Future Perspectives

    NARCIS (Netherlands)

    de Tommaso, Marina; Arendt-Nielsen, Lars; Defrin, Ruth; Kunz, Miriam; Pickering, Gisele; Valeriani, Massimiliano

    2016-01-01

    Neurodegenerative diseases are going to increase as the life expectancy is getting longer. The management of neurodegenerative diseases such as Alzheimer's disease (AD) and other dementias, Parkinson's disease (PD) and PD related disorders, motor neuron diseases (MND), Huntington's disease (HD),

  15. Amyloid PET in neurodegenerative diseases with dementia.

    Science.gov (United States)

    Camacho, V; Gómez-Grande, A; Sopena, P; García-Solís, D; Gómez Río, M; Lorenzo, C; Rubí, S; Arbizu, J

    2018-05-15

    Alzheimer's disease (AD) is a neurodegenerative condition characterized by progressive cognitive decline and memory loss, and is the most common form of dementia. Amyloid plaques with neurofibrillary tangles are a neuropathological hallmark of AD that produces synaptic dysfunction and culminates later in neuronal loss. Amyloid PET is a useful, available and non-invasive technique that provides in vivo information about the cortical amyloid burden. In the latest revised criteria for the diagnosis of AD biomarkers were defined and integrated: pathological and diagnostic biomarkers (increased retention on fibrillar amyloid PET or decreased Aβ 1-42 and increased T-Tau or P-Tau in CSF) and neurodegeneration or topographical biomarkers (temporoparietal hypometabolism on 18 F-FDG PET and temporal atrophy on MRI). Recently specific recommendations have been created as a consensus statement on the appropriate use of the imaging biomarkers, including amyloid PET: early-onset cognitive impairment/dementia, atypical forms of AD, mild cognitive impairment with early age of onset, and to differentiate between AD and other neurodegenerative diseases that occur with dementia. Amyloid PET is also contributing to the development of new therapies for AD, as well as in research studies for the study of other neurodegenerative diseases that occur with dementia where the deposition of Aβ amyloid is involved in its pathogenesis. In this paper, we review some general concepts and study the use of amyloid PET in depth and its relationship with neurodegenerative diseases and other diagnostic techniques. Copyright © 2018 Sociedad Española de Medicina Nuclear e Imagen Molecular. Publicado por Elsevier España, S.L.U. All rights reserved.

  16. Olfactory Memory Impairment in Neurodegenerative Diseases

    OpenAIRE

    Bahuleyan, Biju; Singh, Satendra

    2012-01-01

    Olfactory disorders are noted in a majority of neurodegenerative diseases, but they are often misjudged and are rarely rated in the clinical setting. Severe changes in the olfactory tests are observed in Parkinson's disease. Olfactory deficits are an early feature in Alzheimer's disease and they worsen with the disease progression. Alterations in the olfactory function are also noted after severe head injuries, temporal lobe epilepsy, multiple sclerosis, and migraine. The purpose of the prese...

  17. Synthetic prions and other human neurodegenerative proteinopathies.

    Science.gov (United States)

    Le, Nhat Tran Thanh; Narkiewicz, Joanna; Aulić, Suzana; Salzano, Giulia; Tran, Hoa Thanh; Scaini, Denis; Moda, Fabio; Giachin, Gabriele; Legname, Giuseppe

    2015-09-02

    Transmissible spongiform encephalopathies (TSE) are a heterogeneous group of neurodegenerative disorders. The common feature of these diseases is the pathological conversion of the normal cellular prion protein (PrP(C)) into a β-structure-rich conformer-termed PrP(Sc). The latter can induce a self-perpetuating process leading to amplification and spreading of pathological protein assemblies. Much evidence suggests that PrP(Sc) itself is able to recruit and misfold PrP(C) into the pathological conformation. Recent data have shown that recombinant PrP(C) can be misfolded in vitro and the resulting synthetic conformers are able to induce the conversion of PrP(C) into PrP(Sc)in vivo. In this review we describe the state-of-the-art of the body of literature in this field. In addition, we describe a cell-based assay to test synthetic prions in cells, providing further evidence that synthetic amyloids are able to template conversion of PrP into prion inclusions. Studying prions might help to understand the pathological mechanisms governing other neurodegenerative diseases. Aggregation and deposition of misfolded proteins is a common feature of several neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and other disorders. Although the proteins implicated in each of these diseases differ, they share a common prion mechanism. Recombinant proteins are able to aggregate in vitro into β-rich amyloid fibrils, sharing some features of the aggregates found in the brain. Several studies have reported that intracerebral inoculation of synthetic aggregates lead to unique pathology, which spread progressively to distal brain regions and reduced survival time in animals. Here, we review the prion-like features of different proteins involved in neurodegenerative disorders, such as α-synuclein, superoxide dismutase-1, amyloid-β and tau. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Methods for the prognosus and suagnosis of neurodegenerative diseases

    OpenAIRE

    Naranjo, José Ramón; Mellström, Britt; Rábano, Alberto

    2014-01-01

    [EN] The present invention corresponds to the field of neurobiology and relates to methods for predicting the appearance of a neurodegenerative disease in a subject, for diagnosing the prodromic stage of a neurodegenerative disease in a subject, for predicting whether a subject diagnosed of a prodromic stage of a neurodegenerative disease will develop said neurodegenerative disease and for selecting a subject for a therapy for the prevention and/or treatment of a prodromic stage of a neurode...

  19. Solution of Schroedinger Equation for Two-Dimensional Complex Quartic Potentials

    International Nuclear Information System (INIS)

    Singh, Ram Mehar; Chand, Fakir; Mishra, S. C.

    2009-01-01

    We investigate the quasi-exact solutions of the Schroedinger wave equation for two-dimensional non-hermitian complex Hamiltonian systems within the frame work of an extended complex phase space characterized by x = x 1 + ip 3 , y = x 2 + ip 4 , p x = p 1 + ix 3 , p y = p 2 + ix 4 . Explicit expressions of the energy eigenvalues and the eigenfunctions for ground and first excited states for a complex quartic potential are obtained. Eigenvalue spectra of some variants of the complex quartic potential, including PT-symmetric one, are also worked out. (general)

  20. Transcranial Direct Current Stimulation in Neurodegenerative Disease

    Directory of Open Access Journals (Sweden)

    Argye E. Hillis

    2014-04-01

    Full Text Available We review rationale, challenges, study designs, reported results, and future directions in the use of transcranial direct cranial stimulation (tDCS in neurodegenerative disease, focusing on treatment of spelling in primary progressive aphasia (PPA. Rationale Evidence from both animal studies and human studies indicates that anodal and cathodal tDCS over the brain result in a temporary change in membrane potentials, reducing the threshold for long-term potentiation of neurons in the affected area. This may allow unaffected brain regions to assume functions of diseased regions. Challenges Special challenges in treating individuals with progressive conditions include altered goals of treatment and the possibility that participants may accumulate new deficits over the course of the treatment program that interfere with their ability to understand, retain, or cooperate with aspects of the program. The most serious challenge – particularly for single case designs - is that there may be no stable baseline against which to measure change with treatment. Thus, it is essential to demonstrate that treatment results in a statistically significant change in the slope of decline or improvement. Therefore, demonstration of a significant difference between tDCS and control (sham requires either a large number of participants or a large effect size. Designs The choice of a treatment design reflects these limitations. Group studies with a randomized, double-blind, sham control trial design (without cross-over provide the greatest power to detect a difference between intervention and control conditions, with the fewest participants. A cross-over design, in which all participants (from 1 to many receive both active and sham conditions, in randomized order, requires a larger effect size for the active condition relative to the control condition (or little to no maintenance of treatment gains or carry-over effect to show significant differences between treatment

  1. Beneficial Effects of Green Tea Catechins on Neurodegenerative Diseases

    Directory of Open Access Journals (Sweden)

    Monira Pervin

    2018-05-01

    Full Text Available Tea is one of the most consumed beverages in the world. Green tea, black tea, and oolong tea are made from the same plant Camellia sinensis (L. O. Kuntze. Among them, green tea has been the most extensively studied for beneficial effects on diseases including cancer, obesity, diabetes, and inflammatory and neurodegenerative diseases. Several human observational and intervention studies have found beneficial effects of tea consumption on neurodegenerative impairment, such as cognitive dysfunction and memory loss. These studies supported the basis of tea’s preventive effects of Parkinson’s disease, but few studies have revealed such effects on Alzheimer’s disease. In contrast, several human studies have not reported these favorable effects with regard to tea. This discrepancy may be due to incomplete adjustment of confounding factors, including the method of quantifying consumption, beverage temperature, cigarette smoking, alcohol consumption, and differences in genetic and environmental factors, such as race, sex, age, and lifestyle. Thus, more rigorous human studies are required to understand the neuroprotective effect of tea. A number of laboratory experiments demonstrated the benefits of green tea and green tea catechins (GTCs, such as epigallocatechin gallate (EGCG, and proposed action mechanisms. The targets of GTCs include the abnormal accumulation of fibrous proteins, such as Aβ and α-synuclein, inflammation, elevated expression of pro-apoptotic proteins, and oxidative stress, which are associated with neuronal cell dysfunction and death in the cerebral cortex. Computational molecular docking analysis revealed how EGCG can prevent the accumulation of fibrous proteins. These findings suggest that GTCs have the potential to be used in the prevention and treatment of neurodegenerative diseases and could be useful for the development of new drugs.

  2. An Improved Topology-Potential-Based Community Detection Algorithm for Complex Network

    Directory of Open Access Journals (Sweden)

    Zhixiao Wang

    2014-01-01

    Full Text Available Topology potential theory is a new community detection theory on complex network, which divides a network into communities by spreading outward from each local maximum potential node. At present, almost all topology-potential-based community detection methods ignore node difference and assume that all nodes have the same mass. This hypothesis leads to inaccuracy of topology potential calculation and then decreases the precision of community detection. Inspired by the idea of PageRank algorithm, this paper puts forward a novel mass calculation method for complex network nodes. A node’s mass obtained by our method can effectively reflect its importance and influence in complex network. The more important the node is, the bigger its mass is. Simulation experiment results showed that, after taking node mass into consideration, the topology potential of node is more accurate, the distribution of topology potential is more reasonable, and the results of community detection are more precise.

  3. Infinite dwell time and group delay in resonant electron tunneling through double complex potential barrier

    Science.gov (United States)

    Opacak, Nikola; Milanović, Vitomir; Radovanović, Jelena

    2017-12-01

    Tunneling times in complex potentials are investigated. Analytical expressions for dwell time, self-interference time and group delay are obtained for the case of complex double delta potentials. It is shown that we can always find a set of parameters of the potential so that the tunneling times achieve very large values and even approach infinity for the case of resonance. The phenomenon of infinite tunneling times occurs for only one particular positive value of the imaginary part of the potential, if all other parameters are given.

  4. On solving the Schrödinger equation for a complex deictic potential ...

    Indian Academy of Sciences (India)

    Making use of an ansatz for the eigenfunction, we investigate closed-form solutions of the Schrödinger equation for an even power complex deictic potential and its variant in one dimension. For this purpose, extended complex phase-space approach is utilized and nature of the eigenvalue and the corresponding ...

  5. Liposomes for Targeted Delivery of Active Agents against Neurodegenerative Diseases (Alzheimer's Disease and Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Carlos Spuch

    2011-01-01

    Full Text Available Neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease represent a huge unmet medical need. The prevalence of both diseases is increasing, but the efficacy of treatment is still very limited due to various factors including the blood brain barrier (BBB. Drug delivery to the brain remains the major challenge for the treatment of all neurodegenerative diseases because of the numerous protective barriers surrounding the central nervous system. New therapeutic drugs that cross the BBB are critically needed for treatment of many brain diseases. One of the significant factors on neurotherapeutics is the constraint of the blood brain barrier and the drug release kinetics that cause peripheral serious side effects. Contrary to common belief, neurodegenerative and neurological diseases may be multisystemic in nature, and this presents numerous difficulties for their potential treatment. Overall, the aim of this paper is to summarize the last findings and news related to liposome technology in the treatment of neurodegenerative diseases and demonstrate the potential of this technology for the development of novel therapeutics and the possible applications of liposomes in the two most widespread neurodegenerative diseases, Alzheimer's disease and Parkinson's disease.

  6. Nonpeptide neurotrophic agents useful in the treatment of neurodegenerative diseases such as Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Masaaki Akagi

    2015-02-01

    Full Text Available Developed regions, including Japan, have become “aged societies,” and the number of adults with senile dementias, such as Alzheimer's disease (AD, Parkinson's disease, and Huntington's disease, has also increased in such regions. Neurotrophins (NTs may play a role in the treatment of AD because endogenous neurotrophic factors (NFs prevent neuronal death. However, peptidyl compounds have been unable to cross the blood–brain barrier in clinical studies. Thus, small molecules, which can mimic the functions of NFs, might be promising alternatives for the treatment of neurodegenerative diseases. Natural products, such as or nutraceuticals or those used in traditional medicine, can potentially be used to develop new therapeutic agents against neurodegenerative diseases. In this review, we introduced the neurotrophic activities of polyphenols honokiol and magnolol, which are the main constituents of Magnolia obovata Thunb, and methanol extracts from Zingiber purpureum (BANGLE, which may have potential therapeutic applications in various neurodegenerative disorders.

  7. Reflection at a complex potential barrier in the semiclassical theory of scattering

    International Nuclear Information System (INIS)

    Avishai, Y.; Knoll, J.

    1976-01-01

    The reflection of spherical waves at a complex potential barrier is discussed in the semiclassical approximation. We study the complex WKB method and the Uniform Approximation in the special case of weakly absorptive barriers, typical of surface transparent optical potentials used in heavy-ion reactions. It is found that the complex WKB results lead to a very accurate cross-section despite their inaccuracy in the most important phase shifts. Thereby, the amazing stamina of the WKB has been confirmed once more. (orig.) [de

  8. Deep Machine Learning Application to the Detection of Preclinical Neurodegenerative Diseases of Aging

    Directory of Open Access Journals (Sweden)

    Mathew J. Summers

    2017-12-01

    Full Text Available Artificial intelligence (AI deep learning protocols offer solutions to complex data processing and analysis. Increasingly these solutions are being applied in the healthcare field, most commonly in processing complex medical imaging data used for diagnosis. Current models apply AI to screening populations of patients for markers of disease and report detection accuracy rates exceeding those of human data screening. In this paper, we explore an alternate model for AI deployment, that of monitoring and analysing an individual’s level of function over time. In adopting this approach, we propose that AI may provide highly accurate and reliable detection of preclinical disease states associated with aging-related neurodegenerative diseases. One of the key challenges facing clinical detection of preclinical phases of diseases such as dementia is the high degree of inter-individual variability in aging-related changes to cognitive function. AI based monitoring of an individual over time offers the potential for the early detection of change in function for the individual, rather than relying on comparing the individual’s performance to population norms. We explore an approach to developing AI platforms for individual monitoring and preclinical disease detection and examine the potential benefits to the stakeholders in this technological development.

  9. Circulating progranulin as a biomarker for neurodegenerative diseases.

    Science.gov (United States)

    Ghidoni, Roberta; Paterlini, Anna; Benussi, Luisa

    2012-01-01

    Progranulin is a growth factor involved in the regulation of multiple processes including tumorigenesis, wound repair, development, and inflammation. The recent discovery that mutations in the gene encoding for progranulin (GRN) cause frontotemporal lobar degeneration (FTLD), and other neurodegenerative diseases leading to dementia, has brought renewed interest in progranulin and its functions in the central nervous system. GRN null mutations cause protein haploinsufficiency, leading to a significant decrease in progranulin levels that can be detected in plasma, serum and cerebrospinal fluid (CSF) of mutation carriers. The dosage of circulating progranulin sped up the identification of GRN mutations thus favoring genotype-phenotype correlation studies. Researchers demonstrated that, in GRN null mutation carriers, the shortage of progranulin invariably precedes clinical symptoms and thus mutation carriers are "captured" regardless of their disease status. GRN is a particularly appealing gene for drug targeting, in the way that boosting its expression may be beneficial for mutation carriers, preventing or delaying the onset of GRN-related neurodegenerative diseases. Physiological regulation of progranulin expression level is only partially known. Progranulin expression reflects mutation status and, intriguingly, its levels can be modulated by some additional factor (i.e. genetic background; drugs). Thus, factors increasing the production and secretion of progranulin from the normal gene are promising potential therapeutic avenues. In conclusion, peripheral progranulin is a nonintrusive highly accurate biomarker for early identification of mutation carriers and for monitoring future treatments that might boost the level of this protein.

  10. Sirtuins and Their Roles in Brain Aging and Neurodegenerative Disorders.

    Science.gov (United States)

    Jęśko, Henryk; Wencel, Przemysław; Strosznajder, Robert P; Strosznajder, Joanna B

    2017-03-01

    Sirtuins (SIRT1-SIRT7) are unique histone deacetylases (HDACs) whose activity depends on NAD + levels and thus on the cellular metabolic status. SIRTs regulate energy metabolism and mitochondrial function. They orchestrate the stress response and damage repair. Through these functions sirtuins modulate the course of aging and affect neurodegenerative diseases. SIRTSs interact with multiple signaling proteins, transcription factors (TFs) and poly(ADP-ribose) polymerases (PARPs) another class of NAD + -dependent post-translational protein modifiers. The cross-talk between SIRTs TFs and PARPs is a highly promising research target in a number of brain pathologies. This review describes updated results on sirtuins in brain aging/neurodegeneration. It focuses on SIRT1 but also on the roles of mitochondrial SIRTs (SIRT3, 4, 5) and on SIRT6 and SIRT2 localized in the nucleus and in cytosol, respectively. The involvement of SIRTs in regulation of insulin-like growth factor signaling in the brain during aging and in Alzheimer's disease was also focused. Moreover, we analyze the mechanism(s) and potential significance of interactions between SIRTs and several TFs in the regulation of cell survival and death. A critical view is given on the application of SIRT activators/modulators in therapy of neurodegenerative diseases.

  11. Congo red and protein aggregation in neurodegenerative diseases.

    Science.gov (United States)

    Frid, Petrea; Anisimov, Sergey V; Popovic, Natalija

    2007-01-01

    Congo red is a commonly used histological dye for amyloid detection. The specificity of this staining results from Congo red's affinity for binding to fibril proteins enriched in beta-sheet conformation. Unexpectedly, recent investigations indicate that the dye also possesses the capacity to interfere with processes of protein misfolding and aggregation, stabilizing native protein monomers or partially folded intermediates, while reducing concentration of more toxic protein oligomers. Inhibitory effects of Congo red upon amyloid toxicity may also range from blockade of channel formation and interference with glycosaminoglycans binding or immune functions, to the modulation of gene expression. Particularly, Congo red exhibits ameliorative effect in models of neurodegenerative disorders, such as Alzheimer's, Parkinson's, Huntington's and prion diseases. Another interesting application of Congo red analogues is the development of imaging probes. Based on their small molecular size and penetrability through blood-brain barrier, Congo red congeners can be used for both antemortem and in vivo visualization and quantification of brain amyloids. Therefore, understanding mechanisms involved in dye-amyloidal fibril binding and inhibition of aggregation will provide instructive guides for the design of future compounds, potentially useful for monitoring and treating neurodegenerative diseases.

  12. Microbiota-Brain-Gut Axis and Neurodegenerative Diseases.

    Science.gov (United States)

    Quigley, Eamonn M M

    2017-10-17

    The purposes of this review were as follows: first, to provide an overview of the gut microbiota and its interactions with the gut and the central nervous system (the microbiota-gut-brain axis) in health, second, to review the relevance of this axis to the pathogenesis of neurodegenerative diseases, such as Parkinson's disease, and, finally, to assess the potential for microbiota-targeted therapies. Work on animal models has established the microbiota-gut-brain axis as a real phenomenon; to date, the evidence for its operation in man has been limited and has been confronted by considerable logistical challenges. Animal and translational models have incriminated a disturbed gut microbiota in a number of CNS disorders, including Parkinson's disease; data from human studies is scanty. While a theoretical basis can be developed for the use of microbiota-directed therapies in neurodegenerative disorders, support is yet to come from high-quality clinical trials. In theory, a role for the microbiota-gut-brain axis is highly plausible; clinical confirmation is awaited.

  13. The role of thiamine in neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Irena Bubko

    2015-09-01

    Full Text Available Vitamin B1 (thiamine plays an important role in metabolism. It is indispensable for normal growth and development of the organism. Thiamine has a favourable impact on a number of systems, including the digestive, cardiovascular and nervous systems. It also stimulates the brain and improves the psycho-emotional state. Hence it is often called the vitamin of “reassurance of the spirit”. Thiamine is a water-soluble vitamin. It can be present in the free form as thiamine or as its phosphate esters: mono-, di- or triphosphate. The main source of thiamine as an exogenous vitamin is certain foodstuffs, but trace amounts can be synthesised by microorganisms of the large intestine. The recommended daily intake of thiamine is about 2.0 mg. Since vitamin B1 has no ability to accumulate in the organism, manifestations of its deficiency begin to appear very quickly. The chronic state of thiamine deficiency, to a large extent, because of its function, contributes to the development of neurodegenerative diseases. It was proved that supporting vitamin B1 therapy not only constitutes neuroprotection but can also have a favourable impact on advanced neurodegenerative diseases. This article presents the current state of knowledge as regards the effects of thiamine exerted through this vitamin in a number of diseases such as Parkinson’s disease, Alzheimer’s disease, Wernicke’s encephalopathy or Wernicke-Korsakoff syndrome and Huntington’s disease.

  14. TRPM2, calcium and neurodegenerative diseases

    Science.gov (United States)

    Xie, Yu-Feng; MacDonald, John F; Jackson, Michael F

    2010-01-01

    NMDA receptor overactivation triggers intracellular Ca2+ dysregulation, which has long been thought to be critical for initiating excitotoxic cell death cascades associated with stroke and neurodegenerative disease. The inability of NMDA receptor antagonists to afford neuroprotection in clinical stroke trials has led to a re-evaluation of excitotoxic models of cell death and has focused research efforts towards identifying additional Ca2+ influx pathways. Recent studies indicate that TRPM2, a member of the TRPM subfamily of Ca2+-permeant, non-selective cation channel, plays an important role in mediating cellular responses to a wide range of stimuli that, under certain situations, can induce cell death. These include reactive oxygen and nitrogen species, tumour necrosis factor as well as soluble oli-gomers of amyloid beta. However, the molecular basis of TRPM2 channel involvement in these processes is not fully understood. In this review, we summarize recent studies about the regulation of TRPM2, its interaction with calcium and the possible implications for neurodegenerative diseases. PMID:21383889

  15. Ghrelin and Neurodegenerative Disorders-a Review.

    Science.gov (United States)

    Shi, Limin; Du, Xixun; Jiang, Hong; Xie, Junxia

    2017-03-01

    Ghrelin, the endogenous ligand of the growth hormone secretagogue receptor 1a (GHS-R1a), is a gut-derived, orexigenic peptide hormone that primarily regulates growth hormone secretion, food intake, and energy homeostasis. With the wide expression of GHS-R1a in extra-hypothalamic regions, the physiological role of ghrelin is more extensive than solely its involvement in metabolic function. Ghrelin has been shown to be involved in numerous higher brain functions, such as memory, reward, mood, and sleep. Some of these functions are disrupted in neurodegenerative disorders, including Parkinson's disease (PD), Alzheimer's disease (AD), and Huntington's disease (HD). This link between ghrelin and these neurodegenerative diseases is supported by numerous studies. This review aims to provide a comprehensive overview of the most recent evidence of the novel neuromodulatory role of ghrelin in PD, AD, and HD. Moreover, the changes in circulating and/or central ghrelin levels that are associated with disease progression are also postulated to be a biomarker for clinical diagnosis and therapy.

  16. Chronic traumatic encephalopathy and other neurodegenerative proteinopathies

    Directory of Open Access Journals (Sweden)

    Maria Carmela Tartaglia

    2014-01-01

    Full Text Available Chronic traumatic encephalopathy (CTE is described as a slowly progressive neurodegenerative disease believed to result from multiple concussions. Traditionally, concussions were considered benign events and although most people recover fully, about 10% develop a post-concussive syndrome with persisting neurological, cognitive and neuropsychiatric symptoms. CTE was once thought to be unique to boxers, but it has now been observed in many different athletes having suffered multiple concussions as well as in military personal after repeated blast injuries. Much remains unknown about the development of CTE but its pathological substrate is usually tau, similar to that seen in Alzheimer’s disease and frontotemporal lobar degeneration. The aim of this perspective is to compare and contrast clinical and pathological CTE with the other neurodegenerative proteinopathies and highlight that there is an urgent need for understanding the relationship between concussion and the development of CTE as it may provide a window into the development of a proteinopathy and thus new avenues for treatment.

  17. Role of agmatine in neurodegenerative diseases and epilepsy.

    Science.gov (United States)

    Moretti, Morgana; Matheus, Filipe C; de Oliveira, Paulo A; Neis, Vivian B; Ben, Juliana; Walz, Roger; Rodrigues, Ana Lucia S; Prediger, Rui Daniel

    2014-06-01

    Agmatine, a cationic polyamine synthesized after decarboxylation of L-arginine by the enzyme arginine decarboxylase, is an endogenous neuromodulator that emerges as a potential agent to manage diverse central nervous system (CNS) disorders. Consistent with its neuromodulatory and neuroprotective properties, there is increasing number of preclinical studies demonstrating the beneficial effects of exogenous agmatine administration on depression, anxiety, hypoxic ischemia, nociception, morphine tolerance, memory, Parkinson`s disease, Alzheimer`s disease, traumatic brain injury related alterations/disorders and epilepsy. The aim of this review is to summarize the knowledge about the effects of agmatine in CNS and point out its potential as new pharmacological treatment for diverse neurological and neurodegenerative diseases. Moreover, some molecular mechanisms underlying the neuroprotective effects of agmatine will be discussed.

  18. Modelling Neurodegenerative Diseases Using Human Pluripotent Stem Cells

    DEFF Research Database (Denmark)

    Hall, Vanessa Jane

    2016-01-01

    Neurodegenerative diseases are being modelled in-vitro using human patient-specific, induced pluripotent stem cells and transgenic embryonic stem cells to determine more about disease mechanisms, as well as to discover new treatments for patients. Current research in modelling Alzheimer’s disease......, frontotemporal dementia and Parkinson’s disease using pluripotent stem cells is described, along with the advent of gene-editing, which has been the complimentary tool for the field. Current methods used to model these diseases are predominantly dependent on 2D cell culture methods. Outcomes reveal that only...... that includes studying more complex 3D cell cultures, as well as accelerating aging of the neurons, may help to yield stronger phenotypes in the cultured cells. Thus, the use and application of pluripotent stem cells for modelling disease have already shown to be a powerful approach for discovering more about...

  19. The potential of sarcospan in adhesion complex replacement therapeutics for the treatment of muscular dystrophy.

    Science.gov (United States)

    Marshall, Jamie L; Kwok, Yukwah; McMorran, Brian J; Baum, Linda G; Crosbie-Watson, Rachelle H

    2013-09-01

    Three adhesion complexes span the sarcolemma and facilitate critical connections between the extracellular matrix and the actin cytoskeleton: the dystrophin- and utrophin-glycoprotein complexes and α7β1 integrin. Loss of individual protein components results in a loss of the entire protein complex and muscular dystrophy. Muscular dystrophy is a progressive, lethal wasting disease characterized by repetitive cycles of myofiber degeneration and regeneration. Protein-replacement therapy offers a promising approach for the treatment of muscular dystrophy. Recently, we demonstrated that sarcospan facilitates protein-protein interactions amongst the adhesion complexes and is an important potential therapeutic target. Here, we review current protein-replacement strategies, discuss the potential benefits of sarcospan expression, and identify important experiments that must be addressed for sarcospan to move to the clinic. © 2013 FEBS.

  20. Computational Redox Potential Predictions: Applications to Inorganic and Organic Aqueous Complexes, and Complexes Adsorbed to Mineral Surfaces

    Directory of Open Access Journals (Sweden)

    Krishnamoorthy Arumugam

    2014-04-01

    Full Text Available Applications of redox processes range over a number of scientific fields. This review article summarizes the theory behind the calculation of redox potentials in solution for species such as organic compounds, inorganic complexes, actinides, battery materials, and mineral surface-bound-species. Different computational approaches to predict and determine redox potentials of electron transitions are discussed along with their respective pros and cons for the prediction of redox potentials. Subsequently, recommendations are made for certain necessary computational settings required for accurate calculation of redox potentials. This article reviews the importance of computational parameters, such as basis sets, density functional theory (DFT functionals, and relativistic approaches and the role that physicochemical processes play on the shift of redox potentials, such as hydration or spin orbit coupling, and will aid in finding suitable combinations of approaches for different chemical and geochemical applications. Identifying cost-effective and credible computational approaches is essential to benchmark redox potential calculations against experiments. Once a good theoretical approach is found to model the chemistry and thermodynamics of the redox and electron transfer process, this knowledge can be incorporated into models of more complex reaction mechanisms that include diffusion in the solute, surface diffusion, and dehydration, to name a few. This knowledge is important to fully understand the nature of redox processes be it a geochemical process that dictates natural redox reactions or one that is being used for the optimization of a chemical process in industry. In addition, it will help identify materials that will be useful to design catalytic redox agents, to come up with materials to be used for batteries and photovoltaic processes, and to identify new and improved remediation strategies in environmental engineering, for example the

  1. Effects of Ashwagandha (roots of Withania somnifera) on neurodegenerative diseases.

    Science.gov (United States)

    Kuboyama, Tomoharu; Tohda, Chihiro; Komatsu, Katsuko

    2014-01-01

    Neurodegenerative diseases commonly induce irreversible destruction of central nervous system (CNS) neuronal networks, resulting in permanent functional impairments. Effective medications against neurodegenerative diseases are currently lacking. Ashwagandha (roots of Withania somnifera Dunal) is used in traditional Indian medicine (Ayurveda) for general debility, consumption, nervous exhaustion, insomnia, and loss of memory. In this review, we summarize various effects and mechanisms of Ashwagandha extracts and related compounds on in vitro and in vivo models of neurodegenerative diseases such as Alzheimer's disease and spinal cord injury.

  2. Representations of complex functions, means on the regular n-gon and applications to gravitational potential

    International Nuclear Information System (INIS)

    Bang, D; Elmabsout, B

    2003-01-01

    We present a method to analytically compute means of functions on regular n-gons and to study cyclic quantities of the complex variable. To achieve this, we construct representations of complex functions and compact expressions of their mean based on the use of a scalar product. Applied in the field of celestial mechanics, this method leads to results concerning gravitational potential and relative equilibrium composed by nested polygons

  3. Neurodegenerative diseases: exercising towards neurogenesis and neuroregeneration

    Directory of Open Access Journals (Sweden)

    Eng-Tat Ang

    2010-07-01

    Full Text Available Currently, there is still no effective therapy for neurodegenerative diseases (NDD such as Alzheimer’s disease (AD and Parkinson’s disease (PD despite intensive research and on-going clinical trials. Collectively, these diseases account for the bulk of health care burden associated with age-related neurodegenerative disorders. There is therefore an urgent need to further research into the molecular pathogenesis, histological differentiation, and clinical management of NDD. Importantly, there is also an urgency to understand the similarities and differences between these two diseases so as to identify the common or different upstream and downstream signaling pathways. In this review, the role iron play in NDD will be highlighted, as iron is key to a common underlying pathway in the production of oxidative stress. There is increasing evidence to suggest that oxidative stress predisposed cells to undergo damage to DNA, protein and lipid, and as such a common factor involved in the pathogenesis of AD and PD. The challenge then is to minimize elevated and uncontrolled oxidative stress levels while not affecting basal iron metabolism, as iron plays vital roles in sustaining cellular function. However, overload of iron results in increased oxidative stress due to the Fenton reaction. We discuss evidence to suggest that sustained exercise and diet restriction may be ways to slow the rate of neurodegeneration, by perhaps promoting neurogenesis or antioxidant-related pathways. It is also our intention to cover NDD in a broad sense, in the context of basic and clinical sciences to cater for both clinician’s and the scientist’s needs, and to highlight current research investigating exercise as a therapeutic or preventive measure.

  4. Seeking environmental causes of neurodegenerative disease and envisioning primary prevention.

    Science.gov (United States)

    Spencer, Peter S; Palmer, Valerie S; Kisby, Glen E

    2016-09-01

    Pathological changes of the aging brain are expressed in a range of neurodegenerative disorders that will impact increasing numbers of people across the globe. Research on the causes of these disorders has focused heavily on genetics, and strategies for prevention envision drug-induced slowing or arresting disease advance before its clinical appearance. We discuss a strategic shift that seeks to identify the environmental causes or contributions to neurodegeneration, and the vision of primary disease prevention by removing or controlling exposure to culpable agents. The plausibility of this approach is illustrated by the prototypical neurodegenerative disease amyotrophic lateral sclerosis and parkinsonism-dementia complex (ALS-PDC). This often-familial long-latency disease, once thought to be an inherited genetic disorder but now known to have a predominant or exclusive environmental origin, is in the process of disappearing from the three heavily affected populations, namely Chamorros of Guam and Rota, Japanese residents of Kii Peninsula, Honshu, and Auyu and Jaqai linguistic groups on the island of New Guinea in West Papua, Indonesia. Exposure via traditional food and/or medicine (the only common exposure in all three geographic isolates) to one or more neurotoxins in seed of cycad plants is the most plausible if yet unproven etiology. Neurotoxin dosage and/or subject age at exposure might explain the stratified epidemic of neurodegenerative disease on Guam in which high-incidence ALS peaked and declined before that of PD, only to be replaced today by a dementing disorder comparable to Alzheimer's disease. Exposure to the Guam environment is also linked to the delayed development of ALS among a subset of Chamorro and non-Chamorro Gulf War/Era veterans, a summary of which is reported here for the first time. Lessons learned from this study and from 65 years of research on ALS-PDC include the exceptional value of initial, field-based informal investigation of

  5. Loss of 'complexity' and aging. Potential applications of fractals and chaos theory to senescence

    Science.gov (United States)

    Lipsitz, L. A.; Goldberger, A. L.

    1992-01-01

    The concept of "complexity," derived from the field of nonlinear dynamics, can be adapted to measure the output of physiologic processes that generate highly variable fluctuations resembling "chaos." We review data suggesting that physiologic aging is associated with a generalized loss of such complexity in the dynamics of healthy organ system function and hypothesize that such loss of complexity leads to an impaired ability to adapt to physiologic stress. This hypothesis is supported by observations showing an age-related loss of complex variability in multiple physiologic processes including cardiovascular control, pulsatile hormone release, and electroencephalographic potentials. If further research supports this hypothesis, measures of complexity based on chaos theory and the related geometric concept of fractals may provide new ways to monitor senescence and test the efficacy of specific interventions to modify the age-related decline in adaptive capacity.

  6. Complex energy eigenvalues of a linear potential with a parabolical barrier

    International Nuclear Information System (INIS)

    Malherbe, J.B.

    1978-01-01

    The physical meaning and restrictions of complex energy eigenvalues are briefly discussed. It is indicated that a quasi-stationary phase describes an idealised disintegration system. Approximate resonance-eigenvalues of the one dimensional Schrodinger equation with a linear potential and parabolic barrier are calculated by means of Connor's semiclassical method. This method is based on the generalized WKB-method of Miller and Good. The results obtained confirm the correctness of a model representation which explains the unusual distribution of eigenvalues by certain other linear potentials in a complex energy level [af

  7. Early Diagnosis and Monitoring of Neurodegenerative Langerhans Cell Histiocytosis.

    Directory of Open Access Journals (Sweden)

    Elena Sieni

    Full Text Available Neurodegenerative Langerhans Cell Histiocytosis (ND-LCH is a rare, unpredictable consequence that may devastate the quality of life of patients cured from LCH. We prospectively applied a multidisciplinary diagnostic work-up to early identify and follow-up patients with ND-LCH, with the ultimate goal of better determining the appropriate time for starting therapy.We studied 27 children and young adults with either ND-LCH verified by structural magnetic resonance imaging (MRI (group 1 or specific risk factors for (diabetes insipidus, craniofacial bone lesions, but no evidence of, neurodegenerative MRI changes (group 2. All patients underwent clinical, neurophysiological and MRI studies.Seventeen patients had MRI alterations typical for ND-LCH. Nine showed neurological impairment but only three were symptomatic; 11 had abnormal somatosensory evoked potentials (SEPs, and five had abnormal brainstem auditory evoked potentials (BAEPs. MR spectroscopy (MRS showed reduced cerebellar NAA/Cr ratio in nine patients. SEPs showed sensitivity, specificity, positive predictive value (PPV and negative predictive value (NPV for predicting ND-LCH of 70.6% (95%CI, 44.0%-89.7%, 100% (69.2%-100%, 100% (73.5%-100%, and 66.7% (38.4%-88.2%, respectively. Repeated investigations in group 1 revealed increasingly abnormal EP parameters, or neurological examination, or both, in nine of fifteen patients while MRI remained unchanged in all but one patient.A targeted MRI study should be performed in all patients with risk factors for ND-LCH for early identification of demyelination. The combined use of SEPs and careful neurological evaluation may represent a valuable, low-cost, well-tolerated and easily available methodology to monitor patients from pre-symptomatic to symptomatic stages. We suggest a multidisciplinary protocol including clinical, MRS, and neurophysiological investigations to identify a population target for future therapeutic trials.

  8. A new synthesis route for Os-complex modified redox polymers for potential biofuel cell applications.

    Science.gov (United States)

    Pöller, Sascha; Beyl, Yvonne; Vivekananthan, Jeevanthi; Guschin, Dmitrii A; Schuhmann, Wolfgang

    2012-10-01

    A new synthesis route for Os-complex modified redox polymers was developed. Instead of ligand exchange reactions for coordinative binding of suitable precursor Os-complexes at the polymer, Os-complexes already exhibiting the final ligand shell containing a suitable functional group were bound to the polymer via an epoxide opening reaction. By separation of the polymer synthesis from the ligand exchange reaction at the Os-complex, the modification of the same polymer backbone with different Os-complexes or the binding of the same Os-complex to a number of different polymer backbones becomes feasible. In addition, the Os-complex can be purified and characterized prior to its binding to the polymer. In order to further understand and optimize suitable enzyme/redox polymer systems concerning their potential application in biosensors or biofuel cells, a series of redox polymers was synthesized and used as immobilization matrix for Trametes hirsuta laccase. The properties of the obtained biofuel cell cathodes were compared with similar biocatalytic interfaces derived from redox polymers obtained via ligand exchange reaction of the parent Os-complex with a ligand integrated into the polymer backbone during the polymer synthesis. Copyright © 2011 Elsevier B.V. All rights reserved.

  9. [Sense of smell, physiological ageing and neurodegenerative diseases: II. Ageing and neurodegenerative diseases].

    Science.gov (United States)

    Fusari, A; Molina, J A

    The sense of smell, which was once studied because of its biological and evolutionary significance, is today one of the centres of interest in research on normal and pathological ageing. The latest scientific developments point to an inversely proportional relationship between age and olfactory sensitivity. In certain neurodegenerative diseases this sensory decline is one of the first symptoms of the disorder and is correlated with the progression of the disease. In this work we are going to review the scientific knowledge on loss of sense of smell in ageing and in neurodegenerative diseases, with special attention given to Alzheimer's and Parkinson's diseases. A survey of studies that have examined the olfactory deficits in ageing and in some neurodegenerative diseases offers conclusive results about the presence of these impairments in the early stages of these disorders and even among healthy elderly persons. Although a number of causes contribute to these sensory losses in physiological ageing, a common neurological foundation has been proposed for Alzheimer's and Parkinson's diseases. Nevertheless, despite certain initial similarities, the olfactory deficits shown in these disorders seem to be qualitatively different.

  10. Collisional effects on interaction potential in complex plasma in presence of magnetic field

    Energy Technology Data Exchange (ETDEWEB)

    Bezbaruah, Pratikshya, E-mail: pratphd@tezu.ernet.in; Das, Nilakshi [Department of Physics, Tezpur University, Tezpur, Assam 784028 (India)

    2016-04-15

    Interaction potential in complex plasma with streaming ions is derived analytically in presence of ion-neutral collision and magnetic field. The linear dielectric response function obtained describes the behavior of charged micron sized dust particles in strong collisional limit. A new type of repulsive potential is found to be operative among the dust grains apart from the normal Debye–Hückel potential. The amplitude and shielding length involved in the potential are substantially affected by the parameters describing ion cyclotron frequency, collision frequency among ions and neutrals, and ion streaming. It is also observed that the usual mechanism of ion focusing surrounding the grain is inhibited due to collision. As a result, the attractive wake potential structure is destroyed in the ion flow direction. The horizontal interaction involves only Debye–Hückel potential.

  11. Collisional effects on interaction potential in complex plasma in presence of magnetic field

    International Nuclear Information System (INIS)

    Bezbaruah, Pratikshya; Das, Nilakshi

    2016-01-01

    Interaction potential in complex plasma with streaming ions is derived analytically in presence of ion-neutral collision and magnetic field. The linear dielectric response function obtained describes the behavior of charged micron sized dust particles in strong collisional limit. A new type of repulsive potential is found to be operative among the dust grains apart from the normal Debye–Hückel potential. The amplitude and shielding length involved in the potential are substantially affected by the parameters describing ion cyclotron frequency, collision frequency among ions and neutrals, and ion streaming. It is also observed that the usual mechanism of ion focusing surrounding the grain is inhibited due to collision. As a result, the attractive wake potential structure is destroyed in the ion flow direction. The horizontal interaction involves only Debye–Hückel potential.

  12. On solving the Schrödinger equation for a complex deictic potential ...

    Indian Academy of Sciences (India)

    The imaginary part of the energy eigenvalue exists only if the potential parameters are complex, whereas it reduces to zero for real coupling parameters and the result coincides with those derived from the invariance of Hamiltonian under PT operations. Thus, a non-Hermitian. Hamiltonian possesses real eigenvalue, if it is ...

  13. Comparative Incidence of Conformational, Neurodegenerative Disorders.

    Directory of Open Access Journals (Sweden)

    Jesús de Pedro-Cuesta

    Full Text Available The purpose of this study was to identify incidence and survival patterns in conformational neurodegenerative disorders (CNDDs.We identified 2563 reports on the incidence of eight conditions representing sporadic, acquired and genetic, protein-associated, i.e., conformational, NDD groups and age-related macular degeneration (AMD. We selected 245 papers for full-text examination and application of quality criteria. Additionally, data-collection was completed with detailed information from British, Swedish, and Spanish registries on Creutzfeldt-Jakob disease (CJD forms, amyotrophic lateral sclerosis (ALS, and sporadic rapidly progressing neurodegenerative dementia (sRPNDd. For each condition, age-specific incidence curves, age-adjusted figures, and reported or calculated median survival were plotted and examined.Based on 51 valid reported and seven new incidence data sets, nine out of eleven conditions shared specific features. Age-adjusted incidence per million person-years increased from ≤1.5 for sRPNDd, different CJD forms and Huntington's disease (HD, to 1589 and 2589 for AMD and Alzheimer's disease (AD respectively. Age-specific profiles varied from (a symmetrical, inverted V-shaped curves for low incidences to (b those increasing with age for late-life sporadic CNDDs and for sRPNDd, with (c a suggested, intermediate, non-symmetrical inverted V-shape for fronto-temporal dementia and Parkinson's disease. Frequently, peak age-specific incidences from 20-24 to ≥90 years increased with age at onset and survival. Distinct patterns were seen: for HD, with a low incidence, levelling off at middle age, and long median survival, 20 years; and for sRPNDd which displayed the lowest incidence, increasing with age, and a short median disease duration.These results call for a unified population view of NDDs, with an age-at-onset-related pattern for acquired and sporadic CNDDs. The pattern linking age at onset to incidence magnitude and survival might

  14. Comparative Incidence of Conformational, Neurodegenerative Disorders

    Science.gov (United States)

    de Pedro-Cuesta, Jesús; Rábano, Alberto; Martínez-Martín, Pablo; Ruiz-Tovar, María; Alcalde-Cabero, Enrique; Almazán-Isla, Javier; Avellanal, Fuencisla; Calero, Miguel

    2015-01-01

    Background The purpose of this study was to identify incidence and survival patterns in conformational neurodegenerative disorders (CNDDs). Methods We identified 2563 reports on the incidence of eight conditions representing sporadic, acquired and genetic, protein-associated, i.e., conformational, NDD groups and age-related macular degeneration (AMD). We selected 245 papers for full-text examination and application of quality criteria. Additionally, data-collection was completed with detailed information from British, Swedish, and Spanish registries on Creutzfeldt-Jakob disease (CJD) forms, amyotrophic lateral sclerosis (ALS), and sporadic rapidly progressing neurodegenerative dementia (sRPNDd). For each condition, age-specific incidence curves, age-adjusted figures, and reported or calculated median survival were plotted and examined. Findings Based on 51 valid reported and seven new incidence data sets, nine out of eleven conditions shared specific features. Age-adjusted incidence per million person-years increased from ≤1.5 for sRPNDd, different CJD forms and Huntington's disease (HD), to 1589 and 2589 for AMD and Alzheimer's disease (AD) respectively. Age-specific profiles varied from (a) symmetrical, inverted V-shaped curves for low incidences to (b) those increasing with age for late-life sporadic CNDDs and for sRPNDd, with (c) a suggested, intermediate, non-symmetrical inverted V-shape for fronto-temporal dementia and Parkinson's disease. Frequently, peak age-specific incidences from 20–24 to ≥90 years increased with age at onset and survival. Distinct patterns were seen: for HD, with a low incidence, levelling off at middle age, and long median survival, 20 years; and for sRPNDd which displayed the lowest incidence, increasing with age, and a short median disease duration. Interpretation These results call for a unified population view of NDDs, with an age-at-onset-related pattern for acquired and sporadic CNDDs. The pattern linking age at onset to

  15. Studies on polyaspartamide gadolinium complexes as potential magnetic resonance imaging contrast agents

    International Nuclear Information System (INIS)

    Yan Guoping; Liu Maili; Li Liyun

    2005-01-01

    Purpose: A series of polyaspartamide gadolinium complexes containing pyridoxamine groups were studied as the potential magnetic resonance imaging (MRI) contrast agents for liver enhancement. Methods: These polyaspartamide gadolinium complexes were prepared and evaluated by relaxivity, acute toxicity studies and magnetic resonance imaging of the liver in rats. Results: These polyaspartamide gadolinium complexes have higher relaxation effectiveness than that of the clinically used gadolinium diethylenetriaminepentaacetic acid and possess the low intravenous acute toxicities to Institute for Cancer Research (ICR) mice. Magnetic resonance imaging of the liver in rats indicated that they greatly enhance the contrast of magnetic resonance images and provide prolonged intravascular duration in the liver. Conclusion: These results indicated that the polyaspartamide gadolinium complexes containing pyridoxamine groups could be considered as the appropriate MRI contrast agents for liver enhancement

  16. The potential of sarcospan in adhesion complex replacement therapeutics for the treatment of muscular dystrophy

    Science.gov (United States)

    Marshall, Jamie L.; Kwok, Yukwah; McMorran, Brian; Baum, Linda G.; Crosbie-Watson, Rachelle H.

    2013-01-01

    Three adhesion complexes span the sarcolemma and facilitate critical connections between the extracellular matrix and the actin cytoskeleton: the dystrophin- and utrophin-glycoprotein complexes and α7β1 integrin. Loss of individual protein components results in a loss of the entire protein complex and muscular dystrophy. Muscular dystrophy is a progressive, lethal wasting disease characterized by repetitive cycles of myofiber degeneration and regeneration. Protein replacement therapy offers a promising approach for the treatment of muscular dystrophy. Recently, we demonstrated that sarcospan facilitates protein-protein interactions amongst the adhesion complexes and is an important therapeutic target. Here, we review current protein replacement strategies, discuss the potential benefits of sarcospan expression, and identify important experiments that must be addressed for sarcospan to move to the clinic. PMID:23601082

  17. THE MITOCHONDRIAL DERANGEMENTS IN NEURONAL DEGENER ATION AND NEURODEGENERATIVE DISEASES

    Institute of Scientific and Technical Information of China (English)

    Xue, Qi-ming; Gao, Feng; Chen, Qin-tang

    2000-01-01

    @@There are diverse concepts on the pathogenesis of neuronal degeneration and the neurodegenerative diseases. Among them there are different factors which might influence the initiation of neuronal degeneration as well as the pathogenesis of neurodegenerative diseases, such as Alzheimer′s disease, Parkinson′s disease, motor neuron disease, and so on.

  18. Neurodegenerative diseases of the central motor system in MRI

    International Nuclear Information System (INIS)

    Alfke, K.

    2005-01-01

    Neurodegenerative diseases of the central motor system often lead to discrete but functionally important parenchymal abnormalities in various parts of the brain. MRI is the most sensitive imaging method to detect these abnormalities. Various neurodegenerative diseases are presented with their clinical symptoms and MRI findings. Criteria for differential diagnosis are provided as well. (orig.)

  19. Glial hemichannels and their involvement in aging and neurodegenerative diseases.

    Science.gov (United States)

    Orellana, Juan A; von Bernhardi, Rommy; Giaume, Christian; Sáez, Juan C

    2012-01-26

    During the last two decades, it became increasingly evident that glial cells accomplish a more important role in brain function than previously thought. Glial cells express pannexins and connexins, which are member subunits of two protein families that form membrane channels termed hemichannels. These channels communicate intra- and extracellular compartments and allow the release of autocrine/paracrine signaling molecules [e.g., adenosine triphosphate (ATP), glutamate, nicotinamide adenine dinucleotide, and prostaglandin E2] to the extracellular milieu, as well as the uptake of small molecules (e.g., glucose). An increasing body of evidence has situated glial hemichannels as potential regulators of the beginning and maintenance of homeostatic imbalances observed in diverse brain diseases. Here, we review and discuss the current evidence about the possible role of glial hemichannels on neurodegenerative diseases. A subthreshold pathological threatening condition leads to microglial activation, which keeps active defense and restores the normal function of the central nervous system. However, if the stimulus is deleterious, microglial cells and the endothelium become overactivated, both releasing bioactive molecules (e.g., glutamate, cytokines, prostaglandins, and ATP), which increase the activity of glial hemichannels, reducing the astroglial neuroprotective functions, and further reducing neuronal viability. Because ATP and glutamate are released via glial hemichannels in neurodegenerative conditions, it is expected that they contribute to neurotoxicity. More importantly, toxic molecules released via glial hemichannels could increase the Ca2+ entry in neurons also via neuronal hemichannels, leading to neuronal death. Therefore, blockade of hemichannels expressed by glial cells and/or neurons during neuroinflammation might prevent neurodegeneration.

  20. Animal Toxins as Therapeutic Tools to Treat Neurodegenerative Diseases

    Science.gov (United States)

    de Souza, Jessica M.; Goncalves, Bruno D. C.; Gomez, Marcus V.; Vieira, Luciene B.; Ribeiro, Fabiola M.

    2018-01-01

    Neurodegenerative diseases affect millions of individuals worldwide. So far, no disease-modifying drug is available to treat patients, making the search for effective drugs an urgent need. Neurodegeneration is triggered by the activation of several cellular processes, including oxidative stress, mitochondrial impairment, neuroinflammation, aging, aggregate formation, glutamatergic excitotoxicity, and apoptosis. Therefore, many research groups aim to identify drugs that may inhibit one or more of these events leading to neuronal cell death. Venoms are fruitful natural sources of new molecules, which have been relentlessly enhanced by evolution through natural selection. Several studies indicate that venom components can exhibit selectivity and affinity for a wide variety of targets in mammalian systems. For instance, an expressive number of natural peptides identified in venoms from animals, such as snakes, scorpions, bees, and spiders, were shown to lessen inflammation, regulate glutamate release, modify neurotransmitter levels, block ion channel activation, decrease the number of protein aggregates, and increase the levels of neuroprotective factors. Thus, these venom components hold potential as therapeutic tools to slow or even halt neurodegeneration. However, there are many technological issues to overcome, as venom peptides are hard to obtain and characterize and the amount obtained from natural sources is insufficient to perform all the necessary experiments and tests. Fortunately, technological improvements regarding heterologous protein expression, as well as peptide chemical synthesis will help to provide enough quantities and allow chemical and pharmacological enhancements of these natural occurring compounds. Thus, the main focus of this review is to highlight the most promising studies evaluating animal toxins as therapeutic tools to treat a wide variety of neurodegenerative conditions, including Alzheimer’s disease, Parkinson’s disease, brain

  1. Comparison of Degrees of Potential-Energy-Surface Anharmonicity for Complexes and Clusters with Hydrogen Bonds

    Science.gov (United States)

    Kozlovskaya, E. N.; Doroshenko, I. Yu.; Pogorelov, V. E.; Vaskivskyi, Ye. V.; Pitsevich, G. A.

    2018-01-01

    Previously calculated multidimensional potential-energy surfaces of the MeOH monomer and dimer, water dimer, malonaldehyde, formic acid dimer, free pyridine-N-oxide/trichloroacetic acid complex, and protonated water dimer were analyzed. The corresponding harmonic potential-energy surfaces near the global minima were constructed for series of clusters and complexes with hydrogen bonds of different strengths based on the behavior of the calculated multidimensional potential-energy surfaces. This enabled the introduction of an obvious anharmonicity parameter for the calculated potential-energy surfaces. The anharmonicity parameter was analyzed as functions of the size of the analyzed area near the energy minimum, the number of points over which energies were compared, and the dimensionality of the solved vibrational problem. Anharmonicity parameters for potential-energy surfaces in complexes with strong, medium, and weak H-bonds were calculated under identical conditions. The obtained anharmonicity parameters were compared with the corresponding diagonal anharmonicity constants for stretching vibrations of the bridging protons and the lengths of the hydrogen bridges.

  2. Expression of Nrf2 in neurodegenerative diseases.

    Science.gov (United States)

    Ramsey, Chenere P; Glass, Charles A; Montgomery, Marshall B; Lindl, Kathryn A; Ritson, Gillian P; Chia, Luis A; Hamilton, Ronald L; Chu, Charleen T; Jordan-Sciutto, Kelly L

    2007-01-01

    In response to oxidative stress, the nuclear factor E2-related factor 2 (Nrf2) transcription factor translocates from the cytoplasm into the nucleus and transactivates expression of genes with antioxidant activity. Despite this cellular mechanism, oxidative damage is abundant in Alzheimer and Parkinson disease (AD and PD). To investigate mechanisms by which Nrf2 activity may be aberrant or insufficient in neurodegenerative conditions, we assessed Nrf2 localization in affected brain regions of AD, Lewy body variant of AD (LBVAD), and PD. By immunohistochemistry, Nrf2 is expressed in both the nucleus and the cytoplasm of neurons in normal hippocampi with predominant expression in the nucleus. In AD and LBVAD, Nrf2 was predominantly cytoplasmic in hippocampal neurons and was not a major component of beta amyloid plaques or neurofibrillary tangles. By immunoblotting, we observed a significant decrease in nuclear Nrf2 levels in AD cases. In contrast, Nrf2 was strongly nuclear in PD nigral neurons but cytoplasmic in substantia nigra of normal, AD, and LBVAD cases. These findings suggest that Nrf2-mediated transcription is not induced in neurons in AD despite the presence of oxidative stress. In PD, nuclear localization of Nrf2 is strongly induced, but this response may be insufficient to protect neurons from degeneration.

  3. Computed tomography of neurodegenerative disease in childhood

    International Nuclear Information System (INIS)

    Kataoka, Kenkichi; Nakagawa, Yoshihiro; Hojo, Hiroatsu

    1984-01-01

    Serial computed tomographic scans were performed on seven children with neurodegenerative disorders. In two cases of white-matter diseases (Krabbe's disease and metachromatic leukodystrophy), diffuse, low-density lesions of white matter were visible in the early stage of the diseases. In one case of adrenoleukodystrophy, regional low-density lesions of the white matter around the posterior horns and peculiar high-density strip lesions were visible in the early stage. In two cases of storage-type gray-matter diseases (Tay-Sachs' and infantile Gaucher's disease), there were no abnormalities in the early stage, but diffuse cortical atrophies in the late stage. In one case of Leigh's disease, there were small, low-density lesions of the basal ganglia and multiple low-density lesions of the gray matter in the early stage. In one case of subacute sclerosing panencephalitis, there were no abnormalities in the early stage, but small, low-density lesions of the basal ganglia and diffuse cerebral atrophies in the late stage. Diagnostic values were recognized dominantly in two cases of adrenoleukodystrophy and Leigh's disease. In the other cases, however, serial CT scans were useful in the diagnostic process. (author)

  4. Folic acid, neurodegenerative and neuropsychiatric disease.

    Science.gov (United States)

    Kronenberg, Golo; Colla, Michael; Endres, Matthias

    2009-04-01

    Folic acid plays an important role in neuroplasticity and in the maintenance of neuronal integrity. Folate is a co-factor in one-carbon metabolism during which it promotes the regeneration of methionine from homocysteine, a highly reactive sulfur-containing amino acid. Methionine may then be converted to S-adenosylmethionine (SAM), the principal methyl donor in most biosynthetic methylation reactions. On the cellular level, folate deficiency and hyperhomocysteinemia exert multiple detrimental effects. These include induction of DNA damage, uracil misincorporation into DNA and altered patterns of DNA methylation. Low folate status and elevated homocysteine increase the generation of reactive oxygen species and contribute to excitotoxicity and mitochondrial dysfunction which may lead to apoptosis. Strong epidemiological and experimental evidence links derangements of one-carbon metabolism to vascular, neurodegenerative and neuropsychiatric disease, including most prominently cerebral ischemia, Alzheimer's dementia and depression. Although firm evidence from controlled clinical trials is largely lacking, B-vitamin supplementation and homocysteine reduction may have a role especially in the primary prevention of stroke and dementia as well as as an adjunct to antidepressant pharmacotherapy.

  5. Non-coding RNA and pseudogenes in neurodegenerative diseases: "The (unUsual Suspects"

    Directory of Open Access Journals (Sweden)

    Valerio eCosta

    2012-10-01

    Full Text Available Neurodegenerative disorders and cancer are severe diseases threatening human health. The glaring differences between neurons and cancer cells mask the processes involved in their pathogenesis. Defects in cell cycle, DNA repair and cell differentiation can determine unlimited proliferation in cancer, or conversely, compromise neuronal plasticity, leading to cell death and neurodegeneration.Alteration in regulatory networks affecting gene expression contribute to human diseases' onset, including neurodegenerative disorders, and deregulation of non-coding RNAs - particularly microRNAs - is supposed to have a significant impact.Recently, competitive endogenous RNAs - acting as sponges - have been identified in cancer, indicating a new and intricate regulatory network. Given that neurodegenerative disorders and cancer share altered genes and pathways, and considering the emerging role of microRNAs in neurogenesis, we hypothesize competitive endogenous RNAs may be implicated in neurodegenerative diseases. Here we propose, and computationally predict, such regulatory mechanism may be shared between the diseases. It is predictable that similar regulation occurs in other complex diseases, and further investigation is needed.

  6. Repurposing of Copper(II)-chelating Drugs for the Treatment of Neurodegenerative Diseases.

    Science.gov (United States)

    Lanza, Valeria; Milardi, Danilo; Di Natale, Giuseppe; Pappalardo, Giuseppe

    2018-02-12

    There is mounting urgency to find new drugs for the treatment of neurodegenerative disorders. A large number of reviews have exhaustively described either the molecular or clinical aspects of neurodegenerative diseases such as Alzheimer's (AD) and Parkinson's (PD). Conversely, reports outlining how known drugs in use for other diseases can also be effective as therapeutic agents in neurodegenerative diseases are less reported. This review focuses on the current uses of some copper(II) chelating molecules as potential drug candidates in neurodegeneration. Starting from the well-known harmful relationships existing between the dyshomeostasis and mis-management of metals and AD onset, we surveyed the experimental work reported in the literature, which deals with the repositioning of metal-chelating drugs in the field of neurodegenerative diseases. The reviewed papers were retrieved from common literature and their selection was limited to those describing the biomolecular aspects associated with neuroprotection. In particular, we emphasized the copper(II) coordination abilities of the selected drugs. Copper, together with zinc and iron, are known to play a key role in regulating neuronal functions. Changes in copper homeostasis are crucial for several neurodegenerative disorders. The studies included in this review may provide an overview on the current strategies aimed at repurposing copper (II) chelating drugs for the treatment of neurodegenerative disorders. Starting from the exemplary case of clioquinol repurposing, we discuss the challenge and the opportunities that repurposing of other metal-chelating drugs may provide (e.g. PBT-2, metformin and cyclodipeptides) in the treatment of neurodegenerative disease. In order to improve the success rate of drug repositioning, comprehensive studies on the molecular mechanism and therapeutic efficacy are still required. The present review upholds that drug repurposing makes significant advantages over drug discovery since

  7. The Spectroscopic and Conductive Properties of Ru(II Complexes with Potential Anticancer Properties

    Directory of Open Access Journals (Sweden)

    Adebayo A. Adeniyi

    2014-01-01

    Full Text Available Different density functional methods (DFT have been used to optimize and study the chemistry of five potential anticancer complexes in terms of their electronic, conductive, and spectroscopic properties. Many of the computed properties in addition to the IR and QTAIM analysis of the NMR are dipole moment vector (μi, linear polarizability tensor (αij, first hyperpolarizability tensors (βijk, polarizability exaltation index (Γ, and chemical hardness (η of the complexes. Stable low energy geometries are obtained using basis set with effective core potential (ECP approximation but, in the computation of atomic or molecular properties, the metal Ru atom is better treated with higher all electron basis set like DGDZVP. The spectroscopic features like the IR of the metal-ligand bonds and the isotropic NMR shielding tensor of the coordinated atoms are significantly influenced by the chemical environment of the participating atoms. The carboxylic and pyrazole units are found to significantly enhance the polarizabilities and hyperpolarizabilities of the complexes while the chloride only improves the polarity of the complexes. Fermi contacts (FC have the highest effect followed by the PSO among all the four Ramsey terms which defined the total spin-spin coupling constant J (HZ of these complexes.

  8. Lower urinary tract dysfunction in patients with parkinsonism and other neurodegenerative disorders

    DEFF Research Database (Denmark)

    Winge, Kristian

    2015-01-01

    of incontinence in Alzheimer's disease, but higher cognitive function including attention and self-management may play a role. Incontinence is a major risk factor for loss of independence. The complex pathophysiologic mechanisms of neurodegenerative disorders and hence complex symptoms play important roles......Progressive neurodegenerative disorders are devastating diseases with often fatal outcomes. Lower urinary tract symptoms (LUTS) add to morbidity and increase the risk of becoming dependent on the help of others (e.g., nursing-home referral). In Parkinson's disease (PD), the specific loss...... in LUTS and patient quality of life. Nocturia, incontinence, and urgency as well as poor bladder emptying are the most common symptoms. These symptoms may interact with the core symptoms of the disorders, increasing the risk of incontinence and infection. In rarer neurogenerative disorder LUTS may...

  9. Error Estimates for Approximate Solutions of the Riccati Equation with Real or Complex Potentials

    Science.gov (United States)

    Finster, Felix; Smoller, Joel

    2010-09-01

    A method is presented for obtaining rigorous error estimates for approximate solutions of the Riccati equation, with real or complex potentials. Our main tool is to derive invariant region estimates for complex solutions of the Riccati equation. We explain the general strategy for applying these estimates and illustrate the method in typical examples, where the approximate solutions are obtained by gluing together WKB and Airy solutions of corresponding one-dimensional Schrödinger equations. Our method is motivated by, and has applications to, the analysis of linear wave equations in the geometry of a rotating black hole.

  10. Oxotechnetium and Oxorhenium 3+1 mixed ligand complexes as potential melanoma targeting gents

    International Nuclear Information System (INIS)

    Rey, A.; Giglio, J.; Leon, E.; Paolino, A.; Fernandez, R.; Manta, E.; Leon, A.; Pirmettis, I.; Papadopoulos, M.; Schreiber, F.; Chabalgoity, J.

    2005-01-01

    Tc-99m '3+1' mixed ligand complexes with potential affinity for melanoma have been designed by an integrated approach using N-alkyl substituted benzamides as leader structure. This paper presents the preparation of a series of complexes with general formula Tc-99m O[(CH 3 CH 2 ) 2 N(CH 2 ) 2 N (CH 2 CH 2 ) 2 S) 2 ][RS] and their 'in vivo' evaluation as potential melanoma targeting agents. Tc-99m complexes Tc1, Tc2, Tc3 and Tc4 were prepared by combining the tridentate ligand N,N-bis(2-mercaptoethyl)-N',N'-diethylethylenediamine with 4 different modentate thiols. Labelling was performed by substitution using Tc-99m-glucoheptonate as precursor. All complexes were obtained with high yield ( 85%) and high radiochemical purity (90%). Identity of Tc compounds was corroborated by HPLC coinjection with the analogous rhenium complexes. Biodistribution studies were performed on the murine C57B16 mouse melanoma model obtained by subcutaneous inoculation of melanoma cells B16F1. After intravenous injection, all complexes showed high initial blood, lung and liver uptake but clearance after 12-24 hours was almost complete. Initial tumour uptake was relatively high (0.83.4% dose/g at 2 hrs. post-injection) and retention until 24 hours significant (0.450.88% dose/g). Tumour/blood and tumour/muscle ratios were favourable from 6 to 24 hours after injection due to fast blood and soft tissue clearance. Complex Tc2 showed the best tumour/blood and tumour/muscle ratios at 12 and 24 hours post-injection (1.9-2.4 and 7.5-12.0, respectively). Early and late static gamma-camera images acquired for this compound allowed delineation of the tumour with tumour/soft tissue ratios 7.4 at 12 hours. post/inj.) Complex Tc2 was also administered subcutaneously in the peritumoral region of melanoma bearing mice, in order to avoid high liver and hepatobiliary doses. In this condition, a very high percentage of the injected dose remained in the tumour, even after 24 hours (21.5%/g) with considerably

  11. Parametrization of complex absorbing potentials for time-dependent quantum dynamics

    International Nuclear Information System (INIS)

    Vibok, A.; Balint-Kurti, G.G.

    1992-01-01

    Five different forms of complex absorbing potentials are examined and compared. Such potentials are needed to absorb wavepackets near the edges of grids in time-dependent quantum dynamical calculations. The extent to which the different potentials transmit or reflect an incident wavepacket is quantified, and optimal potential parameters to minimize both the reflection and transmission for each type of potential are derived. A rigorously derived scaling procedure, which permits the derivation of optimal potential parameters for use with any chosen mass or kinetic energy from those optimized for different conditions, is described. Tables are also presented which permit the immediate selection of the parameters for an absorbing potential of a particular form so as to allow a preselected (very small) degree of transmitted plus reflected probability to be attained. It is always desirable to devote a minimal region to the absorbing potential, while at the same time effectively absorbing all of the wavepacket and neither transmitting nor reflecting any of it. The tables presented here enable the use to easily select the potential parameters he will require to attain these goals. 23 refs., 7 figs., 4 tabs

  12. Surface Complexation Modeling of Calcite Zeta Potential Measurement in Mixed Brines for Carbonate Wettability Characterization

    Science.gov (United States)

    Song, J.; Zeng, Y.; Biswal, S. L.; Hirasaki, G. J.

    2017-12-01

    We presents zeta potential measurements and surface complexation modeling (SCM) of synthetic calcite in various conditions. The systematic zeta potential measurement and the proposed SCM provide insight into the role of four potential determining cations (Mg2+, SO42- , Ca2+ and CO32-) and CO2 partial pressure in calcite surface charge formation and facilitate the revealing of calcite wettability alteration induced by brines with designed ionic composition ("smart water"). Brines with varying potential determining ions (PDI) concentration in two different CO2 partial pressure (PCO2) are investigated in experiments. Then, a double layer SCM is developed to model the zeta potential measurements. Moreover, we propose a definition for contribution of charged surface species and quantitatively analyze the variation of charged species contribution when changing brine composition. After showing our model can accurately predict calcite zeta potential in brines containing mixed PDIs, we apply it to predict zeta potential in ultra-low and pressurized CO2 environments for potential applications in carbonate enhanced oil recovery including miscible CO2 flooding and CO2 sequestration in carbonate reservoirs. Model prediction reveals that pure calcite surface will be positively charged in all investigated brines in pressurized CO2 environment (>1atm). Moreover, the sensitivity of calcite zeta potential to CO2 partial pressure in the various brine is found to be in the sequence of Na2CO3 > Na2SO4 > NaCl > MgCl2 > CaCl2 (Ionic strength=0.1M).

  13. Can Different Complex Training Improve the Individual Phenomenon of Post-Activation Potentiation?

    Science.gov (United States)

    Chen, Zong-Rong; Lo, Shin-Liang; Wang, Min-Hsien; Yu, Ching-Fang; Peng, Hsien-Te

    2017-02-01

    The aims of the present study were (a) to determine whether the two types of complex training and vibration complex training would improve the individual phenomenon of post-activation potentiation (PAP) for every athlete in a team setting; and (b) to compare the acute effect of resistance and plyometric exercise, whole body vibration, complex training and vibration complex training on vertical jump performance. The participants were ten male division I college volleyball and basketball players. They were asked to perform three vertical jumps as a pre-test and were then randomly assigned to one of five PAP protocols, resistance exercise using half squat exercise, plyometric exercise using drop jumps with individualized drop height, whole body vibration using squats on a vibration plate, complex training combining resistance exercise with plyometric exercise, vibration complex training combining whole body vibration with plyometric exercise. Three vertical jumps were performed four minutes after the PAP protocol as a post-test. A two-way repeated-measures analysis of variance was used to examine the differences among the five PAP protocols and between the two testing times. Our results showed that the post-test results were significantly improved compared to the pre-test for the vertical jump height (p = .015) in all PAP protocols. There was, however, an individual phenomenon of PAP in the response to all PAP protocols. In conclusion, this study found that resistance and plyometric exercise, whole body vibration, complex training and vibration complex training induce similar group PAP benefits. However, some athletes decreased their performances in some of the exercises in the study. Therefore, it is not recommended for coaches to arrange the exercises in a team setting.

  14. Ionization from short-range potential under action of electromagnetic field of complex configuration

    CERN Document Server

    Rodionov, V N; Kravtsova, G A

    2002-01-01

    The transcendental equation for the complex energy is obtained on the basis of the exactly solvable 3D model of the short-acting potential and the Green time function in the intensive electromagnetic field, constituting the combination of the constant magnetic field and the circular-polarization wave field. The electron quasistationary states parameters in the delta-potential with an account of the action of the intensive external field of complex configuration are calculated. The problem on the possibility of stabilizing the bound states decay of the spinor and scalar particles through the intensive magnetic field is clarified. It is established that the obtained results regime the reexamination of the accepted notion on the stabilizing role of the strong magnetic field by the atoms ionization

  15. Fully unsteady subsonic and supersonic potential aerodynamics for complex aircraft configurations for flutter applications

    Science.gov (United States)

    Tseng, K.; Morino, L.

    1975-01-01

    A general theory for study, oscillatory or fully unsteady potential compressible aerodynamics around complex configurations is presented. Using the finite-element method to discretize the space problem, one obtains a set of differential-delay equations in time relating the potential to its normal derivative which is expressed in terms of the generalized coordinates of the structure. For oscillatory flow, the motion consists of sinusoidal oscillations around a steady, subsonic or supersonic flow. For fully unsteady flow, the motion is assumed to consist of constant subsonic or supersonic speed for time t or = 0 and of small perturbations around the steady state for time t 0.

  16. Friends or Foes: Matrix Metalloproteinases and Their Multifaceted Roles in Neurodegenerative Diseases

    Directory of Open Access Journals (Sweden)

    Marjana Brkic

    2015-01-01

    Full Text Available Neurodegeneration is a chronic progressive loss of neuronal cells leading to deterioration of central nervous system (CNS functionality. It has been shown that neuroinflammation precedes neurodegeneration in various neurodegenerative diseases. Matrix metalloproteinases (MMPs, a protein family of zinc-containing endopeptidases, are essential in (neuroinflammation and might be involved in neurodegeneration. Although MMPs are indispensable for physiological development and functioning of the organism, they are often referred to as double-edged swords due to their ability to also inflict substantial damage in various pathological conditions. MMP activity is strictly controlled, and its dysregulation leads to a variety of pathologies. Investigation of their potential use as therapeutic targets requires a better understanding of their contributions to the development of neurodegenerative diseases. Here, we review MMPs and their roles in neurodegenerative diseases: Alzheimer’s disease (AD, Parkinson’s disease (PD, amyotrophic lateral sclerosis (ALS, Huntington’s disease (HD, and multiple sclerosis (MS. We also discuss MMP inhibition as a possible therapeutic strategy to treat neurodegenerative diseases.

  17. Friends or Foes: Matrix Metalloproteinases and Their Multifaceted Roles in Neurodegenerative Diseases.

    Science.gov (United States)

    Brkic, Marjana; Balusu, Sriram; Libert, Claude; Vandenbroucke, Roosmarijn E

    2015-01-01

    Neurodegeneration is a chronic progressive loss of neuronal cells leading to deterioration of central nervous system (CNS) functionality. It has been shown that neuroinflammation precedes neurodegeneration in various neurodegenerative diseases. Matrix metalloproteinases (MMPs), a protein family of zinc-containing endopeptidases, are essential in (neuro)inflammation and might be involved in neurodegeneration. Although MMPs are indispensable for physiological development and functioning of the organism, they are often referred to as double-edged swords due to their ability to also inflict substantial damage in various pathological conditions. MMP activity is strictly controlled, and its dysregulation leads to a variety of pathologies. Investigation of their potential use as therapeutic targets requires a better understanding of their contributions to the development of neurodegenerative diseases. Here, we review MMPs and their roles in neurodegenerative diseases: Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and multiple sclerosis (MS). We also discuss MMP inhibition as a possible therapeutic strategy to treat neurodegenerative diseases.

  18. Current therapeutic molecules and targets in neurodegenerative diseases based on in silico drug design.

    Science.gov (United States)

    Sehgal, Sheikh Arslan; Hammad, Mirza A; Tahir, Rana Adnan; Akram, Hafiza Nisha; Ahmad, Faheem

    2018-03-15

    As the number of elderly persons increases, neurodegenerative diseases are becoming ubiquitous. There is currently a great need for knowledge concerning management of old-age neurodegenerative diseases; the most important of which are: Alzheimer's disease, Parkinson's disease, Amyotrophic Lateral Sclerosis, and Huntington's disease. To summarize the potential of computationally predicted molecules and targets against neurodegenerative diseases. Review of literature published since 1997 against neurodegenerative diseases, utilizing as keywords: in silico, Alzheimer's disease, Parkinson's disease, Amyotrophic Lateral Sclerosis ALS, and Huntington's disease. Due to the costs associated with experimentation and current ethical law, performing experiments directly on living organisms has become much more difficult. In this scenario, in silico techniques have been successful and have become powerful tools in the search to cure disease. Researchers use the Computer Aided Drug Design pipeline which: 1) generates 3-dimensional structures of target proteins through homology modeling 2) achieves stabilization through molecular dynamics simulation, and 3) exploits molecular docking through large compound libraries. Next generation sequencing is continually producing enormous amounts of raw sequence data while neuroimaging is producing a multitude of raw image data. To solve such pressing problems, these new tools and algorithms are required. This review elaborates precise in silico tools and techniques for drug targets, active molecules, and molecular docking studies, together with future prospects and challenges concerning possible breakthroughs in Alzheimer's, Parkinson's, Amyotrophic Lateral Sclerosis, and Huntington's disease. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  19. PAMAM Dendrimers as Potential Carriers of Gadolinium Complexes of Iminodiacetic Acid Derivatives for Magnetic Resonance Imaging

    Directory of Open Access Journals (Sweden)

    Magdalena Markowicz-Piasecka

    2015-01-01

    Full Text Available This is the first study describing the utilization of PAMAM dendrimers as delivery vehicles of novel magnetic resonance imaging (MRI contrast agents. The purpose of this paper was to establish the potential of G4 PAMAM dendrimers as carriers of gadolinium complexes of iminodiacetic acid derivatives and determine imaging properties of synthesized compounds in in vivo studies. Furthermore, we examined the influence of four synthesized complexes on the process of clot formation, stabilization, and lysis and on amidolytic activity of thrombin. Biodistribution studies have shown that the compounds composed of PAMAM G4 dendrimers and gadolinium complexes of iminodiacetic acid derivatives increase signal intensity preferably in liver in range of 59–116% in MRI studies which corresponds with the greatest accumulation of gadolinium after administration of the compounds. Synthesized compounds affect kinetic parameters of the proces of clot formation, its stabilization, and lysis. However, only one synthesized compound at concentration 10-fold higher than potential plasma concentrations contributed to the increase of general parameters such as the overall potential of clot formation and lysis (↑CLAUC and total time of the process (↑T. Results of described studies provide additional insight into delivery properties of PAMAM dendrimers but simultaneously underscore the necessity for further research.

  20. Hydrogen Isotopes in Amino Acids and Soils Offer New Potential to Study Complex Processes

    Science.gov (United States)

    Fogel, M. L.; Newsome, S. D.; Williams, E. K.; Bradley, C. J.; Griffin, P.; Nakamoto, B. J.

    2016-12-01

    Hydrogen isotopes have been analyzed extensively in the earth and biogeosciences to trace water through various environmental systems. The majority of the measurements have been made on water in rocks and minerals (inorganic) or non-exchangeable H in lipids (organic), important biomarkers that represent a small fraction of the organic molecules synthesized by living organisms. Our lab has been investigating hydrogen isotopes in amino acids and complex soil organic matter, which have traditionally been thought to be too complex to interpret owing to complications from potentially exchangeable hydrogen. For the amino acids, we show how hydrogen in amino acids originates from two sources, food and water, and demonstrate that hydrogen isotopes can be routed directly between organisms. Amino acid hydrogen isotopes may unravel cycling in extremophiles in order to discover novel biochemical pathways central to the organism. For soil organic matter, recent approaches to understanding the origin of soil organic matter are pointing towards root exudates along with microbial biomass as the source, rather than aboveground leaf litter. Having an isotope tracer in very complex, potentially exchangeable organic matter can be handled with careful experimentation. Although no new instrumentation is being used per se, extension of classes of organic matter to isotope measurements has potential to open up new doors for understanding organic matter cycling on earth and in planetary materials.

  1. Preparation and characterization of tetrandrine-phospholipid complex loaded lipid nanocapsules as potential oral carriers

    Directory of Open Access Journals (Sweden)

    Zhao YQ

    2013-10-01

    Full Text Available Yi-qing Zhao, Li-ping Wang, Chao Ma, Kun Zhao, Ying Liu, Nian-ping FengSchool of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of ChinaBackground: Tetrandrine is an active constituent that is extracted from the root tuber of the Chinese herb Stephania tetrandra S. Moore. It has shown various pharmacological effects, such as antitumor activity, multidrug resistance reversal, and hepatic fibrosis resistance. In clinical applications, it has been used to treat hypertension, pneumosilicosis, and lung cancer. However, the poor water solubility of tetrandrine has limited its application. In this study, a newly emerging oral drug carrier of phospholipid complex loaded lipid nanocapsules was developed to improve the oral bioavailability of tetrandrine.Methods: The phospholipid complex was prepared with the solvent-evaporation method to enhance the liposolubility of tetrandrine. The formation of the phospholipid complex was confirmed with a solubility study, infrared spectroscopy, and a differential scanning calorimetry (DSC analysis. The tetrandrine-phospholipid complex loaded lipid nanocapsules (TPC-LNCs were prepared using the phase inversion method. Lyophilization was performed with mannitol (10% as a cryoprotectant. TPC-LNCs were characterized according to their particle size, zeta potential, encapsulation efficiency, morphology by transmission electron microscopy, and crystallinity by DSC. In addition, the in vitro release of tetrandrine from TPC-LNCs was examined to potentially illustrate the in vivo release behavior. The in vivo bioavailability of TPC-LNCs was studied and compared to tetrandrine tablets in rats.Results: The liposolubility of tetrandrine in n-octanol improved from 8.34 µg/mL to 35.64 µg/mL in the tetrandrine-phospholipid complex. The prepared TPC-LNCs were spherical-shaped particles with a small size of 40 nm and a high encapsulation efficiency of 93.9%. DSC measurements revealed

  2. Shifts in wind energy potential following land-use driven vegetation dynamics in complex terrain.

    Science.gov (United States)

    Fang, Jiannong; Peringer, Alexander; Stupariu, Mihai-Sorin; Pǎtru-Stupariu, Ileana; Buttler, Alexandre; Golay, Francois; Porté-Agel, Fernando

    2018-10-15

    Many mountainous regions with high wind energy potential are characterized by multi-scale variabilities of vegetation in both spatial and time dimensions, which strongly affect the spatial distribution of wind resource and its time evolution. To this end, we developed a coupled interdisciplinary modeling framework capable of assessing the shifts in wind energy potential following land-use driven vegetation dynamics in complex mountain terrain. It was applied to a case study area in the Romanian Carpathians. The results show that the overall shifts in wind energy potential following the changes of vegetation pattern due to different land-use policies can be dramatic. This suggests that the planning of wind energy project should be integrated with the land-use planning at a specific site to ensure that the expected energy production of the planned wind farm can be reached over its entire lifetime. Moreover, the changes in the spatial distribution of wind and turbulence under different scenarios of land-use are complex, and they must be taken into account in the micro-siting of wind turbines to maximize wind energy production and minimize fatigue loads (and associated maintenance costs). The proposed new modeling framework offers, for the first time, a powerful tool for assessing long-term variability in local wind energy potential that emerges from land-use change driven vegetation dynamics over complex terrain. Following a previously unexplored pathway of cause-effect relationships, it demonstrates a new linkage of agro- and forest policies in landscape development with an ultimate trade-off between renewable energy production and biodiversity targets. Moreover, it can be extended to study the potential effects of micro-climatic changes associated with wind farms on vegetation development (growth and patterning), which could in turn have a long-term feedback effect on wind resource distribution in mountainous regions. Copyright © 2018 Elsevier B.V. All rights

  3. Oxidative Stress in Neurodegenerative Diseases: Mechanisms and Therapeutic Perspectives

    Directory of Open Access Journals (Sweden)

    Ailton Melo

    2011-01-01

    Full Text Available The incidence and prevalence of neurodegenerative diseases (ND increase with life expectancy. This paper reviews the role of oxidative stress (OS in ND and pharmacological attempts to fight against reactive oxygen species (ROS-induced neurodegeneration. Several mechanisms involved in ROS generation in neurodegeneration have been proposed. Recent articles about molecular pathways involved in ROS generation were reviewed. The progress in the development of neuroprotective therapies has been hampered because it is difficult to define targets for treatment and determine what should be considered as neuroprotective. Therefore, the attention was focused on researches about pharmacological targets that could protect neurons against OS. Since it is necessary to look for genes as the ultimate controllers of all biological processes, this paper also tried to identify gerontogenes involved in OS and neurodegeneration. Since neurons depend on glial cells to survive, recent articles about the functioning of these cells in aging and ND were also reviewed. Finally, clinical trials testing potential neuroprotective agents were critically reviewed. Although several potential drugs have been screened in in vitro and in vivo models of ND, these results were not translated in benefit of patients, and disappointing results were obtained in the majority of clinical trials.

  4. Neuroanatomy of Shared Conversational Laughter in Neurodegenerative Disease

    Directory of Open Access Journals (Sweden)

    Peter S. Pressman

    2018-06-01

    Full Text Available Perceiving another person's emotional expression often sparks a corresponding signal in the observer. Shared conversational laughter is a familiar example. Prior studies of shared laughter have made use of task-based functional neuroimaging. While these methods offer insight in a controlled setting, the ecological validity of such controlled tasks has limitations. Here, we investigate the neural correlates of shared laughter in patients with one of a variety of neurodegenerative disease syndromes (N = 75, including Alzheimer's disease (AD, behavioral variant frontotemporal dementia (bvFTD, right and left temporal variants of semantic dementia (rtvFTD, svPPA, nonfluent/agrammatic primary progressive aphasia (nfvPPA, corticobasal syndrome (CBS, and progressive supranuclear palsy (PSP. Patients were recorded in a brief unrehearsed conversation with a partner (e.g., a friend or family member. Laughter was manually labeled, and an automated system was used to assess the timing of that laughter relative to the partner's laughter. The probability of each participant with neurodegenerative disease laughing during or shortly after his or her partners' laughter was compared to differences in brain morphology using voxel-based morphometry, thresholded based on cluster size and a permutation method and including age, sex, magnet strength, disease-specific atrophy and total intracranial volumes as covariates. While no significant correlations were found at the critical T value, at a corrected voxelwise threshold of p < 0.005, a cluster in the left posterior cingulate gyrus demonstrated a trend at p = 0.08 (T = 4.54. Exploratory analysis with a voxelwise threshold of p = 0.001 also suggests involvement of the left precuneus (T = 3.91 and right fusiform gyrus (T = 3.86. The precuneus has been previously implicated in the detection of socially complex laughter, and the fusiform gyrus has a well-described role in the recognition and processing of others

  5. Self-potential and Complex Conductivity Monitoring of In Situ Hydrocarbon Remediation in Microbial Fuel Cell

    Science.gov (United States)

    Zhang, C.; Revil, A.; Ren, Z.; Karaoulis, M.; Mendonca, C. A.

    2013-12-01

    Petroleum hydrocarbon contamination of soil and groundwater in both non-aqueous phase liquid and dissolved forms generated from spills and leaks is a wide spread environmental issue. Traditional cleanup of hydrocarbon contamination in soils and ground water using physical, chemical, and biological remedial techniques is often expensive and ineffective. Recent studies show that the microbial fuel cell (MFC) can simultaneously enhance biodegradation of hydrocarbons in soil and groundwater and yield electricity. Non-invasive geophysical techniques such as self-potential (SP) and complex conductivity (induced polarization) have shown the potential to detect and characterize the nature of electron transport mechanism of in situ bioremediation of organic contamination plumes. In this study, we deployed both SP and complex conductivity in lab scale MFCs to monitor time-laps geophysical response of degradation of hydrocarbons by MFC. Two different sizes of MFC reactors were used in this study (DI=15 cm cylinder reactor and 94.5cm x 43.5 cm rectangle reactor), and the initial hydrocarbon concentration is 15 g diesel/kg soil. SP and complex conductivity measurements were measured using non-polarizing Ag/AgCl electrodes. Sensitivity study was also performed using COMSOL Multiphysics to test different electrode configurations. The SP measurements showed stronger anomalies adjacent to the MFC than locations afar, and both real and imaginary parts of complex conductivity are greater in areas close to MFC than areas further away and control samples without MFC. The joint use of SP and complex conductivity could in situ evaluate the dynamic changes of electrochemical parameters during this bioremediation process at spatiotemporal scales unachievable with traditional sampling methods. The joint inversion of these two methods to evaluate the efficiency of MFC enhanced hydrocarbon remediation in the subsurface.

  6. Formation of competitive potential of the machine-building complex of the region

    Directory of Open Access Journals (Sweden)

    Oleg Ivanovich Botkin

    2014-03-01

    Full Text Available The article describes the features of competitive potential of regional machine-building complex in a globalized world economy. The purpose of the research is the development of theoretically reasonable economic basis of the machine-building complex considering  the  features of business in the conditions of the WTO. In the work, the hypothesis of a special role of the external economic factors locates in development of the enterprises of regional industrial complexes. The study of the theoretical provisions defining the development of the region revealed the factors determining influence of the international trade agreements on spatial localization of the industry. The main attention is paid to an analytical assessment of the current state and the trends, which have developed in the period of post-crisis economic recovery. Analysis of the main indicators of attractiveness has revealed the weak position of local industrial enterprises in the WTO. The directions of strengthening of the competitive capacity of the local industrial enterprises are defined. The obtained results allow us to increase the sustainability of the industry by means of effective management mechanism improvements and to create favorable operating conditions of a machine-building complex of the region

  7. Pharmacogenetics in Neurodegenerative Diseases: Implications for Clinical Trials.

    Science.gov (United States)

    Tortelli, Rosanna; Seripa, Davide; Panza, Francesco; Solfrizzi, Vincenzo; Logroscino, Giancarlo

    2016-01-01

    Pharmacogenetics has become extremely important over the last 20 years for identifying individuals more likely to be responsive to pharmacological interventions. The role of genetic background as a predictor of drug response is a young and mostly unexplored field in neurodegenerative diseases. Mendelian mutations in neurodegenerative diseases have been used as models for early diagnosis and intervention. On the other hand, genetic polymorphisms or risk factors for late-onset Alzheimer's disease (AD) or other neurodegenerative diseases, probably influencing drug response, are hardly taken into account in randomized clinical trial (RCT) design. The same is true for genetic variants in cytochrome P450 (CYP), the principal enzymes influencing drug metabolism. A better characterization of individual genetic background may optimize clinical trial design and personal drug response. This chapter describes the state of the art about the impact of genetic factors in RCTs on neurodegenerative disease, with AD, frontotemporal dementia, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease as examples. Furthermore, a brief description of the genetic bases of drug response focusing on neurodegenerative diseases will be conducted. The role of pharmacogenetics in RCTs for neurodegenerative diseases is still a young, unexplored, and promising field. Genetic tools allow increased sophistication in patient profiling and treatment optimization. Pharmaceutical companies are aware of the value of collecting genetic data during their RCTs. Pharmacogenetic research is bidirectional with RCTs: efficacy data are correlated with genetic polymorphisms, which in turn define subjects for treatment stratification. © 2016 S. Karger AG, Basel.

  8. Temperature and ionic strength influences on actinide(VI)/(V) redox potentials for carbonate limiting complexes

    International Nuclear Information System (INIS)

    Capdevila, H.; Vitorge, P.

    1998-01-01

    Actinide behaviour was studied in two limiting aqueous solutions: acidic and carbonate. Cyclic voltametry was validated with well-known U redox system. SIT was used to account for I influence. Taylor's series expansions to the second order were used to account for T influence. Redox potentials of actinide couples had previously been measured in non complexing media. The above data treatments give standard values for redox potential E 0 , for the corresponding entropy ΔS 0 , enthalpy ΔH 0 and heat capacity ΔC p 0 changes, and also for the corresponding excess values (i.e. the variation of these thermodynamic constants with ionic strength). This methodology was here used in carbonate media to measure the potential of the redox couple PuO 2 (CO 3 ) 3 4- /PuO 2 (CO 3 ) 3 5- from 5 to 70 degC and from I = 0.5 to 4.5 M in Na 2 CO 3 , NaClO 4 media. Experimental details and full results are given for Pu. Only final results are given for Np. Previous and/or published data for U and Am are discussed. E and ΔS variations with T or I were enough to be measured. The values obtained for the fitted SIT coefficients Δε, and for ΔS and ΔCp are similar for U, Np and Pu redox reactions. Using this analogy for Am missing data is discussed. β 3 V /β 3 VI formation constant ratio of the carbonate limiting complexes were deduced from the potential shift from complexing to non complexing media for the Actinide(VI)/Actinide(V) redox couples. β 3 V (U and Pu) and β 3 VI (Np) were finally proposed using published β3 VI (U and Pu) and β 3 V (Np). For Am, this data treatment was used to discuss the AmO 2 2+ / AmO 2 + redox potential

  9. The intersection between growth factors, autophagy and ER stress: A new target to treat neurodegenerative diseases?

    Science.gov (United States)

    Garcia-Huerta, Paula; Troncoso-Escudero, Paulina; Jerez, Carolina; Hetz, Claudio; Vidal, Rene L

    2016-10-15

    One of the salient features of most neurodegenerative diseases is the aggregation of specific proteins in the brain. This proteostasis imbalance is proposed as a key event triggering the neurodegenerative cascade. The unfolded protein response (UPR) and autophagy pathways are emerging as critical processes implicated in handling disease-related misfolded proteins. However, in some conditions, perturbations in the buffering capacity of the proteostasis network may be part of the etiology of the disease. Thus, pharmacological or gene therapy strategies to enhance autophagy or UPR responses are becoming an attractive target for disease intervention. Here, we discuss current evidence depicting the complex involvement of autophagy and ER stress in brain diseases. Novel pathways to modulate protein misfolding are discussed including the relation between aging and growth factor signaling. This article is part of a Special Issue entitled SI:Autophagy. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Complexation of Eu(III) with a polymeric cement additive as a potential carrier of actinides

    Energy Technology Data Exchange (ETDEWEB)

    Lippold, Holger; Becker, Michael [Helmholtz-Zentrum Dresden-Rossendorf e.V., Dresden (Germany). Reactive Transport

    2017-06-01

    In the long term, cementitious materials in a final repository will be exposed to leaching processes generating highly alkaline solutions. Polymeric additives, so-called superplasticizers, are considered as potential mobilizing agents for released radionuclides, since it is uncertain whether complete degradation will take place under the evolving aqueous conditions. Regarding the complexing properties of superplasticizers, there are only indirect assessments so far. In this study, first systematic investigations on complexation with Eu(III) as an analogue of trivalent actinides were performed at variable pH and electrolyte content (NaCl, CaCl{sub 2}) using ultrafiltration as a separation method. A stability constant was derived according to the charge neutralization model. For this purpose, the proton exchange capacity was determined by potentiometric titration.

  11. Generalized Bloch Theorem for Complex Periodic Potentials - A Powerful Application to Quantum Transport Calculations

    International Nuclear Information System (INIS)

    Zhang, Xiaoguang; Varga, Kalman; Pantelides, Sokrates T

    2007-01-01

    Band-theoretic methods with periodically repeated supercells have been a powerful approach for ground-state electronic structure calculations, but have not so far been adapted for quantum transport problems with open boundary conditions. Here we introduce a generalized Bloch theorem for complex periodic potentials and use a transfer-matrix formulation to cast the transmission probability in a scattering problem with open boundary conditions in terms of the complex wave vectors of a periodic system with absorbing layers, allowing a band technique for quantum transport calculations. The accuracy and utility of the method is demonstrated by the model problems of the transmission of an electron over a square barrier and the scattering of a phonon in an inhomogeneous nanowire. Application to the resistance of a twin boundary in nanocrystalline copper yields excellent agreement with recent experimental data

  12. Characteristics of gadolinium-DTPA complex: a potential NMR contrast agent

    International Nuclear Information System (INIS)

    Weinmann, H.J.; Brasch, R.C.; Press, W.R.; Wesbey, G.E.

    1984-01-01

    Chelation of the rare-earth element gadolinium (Gd) with diethylenetriaminepentaacetic acid (DTPA) results in a strongly paramagnetic, stable complex that is well tolerated in animals. The strongly paramagnetic gadolinium complex reduces hydrogen-proton relaxation times even in low concentrations (less than 0.01 mmol/L). The pharmacokinetic behavior of intravenously delivered Gd-DTPA is similar to the well known iodinated contrast agents used in urography and angiography; excretion is predominately through the kidneys with greater than 90% recovery in 24 hr. The intravenous LD 50 of the meglumine salt of Gd-DTPA is 10 mmol/kg for the rat; in vivo there is no evidence of dissociation of the gadolinium ion from the DTPA ligand. The combination of strong proton relaxation, in-vivo stability, rapid urinary excretion, and high tolerance favors the further development and the potential clinical application of gadolinium-DTPA as a contrast enhancer in magnetic resonance imaging

  13. Scattering in a spherical potential: Motion of complex-plane poles and zeros

    International Nuclear Information System (INIS)

    Arndt, R.A.; Roper, L.D.

    1989-01-01

    Scattering of spinless nucleons in a spherical potential is examined with the use of a computer graphics simulation VSCAT. The potential is defined stepwise and the Schroedinger equation is solved to obtain wavefunctions, scattering phases, partial-wave total cross sections, and differential cross sections, which are then displayed graphically. For the particular case of a square well, partial-wave amplitudes are displayed over the complex momentum plane in a three-dimensional plot. The well depth is then varied to follow the motion of poles in the complex momentum plane as they become resonances and then are bound states. Also displayed are the partial-wave zeros, which are required to satisfy Levinson's theorem for multiple states. The requirement on well depth is developed to produce a specified number of bound states and enumerate the energies which, at a given well depth, create equal scattering phases in adjoining partial waves δ/sub l//sub -1/ = δ/sub l/ = δ/sub l//sub +1/. This symmetry of scattering phases exists for both repulsive and attractive square potentials. A square repulsive core is also studied, which has the same triple-point symmetry as the square well

  14. Protein kinase A governs oxidative phosphorylation kinetics and oxidant emitting potential at complex I

    Directory of Open Access Journals (Sweden)

    Daniel Stephen Lark

    2015-11-01

    Full Text Available The mitochondrial electron transport system (ETS is responsible for setting and maintaining both the energy and redox charges throughout the cell. Reversible phosphorylation of mitochondrial proteins, particularly via the soluble adenylyl cyclase (sAC/cyclic AMP (cAMP/Protein kinase A (PKA axis, has recently been revealed as a potential mechanism regulating the ETS. However, the governance of cAMP/PKA signaling and its implications on ETS function are incompletely understood. In contrast to prior reports using exogenous bicarbonate, we provide evidence that endogenous CO2 produced by increased tricarboxylic acid (TCA cycle flux is insufficient to increase mitochondrial cAMP levels, and that exogenous addition of membrane permeant 8Br-cAMP does not enhance mitochondrial respiratory capacity. We also report important non-specific effects of commonly used inhibitors of sAC which preclude their use in studies of mitochondrial function. In isolated liver mitochondria, inhibition of PKA reduces complex I-, but not complex II-supported respiratory capacity. In permeabilized myofibers, inhibition of PKA lowers both the Km and Vmax for complex I-supported respiration as well as succinate-supported H2O2 emitting potential. In summary, the data provided here improve our understanding of how mitochondrial cAMP production is regulated, illustrate a need for better tools to examine the impact of sAC activity on mitochondrial biology, and suggest that cAMP/PKA signaling contributes to the governance of electron flow through complex I of the ETS.

  15. Potentials and challenges of integration for complex metal oxides in CMOS devices and beyond

    International Nuclear Information System (INIS)

    Kim, Y; Pham, C; Chang, J P

    2015-01-01

    This review focuses on recent accomplishments on complex metal oxide based multifunctional materials and the potential they hold in advancing integrated circuits. It begins with metal oxide based high-κ materials to highlight the success of their integration since 45 nm complementary metal–oxide–semiconductor (CMOS) devices. By simultaneously offering a higher dielectric constant for improved capacitance as well as providing a thicker physical layer to prevent the quantum mechanical tunnelling of electrons, high-κ materials have enabled the continued down-scaling of CMOS based devices. The most recent technology driver has been the demand to lower device power consumption, which requires the design and synthesis of novel materials, such as complex metal oxides that exhibit remarkable tunability in their ferromagnetic, ferroelectric and multiferroic properties. These properties make them suitable for a wide variety of applications such as magnetoelectric random access memory, radio frequency band pass filters, antennae and magnetic sensors. Single-phase multiferroics, while rare, offer unique functionalities which have motivated much scientific and technological research to ascertain the origins of their multiferroicity and their applicability to potential devices. However, due to the weak magnetoelectric coupling for single-phase multiferroics, engineered multiferroic composites based on magnetostrictive ferromagnets interfacing piezoelectrics or ferroelectrics have shown enhanced multiferroic behaviour from effective strain coupling at the interface. In addition, nanostructuring of the ferroic phases has demonstrated further improvement in the coupling effect. Therefore, single-phase and engineered composite multiferroics consisting of complex metal oxides are reviewed in terms of magnetoelectric coupling effects and voltage controlled ferromagnetic properties, followed by a review on the integration challenges that need to be overcome to realize the

  16. Neurodegenerative Diseases: Might Citrus Flavonoids Play a Protective Role?

    Directory of Open Access Journals (Sweden)

    Santa Cirmi

    2016-09-01

    Full Text Available Neurodegenerative diseases (ND result from the gradual and progressive degeneration of the structure and function of the central nervous system or the peripheral nervous system or both. They are characterized by deterioration of neurons and/or myelin sheath, disruption of sensory information transmission and loss of movement control. There is no effective treatment for ND, and the drugs currently marketed are symptom-oriented, albeit with several side effects. Within the past decades, several natural remedies have gained attention as potential neuroprotective drugs. Moreover, an increasing number of studies have suggested that dietary intake of vegetables and fruits can prevent or delay the onset of ND. These properties are mainly due to the presence of polyphenols, an important group of phytochemicals that are abundantly present in fruits, vegetables, cereals and beverages. The main class of polyphenols is flavonoids, abundant in Citrus fruits. Our review is an overview on the scientific literature concerning the neuroprotective effects of the Citrus flavonoids in the prevention or treatment of ND. This review may be used as scientific basis for the development of nutraceuticals, food supplements or complementary and alternative drugs to maintain and improve the neurophysiological status.

  17. Does Vitamin C Influence Neurodegenerative Diseases and Psychiatric Disorders?

    Science.gov (United States)

    Luchowska-Kocot, Dorota; Kiełczykowska, Małgorzata; Musik, Irena; Kurzepa, Jacek

    2017-01-01

    Vitamin C (Vit C) is considered to be a vital antioxidant molecule in the brain. Intracellular Vit C helps maintain integrity and function of several processes in the central nervous system (CNS), including neuronal maturation and differentiation, myelin formation, synthesis of catecholamine, modulation of neurotransmission and antioxidant protection. The importance of Vit C for CNS function has been proven by the fact that targeted deletion of the sodium-vitamin C co-transporter in mice results in widespread cerebral hemorrhage and death on post-natal day one. Since neurological diseases are characterized by increased free radical generation and the highest concentrations of Vit C in the body are found in the brain and neuroendocrine tissues, it is suggested that Vit C may change the course of neurological diseases and display potential therapeutic roles. The aim of this review is to update the current state of knowledge of the role of vitamin C on neurodegenerative diseases including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, multiple sclerosis and amyotrophic sclerosis, as well as psychiatric disorders including depression, anxiety and schizophrenia. The particular attention is attributed to understanding of the mechanisms underlying possible therapeutic properties of ascorbic acid in the presented disorders. PMID:28654017

  18. Molecular Pathological Classification of Neurodegenerative Diseases: Turning towards Precision Medicine.

    Science.gov (United States)

    Kovacs, Gabor G

    2016-02-02

    Neurodegenerative diseases (NDDs) are characterized by selective dysfunction and loss of neurons associated with pathologically altered proteins that deposit in the human brain but also in peripheral organs. These proteins and their biochemical modifications can be potentially targeted for therapy or used as biomarkers. Despite a plethora of modifications demonstrated for different neurodegeneration-related proteins, such as amyloid-β, prion protein, tau, α-synuclein, TAR DNA-binding protein 43 (TDP-43), or fused in sarcoma protein (FUS), molecular classification of NDDs relies on detailed morphological evaluation of protein deposits, their distribution in the brain, and their correlation to clinical symptoms together with specific genetic alterations. A further facet of the neuropathology-based classification is the fact that many protein deposits show a hierarchical involvement of brain regions. This has been shown for Alzheimer and Parkinson disease and some forms of tauopathies and TDP-43 proteinopathies. The present paper aims to summarize current molecular classification of NDDs, focusing on the most relevant biochemical and morphological aspects. Since the combination of proteinopathies is frequent, definition of novel clusters of patients with NDDs needs to be considered in the era of precision medicine. Optimally, neuropathological categorizing of NDDs should be translated into in vivo detectable biomarkers to support better prediction of prognosis and stratification of patients for therapy trials.

  19. Optimal reflection-free complex absorbing potentials for quantum propagation of wave packets

    International Nuclear Information System (INIS)

    Shemer, Oded; Brisker, Daria; Moiseyev, Nimrod

    2005-01-01

    The conditions for optimal reflection-free complex-absorbing potentials (CAPs) are discussed. It is shown that the CAPs as derived from the smooth-exterior-scaling transformation of the Hamiltonian [J. Phys. B 31, 1431 (1998)] serve as optimal reflection-free CAPs (RF CAPs) in wave-packet propagation calculations of open systems. The initial wave packet, Φ(t=0), can be located in the interaction region (as in half collision experiments) where the CAPs have vanished or in the asymptote where V CAP ≠0. As we show, the optimal CAPs can be introduced also in the region where the physical potential has not vanished. The unavoided reflections due to the use of a finite number of grid points (or basis functions) are discussed. A simple way to reduce the 'edge-grid' reflection effect is described

  20. Complex singularities of the critical potential in the large-N limit

    International Nuclear Information System (INIS)

    Meurice, Y.

    2003-01-01

    We show with two numerical examples that the conventional expansion in powers of the field for the critical potential of 3-dimensional O(N) models in the large-N limit does not converge for values of φ 2 larger than some critical value. This can be explained by the existence of conjugated branch points in the complex φ 2 plane. Pade approximants [L+3/L] for the critical potential apparently converge at large φ 2 . This allows high-precision calculation of the fixed point in a more suitable set of coordinates. We argue that the singularities are generic and not an artifact of the large-N limit. We show that ignoring these singularities may lead to inaccurate approximations

  1. Auditory evoked potentials to abrupt pitch and timbre change of complex tones: electrophysiological evidence of 'streaming'?

    Science.gov (United States)

    Jones, S J; Longe, O; Vaz Pato, M

    1998-03-01

    Examination of the cortical auditory evoked potentials to complex tones changing in pitch and timbre suggests a useful new method for investigating higher auditory processes, in particular those concerned with 'streaming' and auditory object formation. The main conclusions were: (i) the N1 evoked by a sudden change in pitch or timbre was more posteriorly distributed than the N1 at the onset of the tone, indicating at least partial segregation of the neuronal populations responsive to sound onset and spectral change; (ii) the T-complex was consistently larger over the right hemisphere, consistent with clinical and PET evidence for particular involvement of the right temporal lobe in the processing of timbral and musical material; (iii) responses to timbral change were relatively unaffected by increasing the rate of interspersed changes in pitch, suggesting a mechanism for detecting the onset of a new voice in a constantly modulated sound stream; (iv) responses to onset, offset and pitch change of complex tones were relatively unaffected by interfering tones when the latter were of a different timbre, suggesting these responses must be generated subsequent to auditory stream segregation.

  2. Cytogenotoxic effects of two potential anticancer Ruthenium(III Schiff Bases complexes

    Directory of Open Access Journals (Sweden)

    Izet Eminovic

    2016-10-01

    Full Text Available Introduction: Treatment of cancer has been subject of great interest. Researchers are continuously searching for new medicines. In this sense, ruthenium complexes have big potential. Some evidences suggest that ruthenium compounds possess anticancer activities. We synthesized two recently published ruthenium(III complexes with bidentate O,N and tridentate O,O,N Schiff bases derived from 5-substituted salicylaldehyde and aminophenol or anilineare. These compounds showed affinity for binding to the DNA molecule, however, insufficient data are available regarding their possible toxic effects on biological systems.Methods: In the present study we evaluated genotoxic, cytotoxic, and cytostatic effects of Na[RuCl2(L12] and Na[Ru(L22], using the Allium cepa assay.Results: Different toxic effects were observed depending on the substance, tested concentration, and endpoint measured. In general, the tested compounds significantly lowered the root growth and mitotic index values as compared to the control group. Additionally, a wide range of abnormal mitotic stages, both clastogenic and non-clastogenic were observed in the treated cells. Na[RuCl2(L12] significantly increased the frequency of sticky metaphases, chromosome bridges, micronuclei, impaired chromosome segregation, as well as number of apoptotic and necrotic cells over the controls. In contrast, Na[Ru(L22] did not show significant evidence of genotoxicity with regard to chromosome aberrations and micronuclei, however, significant differences were detected in the number of apoptotic and necrotic cells when the highest concentration was applied.Conclusions: In this study we demonstrated antiproliferative effects of Na[RuCl2(L12] and Na[Ru(L22]. At clinical level, these results could be interesting for further studies on anticancer potential of the ruthenium(III complexes using animal models.

  3. Early-Late Heterobimetallic Complexes Linked by Phosphinoamide Ligands. Tuning Redox Potentials and Small Molecule Activation

    Energy Technology Data Exchange (ETDEWEB)

    Thomas, Christine M. [Brandeis Univ., Waltham, MA (United States)

    2015-08-01

    Recent attention in the chemical community has been focused on the energy efficient and environmentally benign conversion of abundant small molecules (CO2, H2O, etc.) to useful liquid fuels. This project addresses these goals by examining fundamental aspects of catalyst design to ultimately access small molecule activation processes under mild conditions. Specifically, Thomas and coworkers have targetted heterobimetallic complexes that feature metal centers with vastly different electronic properties, dictated both by their respective positions on the periodic table and their coordination environment. Unlike homobimetallic complexes featuring identical or similar metals, the bonds between metals in early/late heterobimetallics are more polarized, with the more electron-rich late metal center donating electron density to the more electron-deficient early metal center. While metal-metal bonds pose an interesting strategy for storing redox equivalents and stabilizing reactive metal fragments, the polar character of metal-metal bonds in heterobimetallic complexes renders these molecules ideally poised to react with small molecule substrates via cleavage of energy-rich single and double bonds. In addition, metal-metal interactions have been shown to dramatically affect redox potentials and promote multielectron redox activity, suggesting that metal-metal interactions may provide a mechanism to tune redox potentials and access substrate reduction/activation at mild overpotentials. This research project has provided a better fundamental understanding of how interactions between transition metals can be used as a strategy to promote and/or control chemical transformations related to the clean production of fuels. While this project focused on the study of homogeneous systems, it is anticipated that the broad conclusions drawn from these investigations will be applicable to heterogeneous catalysis as well, particularly on heterogeneous processes that occur at interfaces in

  4. Institutional Analysis of Knowledge Generation Resource Potential at the Enterprises of Regional Military-Industrial Complex

    Directory of Open Access Journals (Sweden)

    Evgeny Vasilyevich Popov

    2016-09-01

    Full Text Available The article is devoted to the processes of knowledge generation at the enterprises of military-industrial complex, which are the leaders of the regional innovative activity. The target of the research is to develop the methodology based on the use of resource application potential for increasing the efficiency of knowledge generation at the instrument-making enterprises of military-industrial complex. The system analysis of the knowledge generation processes is conducted at one of them. It allows to draw a conclusion that such enterprises have a lack of the institutes of knowledge generation processes. The authors are offered a technique of the development of the knowledge generation system at the military-industrial enterprises based on the accounting of assets and opportunities of the enterprise in the realization of intellectual activity. The developed technique is based on the determination of the horizontal resource potential of knowledge generation and allows to determine the potential of resource application at each stage of product life cycle. The comparison of the actual and theoretical values of horizontal resource potential allows to correct the distribution of a share of each of resources within a stage, and therefore, to optimize the realization of tasks at a specific stage. The offered tools were implemented in 2015 at one of the regional military-Industrial enterprises. The methodological tools of the research include the methods of expert assessment, mathematical statistics and the institutional analysis. On the basis of the offered technique and received empirical results, the institutional spiral of knowledge generation during the filling of state order at the military-industrial enterprise is developed. Its implementation will promote the decrease in the level of uncertainty during the whole life cycle of innovative activity product. The developed institutional spiral of knowledge generation at instrument-making military

  5. Physical Exercise-Induced Adult Neurogenesis: A Good Strategy to Prevent Cognitive Decline in Neurodegenerative Diseases?

    Directory of Open Access Journals (Sweden)

    Suk-yu Yau

    2014-01-01

    Full Text Available Cumulative evidence has indicated that there is an important role for adult hippocampal neurogenesis in cognitive function. With the increasing prevalence of cognitive decline associated with neurodegenerative diseases among the ageing population, physical exercise, a potent enhancer of adult hippocampal neurogenesis, has emerged as a potential preventative strategy/treatment to reduce cognitive decline. Here we review the functional role of adult hippocampal neurogenesis in learning and memory, and how this form of structural plasticity is altered in neurodegenerative diseases known to involve cognitive impairment. We further discuss how physical exercise may contribute to cognitive improvement in the ageing brain by preserving adult neurogenesis, and review the recent approaches for measuring changes in neurogenesis in the live human brain.

  6. Lamina-specific contribution of glutamatergic and GABAergic potentials to hippocampal sharp wave-ripple complexes.

    Science.gov (United States)

    Schönberger, Jan; Draguhn, Andreas; Both, Martin

    2014-01-01

    The mammalian hippocampus expresses highly organized patterns of neuronal activity which form a neuronal correlate of spatial memories. These memory-encoding neuronal ensembles form on top of different network oscillations which entrain neurons in a state- and experience-dependent manner. The mechanisms underlying activation, timing and selection of participating neurons are incompletely understood. Here we studied the synaptic mechanisms underlying one prominent network pattern called sharp wave-ripple complexes (SPW-R) which are involved in memory consolidation during sleep. We recorded SPW-R with extracellular electrodes along the different layers of area CA1 in mouse hippocampal slices. Contribution of glutamatergic excitation and GABAergic inhibition, respectively, was probed by local application of receptor antagonists into s. radiatum, pyramidale and oriens. Laminar profiles of field potentials show that GABAergic potentials contribute substantially to sharp waves and superimposed ripple oscillations in s. pyramidale. Inhibitory inputs to s. pyramidale and s. oriens are crucial for action potential timing by ripple oscillations, as revealed by multiunit-recordings in the pyramidal cell layer. Glutamatergic afferents, on the other hand, contribute to sharp waves in s. radiatum where they also evoke a fast oscillation at ~200 Hz. Surprisingly, field ripples in s. radiatum are slightly slower than ripples in s. pyramidale, resulting in a systematic shift between dendritic and somatic oscillations. This complex interplay between dendritic excitation and perisomatic inhibition may be responsible for the precise timing of discharge probability during the time course of SPW-R. Together, our data illustrate a complementary role of spatially confined excitatory and inhibitory transmission during highly ordered network patterns in the hippocampus.

  7. Modeling neurodegenerative diseases with patient-derived induced pluripotent cells: Possibilities and challenges.

    Science.gov (United States)

    Poon, Anna; Zhang, Yu; Chandrasekaran, Abinaya; Phanthong, Phetcharat; Schmid, Benjamin; Nielsen, Troels T; Freude, Kristine K

    2017-10-25

    The rising prevalence of progressive neurodegenerative diseases coupled with increasing longevity poses an economic burden at individual and societal levels. There is currently no effective cure for the majority of neurodegenerative diseases and disease-affected tissues from patients have been difficult to obtain for research and drug discovery in pre-clinical settings. While the use of animal models has contributed invaluable mechanistic insights and potential therapeutic targets, the translational value of animal models could be further enhanced when combined with in vitro models derived from patient-specific induced pluripotent stem cells (iPSCs) and isogenic controls generated using CRISPR-Cas9 mediated genome editing. The iPSCs are self-renewable and capable of being differentiated into the cell types affected by the diseases. These in vitro models based on patient-derived iPSCs provide the opportunity to model disease development, uncover novel mechanisms and test potential therapeutics. Here we review findings from iPSC-based modeling of selected neurodegenerative diseases, including Alzheimer's disease, frontotemporal dementia and spinocerebellar ataxia. Furthermore, we discuss the possibilities of generating three-dimensional (3D) models using the iPSCs-derived cells and compare their advantages and disadvantages to conventional two-dimensional (2D) models. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Targeting Microglial KATP Channels to Treat Neurodegenerative Diseases: A Mitochondrial Issue

    Directory of Open Access Journals (Sweden)

    Manuel J. Rodríguez

    2013-01-01

    Full Text Available Neurodegeneration is a complex process involving different cell types and neurotransmitters. A common characteristic of neurodegenerative disorders is the occurrence of a neuroinflammatory reaction in which cellular processes involving glial cells, mainly microglia and astrocytes, are activated in response to neuronal death. Microglia do not constitute a unique cell population but rather present a range of phenotypes closely related to the evolution of neurodegeneration. In a dynamic equilibrium with the lesion microenvironment, microglia phenotypes cover from a proinflammatory activation state to a neurotrophic one directly involved in cell repair and extracellular matrix remodeling. At each moment, the microglial phenotype is likely to depend on the diversity of signals from the environment and of its response capacity. As a consequence, microglia present a high energy demand, for which the mitochondria activity determines the microglia participation in the neurodegenerative process. As such, modulation of microglia activity by controlling microglia mitochondrial activity constitutes an innovative approach to interfere in the neurodegenerative process. In this review, we discuss the mitochondrial KATP channel as a new target to control microglia activity, avoid its toxic phenotype, and facilitate a positive disease outcome.

  9. Mitochondrial enzymes and endoplasmic reticulum calcium stores as targets of oxidative stress in neurodegenerative diseases.

    Science.gov (United States)

    Gibson, Gary E; Huang, Hsueh-Meei

    2004-08-01

    Considerable evidence indicates that oxidative stress accompanies age-related neurodegenerative diseases. Specific mechanisms by which oxidative stress leads to neurodegeneration are unknown. Two targets of oxidative stress that are known to change in neurodegenerative diseases are the mitochondrial enzyme alpha-ketoglutarate dehydrogenase complex (KGDHC) and endoplasmic reticulum calcium stores. KGDHC activities are diminished in all common neurodegenerative diseases and the changes are particularly well documented in Alzheimer's disease (AD). A second change that occurs in cells from AD patients is an exaggerated endoplasmic reticulum calcium store [i.e., bombesin-releasable calcium stores (BRCS)]. H(2)O(2), a general oxidant, changes both variables in the same direction as occurs in disease. Other oxidants selectively alter these variables. Various antioxidants were used to help define the critical oxidant species that modifies these responses. All of the antioxidants diminish the oxidant-induced carboxy-dichlorofluorescein (cDCF) detectable reactive oxygen species (ROS), but have diverse actions on these cellular processes. For example, alpha-keto-beta-methyl-n-valeric acid (KMV) diminishes the H(2)O(2) effects on BRCS, while trolox and DMSO exaggerate the response. Acute trolox treatment does not alter H(2)O(2)-induced changes in KGDHC, whereas chronic treatment with trolox increases KGDHC almost threefold. The results suggest that KGDHC and BRCS provide targets by which oxidative stress may induce neurodegeneration and a useful tool for selecting antioxidants for reversing age-related neurodegeneration.

  10. The role of the immune system in neurodegenerative disorders: Adaptive or maladaptive?

    Science.gov (United States)

    Doty, Kevin R; Guillot-Sestier, Marie-Victoire; Town, Terrence

    2015-08-18

    Neurodegenerative diseases share common features, including catastrophic neuronal loss that leads to cognitive or motor dysfunction. Neuronal injury occurs in an inflammatory milieu that is populated by resident and sometimes, infiltrating, immune cells - all of which participate in a complex interplay between secreted inflammatory modulators and activated immune cell surface receptors. The importance of these immunomodulators is highlighted by the number of immune factors that have been associated with increased risk of neurodegeneration in recent genome-wide association studies. One of the more difficult tasks for designing therapeutic strategies for immune modulation against neurodegenerative diseases is teasing apart beneficial from harmful signals. In this regard, learning more about the immune components of these diseases has yielded common themes. These unifying concepts should eventually enable immune-based therapeutics for treatment of Alzheimer׳s and Parkinson׳s diseases and amyotrophic lateral sclerosis. Targeted immune modulation should be possible to temper maladaptive factors, enabling beneficial immune responses in the context of neurodegenerative diseases. This article is part of a Special Issue entitled SI: Neuroimmunology in Health And Disease. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. A neural network underlying intentional emotional facial expression in neurodegenerative disease

    Directory of Open Access Journals (Sweden)

    Kelly A. Gola

    2017-01-01

    Full Text Available Intentional facial expression of emotion is critical to healthy social interactions. Patients with neurodegenerative disease, particularly those with right temporal or prefrontal atrophy, show dramatic socioemotional impairment. This was an exploratory study examining the neural and behavioral correlates of intentional facial expression of emotion in neurodegenerative disease patients and healthy controls. One hundred and thirty three participants (45 Alzheimer's disease, 16 behavioral variant frontotemporal dementia, 8 non-fluent primary progressive aphasia, 10 progressive supranuclear palsy, 11 right-temporal frontotemporal dementia, 9 semantic variant primary progressive aphasia patients and 34 healthy controls were video recorded while imitating static images of emotional faces and producing emotional expressions based on verbal command; the accuracy of their expression was rated by blinded raters. Participants also underwent face-to-face socioemotional testing and informants described participants' typical socioemotional behavior. Patients' performance on emotion expression tasks was correlated with gray matter volume using voxel-based morphometry (VBM across the entire sample. We found that intentional emotional imitation scores were related to fundamental socioemotional deficits; patients with known socioemotional deficits performed worse than controls on intentional emotion imitation; and intentional emotional expression predicted caregiver ratings of empathy and interpersonal warmth. Whole brain VBMs revealed a rightward cortical atrophy pattern homologous to the left lateralized speech production network was associated with intentional emotional imitation deficits. Results point to a possible neural mechanisms underlying complex socioemotional communication deficits in neurodegenerative disease patients.

  12. In silico studies in drug research against neurodegenerative diseases.

    Science.gov (United States)

    Makhouri, Farahnaz Rezaei; Ghasemi, Jahan B

    2017-08-22

    Neurodegenerative diseases such as Alzheimer's disease (AD), progressive neurodegenerative forms of Huntington's disease, Parkinson's disease (PD), amyotrophic lateral sclerosis, spinal cerebellar ataxias, and spinal and bulbar muscular atrophy are described by slow and selective dysfunction and degeneration of neurons and axons in the central nervous system (CNS). Computer-aided or in silico design methods have matured into powerful tools for reducing the number of ligands that should be screened in experimental assays. In the present review, the authors provide a basic background about neurodegenerative diseases and in silico techniques in the drug research. Furthermore, they review the various in silico studies reported against various targets in neurodegenerative diseases, including homology modeling, molecular docking, virtual high-throughput screening, quantitative structure activity relationship (QSAR), hologram quantitative structure activity relationship (HQSAR), 3D pharmacophore mapping, proteochemometrics modeling (PCM), fingerprints, fragment-based drug discovery, Monte Carlo simulation, molecular dynamic (MD) simulation, quantum-mechanical methods for drug design, support vector machines, and machine learning approaches. Neurodegenerative diseases have a multifactorial pathoetiological origin, so scientists have become persuaded that a multi-target therapeutic strategy aimed at the simultaneous targeting of multiple proteins (and therefore etiologies) involved in the development of a disease is recommended in future. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  13. Influence of the absorptive part of the complex potential on the S-Matrix poles

    International Nuclear Information System (INIS)

    Grama, C.; Grama, N.; Zamfirescu, I

    2001-01-01

    Although the polology of the S-matrix has been extensively studied, it occurred that some aspects remained disputable in the case of complex central potential V(r)=gV(r), g in C . These aspects are related to the origin of the observed narrow Σ-hypernuclear states that have been interpreted by Gal, Toker and Alexander as states which correspond to S-matrix poles situated in the second k-plane quadrant. From the analytical properties of the S-matrix for a real potential it results that there is no pole in the first and second k-plane quadrants, except for the imaginary k-axis. By switching on the absorption the S-matrix poles for real potential can evolve into the second quadrant of the k-plane. A critical study of the Σ-hypernuclear states needs the analysis of the motion of the S-matrix poles in the k-plane for variable complex coupling strength g. Recently contradictory opinions relative to the S-matrix poles trajectories in the complex k-plane for a complex square potential occurred. According to some authors the poles in the second quadrant can occur either from bound state poles moving anticlockwise, or from virtual state poles and capture resonant state poles moving clockwise as the absorption is switched on. Dabrowski argues that the statement made by Gal et al, Bonetti et al and Oset et al concerning the movement of the virtual poles with increasing absorptive potential is in general not correct. Dabrowski relates the direction in which the pole moves when the potential absorption increases to the direction in which the pole moves with increasing the real part of the potential, without clarifying this last question. For example, two poles moving in opposite directions along the imaginary k-axis are associated by Dabrowski to the same state. This is a wrong result, because one should associate a single pole to each quantum state. The aim of our work is to study the influence of the absorptive part of the potential on the S-matrix poles for the non

  14. Bioinformatics Mining and Modeling Methods for the Identification of Disease Mechanisms in Neurodegenerative Disorders

    Directory of Open Access Journals (Sweden)

    Martin Hofmann-Apitius

    2015-12-01

    Full Text Available Since the decoding of the Human Genome, techniques from bioinformatics, statistics, and machine learning have been instrumental in uncovering patterns in increasing amounts and types of different data produced by technical profiling technologies applied to clinical samples, animal models, and cellular systems. Yet, progress on unravelling biological mechanisms, causally driving diseases, has been limited, in part due to the inherent complexity of biological systems. Whereas we have witnessed progress in the areas of cancer, cardiovascular and metabolic diseases, the area of neurodegenerative diseases has proved to be very challenging. This is in part because the aetiology of neurodegenerative diseases such as Alzheimer´s disease or Parkinson´s disease is unknown, rendering it very difficult to discern early causal events. Here we describe a panel of bioinformatics and modeling approaches that have recently been developed to identify candidate mechanisms of neurodegenerative diseases based on publicly available data and knowledge. We identify two complementary strategies—data mining techniques using genetic data as a starting point to be further enriched using other data-types, or alternatively to encode prior knowledge about disease mechanisms in a model based framework supporting reasoning and enrichment analysis. Our review illustrates the challenges entailed in integrating heterogeneous, multiscale and multimodal information in the area of neurology in general and neurodegeneration in particular. We conclude, that progress would be accelerated by increasing efforts on performing systematic collection of multiple data-types over time from each individual suffering from neurodegenerative disease. The work presented here has been driven by project AETIONOMY; a project funded in the course of the Innovative Medicines Initiative (IMI; which is a public-private partnership of the European Federation of Pharmaceutical Industry Associations

  15. Redox Imbalance and Viral Infections in Neurodegenerative Diseases

    Directory of Open Access Journals (Sweden)

    Dolores Limongi

    2016-01-01

    Full Text Available Reactive oxygen species (ROS are essential molecules for many physiological functions and act as second messengers in a large variety of tissues. An imbalance in the production and elimination of ROS is associated with human diseases including neurodegenerative disorders. In the last years the notion that neurodegenerative diseases are accompanied by chronic viral infections, which may result in an increase of neurodegenerative diseases progression, emerged. It is known in literature that enhanced viral infection risk, observed during neurodegeneration, is partly due to the increase of ROS accumulation in brain cells. However, the molecular mechanisms of viral infection, occurring during the progression of neurodegeneration, remain unclear. In this review, we discuss the recent knowledge regarding the role of influenza, herpes simplex virus type-1, and retroviruses infection in ROS/RNS-mediated Parkinson’s disease (PD, Alzheimer’s disease (AD, and amyotrophic lateral sclerosis (ALS.

  16. The Function of the Mitochondrial Calcium Uniporter in Neurodegenerative Disorders

    Directory of Open Access Journals (Sweden)

    Yajin Liao

    2017-02-01

    Full Text Available The mitochondrial calcium uniporter (MCU—a calcium uniporter on the inner membrane of mitochondria—controls the mitochondrial calcium uptake in normal and abnormal situations. Mitochondrial calcium is essential for the production of adenosine triphosphate (ATP; however, excessive calcium will induce mitochondrial dysfunction. Calcium homeostasis disruption and mitochondrial dysfunction is observed in many neurodegenerative disorders. However, the role and regulatory mechanism of the MCU in the development of these diseases are obscure. In this review, we summarize the role of the MCU in controlling oxidative stress-elevated mitochondrial calcium and its function in neurodegenerative disorders. Inhibition of the MCU signaling pathway might be a new target for the treatment of neurodegenerative disorders.

  17. Genetic enhancement of macroautophagy in vertebrate models of neurodegenerative diseases.

    Science.gov (United States)

    Ejlerskov, Patrick; Ashkenazi, Avraham; Rubinsztein, David C

    2018-04-03

    Most of the neurodegenerative diseases that afflict humans manifest with the intraneuronal accumulation of toxic proteins that are aggregate-prone. Extensive data in cell and neuronal models support the concept that such proteins, like mutant huntingtin or alpha-synuclein, are substrates for macroautophagy (hereafter autophagy). Furthermore, autophagy-inducing compounds lower the levels of such proteins and ameliorate their toxicity in diverse animal models of neurodegenerative diseases. However, most of these compounds also have autophagy-independent effects and it is important to understand if similar benefits are seen with genetic strategies that upregulate autophagy, as this strengthens the validity of this strategy in such diseases. Here we review studies in vertebrate models using genetic manipulations of core autophagy genes and describe how these improve pathology and neurodegeneration, supporting the validity of autophagy upregulation as a target for certain neurodegenerative diseases. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. Interaction between -Synuclein and Other Proteins in Neurodegenerative Disorders

    Directory of Open Access Journals (Sweden)

    Kurt A. Jellinger

    2011-01-01

    Full Text Available Protein aggregation is a common characteristic of many neurodegenerative disorders, and the interaction between pathological/toxic proteins to cause neurodegeneration is a hot topic of current neuroscience research. Despite clinical, genetic, and experimental differences, evidence increasingly indicates considerable overlap between synucleinopathies and tauopathies or other protein-misfolding diseases. Inclusions, characteristics of these disorders, also occurring in other neurodegenerative diseases, suggest interactions of pathological proteins engaging common downstream pathways. Novel findings that have shifted our understanding in the role of pathologic proteins in the pathogenesis of Parkinson and Alzheimer diseases have confirmed correlations/overlaps between these and other neurodegenerative disorders. The synergistic effects of α-synuclein, hyperphosphorylated tau, amyloid-β, and other pathologic proteins, and the underlying molecular pathogenic mechanisms, including induction and spread of protein aggregates, are critically reviewed, suggesting a dualism or triad of neurodegeneration in protein-misfolding disorders, although the etiology of most of these processes is still mysterious.

  19. Pharmacological Alternatives for the Treatment of Neurodegenerative Disorders: Wasp and Bee Venoms and Their Components as New Neuroactive Tools.

    Science.gov (United States)

    Silva, Juliana; Monge-Fuentes, Victoria; Gomes, Flávia; Lopes, Kamila; dos Anjos, Lilian; Campos, Gabriel; Arenas, Claudia; Biolchi, Andréia; Gonçalves, Jacqueline; Galante, Priscilla; Campos, Leandro; Mortari, Márcia

    2015-08-18

    Neurodegenerative diseases are relentlessly progressive, severely impacting affected patients, families and society as a whole. Increased life expectancy has made these diseases more common worldwide. Unfortunately, available drugs have insufficient therapeutic effects on many subtypes of these intractable diseases, and adverse effects hamper continued treatment. Wasp and bee venoms and their components are potential means of managing or reducing these effects and provide new alternatives for the control of neurodegenerative diseases. These venoms and their components are well-known and irrefutable sources of neuroprotectors or neuromodulators. In this respect, the present study reviews our current understanding of the mechanisms of action and future prospects regarding the use of new drugs derived from wasp and bee venom in the treatment of major neurodegenerative disorders, including Alzheimer's Disease, Parkinson's Disease, Epilepsy, Multiple Sclerosis and Amyotrophic Lateral Sclerosis.

  20. Retinal nerve fibre layer loss in hereditary spastic paraplegias is restricted to complex phenotypes

    Directory of Open Access Journals (Sweden)

    Wiethoff Sarah

    2012-11-01

    Full Text Available Abstract Background Reduction of retinal nerve fibre layer (RNFL thickness was shown as part of the neurodegenerative process in a range of different neurodegenerative pathologies including Alzheimer′s disease (AD, idiopathic Parkinson’s disease (PD, spinocerebellar ataxia (SCA and multiple system atrophy (MSA. To further clarify the specificity of RNFL thinning as a potential marker of neurodegenerative diseases we investigated RNFL thickness in Hereditary Spastic Paraplegia (HSP, an axonal, length-dependent neurodegenerative pathology of the upper motor neurons. Methods Spectral domain optical coherence tomography (OCT was performed in 28 HSP patients (clinically: pure HSP = 22, complicated HSP = 6; genetic subtypes: SPG4 = 13, SPG5 = 1, SPG7 = 3, genetically unclassified: 11 to quantify peripapillary RNFL thickness. Standardized examination assessed duration of disease, dependency on assistive walking aids and severity of symptoms quantified with Spastic Paraplegia Rating Scale (SPRS. Results HSP patients demonstrated no significant thinning of global RNFL (pglobal = 0.61. Subgroup analysis revealed significant reduction in temporal and temporal inferior sectors for patients with complex (p Conclusion Clinically pure HSP patients feature no significant reduction in RNFL, whereas complex phenotypes display an abnormal thinning of temporal and temporal inferior RNFL. Our data indicate that RNFL thinning does not occur unspecifically in all neurodegenerative diseases but is in HSP restricted to subtypes with multisystemic degeneration.

  1. Study of local currents in low dimension materials using complex injecting potentials

    Science.gov (United States)

    He, Shenglai; Covington, Cody; Varga, Kálmán

    2018-04-01

    A complex potential is constructed to inject electrons into the conduction band, mimicking electron currents in nanoscale systems. The injected electrons are time propagated until a steady state is reached. The local current density can then be calculated to show the path of the conducting electrons on an atomistic level. The method allows for the calculation of the current density vectors within the medium as a function of energy of the conducting electron. Using this method, we investigate the electron pathway of graphene nanoribbons in various structures, molecular junctions, and black phosphorus nanoribbons. By analyzing the current flow through the structures, we find strong dependence on the structural geometry and the energy of the injected electrons. This method may be of general use in the study of nano-electronic materials and interfaces.

  2. Complex absorbing potentials within EOM-CC family of methods: Theory, implementation, and benchmarks

    Energy Technology Data Exchange (ETDEWEB)

    Zuev, Dmitry; Jagau, Thomas-C.; Krylov, Anna I. [Department of Chemistry, University of Southern California, Los Angeles, California 90089-0482 (United States); Bravaya, Ksenia B. [Department of Chemistry, Boston University, Boston, Massachusetts 02215-2521 (United States); Epifanovsky, Evgeny [Department of Chemistry, University of Southern California, Los Angeles, California 90089-0482 (United States); Department of Chemistry, University of California, Berkeley, California 94720 (United States); Q-Chem, Inc., 6601 Owens Drive, Suite 105 Pleasanton, California 94588 (United States); Shao, Yihan [Q-Chem, Inc., 6601 Owens Drive, Suite 105 Pleasanton, California 94588 (United States); Sundstrom, Eric; Head-Gordon, Martin [Department of Chemistry, University of California, Berkeley, California 94720 (United States)

    2014-07-14

    A production-level implementation of equation-of-motion coupled-cluster singles and doubles (EOM-CCSD) for electron attachment and excitation energies augmented by a complex absorbing potential (CAP) is presented. The new method enables the treatment of metastable states within the EOM-CC formalism in a similar manner as bound states. The numeric performance of the method and the sensitivity of resonance positions and lifetimes to the CAP parameters and the choice of one-electron basis set are investigated. A protocol for studying molecular shape resonances based on the use of standard basis sets and a universal criterion for choosing the CAP parameters are presented. Our results for a variety of π{sup *} shape resonances of small to medium-size molecules demonstrate that CAP-augmented EOM-CCSD is competitive relative to other theoretical approaches for the treatment of resonances and is often able to reproduce experimental results.

  3. Adenosine deaminase complexing protein (ADCP): a transformation sensitive protein with potentials of a cancer marker.

    Science.gov (United States)

    Herbschleb-Voogt, E; Ten Kate, J; Meera Khan, P

    1983-01-01

    Several observations by independent investigators in the past have indicated that adenosine deaminase complexing protein (ADCP), present in considerable quantities in certain human tissues, was absent or decreased in the cancers originated from them. During the present study, electrophoretic analysis of adenosine deaminase (ADA) isozymes and radioimmunoassay for ADCP in the primary fibroblasts and the transformed as well as certain tumor derived cell lines have demonstrated that ADCP present in large quantities in the primary cells was absent or nearly absent in the transformed or tumor-derived cell lines. Though the mechanisms involved are not yet clear, the above observations indicate that ADCP has the potentials of a useful marker in the studies on transformed cells and cancer tissues.

  4. Probabilities in quantum cosmological models: A decoherent histories analysis using a complex potential

    International Nuclear Information System (INIS)

    Halliwell, J. J.

    2009-01-01

    In the quantization of simple cosmological models (minisuperspace models) described by the Wheeler-DeWitt equation, an important step is the construction, from the wave function, of a probability distribution answering various questions of physical interest, such as the probability of the system entering a given region of configuration space at any stage in its entire history. A standard but heuristic procedure is to use the flux of (components of) the wave function in a WKB approximation. This gives sensible semiclassical results but lacks an underlying operator formalism. In this paper, we address the issue of constructing probability distributions linked to the Wheeler-DeWitt equation using the decoherent histories approach to quantum theory. The key step is the construction of class operators characterizing questions of physical interest. Taking advantage of a recent decoherent histories analysis of the arrival time problem in nonrelativistic quantum mechanics, we show that the appropriate class operators in quantum cosmology are readily constructed using a complex potential. The class operator for not entering a region of configuration space is given by the S matrix for scattering off a complex potential localized in that region. We thus derive the class operators for entering one or more regions in configuration space. The class operators commute with the Hamiltonian, have a sensible classical limit, and are closely related to an intersection number operator. The definitions of class operators given here handle the key case in which the underlying classical system has multiple crossings of the boundaries of the regions of interest. We show that oscillatory WKB solutions to the Wheeler-DeWitt equation give approximate decoherence of histories, as do superpositions of WKB solutions, as long as the regions of configuration space are sufficiently large. The corresponding probabilities coincide, in a semiclassical approximation, with standard heuristic procedures

  5. Global warming and neurodegenerative disorders: speculations on their linkage

    Science.gov (United States)

    Habibi, Laleh; Perry, George; Mahmoudi, Morteza

    2014-01-01

    Climate change is having considerable impact on biological systems. Eras of ice ages and warming shaped the contemporary earth and origin of creatures including humans. Warming forces stress conditions on cells. Therefore, cells evolved elaborate defense mechanisms, such as creation of heat shock proteins, to combat heat stress. Global warming is becoming a crisis and this process would yield an undefined increasing rate of neurodegenerative disorders in future decades. Since heat stress is known to have a degenerative effects on neurons and, conversely, cold conditions have protective effect on these cells, we hypothesize that persistent heat stress forced by global warming might play a crucial role in increasing neurodegenerative disorders. PMID:25671171

  6. Global warming and neurodegenerative disorders: speculations on their linkage.

    Science.gov (United States)

    Habibi, Laleh; Perry, George; Mahmoudi, Morteza

    2014-01-01

    Climate change is having considerable impact on biological systems. Eras of ice ages and warming shaped the contemporary earth and origin of creatures including humans. Warming forces stress conditions on cells. Therefore, cells evolved elaborate defense mechanisms, such as creation of heat shock proteins, to combat heat stress. Global warming is becoming a crisis and this process would yield an undefined increasing rate of neurodegenerative disorders in future decades. Since heat stress is known to have a degenerative effects on neurons and, conversely, cold conditions have protective effect on these cells, we hypothesize that persistent heat stress forced by global warming might play a crucial role in increasing neurodegenerative disorders.

  7. Nanomedicine and neurodegenerative disorders: so close yet so far.

    Science.gov (United States)

    Tosi, Giovanni; Vandelli, Maria Angela; Forni, Flavio; Ruozi, Barbara

    2015-07-01

    This editorial provides an overview of the main advantages of the use of nanomedicine-based approach for innovation in the treatment of neurodegenerative diseases. Besides these aspects, a critical analysis on the main causes that slow the application of nanomedicine to brain disorders is given along with the identification of possible solutions and possible interventions. Better communication between the main players of research in this field and a detailed understanding of the most critical issues to be addressed should help in defining future directions towards the improvement and, finally, the clinical application of nanomedicine to neurodegenerative diseases.

  8. Loss of Neuroprotective Factors in Neurodegenerative Dementias: The End or the Starting Point?

    Science.gov (United States)

    Benussi, Luisa; Binetti, Giuliano; Ghidoni, Roberta

    2017-01-01

    Recent clinical, genetic and biochemical experimental evidences highlight the existence of common molecular pathways underlying neurodegenerative diseases. In this review, we will explore a key common pathological mechanism, i.e., the loss of neuroprotective factors, across the three major neurodegenerative diseases leading to dementia: Alzheimer's disease (AD), Frontotemporal dementia (FTD) and Lewy body dementia (LBD). We will report evidences that the Brain Derived Neurotrophic Factor (BDNF), the most investigated and characterized brain neurotrophin, progranulin, a multi-functional adipokine with trophic and growth factor properties, and cystatin C, a neuroprotective growth factor, are reduced in AD, FTD, and LBD. Moreover, we will review the molecular mechanism underlying the loss of neuroprotective factors in neurodegenerative diseases leading to dementia, with a special focus on endo-lysosomal pathway and intercellular communication mediated by extracellular vesicles. Exploring the shared commonality of disease mechanisms is of pivotal importance to identify novel potential therapeutic targets and to develop treatments to delay, slow or block disease progression. PMID:29249935

  9. Loss of Neuroprotective Factors in Neurodegenerative Dementias: The End or the Starting Point?

    Directory of Open Access Journals (Sweden)

    Luisa Benussi

    2017-12-01

    Full Text Available Recent clinical, genetic and biochemical experimental evidences highlight the existence of common molecular pathways underlying neurodegenerative diseases. In this review, we will explore a key common pathological mechanism, i.e., the loss of neuroprotective factors, across the three major neurodegenerative diseases leading to dementia: Alzheimer's disease (AD, Frontotemporal dementia (FTD and Lewy body dementia (LBD. We will report evidences that the Brain Derived Neurotrophic Factor (BDNF, the most investigated and characterized brain neurotrophin, progranulin, a multi-functional adipokine with trophic and growth factor properties, and cystatin C, a neuroprotective growth factor, are reduced in AD, FTD, and LBD. Moreover, we will review the molecular mechanism underlying the loss of neuroprotective factors in neurodegenerative diseases leading to dementia, with a special focus on endo-lysosomal pathway and intercellular communication mediated by extracellular vesicles. Exploring the shared commonality of disease mechanisms is of pivotal importance to identify novel potential therapeutic targets and to develop treatments to delay, slow or block disease progression.

  10. Mitochondrial dysfunction in the neuro-degenerative and cardio-degenerative disease, Friedreich's ataxia.

    Science.gov (United States)

    Chiang, Shannon; Kalinowski, Danuta S; Jansson, Patric J; Richardson, Des R; Huang, Michael L-H

    2017-08-04

    Mitochondrial homeostasis is essential for maintaining healthy cellular function and survival. The detrimental involvement of mitochondrial dysfunction in neuro-degenerative diseases has recently been highlighted in human conditions, such as Parkinson's, Alzheimer's and Huntington's disease. Friedreich's ataxia (FA) is another neuro-degenerative, but also cardio-degenerative condition, where mitochondrial dysfunction plays a crucial role in disease progression. Deficient expression of the mitochondrial protein, frataxin, is the primary cause of FA, which leads to adverse alterations in whole cell and mitochondrial iron metabolism. Dys-regulation of iron metabolism in these compartments, results in the accumulation of inorganic iron deposits in the mitochondrial matrix that is thought to potentiate oxidative damage observed in FA. Therefore, the maintenance of mitochondrial homeostasis is crucial in the progression of neuro-degenerative conditions, particularly in FA. In this review, vital mitochondrial homeostatic processes and their roles in FA pathogenesis will be discussed. These include mitochondrial iron processing, mitochondrial dynamics (fusion and fission processes), mitophagy, mitochondrial biogenesis, mitochondrial energy production and calcium metabolism. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Neuroproteases in peptide neurotransmission and neurodegenerative diseases: applications to drug discovery research.

    Science.gov (United States)

    Hook, Vivian Y H

    2006-01-01

    The nervous system represents a key area for development of novel therapeutic agents for the treatment of neurological and neurodegenerative diseases. Recent research has demonstrated the critical importance of neuroproteases for the production of specific peptide neurotransmitters and for the production of toxic peptides in major neurodegenerative diseases that include Alzheimer, Huntington, and Parkinson diseases. This review illustrates the successful criteria that have allowed identification of proteases responsible for converting protein precursors into active peptide neurotransmitters, consisting of dual cysteine protease and subtilisin-like protease pathways in neuroendocrine cells. These peptide neurotransmitters are critical regulators of neurologic conditions, including analgesia and cognition, and numerous behaviors. Importantly, protease pathways also represent prominent mechanisms in neurodegenerative diseases, especially Alzheimer, Huntington, and Parkinson diseases. Recent studies have identified secretory vesicle cathepsin B as a novel beta-secretase for production of the neurotoxic beta-amyloid (Abeta) peptide of Alzheimer disease. Moreover, inhibition of cathepsin B reduces Abeta peptide levels in brain. These neuroproteases potentially represent new drug targets that should be explored in future pharmaceutical research endeavors for drug discovery.

  12. Head trauma in sport and neurodegenerative disease: an issue whose time has come?

    Science.gov (United States)

    Pearce, Neil; Gallo, Valentina; McElvenny, Damien

    2015-03-01

    A number of small studies and anecdotal reports have been suggested that sports involving repeated head trauma may have long-term risks of neurodegenerative disease. There are now plausible mechanisms for these effects, and a recognition that these problems do not just occur in former boxers, but in a variety of sports involving repeated concussions, and possibly also in sports in which low-level head trauma is common. These neurodegenerative effects potentially include increased risks of impaired cognitive function and dementia, Parkinson's disease, and amyotrophic lateral sclerosis. Many would argue for taking a precautionary approach and immediately banning or restricting sports such as boxing. However, there are important public health issues in terms of how wide the net should be cast in terms of other sports, and what remedial measures could be taken? This in turn requires a major research effort involving both clinical and basic research to understand the underlying mechanisms, leading from head trauma to neurodegenerative disease and epidemiologic studies to assess the long-term consequences. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. On the number of eigenvalues of the discrete one-dimensional Dirac operator with a complex potential

    Science.gov (United States)

    Hulko, Artem

    2018-03-01

    In this paper we define a one-dimensional discrete Dirac operator on Z . We study the eigenvalues of the Dirac operator with a complex potential. We obtain bounds on the total number of eigenvalues in the case where V decays exponentially at infinity. We also estimate the number of eigenvalues for the discrete Schrödinger operator with complex potential on Z . That is we extend the result obtained by Hulko (Bull Math Sci, to appear) to the whole Z.

  14. Mass spectrometry-based metabolomics: Targeting the crosstalk between gut microbiota and brain in neurodegenerative disorders.

    Science.gov (United States)

    Luan, Hemi; Wang, Xian; Cai, Zongwei

    2017-11-12

    Metabolomics seeks to take a "snapshot" in a time of the levels, activities, regulation and interactions of all small molecule metabolites in response to a biological system with genetic or environmental changes. The emerging development in mass spectrometry technologies has shown promise in the discovery and quantitation of neuroactive small molecule metabolites associated with gut microbiota and brain. Significant progress has been made recently in the characterization of intermediate role of small molecule metabolites linked to neural development and neurodegenerative disorder, showing its potential in understanding the crosstalk between gut microbiota and the host brain. More evidence reveals that small molecule metabolites may play a critical role in mediating microbial effects on neurotransmission and disease development. Mass spectrometry-based metabolomics is uniquely suitable for obtaining the metabolic signals in bidirectional communication between gut microbiota and brain. In this review, we summarized major mass spectrometry technologies including liquid chromatography-mass spectrometry, gas chromatography-mass spectrometry, and imaging mass spectrometry for metabolomics studies of neurodegenerative disorders. We also reviewed the recent advances in the identification of new metabolites by mass spectrometry and metabolic pathways involved in the connection of intestinal microbiota and brain. These metabolic pathways allowed the microbiota to impact the regular function of the brain, which can in turn affect the composition of microbiota via the neurotransmitter substances. The dysfunctional interaction of this crosstalk connects neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease and Huntington's disease. The mass spectrometry-based metabolomics analysis provides information for targeting dysfunctional pathways of small molecule metabolites in the development of the neurodegenerative diseases, which may be valuable for the

  15. Relationships between Rapid Eye Movement Sleep Behavior Disorder and Neurodegenerative Diseases: Clinical Assessments, Biomarkers, and Treatment

    Science.gov (United States)

    Li, Min; Wang, Li; Liu, Jiang-Hong; Zhan, Shu-Qin

    2018-01-01

    Objective: Rapid eye movement sleep behavior disorder (RBD) is characterized by dream enactment and loss of muscle atonia during rapid eye movement sleep. RBD is closely related to α-synucleinopathies including Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. Many studies have investigated the markers of imaging and neurophysiological, genetic, cognitive, autonomic function of RBD and their predictive value for neurodegenerative diseases. This report reviewed the progress of these studies and discussed their limitations and future research directions. Data Sources: Using the combined keywords: “RBD”, “neurodegenerative disease”, “Parkinson disease”, and “magnetic resonance imaging”, the PubMed/MEDLINE literature search was conducted up to January 1, 2018. Study Selection: A total of 150 published articles were initially identified citations. Of the 150 articles, 92 articles were selected after further detailed review. This study referred to all the important English literature in full. Results: Single-nucleotide polymorphisms in SCARB2 (rs6812193) and MAPT (rs12185268) were significantly associated with RBD. The olfactory loss, autonomic dysfunction, marked electroencephalogram slowing during both wakefulness and rapid eye movement sleep, and cognitive impairments were potential predictive markers for RBD conversion to neurodegenerative diseases. Traditional structural imaging studies reported relatively inconsistent results, whereas reduced functional connectivity between the left putamen and substantia nigra and dopamine transporter uptake demonstrated by functional imaging techniques were relatively consistent findings. Conclusions: More longitudinal studies should be conducted to evaluate the predictive value of biomarkers of RBD. Moreover, because the glucose and dopamine metabolisms are not specific for assessing cognitive cognition, the molecular metabolism directly related to cognition should be investigated

  16. Gadolinium(III-DOTA Complex Functionalized with BODIPY as a Potential Bimodal Contrast Agent for MRI and Optical Imaging

    Directory of Open Access Journals (Sweden)

    Matthias Ceulemans

    2015-11-01

    Full Text Available The synthesis and characterization of a novel gadolinium(III DOTA complex functionalized with a boron-dipyrromethene derivative (BODIPY is described. The assembly of the complex relies on azide diazotransfer chemistry in a copper tube flow reactor. The azide thus formed is coupled directly with an alkyne via click chemistry, resulting into a paramagnetic and luminescent gadolinium(III complex. Luminescent data and relaxometric properties of the complex have been evaluated, suggesting the potential applicability of the complexes as a bimodal contrast agent for magnetic resonance and optical imaging. The complex displays a bright emission at 523 nm with an absorption maximum of 507 nm and high quantum yields of up to 83% in water. The proton relaxivity of the complex measured at 310 K and at frequencies of 20 and 60 MHz had the values of 3.9 and 3.6 s−1·mM−1, respectively.

  17. Induced tauopathy in a novel 3D-culture model mediates neurodegenerative processes: a real-time study on biochips.

    Directory of Open Access Journals (Sweden)

    Diana Seidel

    Full Text Available Tauopathies including Alzheimer's disease represent one of the major health problems of aging population worldwide. Therefore, a better understanding of tau-dependent pathologies and consequently, tau-related intervention strategies is highly demanded. In recent years, several tau-focused therapies have been proposed with the aim to stop disease progression. However, to develop efficient active pharmaceutical ingredients for the broad treatment of Alzheimer's disease patients, further improvements are necessary for understanding the detailed neurodegenerative processes as well as the mechanism and side effects of potential active pharmaceutical ingredients (API in the neuronal system. In this context, there is a lack of suitable complex in vitro cell culture models recapitulating major aspects of taupathological degenerative processes in sufficient time and reproducible manner.Herewith, we describe a novel 3D SH-SY5Y cell-based, tauopathy model that shows advanced characteristics of matured neurons in comparison to monolayer cultures without the need of artificial differentiation promoting agents. Moreover, the recombinant expression of a novel highly pathologic fourfold mutated human tau variant lead to a fast and emphasized degeneration of neuritic processes. The neurodegenerative effects could be analyzed in real time and with high sensitivity using our unique microcavity array-based impedance spectroscopy measurement system. We were able to quantify a time- and concentration-dependent relative impedance decrease when Alzheimer's disease-like tau pathology was induced in the neuronal 3D cell culture model. In combination with the collected optical information, the degenerative processes within each 3D-culture could be monitored and analyzed. More strikingly, tau-specific regenerative effects caused by tau-focused active pharmaceutical ingredients could be quantitatively monitored by impedance spectroscopy.Bringing together our novel complex 3

  18. Mechanisms of action of brain insulin against neurodegenerative diseases.

    Science.gov (United States)

    Ramalingam, Mahesh; Kim, Sung-Jin

    2014-06-01

    Insulin, a pancreatic hormone, is best known for its peripheral effects on the metabolism of glucose, fats and proteins. There is a growing body of evidence linking insulin action in the brain to neurodegenerative diseases. Insulin present in central nervous system is a regulator of central glucose metabolism nevertheless this glucoregulation is not the main function of insulin in the brain. Brain is known to be specifically vulnerable to oxidative products relative to other organs and altered brain insulin signaling may cause or promote neurodegenerative diseases which invalidates and reduces the quality of life. Insulin located within the brain is mostly of pancreatic origin or is produced in the brain itself crosses the blood-brain barrier and enters the brain via a receptor-mediated active transport system. Brain Insulin, insulin receptor and insulin receptor substrate-mediated signaling pathways play important roles in the regulation of peripheral metabolism, feeding behavior, memory and maintenance of neural functions such as neuronal growth and differentiation, neuromodulation and neuroprotection. In the present review, we would like to summarize the novel biological and pathophysiological roles of neuronal insulin in neurodegenerative diseases and describe the main signaling pathways in use for therapeutic strategies in the use of insulin to the cerebral tissues and their biological applications to neurodegenerative diseases.

  19. Prediction of neurodegenerative diseases from functional brain imaging data

    NARCIS (Netherlands)

    Mudali, Deborah

    2016-01-01

    Neurodegenerative diseases are a challenge, especially in the developed society where life expectancy is high. Since these diseases progress slowly, they are not easy to diagnose at an early stage. Moreover, they portray similar disease features, which makes them hard to differentiate. In this

  20. Molecular Chaperone Dysfunction in Neurodegenerative Diseases and Effects of Curcumin

    Directory of Open Access Journals (Sweden)

    Panchanan Maiti

    2014-01-01

    Full Text Available The intra- and extracellular accumulation of misfolded and aggregated amyloid proteins is a common feature in several neurodegenerative diseases, which is thought to play a major role in disease severity and progression. The principal machineries maintaining proteostasis are the ubiquitin proteasomal and lysosomal autophagy systems, where heat shock proteins play a crucial role. Many protein aggregates are degraded by the lysosomes, depending on aggregate size, peptide sequence, and degree of misfolding, while others are selectively tagged for removal by heat shock proteins and degraded by either the proteasome or phagosomes. These systems are compromised in different neurodegenerative diseases. Therefore, developing novel targets and classes of therapeutic drugs, which can reduce aggregates and maintain proteostasis in the brains of neurodegenerative models, is vital. Natural products that can modulate heat shock proteins/proteosomal pathway are considered promising for treating neurodegenerative diseases. Here we discuss the current knowledge on the role of HSPs in protein misfolding diseases and knowledge gained from animal models of Alzheimer’s disease, tauopathies, and Huntington’s diseases. Further, we discuss the emerging treatment regimens for these diseases using natural products, like curcumin, which can augment expression or function of heat shock proteins in the cell.

  1. Quantitative analysis on electrooculography (EOG) for neurodegenerative disease

    Science.gov (United States)

    Liu, Chang-Chia; Chaovalitwongse, W. Art; Pardalos, Panos M.; Seref, Onur; Xanthopoulos, Petros; Sackellares, J. C.; Skidmore, Frank M.

    2007-11-01

    Many studies have documented abnormal horizontal and vertical eye movements in human neurodegenerative disease as well as during altered states of consciousness (including drowsiness and intoxication) in healthy adults. Eye movement measurement may play an important role measuring the progress of neurodegenerative diseases and state of alertness in healthy individuals. There are several techniques for measuring eye movement, Infrared detection technique (IR). Video-oculography (VOG), Scleral eye coil and EOG. Among those available recording techniques, EOG is a major source for monitoring the abnormal eye movement. In this real-time quantitative analysis study, the methods which can capture the characteristic of the eye movement were proposed to accurately categorize the state of neurodegenerative subjects. The EOG recordings were taken while 5 tested subjects were watching a short (>120 s) animation clip. In response to the animated clip the participants executed a number of eye movements, including vertical smooth pursued (SVP), horizontal smooth pursued (HVP) and random saccades (RS). Detection of abnormalities in ocular movement may improve our diagnosis and understanding a neurodegenerative disease and altered states of consciousness. A standard real-time quantitative analysis will improve detection and provide a better understanding of pathology in these disorders.

  2. Absence of consensus in diagnostic criteria for familial neurodegenerative diseases.

    LENUS (Irish Health Repository)

    Byrne, Susan

    2012-04-01

    A small proportion of cases seen in neurodegenerative conditions such as amyotrophic lateral sclerosis (ALS), Parkinson\\'s disease and Alzheimer disease are familial. These familial cases are usually clinically indistinguishable from sporadic cases. Identifying familial cases is important both in terms of clinical guidance for family members and for gene discovery.

  3. Protection against neurodegenerative disease on Earth and in space

    Science.gov (United States)

    Takamatsu, Yoshiki; Koike, Wakako; Takenouchi, Takato; Sugama, Shuei; Wei, Jianshe; Waragai, Masaaki; Sekiyama, Kazunari; Hashimoto, Makoto

    2016-01-01

    All living organisms have evolutionarily adapted themselves to the Earth’s gravity, and failure to adapt to gravity changes may lead to pathological conditions. This perspective may also apply to abnormal aging observed in bedridden elderly patients with aging-associated diseases such as osteoporosis and sarcopenia. Given that bedridden elderly patients are partially analogous to astronauts in that both cannot experience the beneficial effects of gravity on the skeletal system and may suffer from bone loss and muscle weakness, one may wonder whether there are gravity-related mechanisms underlying diseases among the elderly. In contrast to numerous studies of the relevance of microgravity in skeletal disorders, little attention has been paid to neurodegenerative diseases. Therefore, the objective of this paper is to discuss the possible relevance of microgravity in these diseases. We particularly noted a proteomics paper showing that levels of hippocampal proteins, including β-synuclein and carboxyl-terminal ubiquitin hydrolase L1, which have been linked to familial neurodegenerative diseases, were significantly decreased in the hippocampus of mice subjected to hindlimb suspension, a model of microgravity. We suggest that microgravity-induced neurodegeneration may be further exacerbated by diabetes and other factors. On the basis of this view, prevention of neurodegenerative diseases through ‘anti-diabetes’ and ‘hypergravity’ approaches may be important as a common therapeutic approach on Earth and in space. Collectively, neurodegenerative diseases and space medicine may be linked to each other more strongly than previously thought. PMID:28725728

  4. Predictive gene testing for Huntington disease and other neurodegenerative disorders.

    Science.gov (United States)

    Wedderburn, S; Panegyres, P K; Andrew, S; Goldblatt, J; Liebeck, T; McGrath, F; Wiltshire, M; Pestell, C; Lee, J; Beilby, J

    2013-12-01

    Controversies exist around predictive testing (PT) programmes in neurodegenerative disorders. This study sets out to answer the following questions relating to Huntington disease (HD) and other neurodegenerative disorders: differences between these patients in their PT journeys, why and when individuals withdraw from PT, and decision-making processes regarding reproductive genetic testing. A case series analysis of patients having PT from the multidisciplinary Western Australian centre for PT over the past 20 years was performed using internationally recognised guidelines for predictive gene testing in neurodegenerative disorders. Of 740 at-risk patients, 518 applied for PT: 466 at risk of HD, 52 at risk of other neurodegenerative disorders - spinocerebellar ataxias, hereditary prion disease and familial Alzheimer disease. Thirteen percent withdrew from PT - 80.32% of withdrawals occurred during counselling stages. Major withdrawal reasons related to timing in the patients' lives or unknown as the patient did not disclose the reason. Thirty-eight HD individuals had reproductive genetic testing: 34 initiated prenatal testing (of which eight withdrew from the process) and four initiated pre-implantation genetic diagnosis. There was no recorded or other evidence of major psychological reactions or suicides during PT. People withdrew from PT in relation to life stages and reasons that are unknown. Our findings emphasise the importance of: (i) adherence to internationally recommended guidelines for PT; (ii) the role of the multidisciplinary team in risk minimisation; and (iii) patient selection. © 2013 The Authors; Internal Medicine Journal © 2013 Royal Australasian College of Physicians.

  5. Ghrelin: a link between ageing, metabolism and neurodegenerative disorders

    NARCIS (Netherlands)

    Stoyanova, Irina

    2014-01-01

    Along with the increase in life expectancy over the last century comes the increased risk for development of age-related disorders, including metabolic and neurodegenerative diseases such as Alzheimer's, Parkinson's and Huntington's diseases. These chronic disorders share two main characteristics:

  6. NSAIDs and cardiovascular drugs in neurodegenerative and cerebrovascular diseases

    NARCIS (Netherlands)

    M.D.M. Haag (Mendel)

    2009-01-01

    textabstractNeurodegenerative and cerebrovascular diseases are frequent in elderly populations and comprise primarily of dementia (mainly Alzheimer disease (AD)), Parkinson disease (PD) and stroke. The prevalence of these neurological disorders rises with older age. From 55 years to 90 years and

  7. A knowledge based approach to matching human neurodegenerative disease and animal models

    Directory of Open Access Journals (Sweden)

    Maryann E Martone

    2013-05-01

    Full Text Available Neurodegenerative diseases present a wide and complex range of biological and clinical features. Animal models are key to translational research, yet typically only exhibit a subset of disease features rather than being precise replicas of the disease. Consequently, connecting animal to human conditions using direct data-mining strategies has proven challenging, particularly for diseases of the nervous system, with its complicated anatomy and physiology. To address this challenge we have explored the use of ontologies to create formal descriptions of structural phenotypes across scales that are machine processable and amenable to logical inference. As proof of concept, we built a Neurodegenerative Disease Phenotype Ontology and an associated Phenotype Knowledge Base using an entity-quality model that incorporates descriptions for both human disease phenotypes and those of animal models. Entities are drawn from community ontologies made available through the Neuroscience Information Framework and qualities are drawn from the Phenotype and Trait Ontology. We generated ~1200 structured phenotype statements describing structural alterations at the subcellular, cellular and gross anatomical levels observed in 11 human neurodegenerative conditions and associated animal models. PhenoSim, an open source tool for comparing phenotypes, was used to issue a series of competency questions to compare individual phenotypes among organisms and to determine which animal models recapitulate phenotypic aspects of the human disease in aggregate. Overall, the system was able to use relationships within the ontology to bridge phenotypes across scales, returning non-trivial matches based on common subsumers that were meaningful to a neuroscientist with an advanced knowledge of neuroanatomy. The system can be used both to compare individual phenotypes and also phenotypes in aggregate. This proof of concept suggests that expressing complex phenotypes using formal

  8. Complexity and availability for fusion power plants: The potential advantages of inertial fusion energy

    International Nuclear Information System (INIS)

    Perkins, L.J.

    1997-01-01

    Probably the single largest advantage of the inertial route to fusion energy (IFE) is the perception that its power plant embodiments could achieve acceptable capacity factors. This is a result of its relative simplicity, the decoupling of the driver and reactor chamber, and the potential to employ thick liquid walls. The author examines these issues in terms of the complexity, reliability, maintainability and, therefore, availability of both magnetic and inertial fusion power plants and compares these factors with corresponding scheduled and unscheduled outage data from present day fission experience. The author stresses that, given the simple nature of a fission core, the vast majority of unplanned outages in fission plants are due to failures outside the reactor vessel itself. Given one must be prepared for similar outages in the analogous plant external to a fusion power core, this puts severe demands on the reliability required of the fusion core itself. The author indicates that such requirements can probably be met for IFE plants. He recommends that this advantage be promoted by performing a quantitative reliability and availability study for a representative IFE power plant and suggests that databases are probably adequate for this task. 40 refs., 4 figs., 3 tabs

  9. Biocompatible Polyelectrolyte Complex Nanoparticles from Lactoferrin and Pectin as Potential Vehicles for Antioxidative Curcumin.

    Science.gov (United States)

    Yan, Jing-Kun; Qiu, Wen-Yi; Wang, Yao-Yao; Wu, Jian-Yong

    2017-07-19

    Polyelectrolyte complex nanoparticles (PEC NPs) were fabricated via electrostatic interactions between positively charged heat-denatured lactoferrin (LF) particles and negatively charged pectin. The obtained PEC NPs were then utilized as curcumin carriers. PEC NPs were prepared by mixing 1.0 mg/mL solutions of heat-denatured LF and pectin at a mass ratio of 1:1 (w/w) in the absence of NaCl at pH 4.50. PEC NPs that were prepared under optimized conditions were spherical in shape with a particle size of ∼208 nm and zeta potential of ∼-32 mV. Hydrophobic curcumin was successfully encapsulated into LF/pectin PEC NPs with high encapsulation efficiency (∼85.3%) and loading content (∼13.4%). The in vitro controlled release and prominent antioxidant activities of curcumin from LF/pectin PEC NPs were observed. The present work provides a facile and fast method to synthesize nanoscale food-grade delivery systems for the improved water solubility, controlled release, and antioxidant activity of hydrophobic curcumin.

  10. Complex-scaling of screened Coulomb potentials for resonance calculations utilizing the modified Bessel functions

    Science.gov (United States)

    Jiao, Li-Guang; Ho, Yew Kam

    2014-05-01

    The screened Coulomb potential (SCP) has been extensively used in atomic physics, nuclear physics, quantum chemistry and plasma physics. However, an accurate calculation for atomic resonances under SCP is still a challenging task for various methods. Within the complex-scaling computational scheme, we have developed a method utilizing the modified Bessel functions to calculate doubly-excited resonances in two-electron atomic systems with configuration interaction-type basis. To test the validity of our method, we have calculated S- and P-wave resonance states of the helium atom with various screening strengths, and have found good agreement with earlier calculations using different methods. Our present method can be applied to calculate high-lying resonances associated with high excitation thresholds of the He+ ion, and with high-angular-momentum states. The derivation and calculation details of our present investigation together with new results of high-angular-momentum states will be presented at the meeting. Supported by NSC of Taiwan.

  11. Complexity versus availability for fusion: The potential advantages of inertial fusion energy

    International Nuclear Information System (INIS)

    Perkins, L.J.

    1996-01-01

    Probably the single largest advantage of the inertial route to fusion energy (IFE) is the perception that its power plant embodiments could achieve acceptable capacity factors. This is a result of its relative simplicity, the decoupling of the driver and reactor chamber, and the potential to employ thick liquid walls. We examine these issues in terms of the complexity, reliability, maintainability and, therefore, availability of both magnetic and inertial fusion power plants and compare these factors with corresponding scheduled and unscheduled outage data from present day fission experience. We stress that, given the simple nature of a fission core, the vast majority of unplanned outages in fission plants are due to failures outside the reactor vessel itself Given we must be prepared for similar outages in the analogous plant external to a fusion power core, this puts severe demands on the reliability required of the fusion core itself. We indicate that such requirements can probably be met for IFE plants. We recommend that this advantage be promoted by performing a quantitative reliability and availability study for a representative IFE power plant and suggest that databases are probably adequate for this task

  12. The evaluation of complex interventions in palliative care: an exploration of the potential of case study research strategies.

    Science.gov (United States)

    Walshe, Catherine

    2011-12-01

    Complex, incrementally changing, context dependent and variable palliative care services are difficult to evaluate. Case study research strategies may have potential to contribute to evaluating such complex interventions, and to develop this field of evaluation research. This paper explores definitions of case study (as a unit of study, a process, and a product) and examines the features of case study research strategies which are thought to confer benefits for the evaluation of complex interventions in palliative care settings. Ten features of case study that are thought to be beneficial in evaluating complex interventions in palliative care are discussed, drawing from exemplars of research in this field. Important features are related to a longitudinal approach, triangulation, purposive instance selection, comprehensive approach, multiple data sources, flexibility, concurrent data collection and analysis, search for proving-disproving evidence, pattern matching techniques and an engaging narrative. The limitations of case study approaches are discussed including the potential for subjectivity and their complex, time consuming and potentially expensive nature. Case study research strategies have great potential in evaluating complex interventions in palliative care settings. Three key features need to be exploited to develop this field: case selection, longitudinal designs, and the use of rival hypotheses. In particular, case study should be used in situations where there is interplay and interdependency between the intervention and its context, such that it is difficult to define or find relevant comparisons.

  13. The South African developmental landscape: restricted potentials or expansive, complex adaptive opportunities?

    Directory of Open Access Journals (Sweden)

    C J Burman

    2013-07-01

    Full Text Available This article argues that the South African developmental landscape is currently locked into an overly technical, path dependent paradigm that is unlikely to be capable of embracing the complex challenges identified by the recent National Development Plan. The article explores the internal logic of the existing path dependent, technical condition from the perspective of complexity, in the context of the Department of Science and Technology’s Fifth Grand Challenge and “continuous change”. It is argued that drawing ideas from complexity into future developmental trajectories can add value to the National Development Plan: Vision 2030, but to do so will require dynamic mind-set shifts across multiple developmental scales and interfaces if new approaches to managing development that embraces complexity, rather than denies it, is to emerge. Keywords: development; complexity; path dependency; epistemological vigilance; sense-making; National Development Plan Disciplines: Complexity Studies; Transdisciplinary studies; Management studies; Public management; Political studies; Economics; Development Studies

  14. Characterization of tetraaza-AC8, a surfactant with cation complexing potential

    International Nuclear Information System (INIS)

    Arleth, Lise

    1995-01-01

    Being a surfactant with cation complexing potential, the Tetraaza-AC8 can, in the long term, possibly be applied for the selection and extraction of specific cations. This can be of interest for the handling of radioactive waste or in the chemical industries for extraction of rare earth molecules as for example Rhodium. A thorough characterization of the behavior and abilities of Tetraaza-AC8 is necessary before one can even think of taking it into a larger production with sight of a specific application. This project deals with the characterization of the behavior and abilities of Tetraaza- AC8. In order to make use of the surface active properties of Tetraaza-AC8 it is necessary to dissolve it in some kind of solvent. As water is an important solvent which is, in addition, both inexpensive and non-polluting it is the natural choice. The aim of the project can then precised as follows: To study the micelle formation of dilute aqueous solutions of Tetraaza- AC8 and to determine how the micelle formation is influenced by the addition of respectively CsF, CuF_2 and RhCl_3 to the solutions The primary method of analysis is small-angle scattering. As small-angle x-ray scattering (SAXS) and small-angle neutron scattering (SANS) emphasizes different parts of the micellar structure, the combination of the methods allows a good determination of the micellar shape. In order to support the interpretation of scattering data, density measurements, surface tension measurements and UV/visible light spectroscopy are also performed. The scattering data have been analyzed according to two fundamentally different methods of analysis namely the method of indirect Fourier transform and the method of fitting molecular based models of the micelles to the scattering spectra. The first chapter contains a short introduction to the field of surfactants and complexing macrocycles. The chemical structure of Tetraaza-AC8 will be explained and motivated. A short description of the synthesis

  15. Unquenched Complex Dirac Spectra at Nonzero Chemical Potential: Two-Color QCD Lattice Data versus Matrix Model

    International Nuclear Information System (INIS)

    Akemann, Gernot; Bittner, Elmar

    2006-01-01

    We compare analytic predictions of non-Hermitian chiral random matrix theory with the complex Dirac operator eigenvalue spectrum of two-color lattice gauge theory with dynamical fermions at nonzero chemical potential. The Dirac eigenvalues come in complex conjugate pairs, making the action of this theory real and positive for our choice of two staggered flavors. This enables us to use standard Monte Carlo simulations in testing the influence of the chemical potential and quark mass on complex eigenvalues close to the origin. We find excellent agreement between the analytic predictions and our data for two different volumes over a range of chemical potentials below the chiral phase transition. In particular, we detect the effect of unquenching when going to very small quark masses

  16. Olfaction in Neurologic and Neurodegenerative Diseases: A Literature Review

    Directory of Open Access Journals (Sweden)

    Godoy, Maria Dantas Costa Lima

    2015-01-01

    Full Text Available Introduction Loss of smell is involved in various neurologic and neurodegenerative diseases, such as Parkinson disease and Alzheimer disease. However, the olfactory test is usually neglected by physicians at large. Objective The aim of this study was to review the current literature about the relationship between olfactory dysfunction and neurologic and neurodegenerative diseases. Data Synthesis Twenty-seven studies were selected for analysis, and the olfactory system, olfaction, and the association between the olfactory dysfunction and dementias were reviewed. Furthermore, is described an up to date in olfaction. Conclusion Otolaryngologist should remember the importance of olfaction evaluation in daily practice. Furthermore, neurologists and physicians in general should include olfactory tests in the screening of those at higher risk of dementia.

  17. LSTM for diagnosis of neurodegenerative diseases using gait data

    Science.gov (United States)

    Zhao, Aite; Qi, Lin; Li, Jie; Dong, Junyu; Yu, Hui

    2018-04-01

    Neurodegenerative diseases (NDs) usually cause gait disorders and postural disorders, which provides an important basis for NDs diagnosis. By observing and analyzing these clinical manifestations, medical specialists finally give diagnostic results to the patient, which is inefficient and can be easily affected by doctors' subjectivity. In this paper, we propose a two-layer Long Short-Term Memory (LSTM) model to learn the gait patterns exhibited in the three NDs. The model was trained and tested using temporal data that was recorded by force-sensitive resistors including time series, such as stride interval and swing interval. Our proposed method outperforms other methods in literature in accordance with accuracy of the predicted diagnostic result. Our approach aims at providing the quantitative assessment so that to indicate the diagnosis and treatment of these neurodegenerative diseases in clinic

  18. Maillard reaction versus other nonenzymatic modifications in neurodegenerative processes.

    Science.gov (United States)

    Pamplona, Reinald; Ilieva, Ekaterina; Ayala, Victoria; Bellmunt, Maria Josep; Cacabelos, Daniel; Dalfo, Esther; Ferrer, Isidre; Portero-Otin, Manuel

    2008-04-01

    Nonenzymatic protein modifications are generated from direct oxidation of amino acid side chains and from reaction of the nucleophilic side chains of specific amino acids with reactive carbonyl species. These reactions give rise to specific markers that have been analyzed in different neurodegenerative diseases sharing protein aggregation, such as Alzheimer's disease, Pick's disease, Parkinson's disease, dementia with Lewy bodies, Creutzfeldt-Jakob disease, and amyotrophic lateral sclerosis. Collectively, available data demonstrate that oxidative stress homeostasis, mitochondrial function, and energy metabolism are key factors in determining the disease-specific pattern of protein molecular damage. In addition, these findings suggest the lack of a "gold marker of oxidative stress," and, consequently, they strengthen the need for a molecular dissection of the nonenzymatic reactions underlying neurodegenerative processes.

  19. Transposable elements in TDP-43-mediated neurodegenerative disorders.

    Directory of Open Access Journals (Sweden)

    Wanhe Li

    Full Text Available Elevated expression of specific transposable elements (TEs has been observed in several neurodegenerative disorders. TEs also can be active during normal neurogenesis. By mining a series of deep sequencing datasets of protein-RNA interactions and of gene expression profiles, we uncovered extensive binding of TE transcripts to TDP-43, an RNA-binding protein central to amyotrophic lateral sclerosis (ALS and frontotemporal lobar degeneration (FTLD. Second, we find that association between TDP-43 and many of its TE targets is reduced in FTLD patients. Third, we discovered that a large fraction of the TEs to which TDP-43 binds become de-repressed in mouse TDP-43 disease models. We propose the hypothesis that TE mis-regulation contributes to TDP-43 related neurodegenerative diseases.

  20. Astrocytes in neurodegenerative diseases (I): function and molecular description.

    Science.gov (United States)

    Guillamón-Vivancos, T; Gómez-Pinedo, U; Matías-Guiu, J

    2015-03-01

    Astrocytes have been considered mere supporting cells in the CNS. However, we now know that astrocytes are actively involved in many of the functions of the CNS and may play an important role in neurodegenerative diseases. This article reviews the roles astrocytes play in CNS development and plasticity; control of synaptic transmission; regulation of blood flow, energy, and metabolism; formation of the blood-brain barrier; regulation of the circadian rhythms, lipid metabolism and secretion of lipoproteins; and in neurogenesis. Astrocyte markers and the functions of astrogliosis are also described. Astrocytes play an active role in the CNS. A good knowledge of astrocytes is essential to understanding the mechanisms of neurodegenerative diseases. Copyright © 2012 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  1. Memory in neurodegenerative disease: biological, cognitive, and clinical perspectives

    National Research Council Canada - National Science Library

    Tröster, Alexander I

    1998-01-01

    ... of memory dysfunction in neurodegenerative disease  . ,  . ,     .  100 6 Functional neuroimaging correlates...

  2. Progranulin: At the interface of neurodegenerative and metabolic diseases

    OpenAIRE

    Nguyen, Andrew D.; Nguyen, Thi A.; Martens, Lauren Herl; Mitic, Laura L.; Farese, Robert V.

    2013-01-01

    Progranulin is a widely expressed, cysteine-rich, secreted glycoprotein originally discovered for its growth factor–like properties. Its subsequent identification as a causative gene for frontotemporal dementia (FTD), a devastating early-onset neurodegenerative disease, has catalyzed a surge of new discoveries about progranulin’s function in the brain. More recently, progranulin was recognized as an adipokine involved in diet-induced obesity and insulin resistance, revealing its metabolic fun...

  3. Cerebral correlates of psychotic syndromes in neurodegenerative diseases

    OpenAIRE

    Jellinger, Kurt A

    2012-01-01

    Abstract Psychosis has been recognized as a common feature in neurodegenerative diseases and a core feature of dementia that worsens most clinical courses. It includes hallucinations, delusions including paranoia, aggressive behaviour, apathy and other psychotic phenomena that occur in a wide range of degenerative disorders including Alzheimer?s disease, synucleinopathies (Parkinson?s disease, dementia with Lewy bodies), Huntington?s disease, frontotemporal degenerations, motoneuron and prion...

  4. Sleep and caregiving : sleeping practices of couples facing neurodegenerative diseases

    OpenAIRE

    Casini , Elisa

    2017-01-01

    This doctoral dissertation in sociology examines the sleep practices of ageing couples confronted with neuro-degenerative conditions. It aims to understand the time- and space-related aspects of these sleep practices, so central to couples’ lives, throughout the different stages of illness, and places particular emphasis on gender-based relations. Thirty couples were interviewed in their homes, 12 of whom were affected by Lewy Body Dementia and 18 by Alzheimer’s Disease. Empirical methods suc...

  5. Complex of rutin with β-cyclodextrin as potential delivery system.

    Directory of Open Access Journals (Sweden)

    Magdalena Paczkowska

    Full Text Available This study aimed to obtain and characterize an RU-β-CD complex in the context of investigating the possibility of changes in the solubility, stability, antioxidative and microbiological activity as well as permeability of complexated rutin as against its free form. The formation of the RU-β-CD complex via a co-grinding technique was confirmed by using DSC, SEM, FT-IR and Raman spectroscopy, and its geometry was assessed through molecular modeling. It was found that the stability and solubility of the so-obtained complex were greater compared to the free form; however, a slight decrease was observed inits antibacterial potency. An examination of changes in the EPR spectra of thecomplex excluded any reducing effect of complexation on the antioxidative activity of rutin. Considering the prospect of preformulation studies involving RU-β-CD complexes, of significance is also the observed possibility of prolongedly releasing rutin from the complex at a constant level over along period of 20 h, and the fact that twice as much complexated rutin was able topermeate compared to its free form.

  6. Trivalent rare earth complexes of some potential antiinflammatory and antipyretic compounds

    International Nuclear Information System (INIS)

    Basak, Devashish

    1994-01-01

    Binary complexes of 2-aminobenzoic acid (2-ABA), 3-aminobenzoic acid (3-ABA) and 4-aminobenzoic acid (4-ABA) with La(III), Pr(III), Nd(III), Sm(III) and Gd(III) have been studied paper electrophoretically at different temperatures and a constant ionic strength. The stability constants of the complexes have been reported. (author). 6 refs., 1 tab

  7. Exploring the potential relevance of human-specific genes to complex disease

    Directory of Open Access Journals (Sweden)

    Cooper David N

    2011-01-01

    Full Text Available Abstract Although human disease genes generally tend to be evolutionarily more ancient than non-disease genes, complex disease genes appear to be represented more frequently than Mendelian disease genes among genes of more recent evolutionary origin. It is therefore proposed that the analysis of human-specific genes might provide new insights into the genetics of complex disease. Cross-comparison with the Human Gene Mutation Database (http://www.hgmd.org revealed a number of examples of disease-causing and disease-associated mutations in putatively human-specific genes. A sizeable proportion of these were missense polymorphisms associated with complex disease. Since both human-specific genes and genes associated with complex disease have often experienced particularly rapid rates of evolutionary change, either due to weaker purifying selection or positive selection, it is proposed that a significant number of human-specific genes may play a role in complex disease.

  8. Emulation of Physician Tasks in Eye-Tracked Virtual Reality for Remote Diagnosis of Neurodegenerative Disease.

    Science.gov (United States)

    Orlosky, Jason; Itoh, Yuta; Ranchet, Maud; Kiyokawa, Kiyoshi; Morgan, John; Devos, Hannes

    2017-04-01

    For neurodegenerative conditions like Parkinson's disease, early and accurate diagnosis is still a difficult task. Evaluations can be time consuming, patients must often travel to metropolitan areas or different cities to see experts, and misdiagnosis can result in improper treatment. To date, only a handful of assistive or remote methods exist to help physicians evaluate patients with suspected neurological disease in a convenient and consistent way. In this paper, we present a low-cost VR interface designed to support evaluation and diagnosis of neurodegenerative disease and test its use in a clinical setting. Using a commercially available VR display with an infrared camera integrated into the lens, we have constructed a 3D virtual environment designed to emulate common tasks used to evaluate patients, such as fixating on a point, conducting smooth pursuit of an object, or executing saccades. These virtual tasks are designed to elicit eye movements commonly associated with neurodegenerative disease, such as abnormal saccades, square wave jerks, and ocular tremor. Next, we conducted experiments with 9 patients with a diagnosis of Parkinson's disease and 7 healthy controls to test the system's potential to emulate tasks for clinical diagnosis. We then applied eye tracking algorithms and image enhancement to the eye recordings taken during the experiment and conducted a short follow-up study with two physicians for evaluation. Results showed that our VR interface was able to elicit five common types of movements usable for evaluation, physicians were able to confirm three out of four abnormalities, and visualizations were rated as potentially useful for diagnosis.

  9. Sleep facilitates clearance of metabolites from the brain: glymphatic function in aging and neurodegenerative diseases.

    Science.gov (United States)

    Mendelsohn, Andrew R; Larrick, James W

    2013-12-01

    Decline of cognition and increasing risk of neurodegenerative diseases are major problems associated with aging in humans. Of particular importance is how the brain removes potentially toxic biomolecules that accumulate with normal neuronal function. Recently, a biomolecule clearance system using convective flow between the cerebrospinal fluid (CSF) and interstitial fluid (ISF) to remove toxic metabolites in the brain was described. Xie and colleagues now report that in mice the clearance activity of this so-called "glymphatic system" is strongly stimulated by sleep and is associated with an increase in interstitial volume, possibly by shrinkage of astroglial cells. Moreover, anesthesia and attenuation of adrenergic signaling can activate the glymphatic system to clear potentially toxic proteins known to contribute to the pathology of Alzheimer disease (AD) such as beta-amyloid (Abeta). Clearance during sleep is as much as two-fold faster than during waking hours. These results support a new hypothesis to answer the age-old question of why sleep is necessary. Glymphatic dysfunction may pay a hitherto unsuspected role in the pathogenesis of neurodegenerative diseases as well as maintenance of cognition. Furthermore, clinical studies suggest that quality and duration of sleep may be predictive of the onset of AD, and that quality sleep may significantly reduce the risk of AD for apolipoprotein E (ApoE) ɛ4 carriers, who have significantly greater chances of developing AD. Further characterization of the glymphatic system in humans may lead to new therapies and methods of prevention of neurodegenerative diseases. A public health initiative to ensure adequate sleep among middle-aged and older people may prove useful in preventing AD, especially in apolipoprotein E (ApoE) ɛ4 carriers.

  10. Comprehension of insincere communication in neurodegenerative disease: lies, sarcasm, and theory of mind.

    Science.gov (United States)

    Shany-Ur, Tal; Poorzand, Pardis; Grossman, Scott N; Growdon, Matthew E; Jang, Jung Y; Ketelle, Robin S; Miller, Bruce L; Rankin, Katherine P

    2012-01-01

    Comprehension of insincere communication is an important aspect of social cognition requiring visual perspective taking, emotion reading, and understanding others' thoughts, opinions, and intentions. Someone who is lying intends to hide their insincerity from the listener, while a sarcastic speaker wants the listener to recognize they are speaking insincerely. We investigated whether face-to-face testing of comprehending insincere communication would effectively discriminate among neurodegenerative disease patients with different patterns of real-life social deficits. We examined ability to comprehend lies and sarcasm from a third-person perspective, using contextual cues, in 102 patients with one of four neurodegenerative diseases (behavioral variant frontotemporal dementia [bvFTD], Alzheimer's disease [AD], progressive supranuclear palsy [PSP], and vascular cognitive impairment) and 77 healthy older adults (normal controls--NCs). Participants answered questions about videos depicting social interactions involving deceptive, sarcastic, or sincere speech using The Awareness of Social Inference Test. All subjects equally understood sincere remarks, but bvFTD patients displayed impaired comprehension of lies and sarcasm compared with NCs. In other groups, impairment was not disease-specific but was proportionate to general cognitive impairment. Analysis of the task components revealed that only bvFTD patients were impaired on perspective taking and emotion reading elements and that both bvFTD and PSP patients had impaired ability to represent others' opinions and intentions (i.e., theory of mind). Test performance correlated with informants' ratings of subjects' empathy, perspective taking and neuropsychiatric symptoms in everyday life. Comprehending insincere communication is complex and requires multiple cognitive and emotional processes vulnerable across neurodegenerative diseases. However, bvFTD patients show uniquely focal and severe impairments at every level

  11. Cerebral correlates of psychotic syndromes in neurodegenerative diseases.

    Science.gov (United States)

    Jellinger, Kurt A

    2012-05-01

    Psychosis has been recognized as a common feature in neurodegenerative diseases and a core feature of dementia that worsens most clinical courses. It includes hallucinations, delusions including paranoia, aggressive behaviour, apathy and other psychotic phenomena that occur in a wide range of degenerative disorders including Alzheimer's disease, synucleinopathies (Parkinson's disease, dementia with Lewy bodies), Huntington's disease, frontotemporal degenerations, motoneuron and prion diseases. Many of these psychiatric manifestations may be early expressions of cognitive impairment, but often there is a dissociation between psychotic/behavioural symptoms and the rather linear decline in cognitive function, suggesting independent pathophysiological mechanisms. Strictly neuropathological explanations are likely to be insufficient to explain them, and a large group of heterogeneous factors (environmental, neurochemical changes, genetic factors, etc.) may influence their pathogenesis. Clinico-pathological evaluation of behavioural and psychotic symptoms (PS) in the setting of neurodegenerative and dementing disorders presents a significant challenge for modern neurosciences. Recognition and understanding of these manifestations may lead to the development of more effective preventive and therapeutic options that can serve to delay long-term progression of these devastating disorders and improve the patients' quality of life. A better understanding of the pathophysiology and distinctive pathological features underlying the development of PS in neurodegenerative diseases may provide important insights into psychotic processes in general. © 2011 The Author Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

  12. Neural Substrates of Spontaneous Narrative Production in Focal Neurodegenerative Disease

    Science.gov (United States)

    Gola, Kelly A.; Thorne, Avril; Veldhuisen, Lisa D.; Felix, Cordula M.; Hankinson, Sarah; Pham, Julie; Shany-Ur, Tal; Schauer, Guido P.; Stanley, Christine M.; Glenn, Shenly; Miller, Bruce L.; Rankin, Katherine P.

    2016-01-01

    Conversational storytelling integrates diverse cognitive and socio-emotional abilities that critically differ across neurodegenerative disease groups and may have diagnostic relevance and predict anatomic changes. The present study employed mixed methods discourse and quantitative analyses to delineate patterns of storytelling across focal neurodegenerative disease groups, and to clarify the neuroanatomical contributions to common storytelling characteristics in these patients. Transcripts of spontaneous social interactions of 46 participants (15 behavioral variant frontotemporal dementia (bvFTD), 7 semantic variant primary progressive aphasia (svPPA), 12 Alzheimer's disease (AD), and 12 healthy older normal controls) were analysed for storytelling characteristics and frequency, and videos of the interactions were rated for patients' social attentiveness. Compared to controls, svPPAs also told more stories and autobiographical stories, and perseverated on aspects of self during storytelling. ADs told fewer autobiographical stories than NCs, and svPPAs and bvFTDs failed to attend to social cues. Storytelling characteristics were associated with a processing speed and mental flexibility, and voxel-based anatomic analysis of structural magnetic resonance imaging revealed that temporal organization, evaluations, and social attention correlated with atrophy corresponding to known intrinsic connectivity networks, including the default mode, limbic, salience, and stable task control networks. Differences in spontaneous storytelling among neurodegenerative groups elucidated diverse cognitive, socio-emotional, and neural contributions to narrative production, with implications for diagnostic screening and therapeutic intervention. PMID:26485159

  13. Dissecting the Molecular Mechanisms of Neurodegenerative Diseases through Network Biology

    Directory of Open Access Journals (Sweden)

    Jose A. Santiago

    2017-05-01

    Full Text Available Neurodegenerative diseases are rarely caused by a mutation in a single gene but rather influenced by a combination of genetic, epigenetic and environmental factors. Emerging high-throughput technologies such as RNA sequencing have been instrumental in deciphering the molecular landscape of neurodegenerative diseases, however, the interpretation of such large amounts of data remains a challenge. Network biology has become a powerful platform to integrate multiple omics data to comprehensively explore the molecular networks in the context of health and disease. In this review article, we highlight recent advances in network biology approaches with an emphasis in brain-networks that have provided insights into the molecular mechanisms leading to the most prevalent neurodegenerative diseases including Alzheimer’s (AD, Parkinson’s (PD and Huntington’s diseases (HD. We discuss how integrative approaches using multi-omics data from different tissues have been valuable for identifying biomarkers and therapeutic targets. In addition, we discuss the challenges the field of network medicine faces toward the translation of network-based findings into clinically actionable tools for personalized medicine applications.

  14. The potentialities of the complexation ultrafiltration technique for the decontamination of fission product contaminated aqueous effluents

    International Nuclear Information System (INIS)

    Thibert, V.

    1995-07-01

    Many nuclear researchers and industrial operators lay emphasis on improving the back end of the fuel cycle. A major problem concerns the liquid wastes generated by the reprocessing plant at La Hague, discharged into the sea after treatment in the Effluent Treatment Station (STE) 3), and which have become crucial matter. The activity of these wastes is well below the current legal limits, and is constantly decreasing these last years. To bring it close to zero, and ambitious goal, entails innovative new reprocessing techniques. We accordingly investigated the possibilities of complexation-ultrafiltration, a technique that uses water-soluble macromolecules to complex the target elements to be separated. We first achieved the strontium (II) separation with poly-acrylic and poly-sulfonic acids. The effects of pH and NaNO 3 concentration influence on Sr (II) complexation were studied. The Sr (II) complexation and concentration phases, followed by cation de-complexation to recover the polymer, were also taken into account. This research, combined with a potentiometric study of the polymers, offered a close understanding of the chemical systems involved, and of the operating conditions and limits of complexation-ultrafiltration. The laboratory results were also validated on a tangential ultrafiltration pilot plant. We then used complexation-ultrafiltration to treat a real effluent generated bu La Hague's STE 3 plant. This experiment demonstrated minimum 90 % decontamination of Sr (II) (with polyacrylate complexing agent), and also for 134-137 Cs (with simple ultrafiltration). The use of two polyamides allowed partial decontamination of the effluent for 60 Co and 106 Ru. This work therefore offers a global approach to complexation-ultrafiltration, from laboratory to pilot scale, on real and simulated effluents. The future of this technique relies chiefly on the ability to solve the problem of polymer recovery. In other respect, complexation-ultrafiltration clearly offers a

  15. Study on the generalized WKB approximation for the inverse scattering problem at fixed energy for complex potentials

    International Nuclear Information System (INIS)

    Pozdnyakov, Yu.A.; Terenetskij, K.O.

    1981-01-01

    The approximate method for solution of the inverse scattering problem (ISP) at fixed energy for complex spherically symmetric potentials decreasing faster 1/r is considered. The method is based on using a generalized WKB approximation. For the designed potential V(r) a sufficiently ''close'' reference potential V(r) has been chosen. For both potentials S-matrix elements (ME) have been calculated and inversion procedure has been carried out. S-ME have been calculated for integral-valued and intermediate angular moment values. S-ME are presented in a graphical form for being restored reference, and restored potentials for proton scattering with Esub(p)=49.48 MeV energy on 12 C nuclei. The restoration is the better the ''closer'' the sought-for potential to the reference one. This allows to specify the potential by means of iterations: the restored potential can be used as a reference one, etc. The operation of a restored potential smoothing before the following iteration is introduced. Drawbacks and advantages of the ISP solution method under consideration are pointed out. The method application is strongly limited by the requirement that the energy should be higher than a certain ''critical'' one. The method is applicable in a wider region of particle energies (in the low-energies direction) than the ordinary WKB method. The method is more simple in realization conformably to complex potentials. The investigations carried out of the proposed ISP solution method at fixed energy for complex spherically-symmetric potentials allow to conclude that the method can be successFully applied to specify the central part of interaction of nucleons, α-particles and heavy ions of average and high energies with atomic nuclei [ru

  16. Studies on inclusion complex as potential systems for enhancement of oral bioavailability of olmesartan medoxomil

    Directory of Open Access Journals (Sweden)

    Hetal Paresh Thakkar

    2012-01-01

    Full Text Available Background: Olmesartan medoxomil (OLM, an anti-hypertensive agent administered orally, has absolute bioavailability of only 26% due to the poor aqueous solubility (7.75 μg/ml. Inclusion complexation with cyclodextrins (CD has been reported to increase the aqueous solubility of various compounds. Aim: The present investigation aimed to enhancing the oral bioavailability of OLM by inclusion complexation with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD. Materials and Methods: The inclusion complexes with HP-β-CD were prepared using two different methods, viz., physical mixture and kneading. The prepared complexes were characterized for various parameters such as drug content, aqueous solubility, dissolution study, in vitro diffusion, intestinal permeability and stability study. The formation of the inclusion complex was confirmed by differential scanning calorimetry, X-ray diffraction, and Fourier transform infrared spectroscopy. Results: The solubility, dissolution, diffusion rate, and intestinal permeability of the prepared complexes were found to be significantly higher than that of the plain drug. Among the two methods used for formation of inclusion complex, KN method gave higher solubility rates and hence is a better method when compared with PM. Conclusion: The approach seems to be promising in improving the oral bioavailability of OLM.

  17. A 3D potential field model of the Pilanesberg Complex shape and structure

    CSIR Research Space (South Africa)

    Lee, SA

    2013-10-01

    Full Text Available ). Mineralization of the Pilanesberg Alkaline Complex. In Mineral Deposits of South Africa 2 (C. R. Anhaeusser& S. Maske, eds.). The Geological Society of South Africa, Johannesburg, South Africa. p. 2215-2228. Michell, R. H. and Liferovich, R. P. (2006... the gabbro-norite of the Rustenburg Layered Suite and red granite of the Lebowa Granite Suite on the western limb of the Bushveld Complex, South Africa (Hansen et al., 2006). The Pilanesberg Complex intruded between 1200 and 1450 Ma during...

  18. Assessment of serum copper, iron and immune complexes in potentially malignant disorders and oral cancer

    Directory of Open Access Journals (Sweden)

    Ritu TIWARI

    Full Text Available Abstract Potentially malignant disorders (PMDs of oral cavity and oral cancer remain a cause of serious concern despite intensive research and development. Diet and immunity have been identified to play a crucial role as modifying factors in these diseases. Our study intended to explore this relationship by estimating and comparing the serum levels of copper, iron and circulating immune complexes (CICs in patients diagnosed with PMDs and oral cancer and normal healthy individuals. In this study, 40 histopathologically diagnosed cases of PMDs and oral cancer were included along with 30 healthy controls and 5 ml of venous blood was drawn using venipuncture. Serum estimation of copper, iron and CIC then followed using the colorimetric and spectrophotometric methods. The data obtained was subjected to statistical analysis using one way ANOVA and Pearson’s Product-Moment Correlation Test. The mean serum copper level was measured as 138.98 ± 10.13µg/100ml in the PMD group and 141.99 ± 21.44 µg/100ml in the oral cancer as compared to 105.5 + 18.81µ/100ml in the controls. The mean serum CIC levels was highest in the oral cancer (9.65 ± 0.16OD470 followed by the PMD group (0.18 + 0.21 OD470 and least in the control group (0.048 ± 0.02OD470. Whereas, the serum levels of iron showed a significant decrease in the PMD group (110.9 ± 10.54 µg/100ml and the oral cancer group (114.29 ± 25.83 µg/100ml as compared with the control group (136.85 ± 14.48 µg/100ml. There was no positive correlation obtained between the three groups with respect to the chosen parameters indicating that the variables were independent of each other. It can be thus be ascertained that trace elements like copper and iron as well as humoral responses (CICs have a close relationship with PMDs and oral cancers.

  19. Investigation of the host-guest complexation between 4-sulfocalix[4]arene and nedaplatin for potential use in drug delivery

    Science.gov (United States)

    Fahmy, Sherif Ashraf; Ponte, Fortuna; Abd El-Rahman, Mohamed K.; Russo, Nino; Sicilia, Emilia; Shoeib, Tamer

    2018-03-01

    Macromolecules including macrocyclic species have been reported to have the potential to encapsulate biologically active compounds such as drugs through host-guest complexation to increase their solubility, stability and bioavailability. In this paper the first experimental and theoretical investigation of the complexation between nedaplatin, a second generation antineoplastic drug, and p-4-sulfocalix[4]arene, a macromolecule possessing a bipolar amphiphilic structure with good biocompatibility and relatively low haemolytic toxicity for potential use as a drug delivery system is presented. Data from 1H NMR, UV, Job's plot analysis, HPLC and DFT calculations are detailed and suggest the formation of a 1:1 complex. The stability constant of the complex was experimentally estimated to be 3.6 × 104 M- 1 and 2.1 × 104 M- 1 which correspond to values of - 6.2 and - 5.9 kcal mol- 1, respectively for the free energy of complexation while the interaction free energy is calculated to be - 4.9 kcal mol- 1. The formed species is shown to be stabilised in solution through hydrogen bonding between the host and the guest which may allow for this strategy to be effective for potential use in drug delivery.

  20. Microscopic models for proton transfer in water and strongly hydrogen-bonded complexes with a single-well proton potential

    DEFF Research Database (Denmark)

    Kuznetsov, A.M.; Ulstrup, Jens

    2004-01-01

    A new mechanism and formalism for proton transfer in donor-acceptor complexes with long hydrogen bonds introduced recently [1], is applied to a proton transfer in liquid water. "Structural diffusion" of hydroxonium ions is regarded as totally adiabatic process, with synchronous hindered translation...... of two closest water molecules to and from the reaction complex as crucial steps. The water molecules induce a "gated" shift of the proton from the donor to the acceptor in the double-well potential with simultaneous breaking/formation of hydrogen bonds between these molecules and the proton donor...... and acceptor. The short-range and long-range proton transfer as "structural diffusion" of Zundel complexes is also considered. The theoretical formalism is illustrated with the use of Morse, exponential, and harmonic molecular potentials. This approach is extended to proton transfer in strongly hydrogen...

  1. Mitochondrial membrane potential in human neutrophils is maintained by complex III activity in the absence of supercomplex organisation

    NARCIS (Netherlands)

    van Raam, Bram J.; Sluiter, Wim; de Wit, Elly; Roos, Dirk; Verhoeven, Arthur J.; Kuijpers, Taco W.

    2008-01-01

    BACKGROUND: Neutrophils depend mainly on glycolysis for their energy provision. Their mitochondria maintain a membrane potential (Deltapsi(m)), which is usually generated by the respiratory chain complexes. We investigated the source of Deltapsi(m) in neutrophils, as compared to peripheral blood

  2. Mitochondrial membrane potential in human neutrophils is maintained by complex III activity in the absence of supercomplex organisation

    NARCIS (Netherlands)

    B.J. van Raam (Bram); W.J. Sluiter (Wim); F.R.C. de Wit (Frank); D. Roos (Dirk); A.J. Verhoeven (Arthur); T.W. Kuijpers (Taco W.)

    2008-01-01

    textabstractBackground: Neutrophils depend mainly on glycolysis for their enegry provision. Their mitochondria maintain a membrace potential (ΔΨm), which is usually generated by the repiratory chain complexes. We investigated the source of ΔΨm in neutrophils, as compared to peripheral blood

  3. Beer and bread to brains and beyond: can yeast cells teach us about neurodegenerative disease?

    Science.gov (United States)

    Gitler, Aaron D

    2008-01-01

    For millennia, humans have harnessed the astonishing power of yeast, producing such culinary masterpieces as bread, beer and wine. Therefore, in this new millennium, is it very farfetched to ask if we can also use yeast to unlock some of the modern day mysteries of human disease? Remarkably, these seemingly simple cells possess most of the same basic cellular machinery as the neurons in the brain. We and others have been using the baker's yeast, Saccharomyces cerevisiae, as a model system to study the mechanisms of devastating neurodegenerative diseases such as Parkinson's, Huntington's, Alzheimer's and amyotrophic lateral sclerosis. While very different in their pathophysiology, they are collectively referred to as protein-misfolding disorders because of the presence of misfolded and aggregated forms of various proteins in the brains of affected individuals. Using yeast genetics and the latest high-throughput screening technologies, we have identified some of the potential causes underpinning these disorders and discovered conserved genes that have proven effective in preventing neuron loss in animal models. Thus, these genes represent new potential drug targets. In this review, I highlight recent work investigating mechanisms of cellular toxicity in a yeast Parkinson's disease model and discuss how similar approaches are being applied to additional neurodegenerative diseases.

  4. Raman Spectroscopy: An Emerging Tool in Neurodegenerative Disease Research and Diagnosis.

    Science.gov (United States)

    Devitt, George; Howard, Kelly; Mudher, Amrit; Mahajan, Sumeet

    2018-03-21

    The pathogenesis underlining many neurodegenerative diseases remains incompletely understood. The lack of effective biomarkers and disease preventative medicine demands the development of new techniques to efficiently probe the mechanisms of disease and to detect early biomarkers predictive of disease onset. Raman spectroscopy is an established technique that allows the label-free fingerprinting and imaging of molecules based on their chemical constitution and structure. While analysis of isolated biological molecules has been widespread in the chemical community, applications of Raman spectroscopy to study clinically relevant biological species, disease pathogenesis, and diagnosis have been rapidly increasing since the past decade. The growing number of biomedical applications has shown the potential of Raman spectroscopy for detection of novel biomarkers that could enable the rapid and accurate screening of disease susceptibility and onset. Here we provide an overview of Raman spectroscopy and related techniques and their application to neurodegenerative diseases. We further discuss their potential utility in research, biomarker detection, and diagnosis. Challenges to routine use of Raman spectroscopy in the context of neuroscience research are also presented.

  5. Glucose 6 phosphatase dehydrogenase (G6PD and neurodegenerative disorders: Mapping diagnostic and therapeutic opportunities

    Directory of Open Access Journals (Sweden)

    Manju Tiwari

    2017-12-01

    Full Text Available Glucose 6 phosphate dehydrogenase (G6PD is a key and rate limiting enzyme in the pentose phosphate pathway (PPP. The physiological significance of enzyme is providing reduced energy to specific cells like erythrocyte by maintaining co-enzyme nicotinamide adenine dinucleotide phosphate (NADPH. There are preponderance research findings that demonstrate the enzyme (G6PD role in the energy balance, and it is associated with blood-related diseases and disorders, primarily the anemia resulted from G6PD deficiency. The X-linked genetic deficiency of G6PD and associated non-immune hemolytic anemia have been studied widely across the globe. Recent advancement in biology, more precisely neuroscience has revealed that G6PD is centrally involved in many neurological and neurodegenerative disorders. The neuroprotective role of the enzyme (G6PD has also been established, as well as the potential of G6PD in oxidative damage and the Reactive Oxygen Species (ROS produced in cerebral ischemia. Though G6PD deficiency remains a global health issue, however, a paradigm shift in research focusing the potential of the enzyme in neurological and neurodegenerative disorders will surely open a new avenue in diagnostics and enzyme therapeutics. Here, in this study, more emphasis was made on exploring the role of G6PD in neurological and inflammatory disorders as well as non-immune hemolytic anemia, thus providing diagnostic and therapeutic opportunities.

  6. Regulation of cerebrospinal fluid (CSF) flow in neurodegenerative, neurovascular and neuroinflammatory disease.

    Science.gov (United States)

    Simon, Matthew J; Iliff, Jeffrey J

    2016-03-01

    Cerebrospinal fluid (CSF) circulation and turnover provides a sink for the elimination of solutes from the brain interstitium, serving an important homeostatic role for the function of the central nervous system. Disruption of normal CSF circulation and turnover is believed to contribute to the development of many diseases, including neurodegenerative conditions such as Alzheimer's disease, ischemic and traumatic brain injury, and neuroinflammatory conditions such as multiple sclerosis. Recent insights into CSF biology suggesting that CSF and interstitial fluid exchange along a brain-wide network of perivascular spaces termed the 'glymphatic' system suggest that CSF circulation may interact intimately with glial and vascular function to regulate basic aspects of brain function. Dysfunction within this glial vascular network, which is a feature of the aging and injured brain, is a potentially critical link between brain injury, neuroinflammation and the development of chronic neurodegeneration. Ongoing research within this field may provide a powerful new framework for understanding the common links between neurodegenerative, neurovascular and neuroinflammatory disease, in addition to providing potentially novel therapeutic targets for these conditions. This article is part of a Special Issue entitled: Neuro Inflammation edited by Helga E. de Vries and Markus Schwaninger. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Modeling cognitive deficits following neurodegenerative diseases and traumatic brain injuries with deep convolutional neural networks.

    Science.gov (United States)

    Lusch, Bethany; Weholt, Jake; Maia, Pedro D; Kutz, J Nathan

    2018-06-01

    The accurate diagnosis and assessment of neurodegenerative disease and traumatic brain injuries (TBI) remain open challenges. Both cause cognitive and functional deficits due to focal axonal swellings (FAS), but it is difficult to deliver a prognosis due to our limited ability to assess damaged neurons at a cellular level in vivo. We simulate the effects of neurodegenerative disease and TBI using convolutional neural networks (CNNs) as our model of cognition. We utilize biophysically relevant statistical data on FAS to damage the connections in CNNs in a functionally relevant way. We incorporate energy constraints on the brain by pruning the CNNs to be less over-engineered. Qualitatively, we demonstrate that damage leads to human-like mistakes. Our experiments also provide quantitative assessments of how accuracy is affected by various types and levels of damage. The deficit resulting from a fixed amount of damage greatly depends on which connections are randomly injured, providing intuition for why it is difficult to predict impairments. There is a large degree of subjectivity when it comes to interpreting cognitive deficits from complex systems such as the human brain. However, we provide important insight and a quantitative framework for disorders in which FAS are implicated. Copyright © 2018 Elsevier Inc. All rights reserved.

  8. [Changes in olfaction during ageing and in certain neurodegenerative diseases: up-to-date].

    Science.gov (United States)

    Bianchi, A-J; Guépet-Sordet, H; Manckoundia, P

    2015-01-01

    Olfaction is a complex sensory system, and increasing interest is being shown in the link between olfaction and cognition, notably in the elderly. In this literature review, we revisit the specific neurophysiological features of the olfactory system and odorants that lead to a durable olfactory memory and an emotional memory, for which the implicit component produces subconscious olfactory conditioning. Olfaction is known to affect cognitive abilities and mood. We also consider the impairment of olfactory function due to ageing and to neurodegenerative diseases, in particular Alzheimer's disease and Parkinson's disease, through anatomopathological changes in the peripheral and central olfactory structures. The high frequency of these olfactory disorders as well as their early occurrence in Alzheimer disease and Parkinson disease are in favour of their clinical detection in subjects suffering from these two neurodegenerative diseases. Finally, we analyse the impact of olfactory stimulation on cognitive performance and attention. Current observational data from studies in elderly patients with Alzheimer-type dementia are limited to multiple sensory stimulation methods, such as the Snoezelen method, and aromatherapy. These therapies have shown benefits for dementia-related mood and behaviour disorders in the short term, with few side effects. Since olfactory chemosensory stimulation may be beneficial, it may be proposed in patients with dementia, especially Alzheimer-type dementia, as a complementary or even alternative therapy to existing medical strategies. Copyright © 2014 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  9. Modelling neurodegenerative diseases in vitro: Recent advances in 3D iPSC technologies

    Directory of Open Access Journals (Sweden)

    Elodie J Siney

    2018-03-01

    Full Text Available The discovery of induced pluripotent stem cells (iPSC 12 years ago has fostered the development of innovative patient-derived in vitro models for better understanding of disease mechanisms. This is particularly relevant to neurodegenerative diseases, where availability of live human brain tissue for research is limited and post-mortem interval changes influence readouts from autopsy-derived human tissue. Hundreds of iPSC lines have now been prepared and banked, thanks to several large scale initiatives and cell banks. Patient- or engineered iPSC-derived neural models are now being used to recapitulate cellular and molecular aspects of a variety of neurodegenerative diseases, including early and pre-clinical disease stages. The broad relevance of these models derives from the availability of a variety of differentiation protocols to generate disease-specific cell types and the manipulation to either introduce or correct disease-relevant genetic modifications. Moreover, the use of chemical and physical three-dimensional (3D matrices improves control over the extracellular environment and cellular organization of the models. These iPSC-derived neural models can be utilised to identify target proteins and, importantly, provide high-throughput screening for drug discovery. Choosing Alzheimer’s disease (AD as an example, this review describes 3D iPSC-derived neural models and their advantages and limitations. There is now a requirement to fully characterise and validate these 3D iPSC-derived neural models as a viable research tool that is capable of complementing animal models of neurodegeneration and live human brain tissue. With further optimization of differentiation, maturation and aging protocols, as well as the 3D cellular organisation and extracellular matrix to recapitulate more closely, the molecular extracellular-environment of the human brain, 3D iPSC-derived models have the potential to deliver new knowledge, enable discovery of novel

  10. Contribution of glucocorticoids and glucocorticoid receptors to the regulation of neurodegenerative processes.

    Science.gov (United States)

    Vyas, Sheela; Maatouk, Layal

    2013-12-01

    Isolation of glucocorticoids (GCs) from adrenal glands followed by synthesis led rapidly to their first clinical application, about 70 years ago, for treatment of rheumatoid arthritis. To this day GCs are used in diseases that have an inflammatory component. However, their use is carefully monitored because of harmful side effects. GCs are also synonymous with stress and adaptation. In CNS, GC binds and activates high affinity mineralocorticoid receptor (MR) and low affinity glucocorticoid receptor (GR). GR, whose expression is ubiquitous, is only activated when GC levels rise as during circadian peak and in response to stress. Numerous recent studies have yielded important and new insights on the mechanisms concerning pulsatile secretory pattern of GCs as well as various processes that tightly control their synthesis via hypothalamic-pituitary-adrenal (HPA) axis involving regulated release of corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) from hypothalamus and pituitary, respectively. GR modulates neuronal functions and viability through both genomic and non-genomic actions, and importantly its transcriptional regulatory activity is tightly locked with GC secretory pattern. There is increasing evidence pointing to involvement of GC-GR in neurodegenerative disorders. Patients with Alzheimer's or Parkinson's or Huntington's disease show chronically high cortisol levels suggesting changes occurring in controls of HPA axis. In experimental models of these diseases, chronic stress or GC treatment was found to exacerbate both the clinical symptoms and neurodegenerative processes. However, recent evidence also shows that GC-GR can exert neuroprotective effects. Thus, for any potential therapeutic strategies in these neurodegenerative diseases we need to understand the precise modifications both in HPA axis and in GR activity and find ways to harness their protective actions.

  11. Platinum(II)-gadolinium(III) complexes as potential single-molecular theranostic agents for cancer treatment.

    Science.gov (United States)

    Zhu, Zhenzhu; Wang, Xiaoyong; Li, Tuanjie; Aime, Silvio; Sadler, Peter J; Guo, Zijian

    2014-11-24

    Theranostic agents are emerging multifunctional molecules capable of simultaneous therapy and diagnosis of diseases. We found that platinum(II)-gadolinium(III) complexes with the formula [{Pt(NH3)2Cl}2GdL](NO3)2 possess such properties. The Gd center is stable in solution and the cytoplasm, whereas the Pt centers undergo ligand substitution in cancer cells. The Pt units interact with DNA and significantly promote the cellular uptake of Gd complexes. The cytotoxicity of the Pt-Gd complexes is comparable to that of cisplatin at high concentrations (≥0.1 mM), and their proton relaxivity is higher than that of the commercial magnetic resonance imaging (MRI) contrast agent Gd-DTPA. T1-weighted MRI on B6 mice demonstrated that these complexes can reveal the accumulation of platinum drugs in vivo. Their cytotoxicity and imaging capabilities make the Pt-Gd complexes promising theranostic agents for cancer treatment. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. RutheniumII Complexes bearing Fused Polycyclic Ligands: From Fundamental Aspects to Potential Applications

    Directory of Open Access Journals (Sweden)

    Ludovic Troian-Gautier

    2014-04-01

    Full Text Available In this review, we first discuss the photophysics reported in the literature for mononuclear ruthenium complexes bearing ligands with extended aromaticity such as dipyrido[3,2-a:2',3'-c]phenazine (DPPZ, tetrapyrido[3,2-a:2',3'-c:3'',2''-h:2''',3'''-j]-phenazine (TPPHZ,  tetrapyrido[3,2-a:2',3'-c:3'',2''-h:2''',3'''-j]acridine (TPAC, 1,10-phenanthrolino[5,6-b]1,4,5,8,9,12-hexaazatriphenylene (PHEHAT 9,11,20,22-tetraaza- tetrapyrido[3,2-a:2',3'-c:3'',2''-l:2''',3'''-n]pentacene (TATPP, etc. Photophysical properties of binuclear and polynuclear complexes based on these extended ligands are then reported. We finally develop the use of binuclear complexes with extended π-systems for applications such as photocatalysis.

  13. A study on utilization improvement of cogeneration potential in a complex industrial steam and power plant

    International Nuclear Information System (INIS)

    Mierka, O.; Variny, M.

    2012-01-01

    Efficient cogeneration is widely acknowledged as one of measures reducing primary energy use and emissions of greenhouse gases and other pollutants. This contribution bears on analyses of complex industrial power plants, incorporating the concept of exergetic and exergoecomic balances-a concept that has been rarely utilized in Slovakia up to day. Emphasis is laid on synergic use of marginal and exergoecomic analysis, thus assessing the economics of various complex cogeneration units' operational modes. The whole study, together with resulting recommendations for cogeneration efficiency improvement of the given unit is an excerpt of corresponding author's doctoral thesis. (Authors)

  14. A study on utilization improvement of cogeneration potential in a complex industrial steam and power plant

    International Nuclear Information System (INIS)

    Mierka, O.; Variny, M.

    2012-01-01

    Efficient cogeneration is widely acknowledged as one of measures reducing primary energy use and emissions of greenhouse gases and other pollutants. This contribution bears on analyses of complex industrial power plants, incorporating the concept of exergetic and exergoeconomic balances-a concept that has been rarely utilized in Slovakia up to day. Emphasis is laid on synergic use of marginal and exergoeconomic analysis, thus assessing the economics of various complex cogeneration units' operational modes. The whole study, together with resulting recommendations for cogeneration efficiency improvement of the given unit is an excerpt of corresponding author's doctoral thesis. (Authors)

  15. Reverse engineering human neurodegenerative disease using pluripotent stem cell technology.

    Science.gov (United States)

    Liu, Ying; Deng, Wenbin

    2016-05-01

    With the technology of reprogramming somatic cells by introducing defined transcription factors that enables the generation of "induced pluripotent stem cells (iPSCs)" with pluripotency comparable to that of embryonic stem cells (ESCs), it has become possible to use this technology to produce various cells and tissues that have been difficult to obtain from living bodies. This advancement is bringing forth rapid progress in iPSC-based disease modeling, drug screening, and regenerative medicine. More and more studies have demonstrated that phenotypes of adult-onset neurodegenerative disorders could be rather faithfully recapitulated in iPSC-derived neural cell cultures. Moreover, despite the adult-onset nature of the diseases, pathogenic phenotypes and cellular abnormalities often exist in early developmental stages, providing new "windows of opportunity" for understanding mechanisms underlying neurodegenerative disorders and for discovering new medicines. The cell reprogramming technology enables a reverse engineering approach for modeling the cellular degenerative phenotypes of a wide range of human disorders. An excellent example is the study of the human neurodegenerative disease amyotrophic lateral sclerosis (ALS) using iPSCs. ALS is a progressive neurodegenerative disease characterized by the loss of upper and lower motor neurons (MNs), culminating in muscle wasting and death from respiratory failure. The iPSC approach provides innovative cell culture platforms to serve as ALS patient-derived model systems. Researchers have converted iPSCs derived from ALS patients into MNs and various types of glial cells, all of which are involved in ALS, to study the disease. The iPSC technology could be used to determine the role of specific genetic factors to track down what's wrong in the neurodegenerative disease process in the "disease-in-a-dish" model. Meanwhile, parallel experiments of targeting the same specific genes in human ESCs could also be performed to control

  16. Metabolites from invasive pests inhibit mitochondrial complex II: A potential strategy for the treatment of human ovarian carcinoma?

    Energy Technology Data Exchange (ETDEWEB)

    Ferramosca, Alessandra, E-mail: alessandra.ferramosca@unisalento.it [Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, Università del Salento, Lecce (Italy); Conte, Annalea; Guerra, Flora; Felline, Serena [Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, Università del Salento, Lecce (Italy); Rimoli, Maria Grazia [Dipartimento di Farmacia, Università di Napoli Federico II, Napoli (Italy); Mollo, Ernesto [Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche, Pozzuoli (Italy); Zara, Vincenzo [Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, Università del Salento, Lecce (Italy); Terlizzi, Antonio [Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, Università del Salento, Lecce (Italy); Stazione Zoologica Anton Dohrn, Napoli (Italy)

    2016-05-13

    The red pigment caulerpin, a secondary metabolite from the marine invasive green algae Caulerpa cylindracea can be accumulated and transferred along the trophic chain, with detrimental consequences on biodiversity and ecosystem functioning. Despite increasing research efforts to understand how caulerpin modifies fish physiology, little is known on the effects of algal metabolites on mammalian cells. Here we report for the first time the mitochondrial targeting activity of both caulerpin, and its closely related derivative caulerpinic acid, by using as experimental model rat liver mitochondria, a system in which bioenergetics mechanisms are not altered. Mitochondrial function was tested by polarographic and spectrophotometric methods. Both compounds were found to selectively inhibit respiratory complex II activity, while complexes I, III, and IV remained functional. These results led us to hypothesize that both algal metabolites could be used as antitumor agents in cell lines with defects in mitochondrial complex I. Ovarian cancer cisplatin-resistant cells are a good example of cell lines with a defective complex I function on which these molecules seem to have a toxic effect on proliferation. This provided novel insight toward the potential use of metabolites from invasive Caulerpa species for the treatment of human ovarian carcinoma cisplatin-resistant cells. -- Highlights: •Novel insight toward the potential use of the algal metabolites for the treatment of human diseases. •Caulerpin and caulerpinic acid inhibit respiratory complex II activity. •Both algal metabolites could be used as antitumor agents in ovarian cancer cisplatin-resistant cells.

  17. Metabolites from invasive pests inhibit mitochondrial complex II: A potential strategy for the treatment of human ovarian carcinoma?

    International Nuclear Information System (INIS)

    Ferramosca, Alessandra; Conte, Annalea; Guerra, Flora; Felline, Serena; Rimoli, Maria Grazia; Mollo, Ernesto; Zara, Vincenzo; Terlizzi, Antonio

    2016-01-01

    The red pigment caulerpin, a secondary metabolite from the marine invasive green algae Caulerpa cylindracea can be accumulated and transferred along the trophic chain, with detrimental consequences on biodiversity and ecosystem functioning. Despite increasing research efforts to understand how caulerpin modifies fish physiology, little is known on the effects of algal metabolites on mammalian cells. Here we report for the first time the mitochondrial targeting activity of both caulerpin, and its closely related derivative caulerpinic acid, by using as experimental model rat liver mitochondria, a system in which bioenergetics mechanisms are not altered. Mitochondrial function was tested by polarographic and spectrophotometric methods. Both compounds were found to selectively inhibit respiratory complex II activity, while complexes I, III, and IV remained functional. These results led us to hypothesize that both algal metabolites could be used as antitumor agents in cell lines with defects in mitochondrial complex I. Ovarian cancer cisplatin-resistant cells are a good example of cell lines with a defective complex I function on which these molecules seem to have a toxic effect on proliferation. This provided novel insight toward the potential use of metabolites from invasive Caulerpa species for the treatment of human ovarian carcinoma cisplatin-resistant cells. -- Highlights: •Novel insight toward the potential use of the algal metabolites for the treatment of human diseases. •Caulerpin and caulerpinic acid inhibit respiratory complex II activity. •Both algal metabolites could be used as antitumor agents in ovarian cancer cisplatin-resistant cells.

  18. Potential uses of Bayesian networks as tools for synthesis of systematic reviews of complex interventions.

    Science.gov (United States)

    Stewart, G B; Mengersen, K; Meader, N

    2014-03-01

    Bayesian networks (BNs) are tools for representing expert knowledge or evidence. They are especially useful for synthesising evidence or belief concerning a complex intervention, assessing the sensitivity of outcomes to different situations or contextual frameworks and framing decision problems that involve alternative types of intervention. Bayesian networks are useful extensions to logic maps when initiating a review or to facilitate synthesis and bridge the gap between evidence acquisition and decision-making. Formal elicitation techniques allow development of BNs on the basis of expert opinion. Such applications are useful alternatives to 'empty' reviews, which identify knowledge gaps but fail to support decision-making. Where review evidence exists, it can inform the development of a BN. We illustrate the construction of a BN using a motivating example that demonstrates how BNs can ensure coherence, transparently structure the problem addressed by a complex intervention and assess sensitivity to context, all of which are critical components of robust reviews of complex interventions. We suggest that BNs should be utilised to routinely synthesise reviews of complex interventions or empty reviews where decisions must be made despite poor evidence. Copyright © 2013 John Wiley & Sons, Ltd.

  19. Osmium(VI) complexes as a new class of potential anti-cancer agents.

    Science.gov (United States)

    Ni, Wen-Xiu; Man, Wai-Lun; Cheung, Myra Ting-Wai; Sun, Raymond Wai-Yin; Shu, Yuan-Lan; Lam, Yun-Wah; Che, Chi-Ming; Lau, Tai-Chu

    2011-02-21

    A nitridoosmium(VI) complex [Os(VI)(N)(sap)(OH(2))Cl] (H(2)sap = N-salicylidene-2-aminophenol) displays prominent in vitro and in vivo anti-cancer properties, induces S- and G2/M-phase arrest and forms a stable adduct with dianionic 5'-guanosine monophosphate.

  20. Unleashing the IT Potential in the Complex Digital Business Ecosystem of International Trade

    DEFF Research Database (Denmark)

    Jensen, Thomas; Tan, Yao-Hua; Bjørn-Andersen, Niels

    2014-01-01

    The digital ecosystem for import of goods in international trade is analyzed, in-efficiencies are identified and their possible causes are revealed. The business ecosystem is rather complex and interlocked with many actors and various rules and regulations. It is supported by a digital business...

  1. Theoretical Predictions of Redox Potentials of Fischer-Type Chromium Anninocarbene Complexes

    Czech Academy of Sciences Publication Activity Database

    Kvapilová, Hana; Hoskovcová, Irena; Ludvík, Jiří; Záliš, Stanislav

    2014-01-01

    Roč. 33, č. 18 (2014), s. 4964-4972 ISSN 0276-7333 R&D Projects: GA MŠk LD14129; GA ČR GA13-04630S Institutional support: RVO:61388955 Keywords : standard hydrogen electrode * density functional theory * metal carbene complexes Subject RIV: CG - Electrochemistry Impact factor: 4.126, year: 2014

  2. Comparative "Omics" of the Fusarium fujikuroi Species Complex Highlights Differences in Genetic Potential and Metabolite Synthesis

    NARCIS (Netherlands)

    Niehaus, E.-M.; Münsterkötter, M.; Proctor, R.H.; Brown, D.W.; Sharon, A.; Idan, Y.; Oren-Young, L.; Sieber, C.M.; Novák, O.; Pěnčík, A.; Tarkowská, D.; Hromadová, K.; Freeman, S.; Maymon, M.; Elazar, M.; Youssef, S.A.; El-Shabrawy, E.S.M.; Shalaby, A.B.A.; Houterman, P.; Brock, N.L.; Burkhardt, I.; Tsavkelova, E.A.; Dickschat, J.S.; Galuszka, P.; Güldener, U.; Tudzynski, B.

    2016-01-01

    Species of the Fusarium fujikuroi species complex (FFC) cause a wide spectrum of often devastating diseases on diverse agricultural crops, including coffee, fig, mango, maize, rice, and sugarcane. Although species within the FFC are difficult to distinguish by morphology, and their genes often share

  3. Pharmacological Alternatives for the Treatment of Neurodegenerative Disorders: Wasp and Bee Venoms and Their Components as New Neuroactive Tools

    OpenAIRE

    Silva, Juliana; Monge-Fuentes, Victoria; Gomes, Fl?via; Lopes, Kamila; dos Anjos, Lilian; Campos, Gabriel; Arenas, Claudia; Biolchi, Andr?ia; Gon?alves, Jacqueline; Galante, Priscilla; Campos, Leandro; Mortari, M?rcia

    2015-01-01

    Neurodegenerative diseases are relentlessly progressive, severely impacting affected patients, families and society as a whole. Increased life expectancy has made these diseases more common worldwide. Unfortunately, available drugs have insufficient therapeutic effects on many subtypes of these intractable diseases, and adverse effects hamper continued treatment. Wasp and bee venoms and their components are potential means of managing or reducing these effects and provide new alternatives for...

  4. Evidence-based therapy for sleep disorders in neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    LIU Ling

    2013-08-01

    Full Text Available Objective To evaluate the effectiveness of the treatments for sleep disorders in neurodegenerative diseases so as to provide the best therapeutic regimens for the evidence-based treatment. Methods Search PubMed, MEDLINE, Cochrane Library, Wanfang Data and China National Knowledge Infrastructure (CNKI databases with "sleep disorder or sleep disturbance", "neurodegenerative diseases", "Parkinson's disease or PD", "Alzheimer's disease or AD", "multiple system atrophy or MSA" as retrieval words. The quality of the articles were evaluated with Jadad Scale. Results A total of 35 articles, including 2 systematic reviews, 5 randomized controlled trials, 13 clinical controlled trials, 13 case series and 2 epidemiological investigation studies were included for evaluation, 13 of which were high grade and 22 were low grade articles. Clinical evidences showed that: 1 advice on sleep hygiene, careful use of dopaminergic drugs and hypnotic sedative agents should be considered for PD. Bright light therapy (BLT may improve circadian rhythm sleep disorders and clonazepam may be effective for rapid eye movement sleep behavior disorder (RBD. However, to date, very few controlled studies are available to make a recommendation for the management of sleep disorders in PD; 2 treatments for sleep disorders in AD include drug therapy (e.g. melatonin, acetylcholinesterase inhibitors, antipsychotic drugs, antidepressants and non-drug therapy (e.g. BLT, behavior therapy, but very limited evidence shows the effectiveness of these treatments; 3 the first line treatment for sleep-related breathing disorder in MSA is nasal continuous positive airway pressure (nCPAP, and clonazepam is effective for RBD in MSA; 4 there is rare evidence related to the treatment of sleep disorders in dementia with Lewy body (DLB and amyotrophic lateral sclerosis (ALS. Conclusion Evidence-based medicine can provide the best clinical evidence on sleep disorders' treatment in neurodegenerative

  5. Modeling Neuropsychiatric and Neurodegenerative Diseases With Induced Pluripotent Stem Cells.

    Science.gov (United States)

    LaMarca, Elizabeth A; Powell, Samuel K; Akbarian, Schahram; Brennand, Kristen J

    2018-01-01

    Human-induced pluripotent stem cells (hiPSCs) have revolutionized our ability to model neuropsychiatric and neurodegenerative diseases, and recent progress in the field is paving the way for improved therapeutics. In this review, we discuss major advances in generating hiPSC-derived neural cells and cutting-edge techniques that are transforming hiPSC technology, such as three-dimensional "mini-brains" and clustered, regularly interspersed short palindromic repeats (CRISPR)-Cas systems. We examine specific examples of how hiPSC-derived neural cells are being used to uncover the pathophysiology of schizophrenia and Parkinson's disease, and consider the future of this groundbreaking research.

  6. Clinical neurogenetics: behavioral management of inherited neurodegenerative disease.

    Science.gov (United States)

    Wexler, Eric

    2013-11-01

    Psychiatric symptoms often manifest years before overt neurologic signs in patients with inherited neurodegenerative disease. The most frequently cited example of this phenomenon is the early onset of personality changes in "presymptomatic" Huntington patients. In some cases the changes in mood and cognition are even more debilitating than their neurologic symptoms. The goal of this article is to provide the neurologist with a concise primer that can be applied in a busy clinic or private practice. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. REM behaviour disorder detection associated with neurodegenerative diseases

    DEFF Research Database (Denmark)

    Kempfner, Jacob; Sorensen, Gertrud; Zoetmulder, Marielle

    2010-01-01

    Abnormal skeleton muscle activity during REM sleep is characterized as REM Behaviour Disorder (RBD), and may be an early marker for different neurodegenerative diseases. Early detection of RBD is therefore highly important, and in this ongoing study a semi-automatic method for RBD detection......, a computerized algorithm has been attempted implemented. By analysing the REM and non-REM EMG activity, using advanced signal processing tools combined with a statistical classifier, it is possible to discriminate normal and abnormal EMG activity. Due to the small number of patients, the overall performance...

  8. Kaempferol-Phospholipid Complex: Formulation, and Evaluation of Improved Solubility, In Vivo Bioavailability, and Antioxidant Potential of Kaempferol

    Directory of Open Access Journals (Sweden)

    Darshan R. Telange

    2016-12-01

    Full Text Available The current work describes the formulation and evaluation of a phospholipid complex of kaempferol to enhance the latter’s aqueous solubility, in vitro dissolution rate, in vivo antioxidant and hepatoprotective activities, and oral bioavailability. The kaempferol-phospholipid complex was synthesized using a freeze-drying method with the formulation being optimized using a full factorial design (32 approach. Our results include the validation of the mathematical model in order to ascertain the role of specific formulation and process variables that contribute favorably to the formulation’s development. The final product was characterized and confirmed by Differential Scanning Calorimetry (DSC, Fourier Transform Infrared Spectroscopy (FTIR, Proton Nuclear Magnetic Resonance Spectroscopy (1H-NMR, and Powder X-ray Diffraction (PXRD analysis. The aqueous solubility and the in vitro dissolution rate were enhanced compared to that of pure kaempferol. The in vivo antioxidant properties of the kaempferol-phospholipid complex were evaluated by measuring its impact on carbon tetrachloride (CCl4-intoxicated rats. The optimized phospholipid complex improved the liver function test parameters to a significant level by restoration of all elevated liver marker enzymes in CCl4-intoxicated rats. The complex also enhanced the in vivo antioxidant potential by increasing levels of GSH (reduced glutathione, SOD (superoxide dismutase, catalase and decreasing lipid peroxidation, compared to that of pure kaempferol. The final optimized phospholipid complex also demonstrated a significant improvement in oral bioavailability demonstrated by improvements to key pharmacokinetic parameters, compared to that of pure kaempferol.

  9. Porphyrin-containing polyaspartamide gadolinium complexes as potential magnetic resonance imaging contrast agents.

    Science.gov (United States)

    Yan, Guo-Ping; Li, Zhen; Xu, Wei; Zhou, Cheng-Kai; Yang, Lian; Zhang, Qiao; Li, Liang; Liu, Fan; Han, Lin; Ge, Yuan-Xing; Guo, Jun-Fang

    2011-04-04

    Porphyrin-containing polyaspartamide ligands (APTSPP-PHEA-DTPA) were synthesized by the incorporation of diethylenetriaminepentaacetic acid (DTPA) and 5-(4'-aminophenyl)-10,15,20-tris(4'-sulfonatophenyl) porphyrin, trisodium salt (APTSPP) into poly-α,β-[N-(2-hydroxyethyl)-l-aspartamide] (PHEA). These ligands were further reacted with gadolinium chloride to produce macromolecule-gadolinium complexes (APTSPP-PHEA-DTPA-Gd). Experimental data of (1)H NMR, IR, UV and elemental analysis evidenced the formation of the polyaspartamide ligands and gadolinium complexes. In vitro and in vivo property tests indicated that APTSPP-PHEA-DTPA-Gd possessed noticeably higher relaxation effectiveness, less toxicity to HeLa cells, and significantly higher enhanced signal intensities (SI) of the VX2 carcinoma in rabbits with lower injection dose requirement than that of Gd-DTPA. Moreover, APTSPP-PHEA-DTPA-Gd was found to greatly enhance the contrast of MR images of the VX2 carcinoma, providing prolonged intravascular duration, and distinguished the VX2 carcinoma and normal tissues in rabbits according to MR image signal enhancements. These porphyrin-containing polyaspartamide gadolinium complexes can be used as the candidates of contrast agents for targeted MRI to tumors. Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.

  10. Synthesis characterization and biological evaluation of a novel mixed ligand 99mTc complex as potential brain imaging agent

    International Nuclear Information System (INIS)

    Rey, A.; Manta, E.; Leon, A.; Papadopoulos, M.; Pirmettis, Y.; Raptopoulou, C.; Chiotellis, E.; Leon, E.; Mallo, L.

    1998-01-01

    One approach in the design of neutral oxotechnetium complexes is based on the simultaneous substitution of a tridentate dianionic ligand and a monodentate monoanionic coligand on a [Tc(V)O] +3 precursor. Following this ''mixed ligand'' concept, a novel 99m Tc complex with N,N-bis(2-mercaptoethyl)-N'N'-diethylethylenediamine as ligand and 1-octanethiol as coligand is prepared and evaluated as potential brain radiopharmaceutical. Preparation of the complex at tracer level was accomplished by using 99m Tc-glucoheptonate as precursor. The substitution was optimized and a coligand/ligand ratio of 5 was selected. Under this conditions the labeling yield was over 80% and a major product (with radiochemical purity > 80%) was isolated by HPLC methods and used for biological evaluation. Chemical characterization at carrier level was developed using the corresponding rhenium complex as structural model. The Re complex was also prepared by substitution method and isolated as a crystalline product. The crystals were characterized by UV-vis and IR spectra and elemental analysis. Results were consistent with the expected ReOLC structure. X ray crystallographic study demonstrated that the complex adopts a distorted trigonal bipyramidal geometry. The basal plane is defined by the SS atoms of the ligand and the oxo group, while the N of the ligand and the S of the colligand occupy the two apical positions. All sulphur atoms underwent ionization leading to the formation of a neutral compound. 99 Tc complex was also prepared. Although it was not isolated due to the small amount of reagents employed, the HPLC profile was identical to the one observed for the rhenium complex suggesting the same chemical structure. Biodistribution in mice demonstrated early brain uptake, fast blood clearance, excretion through hepatobiliary system and a brain/blood ratio that increased significantly with time. (author)

  11. Genome-wide analysis of a Wnt1-regulated transcriptional network implicates neurodegenerative pathways.

    Science.gov (United States)

    Wexler, Eric M; Rosen, Ezra; Lu, Daning; Osborn, Gregory E; Martin, Elizabeth; Raybould, Helen; Geschwind, Daniel H

    2011-10-04

    Wnt proteins are critical to mammalian brain development and function. The canonical Wnt signaling pathway involves the stabilization and nuclear translocation of β-catenin; however, Wnt also signals through alternative, noncanonical pathways. To gain a systems-level, genome-wide view of Wnt signaling, we analyzed Wnt1-stimulated changes in gene expression by transcriptional microarray analysis in cultured human neural progenitor (hNP) cells at multiple time points over a 72-hour time course. We observed a widespread oscillatory-like pattern of changes in gene expression, involving components of both the canonical and the noncanonical Wnt signaling pathways. A higher-order, systems-level analysis that combined independent component analysis, waveform analysis, and mutual information-based network construction revealed effects on pathways related to cell death and neurodegenerative disease. Wnt effectors were tightly clustered with presenilin1 (PSEN1) and granulin (GRN), which cause dominantly inherited forms of Alzheimer's disease and frontotemporal dementia (FTD), respectively. We further explored a potential link between Wnt1 and GRN and found that Wnt1 decreased GRN expression by hNPs. Conversely, GRN knockdown increased WNT1 expression, demonstrating that Wnt and GRN reciprocally regulate each other. Finally, we provided in vivo validation of the in vitro findings by analyzing gene expression data from individuals with FTD. These unbiased and genome-wide analyses provide evidence for a connection between Wnt signaling and the transcriptional regulation of neurodegenerative disease genes.

  12. FDTD-based Transcranial Magnetic Stimulation model applied to specific neurodegenerative disorders.

    Science.gov (United States)

    Fanjul-Vélez, Félix; Salas-García, Irene; Ortega-Quijano, Noé; Arce-Diego, José Luis

    2015-01-01

    Non-invasive treatment of neurodegenerative diseases is particularly challenging in Western countries, where the population age is increasing. In this work, magnetic propagation in human head is modelled by Finite-Difference Time-Domain (FDTD) method, taking into account specific characteristics of Transcranial Magnetic Stimulation (TMS) in neurodegenerative diseases. It uses a realistic high-resolution three-dimensional human head mesh. The numerical method is applied to the analysis of magnetic radiation distribution in the brain using two realistic magnetic source models: a circular coil and a figure-8 coil commonly employed in TMS. The complete model was applied to the study of magnetic stimulation in Alzheimer and Parkinson Diseases (AD, PD). The results show the electrical field distribution when magnetic stimulation is supplied to those brain areas of specific interest for each particular disease. Thereby the current approach entails a high potential for the establishment of the current underdeveloped TMS dosimetry in its emerging application to AD and PD. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  13. Hippocampal-Prefrontal Circuit and Disrupted Functional Connectivity in Psychiatric and Neurodegenerative Disorders

    Directory of Open Access Journals (Sweden)

    Ming Li

    2015-01-01

    Full Text Available In rodents, the hippocampus has been studied extensively as part of a brain system responsible for learning and memory, and the prefrontal cortex (PFC participates in numerous cognitive functions including working memory, flexibility, decision making, and rewarding learning. The neuronal projections from the hippocampus, either directly or indirectly, to the PFC, referred to as the hippocampal-prefrontal cortex (Hip-PFC circuit, play a critical role in cognitive and emotional regulation and memory consolidation. Although in certain psychiatric and neurodegenerative diseases, structural connectivity viewed by imaging techniques has been consistently found to be associated with clinical phenotype and disease severity, the focus has moved towards the investigation of connectivity correlates of molecular pathology and coupling of oscillation. Moreover, functional and structural connectivity measures have been emerging as potential intermediate biomarkers for neuronal disorders. In this review, we summarize progress on the anatomic, molecular, and electrophysiological characters of the Hip-PFC circuit in cognition and emotion processes with an emphasis on oscillation and functional connectivity, revealing a disrupted Hip-PFC connectivity and electrical activity in psychiatric and neurodegenerative disorders as a promising candidate of neural marker for neuronal disorders.

  14. Assessing Executive Dysfunction in Neurodegenerative Disorders: A Critical Review of Brief Neuropsychological Tools

    Directory of Open Access Journals (Sweden)

    Helena S. Moreira

    2017-11-01

    Full Text Available Executive function (EF has been defined as a multifaceted construct that involves a variety of high-level cognitive abilities such as planning, working memory, mental flexibility, and inhibition. Being able to identify deficits in EF is important for the diagnosis and monitoring of several neurodegenerative disorders, and thus their assessment is a topic of much debate. In particular, there has been a growing interest in the development of neuropsychological screening tools that can potentially provide a reliable quick measure of EF. In this review, we critically discuss the four screening tools of EF currently available in the literature: Executive Interview-25 (EXIT 25, Frontal Assessment Battery (FAB, INECO Frontal Screening (IFS, and FRONTIER Executive Screen (FES. We first describe their features, and then evaluate their psychometric properties, the existing evidence on their neural correlates, and the empirical work that has been conducted in clinical populations. We conclude that the four screening tools generally present appropriate psychometric properties, and are sensitive to impairments in EF in several neurodegenerative conditions. However, more research will be needed mostly with respect to normative data and neural correlates, and to determine the extent to which these tools add specific information to the one provided by global cognition screening tests. More research directly comparing the available tools with each other will also be important to establish in which conditions each of them can be most useful.

  15. Exosomes: vehicles for the transfer of toxic proteins associated with neurodegenerative diseases?

    Science.gov (United States)

    Bellingham, Shayne A; Guo, Belinda B; Coleman, Bradley M; Hill, Andrew F

    2012-01-01

    Exosomes are small membranous vesicles secreted by a number of cell types including neurons and can be isolated from conditioned cell media or bodily fluids such as urine and plasma. Exosome biogenesis involves the inward budding of endosomes to form multivesicular bodies (MVB). When fused with the plasma membrane, the MVB releases the vesicles into the extracellular environment as exosomes. Proposed functions of these vesicles include roles in cell-cell signaling, removal of unwanted proteins, and the transfer of pathogens between cells. One such pathogen which exploits this pathway is the prion, the infectious particle responsible for the transmissible neurodegenerative diseases such as Creutzfeldt-Jakob disease (CJD) of humans or bovine spongiform encephalopathy (BSE) of cattle. Similarly, exosomes are also involved in the processing of the amyloid precursor protein (APP) which is associated with Alzheimer's disease. Exosomes have been shown to contain full-length APP and several distinct proteolytically cleaved products of APP, including Aβ. In addition, these fragments can be modulated using inhibitors of the proteases involved in APP cleavage. These observations provide further evidence for a novel pathway in which PrP and APP fragments are released from cells. Other proteins such as superoxide dismutase I and alpha-synuclein (involved in amyotrophic lateral sclerosis and Parkinson's disease, respectively) are also found associated with exosomes. This review will focus on the role of exosomes in neurodegenerative disorders and discuss the potential of these vesicles for the spread of neurotoxicity, therapeutics, and diagnostics for these diseases.

  16. Effect of meditation on cognitive functions in context of aging and neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Rafał eMarciniak

    2014-01-01

    Full Text Available Effect of different meditation practices on various aspects of mental and physical health is receiving growing attention. The present paper reviews evidence about effects of several mediation practices on cognitive functions in the context of aging and neurodegenerative diseases. The effect of meditation in this area is still poorly explored. Seven studies were detected through the databases search which explores the effect of meditation on attention, memory, executive functions and other miscellaneous measures of cognition in a sample of older people and people suffering from neurodegenerative diseases. Overall, reviewed studies suggested a positive effect of meditation techniques, particularly in the area of attention, as well as memory, verbal fluency and cognitive flexibility. These findings are discussed in the context of MRI studies suggesting structural correlates of the effects. Meditation can be a potentially suitable non-pharmacological intervention aimed at the prevention of cognitive decline in the elderly. However, the conclusions of these studies are limited by their methodological flaws and differences of various types of meditation techniques. Further research in this direction could help to verify the validity of the findings and clarify the problematic aspects.

  17. Integration of Nanobots Into Neural Circuits As a Future Therapy for Treating Neurodegenerative Disorders.

    Science.gov (United States)

    Saniotis, Arthur; Henneberg, Maciej; Sawalma, Abdul-Rahman

    2018-01-01

    Recent neuroscientific research demonstrates that the human brain is becoming altered by technological devices. Improvements in biotechnologies and computer based technologies are now increasing the likelihood for the development of brain augmentation devices in the next 20 years. We have developed the idea of an "Endomyccorhizae like interface" (ELI) nanocognitive device as a new kind of future neuroprosthetic which aims to facilitate neuronal network properties in individuals with neurodegenerative disorders. The design of our ELI may overcome the problems of invasive neuroprosthetics, post-operative inflammation, and infection and neuroprosthetic degradation. The method in which our ELI is connected and integrated to neuronal networks is based on a mechanism similar to endomyccorhizae which is the oldest and most widespread form of plant symbiosis. We propose that the principle of Endomyccorhizae could be relevant for developing a crossing point between the ELI and neuronal networks. Similar to endomyccorhizae the ELI will be designed to form webs, each of which connects multiple neurons together. The ELI will function to sense action potentials and deliver it to the neurons it connects to. This is expected to compensate for neuronal loss in some neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease.

  18. Neural stem cell therapy for neurodegenerative disorders: The role of neurotrophic support.

    Science.gov (United States)

    Marsh, Samuel E; Blurton-Jones, Mathew

    2017-06-01

    Neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, and Huntington's disease currently affect tens of millions of people worldwide. Unfortunately, as the world's population ages, the incidence of many of these diseases will continue to rise and is expected to more than double by 2050. Despite significant research and a growing understanding of disease pathogenesis, only a handful of therapies are currently available and all of them provide only transient benefits. Thus, there is an urgent need to develop novel disease-modifying therapies to prevent the development or slow the progression of these debilitating disorders. A growing number of pre-clinical studies have suggested that transplantation of neural stem cells (NSCs) could offer a promising new therapeutic approach for neurodegeneration. While much of the initial excitement about this strategy focused on the use of NSCs to replace degenerating neurons, more recent studies have implicated NSC-mediated changes in neurotrophins as a major mechanism of therapeutic efficacy. In this mini-review we will discuss recent work that examines the ability of NSCs to provide trophic support to disease-effected neuronal populations and synapses in models of neurodegeneration. We will then also discuss some of key challenges that remain before NSC-based therapies for neurodegenerative diseases can be translated toward potential clinical testing. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Integration of Nanobots Into Neural Circuits As a Future Therapy for Treating Neurodegenerative Disorders

    Directory of Open Access Journals (Sweden)

    Arthur Saniotis

    2018-03-01

    Full Text Available Recent neuroscientific research demonstrates that the human brain is becoming altered by technological devices. Improvements in biotechnologies and computer based technologies are now increasing the likelihood for the development of brain augmentation devices in the next 20 years. We have developed the idea of an “Endomyccorhizae like interface” (ELI nanocognitive device as a new kind of future neuroprosthetic which aims to facilitate neuronal network properties in individuals with neurodegenerative disorders. The design of our ELI may overcome the problems of invasive neuroprosthetics, post-operative inflammation, and infection and neuroprosthetic degradation. The method in which our ELI is connected and integrated to neuronal networks is based on a mechanism similar to endomyccorhizae which is the oldest and most widespread form of plant symbiosis. We propose that the principle of Endomyccorhizae could be relevant for developing a crossing point between the ELI and neuronal networks. Similar to endomyccorhizae the ELI will be designed to form webs, each of which connects multiple neurons together. The ELI will function to sense action potentials and deliver it to the neurons it connects to. This is expected to compensate for neuronal loss in some neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease.

  20. Making oxidation potentials predictable: Coordination of additives applied to the electronic fine tuning of an iron(II) complex

    KAUST Repository

    Haslinger, Stefan

    2014-11-03

    This work examines the impact of axially coordinating additives on the electronic structure of a bioinspired octahedral low-spin iron(II) N-heterocyclic carbene (Fe-NHC) complex. Bearing two labile trans-acetonitrile ligands, the Fe-NHC complex, which is also an excellent oxidation catalyst, is prone to axial ligand exchange. Phosphine- and pyridine-based additives are used for substitution of the acetonitrile ligands. On the basis of the resulting defined complexes, predictability of the oxidation potentials is demonstrated, based on a correlation between cyclic voltammetry experiments and density functional theory calculated molecular orbital energies. Fundamental insights into changes of the electronic properties upon axial ligand exchange and the impact on related attributes will finally lead to target-oriented manipulation of the electronic properties and consequently to the effective tuning of the reactivity of bioinspired systems.

  1. Making oxidation potentials predictable: Coordination of additives applied to the electronic fine tuning of an iron(II) complex

    KAUST Repository

    Haslinger, Stefan; Kü ck, Jens W.; Hahn, Eva M.; Cokoja, Mirza; Pö thig, Alexander; Basset, Jean-Marie; Kü hn, Fritz

    2014-01-01

    This work examines the impact of axially coordinating additives on the electronic structure of a bioinspired octahedral low-spin iron(II) N-heterocyclic carbene (Fe-NHC) complex. Bearing two labile trans-acetonitrile ligands, the Fe-NHC complex, which is also an excellent oxidation catalyst, is prone to axial ligand exchange. Phosphine- and pyridine-based additives are used for substitution of the acetonitrile ligands. On the basis of the resulting defined complexes, predictability of the oxidation potentials is demonstrated, based on a correlation between cyclic voltammetry experiments and density functional theory calculated molecular orbital energies. Fundamental insights into changes of the electronic properties upon axial ligand exchange and the impact on related attributes will finally lead to target-oriented manipulation of the electronic properties and consequently to the effective tuning of the reactivity of bioinspired systems.

  2. Prions, prion-like prionoids, and neurodegenerative disordersVacancy

    Directory of Open Access Journals (Sweden)

    Ashok Verma

    2016-01-01

    Full Text Available Prion diseases or transmissible spongiform encephalopathies are fatal neurodegenerative diseases characterized by the aggregation and deposition of the misfolded prion protein in the brain. α-synuclein (α-syn-associated multiple system atrophy has been recently shown to be caused by a bona fide α-syn prion strain. Several other misfolded native proteins such as β-amyloid, tau and TDP-43 share some aspects of prions although none of them is shown to be transmissible in nature or in experimental animals. However, these prion-like “prionoids” are causal to a variety of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. The remarkable recent discovery of at least two new α-syn prion strains and their transmissibility in transgenic mice and in vitro cell models raises a distinct question as to whether some specific strain of other prionoids could have the capability of disease transmission in a manner similar to prions. In this overview, we briefly describe human and other mammalian prion diseases and comment on certain similarities between prion and prionoid and the possibility of prion-like transmissibility of some prionoid strains.

  3. The epigenetic bottleneck of neurodegenerative and psychiatric diseases.

    Science.gov (United States)

    Sananbenesi, Farahnaz; Fischer, Andre

    2009-11-01

    The orchestrated expression of genes is essential for the development and survival of every organism. In addition to the role of transcription factors, the availability of genes for transcription is controlled by a series of proteins that regulate epigenetic chromatin remodeling. The two most studied epigenetic phenomena are DNA methylation and histone-tail modifications. Although a large body of literature implicates the deregulation of histone acetylation and DNA methylation with the pathogenesis of cancer, recently epigenetic mechanisms have also gained much attention in the neuroscientific community. In fact, a new field of research is rapidly emerging and there is now accumulating evidence that the molecular machinery that regulates histone acetylation and DNA methylation is intimately involved in synaptic plasticity and is essential for learning and memory. Importantly, dysfunction of epigenetic gene expression in the brain might be involved in neurodegenerative and psychiatric diseases. In particular, it was found that inhibition of histone deacetylases attenuates synaptic and neuronal loss in animal models for various neurodegenerative diseases and improves cognitive function. In this article, we will summarize recent data in the novel field of neuroepigenetics and discuss the question why epigenetic strategies are suitable therapeutic approaches for the treatment of brain diseases.

  4. Autophagy as an essential cellular antioxidant pathway in neurodegenerative disease

    Directory of Open Access Journals (Sweden)

    Samantha Giordano

    2014-01-01

    Full Text Available Oxidative stress including DNA damage, increased lipid and protein oxidation, are important features of aging and neurodegeneration suggesting that endogenous antioxidant protective pathways are inadequate or overwhelmed. Importantly, oxidative protein damage contributes to age-dependent accumulation of dysfunctional mitochondria or protein aggregates. In addition, environmental toxins such as rotenone and paraquat, which are risk factors for the pathogenesis of neurodegenerative diseases, also promote protein oxidation. The obvious approach of supplementing the primary antioxidant systems designed to suppress the initiation of oxidative stress has been tested in animal models and positive results were obtained. However, these findings have not been effectively translated to treating human patients, and clinical trials for antioxidant therapies using radical scavenging molecules such as α-tocopherol, ascorbate and coenzyme Q have met with limited success, highlighting several limitations to this approach. These could include: (1 radical scavenging antioxidants cannot reverse established damage to proteins and organelles; (2 radical scavenging antioxidants are oxidant specific, and can only be effective if the specific mechanism for neurodegeneration involves the reactive species to which they are targeted and (3 since reactive species play an important role in physiological signaling, suppression of endogenous oxidants maybe deleterious. Therefore, alternative approaches that can circumvent these limitations are needed. While not previously considered an antioxidant system we propose that the autophagy-lysosomal activities, may serve this essential function in neurodegenerative diseases by removing damaged or dysfunctional proteins and organelles.

  5. Mitochondrial and Cell Death Mechanisms in Neurodegenerative Diseases

    Directory of Open Access Journals (Sweden)

    Lee J. Martin

    2010-03-01

    Full Text Available Alzheimer’s disease (AD, Parkinson’s disease (PD and amyotrophic lateral sclerosis (ALS are the most common human adult-onset neurodegenerative diseases. They are characterized by prominent age-related neurodegeneration in selectively vulnerable neural systems. Some forms of AD, PD, and ALS are inherited, and genes causing these diseases have been identified. Nevertheless, the mechanisms of the neuronal cell death are unresolved. Morphological, biochemical, genetic, as well as cell and animal model studies reveal that mitochondria could have roles in this neurodegeneration. The functions and properties of mitochondria might render subsets of selectively vulnerable neurons intrinsically susceptible to cellular aging and stress and overlying genetic variations, triggering neurodegeneration according to a cell death matrix theory. In AD, alterations in enzymes involved in oxidative phosphorylation, oxidative damage, and mitochondrial binding of Aβ and amyloid precursor protein have been reported. In PD, mutations in putative mitochondrial proteins have been identified and mitochondrial DNA mutations have been found in neurons in the substantia nigra. In ALS, changes occur in mitochondrial respiratory chain enzymes and mitochondrial cell death proteins. Transgenic mouse models of human neurodegenerative disease are beginning to reveal possible principles governing the biology of selective neuronal vulnerability that implicate mitochondria and the mitochondrial permeability transition pore. This review summarizes how mitochondrial pathobiology might contribute to neuronal death in AD, PD, and ALS and could serve as a target for drug therapy.

  6. Neuronal network disintegration: common pathways linking neurodegenerative diseases.

    Science.gov (United States)

    Ahmed, Rebekah M; Devenney, Emma M; Irish, Muireann; Ittner, Arne; Naismith, Sharon; Ittner, Lars M; Rohrer, Jonathan D; Halliday, Glenda M; Eisen, Andrew; Hodges, John R; Kiernan, Matthew C

    2016-11-01

    Neurodegeneration refers to a heterogeneous group of brain disorders that progressively evolve. It has been increasingly appreciated that many neurodegenerative conditions overlap at multiple levels and therefore traditional clinicopathological correlation approaches to better classify a disease have met with limited success. Neuronal network disintegration is fundamental to neurodegeneration, and concepts based around such a concept may better explain the overlap between their clinical and pathological phenotypes. In this Review, promoters of overlap in neurodegeneration incorporating behavioural, cognitive, metabolic, motor, and extrapyramidal presentations will be critically appraised. In addition, evidence that may support the existence of large-scale networks that might be contributing to phenotypic differentiation will be considered across a neurodegenerative spectrum. Disintegration of neuronal networks through different pathological processes, such as prion-like spread, may provide a better paradigm of disease and thereby facilitate the identification of novel therapies for neurodegeneration. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  7. Examination of Gelatinase Isoforms in Rodent Models of Acute Neurodegenerative Diseases Using Two-Dimensional Zymography.

    Science.gov (United States)

    Chen, Shanyan; Meng, Fanjun; Chen, Zhenzhou; Qu, Zhe; Cui, Jiankun; Gu, Zezong

    2017-01-01

    Pathological activation of gelatinases (matrix metalloproteinase-2 and -9; MMP-2/-9) has been shown to cause a number of detrimental outcomes in neurodegenerative diseases. In gel gelatin zymography is a highly sensitive methodology commonly used in revealing levels of gelatinase activity and in separating the proform and active form of gelatinases, based on their different molecular weights. However, this methodology is inadequate in resolving complex enzyme isoforms, because gelatinase expression and activity can be regulated at transcriptional and/or post-translational levels under in vivo conditions resulting in alternation of their isoelectric focusing (IEF) points. In this chapter, we describe an advanced methodology, termed two-dimensional zymography, combining IEF with zymographic electrophoresis under non-reducing conditions to achieve significant improvement in separation of the gelatinase isoforms in both cell-based and in vivo models for acute brain injuries and neuroinflammation.

  8. [Organ donation after active euthanasia in a patient with a neurodegenerative disease].

    Science.gov (United States)

    van Dijk, Gert; Giezeman, Ariane; Ultee, Fred; Hamers, Raoul

    2013-01-01

    In countries where active euthanasia by a physician is allowed under law - Belgium and the Netherlands - physicians are sometimes confronted with patients who want to donate organs after active euthanasia has been performed. This combination of procedures has been reported in Belgium, and this article is the first description of such a case in the Netherlands. It concerns a patient with a neurodegenerative disease who donated organs after euthanasia. The combination of two complex and controversial procedures - active euthanasia and organ donation - raises important ethical, legal and practical issues. It is suggested that with a thorough preparation and a strict separation of both procedures, organ donation after active euthanasia can strengthen patient autonomy and increase the number of donated organs.

  9. Potential advantages and limitations of the Leo stent in endovascular treatment of complex cerebral aneurysms

    Energy Technology Data Exchange (ETDEWEB)

    Lv Xianli; Li Youxiang; Jiang Chuhan; Yang Xinjian [Beijing Neurosurgical Institute and Beijing Tiantan Hospital, Capital Medical University, 6, Tiantan Xili, 100050 Hebei, Beijing (China); Wu Zhongxue, E-mail: ttyyzjb@sina.com [Beijing Neurosurgical Institute and Beijing Tiantan Hospital, Capital Medical University, 6, Tiantan Xili, 100050 Hebei, Beijing (China)

    2011-08-15

    Objective: The Leo self-expandable stent is a new retractable stent that is delivered via a conventional catheter. The aim of this study was to evaluate the use of this stent for endovascular treatment of complex aneurysms. Methods: Twenty-eight complex cerebral aneurysms (27 saccular and 1 fusiform) in 28 patients were treated electively. They were located at the internal carotid artery (17), basilar trunk (3), anterior cerebral artery (1), anterior communicating artery (3), vertebral artery (2) and middle cerebral artery (2). One aneurysm exhibited recanalization after primary endovascular treatment without stent. Clinical outcome was assessed with the modified Glasgow Outcome Scale. Results: Deployment of Leo stent was successful in 26 lesions, and difficulties in stent positioning due to tortuous cerebral circulation in 2 cases, which were treated with Neuroform stent. Additional coil embolization was performed in 26 lesions. No permanent neurological deficits were encountered consequent to endovascular procedure. Complete or partial occlusion immediately after stent deployment was achieved in all aneurysms. There was no immediate coil embolization was chosen in 3 cases because of subsequent reduced filling of the aneurysms with contrast agent on angiograms. There were 3 asymptomatic parent artery occlusion related to the deployment of the Leo stent, one stent migration. Follow-up revealed patent stents in the remaining cases. No angiographic recurrences arose. Conclusion: The Leo stent is very useful for endovascular treatment of complex cerebral aneurysms because it is easy to navigate and place precisely. A drawback is that in-stent thrombosis caused by stent placement and stiffer delivery catheters to place larger stents.

  10. Hybrid functional calculations of potential hydrogen storage material: Complex dimagnesium iron hydride

    KAUST Repository

    Ul Haq, Bakhtiar; Kanoun, Mohammed; Ahmed, Rashid; Bououdina, M.; Goumri-Said, Souraya

    2014-01-01

    .%) within a reasonable formation energy of -78 kJ mol-1, at room temperature, can be easily achievable, thus making Mg2FeH6 as potential material for practical H2 storage applications. Copyright © 2014, Hydrogen Energy Publications, LLC. Published

  11. Siderophore-drug complexes: potential medicinal applications of the 'Trojan horse' strategy.

    Science.gov (United States)

    Górska, Agnieszka; Sloderbach, Anna; Marszałł, Michał Piotr

    2014-09-01

    The ability of bacteria to develop resistance to antimicrobial agents poses problems in the treatment of numerous bacterial infections. One method to circumvent permeability-mediated drug resistance involves the employment of the 'Trojan horse' strategy. The Trojan horse concept involves the use of bacterial iron uptake systems to enter and kill bacteria. The siderophore-drug complex is recognized by specific siderophore receptors and is then actively transported across the outer membrane. The recently identified benefits of this strategy have led to the synthesis of a series of siderophore-based antibiotics. Several studies have shown that siderophore-drug conjugates make it possible to design antibiotics with improved cell transport and reduce the frequency of resistance mutants. Growing interest in siderophore-drug conjugates for the treatment of human diseases including iron overload, cancer, and malaria has driven the search for new siderophore-drug complexes. This strategy may have special importance for the development of iron oxide nanoparticle-based therapeutics. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Proteins with complex architecture as potential targets for drug design: a case study of Mycobacterium tuberculosis.

    Directory of Open Access Journals (Sweden)

    Bálint Mészáros

    2011-07-01

    Full Text Available Lengthy co-evolution of Homo sapiens and Mycobacterium tuberculosis, the main causative agent of tuberculosis, resulted in a dramatically successful pathogen species that presents considerable challenge for modern medicine. The continuous and ever increasing appearance of multi-drug resistant mycobacteria necessitates the identification of novel drug targets and drugs with new mechanisms of action. However, further insights are needed to establish automated protocols for target selection based on the available complete genome sequences. In the present study, we perform complete proteome level comparisons between M. tuberculosis, mycobacteria, other prokaryotes and available eukaryotes based on protein domains, local sequence similarities and protein disorder. We show that the enrichment of certain domains in the genome can indicate an important function specific to M. tuberculosis. We identified two families, termed pkn and PE/PPE that stand out in this respect. The common property of these two protein families is a complex domain organization that combines species-specific regions, commonly occurring domains and disordered segments. Besides highlighting promising novel drug target candidates in M. tuberculosis, the presented analysis can also be viewed as a general protocol to identify proteins involved in species-specific functions in a given organism. We conclude that target selection protocols should be extended to include proteins with complex domain architectures instead of focusing on sequentially unique and essential proteins only.

  13. Copper (II) and zinc (II) complexes with flavanone derivatives: Identification of potential cholinesterase inhibitors by on-flow assays.

    Science.gov (United States)

    Sarria, André Lucio Franceschini; Vilela, Adriana Ferreira Lopes; Frugeri, Bárbara Mammana; Fernandes, João Batista; Carlos, Rose Maria; da Silva, Maria Fátima das Graças Fernandes; Cass, Quezia Bezerra; Cardoso, Carmen Lúcia

    2016-11-01

    Metal chelates strongly influence the nature and magnitude of pharmacological activities in flavonoids. In recent years, studies have shown that a promising class of flavanone-metal ion complexes can act as selective cholinesterase inhibitors (ChEIs), which has led our group to synthesize a new series of flavanone derivatives (hesperidin, hesperetin, naringin, and naringenin) complexed to either copper (II) or zinc (II) and to evaluate their potential use as selective ChEIs. Most of the synthesized complexes exhibited greater inhibitory activity against acetylcholinesterase (AChE) than against butyrylcholinesterase (BChE). Nine of these complexes constituted potent, reversible, and selective ChEIs with inhibitory potency (IC 50 ) and inhibitory constant (K i ) ranging from 0.02 to 4.5μM. Copper complexes with flavanone-bipyridine derivatives afforded the best inhibitory activity against AChE and BChE. The complex Cu(naringin)(2,2'-bipyridine) (11) gave IC 50 and K i values of 0.012±0.002 and 0.07±0.01μM for huAChE, respectively, which were lower than the inhibitory values obtained for standard galanthamine (IC 50 =206±30.0 and K i =126±18.0μM). Evaluation of the inhibitory activity of this complex against butyrylcholinesterase from human serum (huBChE) gave IC 50 and K i values of 8.0±1.4 and 2.0±0.1μM, respectively. A Liquid Chromatography-Immobilized Capillary Enzyme Reactor by UV detection (LC-ICER-UV) assay allowed us to determine the IC 50 and K i values and the type of mechanism for the best inhibitors. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Functional complexity of the Leishmania granuloma and the potential of in silico modelling

    Directory of Open Access Journals (Sweden)

    John eMoore

    2013-02-01

    Full Text Available AbstractIn human and canine visceral leishmaniasis and in various experimental models of this disease, host resistance is strongly linked to efficient granuloma development. However, it is unknown exactly how the granuloma microenvironment executes an effective antileishmanial response. Recent studies, including using advanced imaging techniques have improved our understanding of granuloma biology, at the cellular level, highlighting heterogeneity in granuloma development and function, and hinting at complex cellular, temporal and spatial dynamics. In this mini-review, we discuss the factors involved in the formation and function of L.donovani-induced hepatic granulomas, as well as their importance in protecting against inflammation-associated tissue damage and the generation of immunity to rechallenge. Finally, we discuss the role that computational, agent-based models may play to answer outstanding questions within the field.

  15. Hexacyanoametallate complexes as potential adsorbent in nuclear fuel cycle. Vol. 3

    Energy Technology Data Exchange (ETDEWEB)

    Benyamin, K; Mekhail, F M [Hot Laboratories Centre, Atomic Energy Authority, Cairo, (Egypt)

    1996-03-01

    The use of coordination polymers of the general formula M{sub 3}{sup 11}[Me(CN){sub 6}]{sub 2}.x H{sub 2} O for the recovery of heavy alkali metals has been studied. The hexacyanometallate complex is used together with silica gel as supporting material. The preparation of such absorbent, cobalt hexacyanocobaltate-silica (Co H C C-Si{sub 2}), and the sorption and elution characteristics under dynamic conditions have also been investigated. A number of parameters affecting the breakthrough capacity such as acidity, particle size, salt concentration, and the nature of the waste solution (e.g. MAW, PWR, BWR, ...) are reported. 2 figs., 3 tabs.

  16. Analytic ab initio-based molecular interaction potential for the BrO⋅H{sub 2}O complex

    Energy Technology Data Exchange (ETDEWEB)

    Hoehn, Ross D.; Kais, Sabre [Department of Chemistry, Purdue University, West Lafayette, Indiana 47907 (United States); Qatar Environment and Energy Research Institute, HBKU, Doha (Qatar); Yeole, Sachin D. [Department of Chemistry, Purdue University, West Lafayette, Indiana 47907 (United States); Francisco, Joseph S., E-mail: jfrancisco3@unl.edu [Department of Chemistry, Purdue University, West Lafayette, Indiana 47907 (United States); Departments of Chemistry, University of Nebraska, Lincoln, Nebraska 68588 (United States)

    2016-05-28

    Radical halogen oxide species play important roles within atmospheric processes, specifically those responsible for the removal of O{sub 3}. To facilitate future investigations on this family of compounds, RCCSD(T)/aug-cc-pVQZ-level electronic structure calculations were employed to generate individual-molecule optimized geometries, as well as to determine the global minimum energy structure for the BrO⋅H{sub 2}O complex. This information facilitated the generation of several one-dimensional potential energy surface (PES) scans for the BrO⋅H{sub 2}O complex. Scans were performed for both the ground state and the first excited state; this inclusion is due to a low-lying first electronic excited-state energy. These rigid-geometry PES scans were used both to generate a novel analytic interaction potential by modifying the existing Thole-type model used for water and to the fitted potential function. This interaction potential features anisotropic atomic polarizabilities facilitating appropriate modeling of the physics regarding the unpaired electron residing within the p-orbitals of the oxygen atom of the bromine oxide radical. The intention of this work is to facilitate future molecular dynamics simulations involving the interaction between the BrO radical and water clusters as a first step in devising possible novel chemistries taking place at the water interface of clouds within the atmosphere.

  17. DFT and TD-DFT calculations of metallotetraphenylporphyrin and metallotetraphenylporphyrin fullerene complexes as potential dye sensitizers for solar cells

    Science.gov (United States)

    El Mahdy, A. M.; Halim, Shimaa Abdel; Taha, H. O.

    2018-05-01

    Density functional theory (DFT) and time-dependent DFT calculations have been employed to model metallotetraphenylporphyrin dyes and metallotetraphenylporphyrin -fullerene complexes in order to investigate the geometries, electronic structures, the density of states, non-linear optical properties (NLO), IR-vis spectra, molecular electrostatic potential contours, and electrophilicity. To calculate the excited states of the tetraphenyl porphyrin analogs, time-dependent density functional theory (TD-DFT) are used. Their UV-vis spectra were also obtained and a comparison with available experimental and theoretical results is included. The results reveal that the metal and the tertiary butyl groups of the dyes are electron donors, and the tetraphenylporphyrin rings are electron acceptors. The HOMOs of the dyes fall within the (TiO2)60 and Ti38O76 band gaps and support the issue of typical interfacial electron transfer reaction. The resulting potential drop of Mn-TPP-C60 increased by ca. 3.50% under the effect of the tertiary butyl groups. The increase in the potential drop indicates that the tertiary butyl complexes could be a better choice for the strong operation of the molecular rectifiers. The introduction of metal atom and tertiary butyl groups to the tetraphenyl porphyrin moiety leads to a stronger response to the external electric field and induces higher photo-to-current conversion efficiency. This also shifts the absorption in the dyes and makes them potential candidates for harvesting light in the entire visible and near IR region for photovoltaic applications.

  18. Intermolecular potential and rovibrational states of the H2O–D2 complex

    International Nuclear Information System (INIS)

    Avoird, Ad van der; Scribano, Yohann; Faure, Alexandre; Weida, Miles J.; Fair, Joanna R.; Nesbitt, David J.

    2012-01-01

    Graphical abstract: H 2 O–D 2 potential surface and pH 2 O–oD 2 ground state wave function, for planar geometries. Highlights: ► The interaction between H 2 O and H 2 is of great astrophysical interest. ► The rovibrational states of H 2 O–D 2 were computed on an ab initio potential surface. ► Results are compared with the rovibrational states of H 2 O–H 2 computed recently. ► We measured the high-resolution infrared spectrum of H 2 O–D 2 in the H 2 O bend region. ► Comparison with the calculations provides information on H 2 O–H 2 potential surface. - Abstract: A five-dimensional intermolecular potential for H 2 O–D 2 was obtained from the full nine-dimensional ab initio potential surface of Valiron et al. [P. Valiron, M. Wernli, A. Faure, L. Wiesenfeld, C. Rist, S. Kedžuch, J. Noga, J. Chem. Phys. 129 (2008) 134306] by averaging over the ground state vibrational wave functions of H 2 O and D 2 . On this five-dimensional potential with a well depth D e of 232.12 cm −1 we calculated the bound rovibrational levels of H 2 O–D 2 for total angular momentum J = 0–3. The method used to compute the rovibrational levels is similar to a scattering approach—it involves a basis of coupled free rotor wave functions for the hindered internal rotations and the overall rotation of the dimer—while it uses a discrete variable representation of the intermolecular distance coordinate R. The basis was adapted to the permutation symmetry associated with the para/ortho (p/o) nature of both H 2 O and D 2 , as well as to inversion symmetry. As expected, the H 2 O–D 2 dimer is more strongly bound than its H 2 O–H 2 isotopologue [cf. A. van der Avoird, D.J. Nesbitt, J. Chem. Phys. 134 (2011) 044314], with dissociation energies D 0 of 46.10, 50.59, 67.43, and 73.53 cm −1 for pH 2 O–oD 2 , oH 2 O–oD 2 , pH 2 O–pD 2 , and oH 2 O–pD 2 . A rotationally resolved infrared spectrum of H 2 O–D 2 was measured in the frequency region of the H 2 O bend

  19. Human sperm bioassay has potential in evaluating the quality of cumulus-oocyte complexes.

    Science.gov (United States)

    Hossain, A M; Rizk, B; Huff, C; Helvacioglu, A; Thorneycroft, I H

    1996-01-01

    Human sperm bioassay is routinely used as a quality control check for the culture media. This is one of the three bioassays chosen by the College of American Pathologists (CAP) for interlaboratory proficiency testing to assess the standards of in vitro fertilization (IVF) and andrology laboratories. This study utilized sperm bioassay to assess the quality of cumulus-oocyte complexes (COCs) retrieved in IVF procedures COCs, harvested from the female partner of IVF couples, undergoing identical ovarian stimulation protocols, were individually inseminated with the sperm of the corresponding male partner. Sperm motility in sperm-COC cocultures were compared. Cocultures were established by inseminating the 103 COCs, retrieved from 18 IVF couples with 1 x 10(5) to 2 x 10(5) sperm of the corresponding male partners of the couples. In all 18 cases, the sperm were prepared identically using the Percoll wash method. The cocultures were maintained for 48 h but the oocytes were removed immediately after the fertilization check (approximately 16 h). The motility of sperm in the cocultures and in the insemination stocks were noted and 17 of 18 sperm stocks used for insemination had similar high preinsemination motility (90.2 +/- 5.0%). At 48 h the sperm motility had significantly decreased in the cocultures compared to the insemination stocks; 52.7 +/- 19.9% versus 67.2 +/- 10.4%. There was no difference in the motility among the small, medium, and large COCs (56.4 +/- 24.6%, 52.5 +/- 17.9%, and 50.8 +/- 20.9%, respectively). In 45% of IVF cases, the motility in cocultures varied widely, falling below as well as above that of their corresponding insemination stocks. Furthermore, the sperm motility varied among the cocultures in both pregnant and nonpregnant patients but the extent of variation appears to be greater in the latter. The inter-COC coculture sperm motility variation most likely is due to the differences in the quality of cumulus-oocyte complexes.

  20. Modeling Neuropsychiatric and Neurodegenerative Diseases With Induced Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Elizabeth A. LaMarca

    2018-04-01

    Full Text Available Human-induced pluripotent stem cells (hiPSCs have revolutionized our ability to model neuropsychiatric and neurodegenerative diseases, and recent progress in the field is paving the way for improved therapeutics. In this review, we discuss major advances in generating hiPSC-derived neural cells and cutting-edge techniques that are transforming hiPSC technology, such as three-dimensional “mini-brains” and clustered, regularly interspersed short palindromic repeats (CRISPR-Cas systems. We examine specific examples of how hiPSC-derived neural cells are being used to uncover the pathophysiology of schizophrenia and Parkinson’s disease, and consider the future of this groundbreaking research.

  1. Extracellular Vesicles in Brain Tumors and Neurodegenerative Diseases

    Directory of Open Access Journals (Sweden)

    Federica Ciregia

    2017-08-01

    Full Text Available Extracellular vesicles (EVs can be classified into apoptotic bodies, microvesicles (MVs, and exosomes, based on their origin or size. Exosomes are the smallest and best characterized vesicles which derived from the endosomal system. These vesicles are released from many different cell types including neuronal cells and their functions in the nervous system are investigated. They have been proposed as novel means for intercellular communication, which takes part not only to the normal neuronal physiology but also to the transmission of pathogenic proteins. Indeed, exosomes are fundamental to assemble and transport proteins during development, but they can also transfer neurotoxic misfolded proteins in pathogenesis. The present review will focus on their roles in neurological diseases, specifically brain tumors, such as glioblastoma (GBM, neuroblastoma (NB, medulloblastoma (MB, and metastatic brain tumors and chronic neurodegenerative diseases, such as Alzheimer, Parkinson, multiple sclerosis (MS, amyotrophic lateral sclerosis (ALS, Huntington, and Prion diseseases highlighting their involvement in spreading neurotoxicity, in therapeutics, and in pathogenesis.

  2. Support system and method for detecting neurodegenerative disorder

    DEFF Research Database (Denmark)

    2013-01-01

    The present invention relates to a system and a method for detection of abnormal motor activity during REM sleep, and further to systems and method for assisting in detecting neurodegenerative disorders such as Parkinson's. One embodiment relates to a method for detection of abnormal motor activity...... during REM sleep comprising the steps of: performing polysomnographic recordings of a sleeping subject, thereby obtaining one or more electromyography (EMG) derivations, preferably surface EMG recordings, and one or more EEG derivations, and/or one or more electrooculargraphy (EOG) derivations, detecting...... one or more REM sleep stages, preferably based on the one or more EEG and/or EOG derivations, determining the level of muscle activity during the one or more REM sleep stages based on the one or more EMG derivations, wherein a subject having an increased level of muscle activity during REM sleep...

  3. Hybrid functional calculations of potential hydrogen storage material: Complex dimagnesium iron hydride

    KAUST Repository

    Ul Haq, Bakhtiar

    2014-06-01

    By employing the state of art first principles approaches, comprehensive investigations of a very promising hydrogen storage material, Mg 2FeH6 hydride, is presented. To expose its hydrogen storage capabilities, detailed structural, elastic, electronic, optical and dielectric aspects have been deeply analysed. The electronic band structure calculations demonstrate that Mg2FeH6 is semiconducting material. The obtained results of the optical bandgap (4.19 eV) also indicate that it is a transparent material for ultraviolet light, thus demonstrating its potential for optoelectronics application. The calculated elastic properties reveal that Mg2FeH6 is highly stiff and stable hydride. Finally, the calculated hydrogen (H2) storage capacity (5.47 wt.%) within a reasonable formation energy of -78 kJ mol-1, at room temperature, can be easily achievable, thus making Mg2FeH6 as potential material for practical H2 storage applications. Copyright © 2014, Hydrogen Energy Publications, LLC. Published by Elsevier Ltd. All rights reserved.

  4. Adenosine deaminase complexing protein (ADCP) expression and metastatic potential in prostatic adenocarcinomas.

    Science.gov (United States)

    Dinjens, W N; Ten Kate, J; Kirch, J A; Tanke, H J; Van der Linden, E P; Van den Ingh, H F; Van Steenbrugge, G J; Meera Khan, P; Bosman, F T

    1990-03-01

    The expression of the adenosine deaminase complexing protein (ADCP) was investigated by immunohistochemistry in the normal and hyperplastic human prostate, in 30 prostatic adenocarcinomas, and in seven human prostatic adenocarcinoma cell lines grown as xenografts in athymic nude mice. In the normal and hyperplastic prostate, ADCP was localized exclusively in the apical membrane and the apical cytoplasm of the glandular epithelial cells. In prostatic adenocarcinomas, four distinct ADCP expression patterns were observed: diffuse cytoplasmic, membranous, both cytoplasmic and membranous, and no ADCP expression. The expression patterns were compared with the presence of metastases. We found an inverse correlation between membranous ADCP immunoreactivity and metastatic propensity. Exclusively membranous ADCP immunoreactivity occurred only in non-metastatic tumours. In contrast, the metastatic tumours showed no or diffuse cytoplasmic ADCP immunoreactivity. This suggests that immunohistochemical detection of ADCP might predict the biological behaviour of prostatic cancer. However, the occurrence of membranous ADCP immunoreactivity in the xenograft of a cell line (PC-EW), derived from a prostatic carcinoma metastasis, indicates that not only the tendency to metastasize modulates ADCP expression.

  5. Impact of Plant-Derived Flavonoids on Neurodegenerative Diseases.

    Science.gov (United States)

    Costa, Silvia Lima; Silva, Victor Diogenes Amaral; Dos Santos Souza, Cleide; Santos, Cleonice Creusa; Paris, Irmgard; Muñoz, Patricia; Segura-Aguilar, Juan

    2016-07-01

    Neurodegenerative disorders have a common characteristic that is the involvement of different cell types, typically the reactivity of astrocytes and microglia, characterizing gliosis, which in turn contributes to the neuronal dysfunction and or death. Flavonoids are secondary metabolites of plant origin widely investigated at present and represent one of the most important and diversified among natural products phenolic groups. Several biological activities are attributed to this class of polyphenols, such as antitumor activity, antioxidant, antiviral, and anti-inflammatory, among others, which give significant pharmacological importance. Our group have observed that flavonoids derived from Brazilian plants Dimorphandra mollis Bent., Croton betulaster Müll. Arg., e Poincianella pyramidalis Tul., botanical synonymous Caesalpinia pyramidalis Tul. also elicit a broad spectrum of responses in astrocytes and neurons in culture as activation of astrocytes and microglia, astrocyte associated protection of neuronal progenitor cells, neuronal differentiation and neuritogenesis. It was observed the flavonoids also induced neuronal differentiation of mouse embryonic stem cells and human pluripotent stem cells. Moreover, with the objective of seeking preclinical pharmacological evidence of these molecules, in order to assess its future use in the treatment of neurodegenerative disorders, we have evaluated the effects of flavonoids in preclinical in vitro models of neuroinflammation associated with Parkinson's disease and glutamate toxicity associated with ischemia. In particular, our efforts have been directed to identify mechanisms involved in the changes in viability, morphology, and glial cell function induced by flavonoids in cultures of glial cells and neuronal cells alone or in interactions and clarify the relation with their neuroprotective and morphogetic effects.

  6. Adult Neurogenesis and Neurodegenerative Diseases: A Systems Biology Perspective

    Science.gov (United States)

    Horgusluoglu, Emrin; Nudelman, Kelly; Nho, Kwangsik; Saykin, Andrew J.

    2016-01-01

    New neurons are generated throughout adulthood in two regions of the brain, the olfactory bulb and dentate gyrus of the hippocampus, and are incorporated into the hippocampal network circuitry; disruption of this process has been postulated to contribute to neurodegenerative diseases including Alzheimer’s disease and Parkinson’s disease. Known modulators of adult neurogenesis include signal transduction pathways, the vascular and immune systems, metabolic factors, and epigenetic regulation. Multiple intrinsic and extrinsic factors such as neurotrophic factors, transcription factors, and cell cycle regulators control neural stem cell proliferation, maintenance in the adult neurogenic niche, and differentiation into mature neurons; these factors act in networks of signaling molecules that influence each other during construction and maintenance of neural circuits, and in turn contribute to learning and memory. The immune system and vascular system are necessary for neuronal formation and neural stem cell fate determination. Inflammatory cytokines regulate adult neurogenesis in response to immune system activation, whereas the vasculature regulates the neural stem cell niche. Vasculature, immune/support cell populations (microglia/astrocytes), adhesion molecules, growth factors, and the extracellular matrix also provide a homing environment for neural stem cells. Epigenetic changes during hippocampal neurogenesis also impact memory and learning. Some genetic variations in neurogenesis related genes may play important roles in the alteration of neural stem cells differentiation into new born neurons during adult neurogenesis, with important therapeutic implications. In this review, we discuss mechanisms of and interactions between these modulators of adult neurogenesis, as well as implications for neurodegenerative disease and current therapeutic research. PMID:26879907

  7. A neurodegenerative vascular burden index and the impact on cognition

    Directory of Open Access Journals (Sweden)

    Sebastian eHeinzel

    2014-07-01

    Full Text Available A wide range of vascular burden factors have been identified to impact vascular function and structure as indicated by carotid intima-media thickness (IMT. On the basis of their impact on IMT, vascular factors may be selected and clustered in a vascular burden index (VBI. Since many vascular factors increase the risk of Alzheimer's disease (AD, a multifactorial neurodegenerative VBI may be related to early pathological processes in AD and cognitive decline in its preclinical stages.We investigated an elderly cohort at risk for neurodegeneration (TREND study, n = 1102 for the multifactorial influence of vascular burden factors on IMT measured by ultrasound. To create a VBI for this cohort, vascular factors and their definitions (considering medical history, medication and/or blood marker data were selected based on their statistical effects on IMT in multiple regressions including age and sex. The impact of the VBI on cognitive performance was assessed using the Trail-Making Test (TMT and the CERAD neuropsychological battery.IMT was significantly predicted by age (standardized β = .26, sex (.09; males > females and the factors included in the VBI: obesity (.18, hypertension (.14, smoking (.08, diabetes (.07, and atherosclerosis (.05, whereas other cardiovascular diseases or hypercholesterolemia were not significant. Individuals with 2 or more VBI factors compared to individuals without had an odds ratio of 3.17 regarding overly increased IMT (≥1.0 mm. The VBI showed an impact on executive control (log(TMT B-A, p = .047 and a trend towards decreased global cognitive function (CERAD total score, p = .057 independent of age, sex and education.A VBI established on the basis of IMT may help to identify individuals with overly increased vascular burden linked to decreased cognitive function indicating neurodegenerative processes. The longitudinal study of this risk cohort will reveal the value of the VBI as prodromal marker for cognitive decline and

  8. Radiosynthesis and biodistribution of 99mTcN-Garenoxacin dithiocarbamate complex a potential infection imaging agent

    International Nuclear Information System (INIS)

    Syed Qaiser Shah; Aakif Ullah Khan; Muhammad Rafiullah Khan

    2011-01-01

    Garenoxacin (GXN) was modified to its dithiocarbamate followed by radiolabeling with technetium-99m ( 99m Tc) through [ 99m Tc-N] 2+ core. The suitability of the 99m TcN-Garenoxacin dithiocarbamate (GXND) complex as a potential multiresistant Staphylococcus aureus (MDRSA) and penicillin-resistant Streptococci (PRSC) infection radiotracer was assessed in artificially infected rats (AFRT). The radiolabeled complex was investigated for its radiochemical purity (RCP), permanence in serum using HPLC and TLC methods. In vitro binding with MDRSA and PRSC was performed at 37 deg C. The 99m TcN-GXND showed maximum RCP of 98.00 ± 0.22% and remained more than 90% stable up to 4 h. The 99m TcN-GXND showed saturated in vitro binding with living MDRSA and PRSC, respectively. The complex showed normal biodistribution in healthy rats (HRT), however in AFRT, seven fold uptakes was observed in infected muscle as compared to inflamed and normal muscles. Based on the high RCP, stability in serum, better in vitro binding with bacteria, biodistribution behavior and the target to non-target (infected to inflamed muscle) ratio, we recommend the 99m TcN-GXND complex for in vivo investigation of MDRSA and PRSC infection in human. (author)

  9. Cyanobacteria, neurotoxins and water resources: are there implications for human neurodegenerative disease?

    Science.gov (United States)

    Metcalf, James S; Codd, Geoffrey A

    2009-01-01

    Cyanobacteria are cosmopolitan microbes that inhabit marine, freshwater and terrestrial environments. Under favourable conditions in waterbodies, they can form massive populations (blooms and scums), which present hazards to human and animal health. Such cyanobacteria often contain a variety of toxic substances (cyanotoxins) that can exist as both cell-associated and free forms in the surrounding water. Some cyanotoxins are highly neurotoxic and act through a variety of mechanisms. Recent findings of the production of the neurotoxin beta-N-methylamino-L-alanine (BMAA) by cyanobacteria in aquatic environments, and of BMAA in brain and cerebrospinal fluid samples of amyotrophic lateral sclerosis and Alzheimer's disease victims, raises the possibility that people may be exposed to waterborne BMAA of cyanobacterial origin and that this may contribute to human neurodegenerative disease. An understanding of the risks presented by waterborne BMAA and of available mitigation strategies to reduce this potential exposure is needed.

  10. Five-class differential diagnostics of neurodegenerative diseases using random undersampling boosting

    DEFF Research Database (Denmark)

    Tong, Tong; Ledig, Christian; Guerrero, Ricardo

    2017-01-01

    Differentiating between different types of neurodegenerative diseases is not only crucial in clinical practice when treatment decisions have to be made, but also has a significant potential for the enrichment of clinical trials. The purpose of this study is to develop a classification framework......-wise grading features) and non-imaging features (CSF measures) were extracted for each subject. In clinical practice, the prevalence of different dementia types is imbalanced, posing challenges for learning an effective classification model. Therefore, we propose the use of the RUSBoost algorithm in order...... to train classifiers and to handle the class imbalance training problem. Furthermore, a multi-class feature selection method based on sparsity is integrated into the proposed framework to improve the classification performance. It also provides a way for investigating the importance of different features...

  11. In-medium P-wave quarkonium from the complex lattice QCD potential

    International Nuclear Information System (INIS)

    Burnier, Yannis; Kaczmarek, Olaf; Rothkopf, Alexander

    2016-01-01

    We extend our lattice QCD potential based study http://dx.doi.org/10.1007/JHEP12(2015)101 of the in-medium properties of heavy quark bound states to P-wave bottomonium and charmonium. Similar to the behavior found in the S-wave channel their spectra show a characteristic broadening, as well as mass shifts to lower energy with increasing temperature. In contrast to the S-wave states, finite angular momentum leads to the survival of spectral peaks even at temperatures, where the continuum threshold reaches below the bound state remnant mass. We elaborate on the ensuing challenges in defining quarkonium dissolution and present estimates of melting temperatures for the spin averaged χ b and χ c states. As an application to heavy-ion collisions we further estimate the contribution of feed down to S-wave quarkonium through the P-wave states after freezeout.

  12. In-medium P-wave quarkonium from the complex lattice QCD potential

    Energy Technology Data Exchange (ETDEWEB)

    Burnier, Yannis [Institute of Theoretical Physics, EPFL,CH-1015 Lausanne (Switzerland); Kaczmarek, Olaf [Fakultät für Physik, Universität Bielefeld,D-33615 Bielefeld (Germany); Rothkopf, Alexander [Institute for Theoretical Physics, Heidelberg University,Philosophenweg 16, 69120 Heidelberg (Germany)

    2016-10-07

    We extend our lattice QCD potential based study http://dx.doi.org/10.1007/JHEP12(2015)101 of the in-medium properties of heavy quark bound states to P-wave bottomonium and charmonium. Similar to the behavior found in the S-wave channel their spectra show a characteristic broadening, as well as mass shifts to lower energy with increasing temperature. In contrast to the S-wave states, finite angular momentum leads to the survival of spectral peaks even at temperatures, where the continuum threshold reaches below the bound state remnant mass. We elaborate on the ensuing challenges in defining quarkonium dissolution and present estimates of melting temperatures for the spin averaged χ{sub b} and χ{sub c} states. As an application to heavy-ion collisions we further estimate the contribution of feed down to S-wave quarkonium through the P-wave states after freezeout.

  13. The Elastin Receptor Complex: a unique matricellular receptor with high anti-tumoral potential

    Directory of Open Access Journals (Sweden)

    Amandine eScandolera

    2016-03-01

    Full Text Available Elastin, one of the longest-lived proteins, confers elasticity to tissues with high mechanical constraints. During aging or pathophysiological conditions such as cancer progression, this insoluble polymer of tropoelastin undergoes an important degradation leading to the release of bioactive elastin-derived peptides (EDP, named elastokines. EDP exhibit several biological functions able to drive tumor development by regulating cell proliferation, invasion, survival, angiogenesis, and matrix metalloproteinase expression in various tumor and stromal cells. Although several receptors have been suggested to bind elastokines (αvβ3 and αvβ5 integrins, galectin-3, their main receptor remains the Elastin Receptor Complex (ERC. This heterotrimer comprises a peripheral subunit, named Elastin Binding Protein (EBP, associated to the Protective Protein/Cathepsin A (PPCA. The latter is bound to a membrane-associated protein called Neuraminidase-1 (Neu-1. The pro-tumoral effects of elastokines have been linked to their binding onto EBP. Additionally, Neu-1 sialidase activity is essential for their signal transduction. Consistently, EDP-EBP interaction and Neu-1 activity emerge as original anti-tumoral targets. Interestingly, besides its direct involvement in cancer progression, the ERC also regulates diabetes outcome and thrombosis, an important risk factor for cancer development and a vascular process highly increased in patients suffering from cancer. In this review, we will describe ERC and elastokines involvement in cancer development suggesting that this unique receptor would be a promising therapeutic target. We will also discuss the pharmacological concepts aiming at blocking its pro-tumoral activities. Finally, its emerging role in cancer-associated complications and pathologies such as diabetes and thrombotic events will be also considered.

  14. On the complexity of the Saccharomyces bayanus taxon: hybridization and potential hybrid speciation.

    Directory of Open Access Journals (Sweden)

    Laura Pérez-Través

    Full Text Available Although the genus Saccharomyces has been thoroughly studied, some species in the genus has not yet been accurately resolved; an example is S. bayanus, a taxon that includes genetically diverse lineages of pure and hybrid strains. This diversity makes the assignation and classification of strains belonging to this species unclear and controversial. They have been subdivided by some authors into two varieties (bayanus and uvarum, which have been raised to the species level by others. In this work, we evaluate the complexity of 46 different strains included in the S. bayanus taxon by means of PCR-RFLP analysis and by sequencing of 34 gene regions and one mitochondrial gene. Using the sequence data, and based on the S. bayanus var. bayanus reference strain NBRC 1948, a hypothetical pure S. bayanus was reconstructed for these genes that showed alleles with similarity values lower than 97% with the S. bayanus var. uvarum strain CBS 7001, and of 99-100% with the non S. cerevisiae portion in S. pastorianus Weihenstephan 34/70 and with the new species S. eubayanus. Among the S. bayanus strains under study, different levels of homozygosity, hybridization and introgression were found; however, no pure S. bayanus var. bayanus strain was identified. These S. bayanus hybrids can be classified into two types: homozygous (type I and heterozygous hybrids (type II, indicating that they have been originated by different hybridization processes. Therefore, a putative evolutionary scenario involving two different hybridization events between a S. bayanus var. uvarum and unknown European S. eubayanus-like strains can be postulated to explain the genomic diversity observed in our S. bayanus var. bayanus strains.

  15. Potential Risk Factors for the Onset of Complex Regional Pain Syndrome Type 1: A Systematic Literature Review

    Directory of Open Access Journals (Sweden)

    Tracey Pons

    2015-01-01

    Full Text Available Anaesthetists in the acute and chronic pain teams are often involved in treating Complex Regional Pain Syndromes. Current literature about the risk factors for the onset of Complex Regional Pain Syndrome Type 1 (CRPS 1 remains sparse. This syndrome has a low prevalence, a highly variable presentation, and no gold standard for diagnosis. In the research setting, the pathogenesis of the syndrome continues to be elusive. There is a growing body of literature that addresses efficacy of a wide range of interventions as well as the likely mechanisms that contribute to the onset of CRPS 1. The objective for this systematic search of the literature focuses on determining the potential risk factors for the onset of CRPS 1. Eligible articles were analysed, dated 1996 to April 2014, and potential risk factors for the onset of CRPS 1 were identified from 10 prospective and 6 retrospective studies. Potential risk factors for the onset of CRPS 1 were found to include being female, particularly postmenopausal female, ankle dislocation or intra-articular fracture, immobilisation, and a report of higher than usual levels of pain in the early phases of trauma. It is not possible to draw definite conclusions as this evidence is heterogeneous and of mixed quality, relevance, and weighting strength against bias and has not been confirmed across multiple trials or in homogenous studies.

  16. Inclusion of the strong interaction in low-energy hydrogen-antihydrogen scattering using a complex potential

    International Nuclear Information System (INIS)

    Armour, E A G; Liu, Y; Vigier, A

    2005-01-01

    The aim of experimentalists currently working on the preparation of antihydrogen is to trap it at very low temperatures so that its properties can be studied. Any process that can lead to loss of antihydrogen is thus of great concern to them. In view of this, we have carried out a calculation of the antiproton annihilation cross section in very low-energy hydrogen-antihydrogen scattering using a complex potential to represent the strong interaction that brings about the annihilation. The potential takes into account the isotopic spin state of the proton and the antiproton and the possibility that they may be in either a singlet or a triplet spin state. The results for the annihilation cross section and the percentage change in the elastic cross section due to the inclusion of the strong interaction are similar to those obtained in a recent calculation (Jonsell et al 2004 J. Phys. B: At. Mol. Opt. Phys. 37 1195), using an effective range expansion. They are smaller by a factor of 2 and 3, respectively, than those obtained in an earlier calculation (Voronin and Carbonell 2001 Nucl. Phys. A 689 529c), using a coupled channel method and a complex strong interaction potential. (letter to the editor)

  17. A new look at auranofin, dextromethorphan and rosiglitazone for reduction of glia-mediated inflammation in neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Jocelyn M Madeira

    2015-01-01

    Full Text Available Neurodegenerative disorders including Alzheimer′s disease are characterized by chronic inflammation in the central nervous system. The two main glial types involved in inflammatory reactions are microglia and astrocytes. While these cells normally protect neurons by providing nutrients and growth factors, disease specific stimuli can induce glial secretion of neurotoxins. It has been hypothesized that reducing glia-mediated inflammation could diminish neuronal loss. This hypothesis is supported by observations that chronic use of non-steroidal anti-inflammatory drugs (NSAIDs is linked with lower incidences of neurodegenerative disease. It is possible that the NSAIDs are not potent enough to appreciably reduce chronic neuroinflammation after disease processes are fully established. Gold thiol compounds, including auranofin, comprise another class of medications effective at reducing peripheral inflammation. We have demonstrated that auranofin inhibits human microglia- and astrocyte-mediated neurotoxicity. Other drugs which are currently used to treat peripheral inflammatory conditions could be helpful in neurodegenerative disease. Three different classes of anti-inflammatory compounds, which have a potential to inhibit neuroinflammation are highlighted below.

  18. Use of Curcumin, a Natural Polyphenol for Targeting Molecular Pathways in Treating Age-Related Neurodegenerative Diseases

    Directory of Open Access Journals (Sweden)

    Panchanan Maiti

    2018-05-01

    Full Text Available Progressive accumulation of misfolded amyloid proteins in intracellular and extracellular spaces is one of the principal reasons for synaptic damage and impairment of neuronal communication in several neurodegenerative diseases. Effective treatments for these diseases are still lacking but remain the focus of much active investigation. Despite testing several synthesized compounds, small molecules, and drugs over the past few decades, very few of them can inhibit aggregation of amyloid proteins and lessen their neurotoxic effects. Recently, the natural polyphenol curcumin (Cur has been shown to be a promising anti-amyloid, anti-inflammatory and neuroprotective agent for several neurodegenerative diseases. Because of its pleotropic actions on the central nervous system, including preferential binding to amyloid proteins, Cur is being touted as a promising treatment for age-related brain diseases. Here, we focus on molecular targeting of Cur to reduce amyloid burden, rescue neuronal damage, and restore normal cognitive and sensory motor functions in different animal models of neurodegenerative diseases. We specifically highlight Cur as a potential treatment for Alzheimer’s, Parkinson’s, Huntington’s, and prion diseases. In addition, we discuss the major issues and limitations of using Cur for treating these diseases, along with ways of circumventing those shortcomings. Finally, we provide specific recommendations for optimal dosing with Cur for treating neurological diseases.

  19. Predicting the Dispersal Potential of an Invasive Polychaete Pest along a Complex Coastal Biome.

    Science.gov (United States)

    David, Andrew A; Matthee, Conrad A; Loveday, Benjamin R; Simon, Carol A

    2016-10-01

    Boccardia proboscidea is a recently introduced polychaete in South Africa where it is a notorious pest of commercially reared abalone. Populations were originally restricted to abalone farms but a recent exodus into the wild at some localities has raised conservation concerns due to the species' invasive status in other parts of the world. Here, we assessed the dispersal potential of B. proboscidea by using a population genetic and oceanographic modeling approach. Since the worm is in its incipient stages of a potential invasion, we used the closely related Polydora hoplura as a proxy due its similar reproductive strategy and its status as a pest of commercially reared oysters in the country. Populations of P. hoplura were sampled from seven different localities and a section of the mtDNA gene, Cyt b and the intron ATPSa was amplified. A high resolution model of the coastal waters around southern Africa was constructed using the Regional Ocean Modeling System. Larvae were represented by passive drifters that were deployed at specific points along the coast and dispersal was quantified after a 12-month integration period. Our results showed discordance between the genetic and modeling data. There was low genetic structure (Φ = 0.04 for both markers) and no geographic patterning of mtDNA and nDNA haplotypes. However, the dispersal model found limited connectivity around Cape Point-a major phylogeographic barrier on the southern African coast. This discordance was attributed to anthropogenic movement of larvae and adult worms due to vectors such as aquaculture and shipping. As such, we hypothesized that cryptic dispersal could be overestimating genetic connectivity. Though wild populations of B. proboscidea could become isolated due to the Cape Point barrier, anthropogenic movement may play the critical role in facilitating the dispersal and spread of this species on the southern African coast. © The Author 2016. Published by Oxford University Press on behalf of the

  20. Complex comprised of dextran magnetite and conjugated cisplatin exhibiting selective hyperthermic and controlled-release potential

    Directory of Open Access Journals (Sweden)

    Akinaga Sonoda

    2010-07-01

    Full Text Available Akinaga Sonoda1, Norihisa Nitta1, Ayumi Nitta-Seko1, Shinich Ohta1, Shigeyuki Takamatsu2, Yoshio Ikehata3, Isamu Nagano3, Jun-ichiro Jo4, Yasuhiko Tabata4, Masashi Takahashi1, Osamu Matsui3, Kiyoshi Murata11Department of Radiology, Shiga University of Medical Science, Setatsukinowa-cho, Otsu, Shiga, 520-2192, Japan; 2Department of Radiology, Graduate School of Medical Science, Kanazawa University, Takara-machi 13-1, Kanazawa Ishikawa, 920-8641, Japan; 3Department of Natural Science and Technology, Graduate School of Engineering, Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan; 4Department of Biomaterials, Institute for Frontier Medical Sciences, Kyoto University, Shogoin kawara-machi 53, Sakyo-ku 606-8507, Kyoto, JapanAbstract: We developed a dextran-magnetite conjugated cisplatin (DM-Cis complex for use in thermal ablation and as a chemotherapeutic drug. To produce DM-Cis we reacted Cis with 1 mL DM (56 mg/mL iron. The temperature rise of DM-Cis was measured in vitro and in vivo under a portable induction-heating (IH device. Platinum desorption from DM-Cis over 24 hours was measured in bovine serum. In in vivo accumulation and magnet and exothermic experiments we used four rat groups. In group 1 we delivered DM-Cis intraperitoneally (ip and placed magnets subcutaneously (sc. In group 2 we injected saline (ip and placed magnets (sc. In group 3 we injected DM-Cis (ip and placed a sc incision (sham. The control (group 4 received an ip injection of saline. Rectus abdominis muscle tissue was stained with hematoxylin-eosin and iron-stained tissue areas (µm2 were calculated. The maximum platinum concentration in DM-Cis was approximately 105.6 µg/mL. Over 24 hours, 33.48% of platinum from DM-Cis was released. There was a significant difference (P < 0.05 in the iron-stained area between group 1 and the other groups. The temperature in muscle tissue registered a maximum of 56°C after about 4 min. DM-Cis may represent a

  1. Conformational Explosion: Understanding the Complexity of the Para-Dialkylbenzene Potential Energy Surfaces

    Science.gov (United States)

    Mishra, Piyush; Hewett, Daniel M.; Zwier, Timothy S.

    2017-06-01

    This talk focuses on the single-conformation spectroscopy of small-chain para-dialkylbenzenes. This work builds on previous studies from our group on long-chain n-alkylbenzenes that identified the first folded structure in octylbenzene. The dialkylbenzenes are representative of a class of molecules that are common components of coal and aviation fuel and are known to be present in vehicle exhaust. We bring the molecules para-diethylbenzene, para-dipropylbenzene and para-dibutylbenzene into the gas phase and cool the molecules in a supersonic expansion. The jet-cooled molecules are then interrogated using laser-induced fluorescence excitation, fluorescence dip IR spectroscopy (FDIRS) and dispersed fluorescence. The LIF spectra in the S_{0}-S_{1} origin region show dramatic increases in the number of resolved transitions with increasing length of alkyl chains, reflecting an explosion in the number of unique low-energy conformations formed when two independent alkyl chains are present. Since the barriers to isomerization of the alkyl chain are similar in size, this results in an 'egg carton' shape to the potential energy surface. We use a combination of electronic frequency shift and alkyl CH stretch infrared spectra to generate a consistent set of conformational assignments.

  2. Complexity and conundrums. Citizens' evaluations of potentially contentious novel food technologies using a deliberative discourse approach.

    Science.gov (United States)

    Greehy, Gráinne M; McCarthy, Mary B; Henchion, Maeve M; Dillon, Emma J; McCarthy, Sinéad N

    2013-11-01

    This research considers the processes involved in the formation of attitudes by citizens on potentially contentious novel food technologies (NFTs). Observations of one-to-one deliberative discourses between food scientists and citizens, during which they discussed these technologies, form the basis of this enquiry. This approach enables an exploration of how individuals construct meaning around as well as interpret information about the technologies. Thematic analysis identifies key features that provide the frameworks for citizens' evaluations. How individuals make sense of these technologies is shaped by their beliefs, values and personal characteristics; their perceptions of power and control over the development and sale of NFT related products; and, the extent to which these products are relevant to their personal lives. Internal negotiations between these influences are evident, and evaluations are based on the relative importance of each influence to the individual. Internal conflicts and tensions are associated with citizens' evolving evaluative processes, which may in turn present as attitude ambivalence and instability. Many challenges are linked with engaging with the general public about these technologies, as levels of knowledge, understanding and interest vary. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. The synthesis, structure and reactivity of iron-bismuth complexes : Potential Molecular Precursors for Multiferroic BiFeO3

    OpenAIRE

    Wójcik, Katarzyna

    2009-01-01

    The thesis presented here is focused on the synthesis of iron-bismuth alkoxides and siloxides as precursors for multiferroic BiFeO3 systems. Spectrum of novel cyclopentadienyl substituted iron-bismuth complexes of the general type [{Cpy(CO)2Fe}BiX2], as potential precursors for cyclopentadienyl iron-bismuth alkoxides or siloxides [{Cpy(CO)2Fe}Bi(OR)2] (R-OtBu, OSiMe2tBu), were obtained and characterised. The use of wide range of cyclopentadienyl rings in the iron carbonyl compounds allowed fo...

  4. Conformational explosion: Understanding the complexity of short chain para-dialkylbenzene potential energy surfaces

    Science.gov (United States)

    Mishra, Piyush; Hewett, Daniel M.; Zwier, Timothy S.

    2018-05-01

    The single-conformation ultraviolet and infrared spectroscopy of three short-chain para-dialkylbenzenes (para-diethylbenzene, para-dipropylbenzene, and para-dibutylbenzene) is reported for the jet-cooled, isolated molecules. The present study builds off previous work on single-chain n-alkylbenzenes, where an anharmonic local mode Hamiltonian method was developed to account for stretch-bend Fermi resonance in the alkyl CH stretch region [D. P. Tabor et al., J. Chem. Phys. 144, 224310 (2016)]. The jet-cooled molecules are interrogated using laser-induced fluorescence (LIF) excitation, fluorescence dip infrared spectroscopy, and dispersed fluorescence. The LIF spectra in the S1 ← S0 origin region show a dramatic increase in the number of resolved transitions with increasing length of the alkyl chains, reflecting an explosion in the number of unique low-energy conformations formed when two independent alkyl chains are present. Since the barriers to isomerization of the alkyl chain are similar in size, this results in an "egg carton" shaped potential energy surface. A combination of electronic frequency shift and alkyl CH stretch infrared spectra is used to generate a consistent set of conformational assignments. Using these experimental techniques in conjunction with computational methods, subsets of origin transitions in the LIF excitation spectrum can be classified into different conformational families. Two conformations are resolved in para-diethylbenzene, seven in para-dipropylbenzene, and about nineteen in para-dibutylbenzene. These chains are largely independent of each other as there are no new single-chain conformations induced by the presence of a second chain. A cursory LIF excitation scan of para-dioctylbenzene shows a broad congested spectrum at frequencies consistent with interactions of alkyl chains with the phenyl π cloud.

  5. A potential neural substrate for processing functional classes of complex acoustic signals.

    Directory of Open Access Journals (Sweden)

    Isabelle George

    Full Text Available Categorization is essential to all cognitive processes, but identifying the neural substrates underlying categorization processes is a real challenge. Among animals that have been shown to be able of categorization, songbirds are particularly interesting because they provide researchers with clear examples of categories of acoustic signals allowing different levels of recognition, and they possess a system of specialized brain structures found only in birds that learn to sing: the song system. Moreover, an avian brain nucleus that is analogous to the mammalian secondary auditory cortex (the caudo-medial nidopallium, or NCM has recently emerged as a plausible site for sensory representation of birdsong, and appears as a well positioned brain region for categorization of songs. Hence, we tested responses in this non-primary, associative area to clear and distinct classes of songs with different functions and social values, and for a possible correspondence between these responses and the functional aspects of songs, in a highly social songbird species: the European starling. Our results clearly show differential neuronal responses to the ethologically defined classes of songs, both in the number of neurons responding, and in the response magnitude of these neurons. Most importantly, these differential responses corresponded to the functional classes of songs, with increasing activation from non-specific to species-specific and from species-specific to individual-specific sounds. These data therefore suggest a potential neural substrate for sorting natural communication signals into categories, and for individual vocal recognition of same-species members. Given the many parallels that exist between birdsong and speech, these results may contribute to a better understanding of the neural bases of speech.

  6. A model for predicting the potential diffusion of solar energy systems in complex urban environments

    International Nuclear Information System (INIS)

    La Gennusa, Maria; Lascari, Giovanni; Rizzo, Gianfranco; Scaccianoce, Gianluca; Sorrentino, Giancarlo

    2011-01-01

    The necessity to reduce greenhouse gases emission produced by energy building consumptions and to cut the energy bill (mainly due to the use of fossil sources) leads to the employment of renewable energy sources in new planned scenarios. In particular, more and more often municipal energy and environmental plans pay great attention to the possibilities of employment of the solar technologies at urban scale. Solar thermal and photovoltaic (PV) systems are, by far, the most suitable tools to be utilized in urban areas. Obviously, the proper adoption of such systems in buildings does call for the availability of calculation methods suitable to provide the actual level of exploitation of solar energy in urban layouts. In this work, a procedure for evaluating the geographical energy potential of building roofs in urban areas is proposed; in particular, the amount of surface on the roof that could be used for the installation of systems able to capture solar radiation for the energy production is investigated. The proposed procedure is based on the use of the GIS technology and 3D cartography. The effectiveness of the proposed method is assessed by means of an application to the town of Palermo (Italy). - Highlights: → The GIS techniques allow to analyze various future scenarios about urban planning. → We propose a procedure for assessing the extension of superficial urban areas useable for the installation of solar systems. → This procedure allow to compile a scale of priority of intervention. → The cost for financing such interventions is compared to the penalty to pay for not achieving the Kyoto goals.

  7. Defects in the COG complex and COG-related trafficking regulators affect neuronal Golgi function.

    Directory of Open Access Journals (Sweden)

    Leslie K Climer

    2015-10-01

    Full Text Available The Conserved Oligomeric Golgi (COG complex is an evolutionarily conserved hetero-octameric protein complex that has been proposed to organize vesicle tethering at the Golgi apparatus. Defects in seven of the eight COG subunits are linked to Congenital Disorders of Glycosylation (CDG-type II, a family of rare diseases involving misregulation of protein glycosylation, alterations in Golgi structure, variations in retrograde trafficking through the Golgi and system-wide clinical pathologies. A troublesome aspect of these diseases are the neurological pathologies such as low IQ, microcephaly and cerebellar atrophy. The essential function of the COG complex is dependent upon interactions with other components of trafficking machinery, such as Rab-GTPases and SNAREs. COG-interacting Rabs and SNAREs have been implicated in neurodegenerative diseases like Alzheimer’s disease and Parkinson’s disease. Defects in Golgi maintenance disrupts trafficking and processing of essential proteins, frequently associated with and contributing to compromised neuron function and human disease. Despite the recent advances in molecular neuroscience, the subcellular bases for most neurodegenerative diseases are poorly understood. This article gives an overview of the potential contributions of the COG complex and its Rab and SNARE partners in the pathogenesis of different neurodegenerative disorders.

  8. Complex mixtures of dissolved pesticides show potential aquatic toxicity in a synoptic study of Midwestern U.S. streams

    Science.gov (United States)

    Nowell, Lisa H.; Moran, Patrick W.; Schmidt, Travis S.; Norman, Julia E.; Nakagaki, Naomi; Shoda, Megan E.; Mahler, Barbara J.; Van Metre, Peter C.; Stone, Wesley W.; Sandstrom, Mark W.; Hladik, Michelle L.

    2018-01-01

    complex pesticide mixtures yet reported in discrete water samples in the U.S. and, using multiple lines of evidence, predicts that pesticides were potentially toxic to nontarget aquatic life in about half of the sampled streams.

  9. The Emerging Role of Proteomics in Precision Medicine: Applications in Neurodegenerative Diseases and Neurotrauma.

    Science.gov (United States)

    Alaaeddine, Rana; Fayad, Mira; Nehme, Eliana; Bahmad, Hisham F; Kobeissy, Firas

    2017-01-01

    neurodegenerative diseases and neurotrauma. However, other applications in proteomics such as "individual" proteome sequencing with its signature PTMs, have not been fully investigated as compared to the achievements in the genomics discipline This infers that proteomics research work has promising potential, yet to be discovered, in the precision medicine and comprises a major component of the personalized medicine infrastructure as it allows individual characterization of disease at the protein level. To conclude, the field of proteomics-based personalized medicine is still in its infancy compared to genomics field due to several technical and instrumentation-based obstacles; however, we anticipate to have this initiative leading in the coming future. This chapter will discuss briefly how neuroproteomics can impact personalized medicine in the fields of neurodegenerative disorders particularly in Alzheimer's disease and brain injury .

  10. Simulating storm surge inundation and damage potential within complex port facilities

    Science.gov (United States)

    Mawdsley, Robert; French, Jon; Fujiyama, Taku; Achutan, Kamalasudhan

    2017-04-01

    flood scenario to perform adaptive responses (e.g. pre-emptive relocation of equipment), as well as estimate the likely duration of any disruption to port and supply chain operation. High resolution numerical inundation modelling, coupled to accurate storm surge forecasting and an agent based port operation model, thus has the potential to significantly reduce damage and disruption costs associated with storm surge impacts on port infrastructure and systems.

  11. Potential Impact of Atmospheric Releases at Russian Far East Nuclear Submarine Complexes

    Energy Technology Data Exchange (ETDEWEB)

    Parker, F.; Mahura, A.; Compton, K.; Brown, K.; Takano, M.; Novikov, V.; Soerensen, J. H.; Baklanov, A.

    2003-02-25

    An ''Assessment of the Impact of Russian Nuclear Fleet Operations on Far Eastern Coastal Regions'' is being performed as part of the Radiation Safety of the Biosphere Project (RAD) of the International Institute for Applied Systems Analysis (IIASA) of Laxenburg, Austria. To the best of our knowledge, this is the first comprehensive unclassified analysis of the potential impact of accidents at the Russian Far East nuclear submarine sites near Vladivostok and Petropavlovsk. We have defined the situation there based upon available information and studies commissioned by RAD in collaboration with Russian research institutes including Russian Research Center-''Kurchatov Institute'', Institute of Northern Environmental Problems and Lazurit Central Design Bureau. Further, in our original work, some in collaboration with the staff of the Danish Meteorological Institute (DMI) and members of the Japan Atomic Energy Research Institute, we have calculated the nuclide trajectories from these sites in the atmospheric boundary layer, less than 1.5 kilometers high, and determined their probability of crossing any of the nearby countries as well as Asiatic Russia. We have further determined the concentrations in each of these crossings as well as the total, dry and wet depositions of nuclides on these areas. Finally, we have calculated the doses to the Japanese Island population from typical winter airflow patterns (those most likely to cross the Islands in the minimum times), strong north winds, weak north winds and cyclonic winds for conditions similar to the Chazhma Bay criticality accident (fresh fuel) and for a criticality accident for the same type of reactor with fuel being withdrawn (spent fuel). The maximum individual committed dosages were less than 2 x 10-7 and 2 x 10-3 mSv, respectively. The long-term external doses by radionuclides deposited on the ground and the internal doses by consumption of foods were not evaluated as it is

  12. Pre-attentive processing of spectrally complex sounds with asynchronous onsets: an event-related potential study with human subjects.

    Science.gov (United States)

    Tervaniemi, M; Schröger, E; Näätänen, R

    1997-05-23

    Neuronal mechanisms involved in the processing of complex sounds with asynchronous onsets were studied in reading subjects. The sound onset asynchrony (SOA) between the leading partial and the remaining complex tone was varied between 0 and 360 ms. Infrequently occurring deviant sounds (in which one out of 10 harmonics was different in pitch relative to the frequently occurring standard sound) elicited the mismatch negativity (MMN), a change-specific cortical event-related potential (ERP) component. This indicates that the pitch of standard stimuli had been pre-attentively coded by sensory-memory traces. Moreover, when the complex-tone onset fell within temporal integration window initiated by the leading-partial onset, the deviants elicited the N2b component. This indexes that involuntary attention switch towards the sound change occurred. In summary, the present results support the existence of pre-perceptual integration mechanism of 100-200 ms duration and emphasize its importance in switching attention towards the stimulus change.

  13. Theoretical investigation of potential energy surface and bound states for the van der Waals complex Ar–BrCl dimer

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Rui [School of Mathematics and Information Science, North China University of Water Resources and Electric Power, Zhengzhou (China); Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Centre for Magnetic Resonance, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan (China); Li, Song, E-mail: lsong@yangtzeu.edu.cn [School of Physics and Optoelectronic Engineering, Yangtze University, Jingzhou (China); Chen, Shan-Jun; Chen, Yan [School of Physics and Optoelectronic Engineering, Yangtze University, Jingzhou (China); Zheng, Li-Min [Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Centre for Magnetic Resonance, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan (China)

    2015-09-08

    Highlights: • A two-dimensional potential for Ar–BrCl is constructed at the CCSD(T) level. • The PES is characterized by three minima and two saddle points between them. • Bound state calculations were carried out for the complex. - Abstract: The intermolecular potential energy surface (PES) of the ground electronic state for the Ar–BrCl dimer is constructed at the CCSD(T) level with the aug-cc-pVQZ basis set and mid-bond functions. The PES is characterized by three minima and two saddle points. The global minimum corresponding to a collinear Ar–BrCl configuration, which has been observed experimentally, is located at R = 4.10 Å and θ = 2.5° with a well depth of −285.207 cm{sup −1}. A nearly T-shaped structure and an anti-linear Ar–ClBr geometry is also predicted. The bound state calculations are preformed to study intermolecular vibrational modes, rotational levels and average structures for the complex. Our transition frequencies, spectroscopic constants and average structures for all isotopomers of the collinear isomer agree well with experimental data. We have also provided pure rotational transitional frequencies for both nearly T-shaped and anti-linear isomers. These results are significant for further experimental investigations of the Ar–BrCl dimer.

  14. Chirality of weakly bound complexes: The potential energy surfaces for the hydrogen-peroxide−noble-gas interactions

    Energy Technology Data Exchange (ETDEWEB)

    Roncaratti, L. F., E-mail: lz@fis.unb.br; Leal, L. A.; Silva, G. M. de [Instituto de Física, Universidade de Brasília, 70910 Brasília (Brazil); Pirani, F. [Dipartimento di Chimica, Biologia e Biotecnologie, Università di Perugia, 06123 Perugia (Italy); Aquilanti, V. [Dipartimento di Chimica, Biologia e Biotecnologie, Università di Perugia, 06123 Perugia (Italy); Instituto de Física, Universidade Federal da Bahia, 40210 Salvador (Brazil); Gargano, R. [Instituto de Física, Universidade de Brasília, 70910 Brasília (Brazil); Departments of Chemistry and Physics, University of Florida, Quantum Theory Project, Gainesville, Florida 32611 (United States)

    2014-10-07

    We consider the analytical representation of the potential energy surfaces of relevance for the intermolecular dynamics of weakly bound complexes of chiral molecules. In this paper we study the H{sub 2}O{sub 2}−Ng (Ng=He, Ne, Ar, Kr, and Xe) systems providing the radial and the angular dependence of the potential energy surface on the relative position of the Ng atom. We accomplish this by introducing an analytical representation which is able to fit the ab initio energies of these complexes in a wide range of geometries. Our analysis sheds light on the role that the enantiomeric forms and the symmetry of the H{sub 2}O{sub 2} molecule play on the resulting barriers and equilibrium geometries. The proposed theoretical framework is useful to study the dynamics of the H{sub 2}O{sub 2} molecule, or other systems involving O–O and S–S bonds, interacting by non-covalent forces with atoms or molecules and to understand how the relative orientation of the O–H bonds changes along collisional events that may lead to a hydrogen bond formation or even to selectivity in chemical reactions.

  15. Gadolinium heteropoly complex K 17[Gd(P 2W 17O 61) 2] as a potential MRI contrast agent

    Science.gov (United States)

    Sun, Guoying; Feng, Jianghua; Wu, Huifeng; Pei, Fengkui; Fang, Ke; Lei, Hao

    2004-10-01

    Gadolinium heteropoly complex K17[Gd(P2W17O61)2] has been evaluated by in vitro and in vivo experiments as a potential contrast agent for magnetic resonance imaging (MRI). The thermal analysis and conductivity study indicate that this complex has good thermal stability and wide pH stability range. The T1 relaxivity is 7.59 mM-1 s-1 in aqueous solution and 7.97 mM-1 s-1 in 0.725 mmol l-1 bovine serum albumin (BSA) solution at 25 °C and 9.39 T, respectively. MR imaging of three male Sprague-Dawley rats showed remarkable enhancement in rat liver after intravenous injection, which persisted longer than with Gd-DTPA. The signal intensity increased by 57.1±16.9% during the whole imaging period at 0.082 mmol kg-1dose. Our preliminary in vitro and in vivo studies indicate that K17[Gd(P2W17O61)2] is a potential liver-specific MRI contrast agent.

  16. Characterizing a neurodegenerative syndrome: primary progressive apraxia of speech.

    Science.gov (United States)

    Josephs, Keith A; Duffy, Joseph R; Strand, Edythe A; Machulda, Mary M; Senjem, Matthew L; Master, Ankit V; Lowe, Val J; Jack, Clifford R; Whitwell, Jennifer L

    2012-05-01

    Apraxia of speech is a disorder of speech motor planning and/or programming that is distinguishable from aphasia and dysarthria. It most commonly results from vascular insults but can occur in degenerative diseases where it has typically been subsumed under aphasia, or it occurs in the context of more widespread neurodegeneration. The aim of this study was to determine whether apraxia of speech can present as an isolated sign of neurodegenerative disease. Between July 2010 and July 2011, 37 subjects with a neurodegenerative speech and language disorder were prospectively recruited and underwent detailed speech and language, neurological, neuropsychological and neuroimaging testing. The neuroimaging battery included 3.0 tesla volumetric head magnetic resonance imaging, [(18)F]-fluorodeoxyglucose and [(11)C] Pittsburg compound B positron emission tomography scanning. Twelve subjects were identified as having apraxia of speech without any signs of aphasia based on a comprehensive battery of language tests; hence, none met criteria for primary progressive aphasia. These subjects with primary progressive apraxia of speech included eight females and four males, with a mean age of onset of 73 years (range: 49-82). There were no specific additional shared patterns of neurological or neuropsychological impairment in the subjects with primary progressive apraxia of speech, but there was individual variability. Some subjects, for example, had mild features of behavioural change, executive dysfunction, limb apraxia or Parkinsonism. Voxel-based morphometry of grey matter revealed focal atrophy of superior lateral premotor cortex and supplementary motor area. Voxel-based morphometry of white matter showed volume loss in these same regions but with extension of loss involving the inferior premotor cortex and body of the corpus callosum. These same areas of white matter loss were observed with diffusion tensor imaging analysis, which also demonstrated reduced fractional anisotropy

  17. Getting an Insight into the Complexity of Major Chronic Inflammatory and Degenerative Diseases: A Potential New Systemic Approach to Their Treatment.

    Science.gov (United States)

    Biava, Pier M; Norbiato, Guido

    2015-01-01

    As the modern society is troubled by multi-factorial diseases, research has been conducted on complex realities including chronic inflammation, cancer, obesity, HIV infection, metabolic syndrome and its detrimental cardiovascular complications as well as depression and other brain disorders. Deterioration of crucial homeostatic mechanisms in such diseases invariably results in activation of inflammatory mediators, chronic inflammation, loss in immunological function, increased susceptibility to diseases, alteration of metabolism, decrease of energy production and neuro-cognitive decline. Regulation of genes expression by epigenetic code is the dominant mechanism for the transduction of environmental inputs, such as stress and inflammation to lasting physiological changes. Acute and chronic stress determines DNA methylation and histone modifications in brain regions which may contribute to neuro-degenerative disorders. Nuclear glucocorticoids receptor interacts with the epigenoma resulting in a cortisol resistance status associated with a deterioration of the metabolic and immune functions. Gonadal steroids receptors have a similar capacity to produce epigenomic reorganization of chromatine structure. Epigenomic-induced reduction in immune cells telomeres length has been observed in many degenerative diseases, including all types of cancer. The final result of these epigenetic alterations is a serious damage to the neuro-endocrine-immune-metabolic adaptive systems. In this study, we propose a treatment with stem cells differentiation stage factors taken from zebrafish embryos which are able to regulate the genes expression of normal and pathological stem cells in a different specific way.

  18. Possible Role of the Transglutaminases in the Pathogenesis of Alzheimer's Disease and Other Neurodegenerative Diseases

    OpenAIRE

    Martin, Antonio; De Vivo, Giulia; Gentile, Vittorio

    2011-01-01

    Transglutaminases are ubiquitous enzymes which catalyze posttranslational modifications of proteins. Recently, transglutaminase-catalyzed post-translational modification of proteins has been shown to be involved in the molecular mechanisms responsible for human diseases. Transglutaminase activity has been hypothesized to be involved also in the pathogenetic mechanisms responsible for several human neurodegenerative diseases. Alzheimer's disease and other neurodegenerative diseases, such as Pa...

  19. Generation of tooth-periodontium complex structures using high-odontogenic potential dental epithelium derived from mouse embryonic stem cells.

    Science.gov (United States)

    Zhang, Yancong; Li, Yongliang; Shi, Ruirui; Zhang, Siqi; Liu, Hao; Zheng, Yunfei; Li, Yan; Cai, Jinglei; Pei, Duanqing; Wei, Shicheng

    2017-06-08

    A number of studies have shown that tooth-like structures can be regenerated using induced pluripotent stem cells and mouse embryonic stem (mES) cells. However, few studies have reported the regeneration of tooth-periodontium complex structures, which are more suitable for clinical tooth transplantation. We established an optimized approach to induce high-odontogenic potential dental epithelium derived from mES cells by temporally controlling bone morphogenic protein 4 (BMP4) function and regenerated tooth-periodontium complex structures in vivo. First, immunofluorescence and quantitative reverse transcription-polymerase chain reaction were used to identify the watershed of skin and the oral ectoderm. LDN193189 was then used to inhibit the BMP4 receptor around the watershed, followed by the addition of exogenous BMP4 to promote BMP4 function. The generated dental epithelium was confirmed by western blot analysis and immunofluorescence. The generated epithelium was ultimately combined with embryonic day 14.5 mouse mesenchyme and transplanted into the renal capsules of nude mice. After 4 weeks, the tooth-periodontium complex structure was examined by micro-computed tomography (CT) and hematoxylin and eosin (H&E) staining. Our study found that the turning point of oral ectoderm differentiation occurred around day 3 after the embryoid body was transferred to a common culture plate. Ameloblastin-positive dental epithelial cells were detected following the temporal regulation of BMP4. Tooth-periodontium complex structures, which included teeth, a periodontal membrane, and alveolar bone, were formed when this epithelium was combined with mouse dental mesenchyme and transplanted into the renal capsules of nude mice. Micro-CT and H&E staining revealed that the generated tooth-periodontium complex structures shared a similar histological structure with normal mouse teeth. An optimized induction method was established to promote the differentiation of mES cells into dental

  20. Peroxiredoxin distribution in the mouse brain with emphasis on neuronal populations affected in neurodegenerative disorders.

    Science.gov (United States)

    Goemaere, Julie; Knoops, Bernard

    2012-02-01

    Redox changes are observed in neurodegenerative diseases, ranging from increased levels of reactive oxygen/nitrogen species and disturbance of antioxidant systems, to nitro-oxidative damage. By reducing hydrogen peroxide, peroxynitrite, and organic hydroperoxides, peroxiredoxins (Prdxs) represent a major potential protective barrier against nitro-oxidative insults in the brain. While recent works have investigated the putative role of Prdxs in neurodegenerative disorders, less is known about their expression in the healthy brain. Here we used immunohistochemistry to map basal expression of Prdxs throughout C57BL/6 mouse brain. We first confirmed the neuronal localization of Prdx2-5 and the glial expression of Prdx1, Prdx4, and Prdx6. Then we performed an in-depth analysis of neuronal Prdx distribution in the brain. Our results show that Prdx2-5 are widely detected in the different neuronal populations, and especially well expressed in the olfactory bulb, in the cerebral cortex, in pons nuclei, in the red nucleus, in all cranial nerve nuclei, in the cerebellum, and in motor neurons of the spinal cord. In contrast, Prdx expression is very low in the dopaminergic neurons of substantia nigra pars compacta and in the CA1/2 pyramidal cells of hippocampus. This low basal expression may contribute to the vulnerability of these neurons to nitro-oxidative attacks occurring in Parkinson's disease and Alzheimer's disease. In addition, we found that Prdx expression levels are unevenly distributed among neurons of a determined region and that distinct regional patterns of expression are observed between isoforms, reinforcing the hypothesis of the nonredundant function of Prdxs. Copyright © 2011 Wiley-Liss, Inc.

  1. TNF signaling inhibition in the CNS: implications for normal brain function and neurodegenerative disease

    Directory of Open Access Journals (Sweden)

    Tansey Malú G

    2008-10-01

    Full Text Available Abstract The role of tumor necrosis factor (TNF as an immune mediator has long been appreciated but its function in the brain is still unclear. TNF receptor 1 (TNFR1 is expressed in most cell types, and can be activated by binding of either soluble TNF (solTNF or transmembrane TNF (tmTNF, with a preference for solTNF; whereas TNFR2 is expressed primarily by microglia and endothelial cells and is preferentially activated by tmTNF. Elevation of solTNF is a hallmark of acute and chronic neuroinflammation as well as a number of neurodegenerative conditions including ischemic stroke, Alzheimer's (AD, Parkinson's (PD, amyotrophic lateral sclerosis (ALS, and multiple sclerosis (MS. The presence of this potent inflammatory factor at sites of injury implicates it as a mediator of neuronal damage and disease pathogenesis, making TNF an attractive target for therapeutic development to treat acute and chronic neurodegenerative conditions. However, new and old observations from animal models and clinical trials reviewed here suggest solTNF and tmTNF exert different functions under normal and pathological conditions in the CNS. A potential role for TNF in synaptic scaling and hippocampal neurogenesis demonstrated by recent studies suggest additional in-depth mechanistic studies are warranted to delineate the distinct functions of the two TNF ligands in different parts of the brain prior to large-scale development of anti-TNF therapies in the CNS. If inactivation of TNF-dependent inflammation in the brain is warranted by additional pre-clinical studies, selective targeting of TNFR1-mediated signaling while sparing TNFR2 activation may lessen adverse effects of anti-TNF therapies in the CNS.

  2. Bodily Sensory Inputs and Anomalous Bodily Experiences in Complex Regional Pain Syndrome: Evaluation of the Potential Effects of Sound Feedback

    Directory of Open Access Journals (Sweden)

    Ana Tajadura-Jiménez

    2017-07-01

    Full Text Available Neuroscientific studies have shown that human's mental body representations are not fixed but are constantly updated through sensory feedback, including sound feedback. This suggests potential new therapeutic sensory approaches for patients experiencing body-perception disturbances (BPD. BPD can occur in association with chronic pain, for example in Complex Regional Pain Syndrome (CRPS. BPD often impacts on emotional, social, and motor functioning. Here we present the results from a proof-of-principle pilot study investigating the potential value of using sound feedback for altering BPD and its related emotional state and motor behavior in those with CRPS. We build on previous findings that real-time alteration of the sounds produced by walking can alter healthy people's perception of their own body size, while also resulting in more active gait patterns and a more positive emotional state. In the present study we quantified the emotional state, BPD, pain levels and gait of twelve people with CRPS Type 1, who were exposed to real-time alteration of their walking sounds. Results confirm previous reports of the complexity of the BPD linked to CRPS, as participants could be classified into four BPD subgroups according to how they mentally visualize their body. Further, results suggest that sound feedback may affect the perceived size of the CRPS affected limb and the pain experienced, but that the effects may differ according to the type of BPD. Sound feedback affected CRPS descriptors and other bodily feelings and emotions including feelings of emotional dominance, limb detachment, position awareness, attention and negative feelings toward the limb. Gait also varied with sound feedback, affecting the foot contact time with the ground in a way consistent with experienced changes in body weight. Although, findings from this small pilot study should be interpreted with caution, they suggest potential applications for regenerating BDP and its related

  3. Bodily Sensory Inputs and Anomalous Bodily Experiences in Complex Regional Pain Syndrome: Evaluation of the Potential Effects of Sound Feedback

    Science.gov (United States)

    Tajadura-Jiménez, Ana; Cohen, Helen; Bianchi-Berthouze, Nadia

    2017-01-01

    Neuroscientific studies have shown that human's mental body representations are not fixed but are constantly updated through sensory feedback, including sound feedback. This suggests potential new therapeutic sensory approaches for patients experiencing body-perception disturbances (BPD). BPD can occur in association with chronic pain, for example in Complex Regional Pain Syndrome (CRPS). BPD often impacts on emotional, social, and motor functioning. Here we present the results from a proof-of-principle pilot study investigating the potential value of using sound feedback for altering BPD and its related emotional state and motor behavior in those with CRPS. We build on previous findings that real-time alteration of the sounds produced by walking can alter healthy people's perception of their own body size, while also resulting in more active gait patterns and a more positive emotional state. In the present study we quantified the emotional state, BPD, pain levels and gait of twelve people with CRPS Type 1, who were exposed to real-time alteration of their walking sounds. Results confirm previous reports of the complexity of the BPD linked to CRPS, as participants could be classified into four BPD subgroups according to how they mentally visualize their body. Further, results suggest that sound feedback may affect the perceived size of the CRPS affected limb and the pain experienced, but that the effects may differ according to the type of BPD. Sound feedback affected CRPS descriptors and other bodily feelings and emotions including feelings of emotional dominance, limb detachment, position awareness, attention and negative feelings toward the limb. Gait also varied with sound feedback, affecting the foot contact time with the ground in a way consistent with experienced changes in body weight. Although, findings from this small pilot study should be interpreted with caution, they suggest potential applications for regenerating BDP and its related bodily feelings in

  4. Recommendations for the Design of Serious Games in Neurodegenerative Diseases.

    Science.gov (United States)

    Ben-Sadoun, Grégory; Manera, Valeria; Alvarez, Julian; Sacco, Guillaume; Robert, Philippe

    2018-01-01

    The use of Serious Games (SG) in the health domain is expanding. In the field of Neurodegenerative Diseases (ND) such as Alzheimer's Disease, SG are currently employed to provide alternative solutions for patients' treatment, stimulation, and rehabilitation. The design of SG for people with ND implies collaborations between professionals in ND and professionals in SG design. As the field is quite young, professionals specialized in both ND and SG are still rare, and recommendations for the design of SG for people with ND are still missing. This perspective paper aims to provide recommendations in terms of ergonomic choices for the design of SG aiming at stimulating people with ND, starting from the existing SG already tested in this population: "MINWii", "Kitchen and Cooking", and "X-Torp". We propose to rely on nine ergonomic criteria: eight ergonomic criteria inspired by works in the domain of office automation: Compatibility, Guidance, Workload, Adaptability, Consistency, Significance of codes, Explicit control and Error management; and one ergonomic criterion related to videogame: the game rules. Perspectives derived from this proposal are also discussed.

  5. Improving drug delivery technology for treating neurodegenerative diseases.

    Science.gov (United States)

    Choonara, Yahya E; Kumar, Pradeep; Modi, Girish; Pillay, Viness

    2016-07-01

    Neurodegenerative diseases (NDs) represent intricate challenges for efficient uptake and transport of drugs to the brain mainly due to the restrictive blood-brain barrier (BBB). NDs are characterized by the loss of neuronal subtypes as sporadic and/or familial and several mechanisms of neurodegeneration have been identified. This review attempts to recap, organize and concisely evaluate the advanced drug delivery systems designed for treating common NDs. It highlights key research gaps and opinionates on new neurotherapies to overcome the BBB as an addition to the current treatments of countering oxidative stress, inflammation and apoptotic mechanisms. Current treatments do not fully address the biological, drug and therapeutic factors faced. This has led to the development of vogue treatments such as nose-to-brain technologies, bio-engineered systems, fusion protein chaperones, stem cells, gene therapy, use of natural compounds, neuroprotectants and even vaccines. However, failure of these treatments is mainly due to the BBB and non-specific delivery in the brain. In order to increase neuroavailability various advanced drug delivery systems provide promising alternatives that are able to augment the treatment of Alzheimer's disease and Parkinson's disease. However, much work is still required in this field beyond the preclinical testing phase.

  6. Molecular origin of polyglutamine aggregation in neurodegenerative diseases.

    Directory of Open Access Journals (Sweden)

    2005-08-01

    Full Text Available Expansion of polyglutamine (polyQ tracts in proteins results in protein aggregation and is associated with cell death in at least nine neurodegenerative diseases. Disease age of onset is correlated with the polyQ insert length above a critical value of 35-40 glutamines. The aggregation kinetics of isolated polyQ peptides in vitro also shows a similar critical-length dependence. While recent experimental work has provided considerable insights into polyQ aggregation, the molecular mechanism of aggregation is not well understood. Here, using computer simulations of isolated polyQ peptides, we show that a mechanism of aggregation is the conformational transition in a single polyQ peptide chain from random coil to a parallel beta-helix. This transition occurs selectively in peptides longer than 37 glutamines. In the beta-helices observed in simulations, all residues adopt beta-strand backbone dihedral angles, and the polypeptide chain coils around a central helical axis with 18.5 +/- 2 residues per turn. We also find that mutant polyQ peptides with proline-glycine inserts show formation of antiparallel beta-hairpins in their ground state, in agreement with experiments. The lower stability of mutant beta-helices explains their lower aggregation rates compared to wild type. Our results provide a molecular mechanism for polyQ-mediated aggregation.

  7. Recommendations for the Design of Serious Games in Neurodegenerative Diseases

    Directory of Open Access Journals (Sweden)

    Grégory Ben-Sadoun

    2018-02-01

    Full Text Available The use of Serious Games (SG in the health domain is expanding. In the field of Neurodegenerative Diseases (ND such as Alzheimer’s Disease, SG are currently employed to provide alternative solutions for patients’ treatment, stimulation, and rehabilitation. The design of SG for people with ND implies collaborations between professionals in ND and professionals in SG design. As the field is quite young, professionals specialized in both ND and SG are still rare, and recommendations for the design of SG for people with ND are still missing. This perspective paper aims to provide recommendations in terms of ergonomic choices for the design of SG aiming at stimulating people with ND, starting from the existing SG already tested in this population: “MINWii”, “Kitchen and Cooking”, and “X-Torp”. We propose to rely on nine ergonomic criteria: eight ergonomic criteria inspired by works in the domain of office automation: Compatibility, Guidance, Workload, Adaptability, Consistency, Significance of codes, Explicit control and Error management; and one ergonomic criterion related to videogame: the game rules. Perspectives derived from this proposal are also discussed.

  8. PENN neurodegenerative disease research - in the spirit of Benjamin Franklin.

    Science.gov (United States)

    Trojanowski, John Q

    2008-01-01

    Benjamin Franklin (1706-1790) was entrepreneur, statesman, supporter of the public good as well as inventor, and his most significant invention was the University of Pennsylvania (PENN). Franklin outlined his plans for a college providing practical and classical instruction to prepare youth for real-world pursuits in his 'Proposals Relating to the Education of Youth in Pensilvania' (1749), and Franklin's spirit of learning to serve society guides PENN to the present day. This is evidenced by the series of articles in this special issue of Neurosignals, describing research conducted by seasoned and newly recruited PENN faculty, addressing consequences of the longevity revolution which defines our epoch at the dawn of this millennium. While aging affects all organ systems, the nervous system is most critical to successful aging. Thus, the articles in this special issue of Neurosignals focus on research at PENN that is designed to prevent or ameliorate aging-related neurodegenerative disorders such as Alzheimer's and Parkinson's disease, amyotrophic lateral sclerosis and frontotemporal dementia. This research could enhance our chances of aging successfully in the continuing longevity revolution, and the essay here provides context and background on this research.

  9. The emerging role of 5-hydroxymethylcytosine in neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Sahar eAl-Mahdawi

    2014-12-01

    Full Text Available DNA methylation primarily occurs within human cells as a 5-methylcytosine (5mC modification of the cytosine bases in CpG dinucleotides. 5mC has proven to be an important epigenetic mark that is involved in the control of gene transcription for processes such as development and differentiation. However, recent studies have identified an alternative modification, 5-hydroxymethylcytosine (5hmC, which is formed by oxidation of 5mC by ten-eleven translocation (TET enzymes. The overall levels of 5hmC in the mammalian genome are approximately 10% of 5mC levels, although higher levels have been detected in tissues of the central nervous system (CNS. The functions of 5hmC are not yet fully known, but evidence suggests that 5hmC may be both an intermediate product during the removal of 5mC by passive or active demethylation processes and also an epigenetic modification in its own right, regulating chromatin or transcriptional factors involved in processes such as neurodevelopment or environmental stress response. This review highlights our current understanding of the role that 5hmC plays in neurodegenerative diseases, including Alzheimer’s disease (AD, amyotrophic lateral sclerosis (ALS, fragile X-associated tremor/ataxia syndrome (FXTAS, Friedreich ataxia (FRDA, Huntington’s disease (HD, and Parkinson’s disease (PD.

  10. A practical approach to temperature effects in dissociative electron attachment cross sections using local complex potential theory

    International Nuclear Information System (INIS)

    Sugioka, Yuji; Takayanagi, Toshiyuki

    2012-01-01

    Highlights: ► Dissociative electron attachment cross sections for polyatomic molecules are calculated by a simple theoretical approach. ► Temperature effects can be reasonably reproduced with the present model. ► All the degrees-of-freedom are taken into account in the present dynamics approach. -- Abstract: We propose a practical computational scheme to obtain temperature dependence of dissociative electron attachment cross sections to polyatomic molecules within a local complex potential theory formalism. First we perform quantum path-integral molecular dynamics simulations on the potential energy surface for the neutral molecule in order to sample initial nuclear configurations as well as momenta. Classical trajectories are subsequently integrated on the potential energy surface for the anionic state and survival probabilities are simultaneously calculated along the obtained trajectories. We have applied this simple scheme to dissociative electron attachment processes to H 2 O and CF 3 Cl, for which several previous studies are available from both the experimental and theoretical sides.

  11. Endocrine-Disrupting Chemicals and Oil and Natural Gas Operations: Potential Environmental Contamination and Recommendations to Assess Complex Environmental Mixtures.

    Science.gov (United States)

    Kassotis, Christopher D; Tillitt, Donald E; Lin, Chung-Ho; McElroy, Jane A; Nagel, Susan C

    2016-03-01

    Hydraulic fracturing technologies, developed over the last 65 years, have only recently been combined with horizontal drilling to unlock oil and gas reserves previously deemed inaccessible. Although these technologies have dramatically increased domestic oil and natural gas production, they have also raised concerns for the potential contamination of local water supplies with the approximately 1,000 chemicals that are used throughout the process, including many known or suspected endocrine-disrupting chemicals. We discuss the need for an endocrine component to health assessments for drilling-dense regions in the context of hormonal and antihormonal activities for chemicals used. We discuss the literature on a) surface and groundwater contamination by oil and gas extraction operations, and b) potential human exposure, particularly in the context of the total hormonal and antihormonal activities present in surface and groundwater from natural and anthropogenic sources; we also discuss initial analytical results and critical knowledge gaps. In light of the potential for environmental release of oil and gas chemicals that can disrupt hormone receptor systems, we recommend methods for assessing complex hormonally active environmental mixtures. We describe a need for an endocrine-centric component for overall health assessments and provide information supporting the idea that using such a component will help explain reported adverse health trends as well as help develop recommendations for environmental impact assessments and monitoring programs.

  12. Evidence for the complex relationship between free amino acid and sugar concentrations and acrylamide-forming potential in potato

    Science.gov (United States)

    Muttucumaru, N; Powers, SJ; Elmore, JS; Briddon, A; Mottram, DS; Halford, NG

    2014-01-01

    Free amino acids and reducing sugars participate in the Maillard reaction during high-temperature cooking and processing. This results not only in the formation of colour, aroma and flavour compounds, but also undesirable contaminants, including acrylamide, which forms when the amino acid that participates in the reaction is asparagine. In this study, tubers of 13 varieties of potato (Solanum tuberosum), which had been produced in a field trial in 2010 and sampled immediately after harvest or after storage for 6 months, were analysed to show the relationship between the concentrations of free asparagine, other free amino acids, sugars and acrylamide-forming potential. The varieties comprised five that are normally used for crisping, seven that are used for French fry production and one that is used for boiling. Acrylamide formation was measured in heated flour, and correlated with glucose and fructose concentration. In French fry varieties, which contain higher concentrations of sugars, acrylamide formation also correlated with free asparagine concentration, demonstrating the complex relationship between precursor concentration and acrylamide-forming potential in potato. Storage of the potatoes for 6 months at 9°C had a significant, variety-dependent impact on sugar and amino acid concentrations and acrylamide-forming potential. PMID:25540460

  13. A practical approach to temperature effects in dissociative electron attachment cross sections using local complex potential theory

    Energy Technology Data Exchange (ETDEWEB)

    Sugioka, Yuji [Department of Chemistry, Saitama University, 255 Shimo-Okubo, Sakura-ku, Saitama City, Saitama 338-8570 (Japan); Takayanagi, Toshiyuki, E-mail: tako@mail.saitama-u.ac.jp [Department of Chemistry, Saitama University, 255 Shimo-Okubo, Sakura-ku, Saitama City, Saitama 338-8570 (Japan)

    2012-09-11

    Highlights: Black-Right-Pointing-Pointer Dissociative electron attachment cross sections for polyatomic molecules are calculated by a simple theoretical approach. Black-Right-Pointing-Pointer Temperature effects can be reasonably reproduced with the present model. Black-Right-Pointing-Pointer All the degrees-of-freedom are taken into account in the present dynamics approach. -- Abstract: We propose a practical computational scheme to obtain temperature dependence of dissociative electron attachment cross sections to polyatomic molecules within a local complex potential theory formalism. First we perform quantum path-integral molecular dynamics simulations on the potential energy surface for the neutral molecule in order to sample initial nuclear configurations as well as momenta. Classical trajectories are subsequently integrated on the potential energy surface for the anionic state and survival probabilities are simultaneously calculated along the obtained trajectories. We have applied this simple scheme to dissociative electron attachment processes to H{sub 2}O and CF{sub 3}Cl, for which several previous studies are available from both the experimental and theoretical sides.

  14. Dietary Tocotrienol/γ-Cyclodextrin Complex Increases Mitochondrial Membrane Potential and ATP Concentrations in the Brains of Aged Mice

    Directory of Open Access Journals (Sweden)

    Anke Schloesser

    2015-01-01

    Full Text Available Brain aging is accompanied by a decrease in mitochondrial function. In vitro studies suggest that tocotrienols, including γ- and δ-tocotrienol (T3, may exhibit neuroprotective properties. However, little is known about the effect of dietary T3 on mitochondrial function in vivo. In this study, we monitored the effect of a dietary T3/γ-cyclodextrin complex (T3CD on mitochondrial membrane potential and ATP levels in the brain of 21-month-old mice. Mice were fed either a control diet or a diet enriched with T3CD providing 100 mg T3 per kg diet for 6 months. Dietary T3CD significantly increased mitochondrial membrane potential and ATP levels compared to those of controls. The increase in MMP and ATP due to dietary T3CD was accompanied by an increase in the protein levels of the mitochondrial transcription factor A (TFAM. Furthermore, dietary T3CD slightly increased the mRNA levels of superoxide dismutase, γ-glutamyl cysteinyl synthetase, and heme oxygenase 1 in the brain. Overall, the present data suggest that T3CD increases TFAM, mitochondrial membrane potential, and ATP synthesis in the brains of aged mice.

  15. Endocrine-disrupting chemicals and oil and natural gas operations: Potential environmental contamination and recommendations to assess complex environmental mixtures

    Science.gov (United States)

    Kassotis, Christopher D.; Tillitt, Donald E.; Lin, Chung-Ho; McElroy, Jane A.; Nagel, Susan C.

    2016-01-01

    Background: Hydraulic fracturing technologies, developed over the last 65 years, have only recently been combined with horizontal drilling to unlock oil and gas reserves previously deemed inaccessible. While these technologies have dramatically increased domestic oil and natural gas production, they have also raised concerns for the potential contamination of local water supplies with the approximately 1,000 chemicals used throughout the process, including many known or suspected endocrine-disrupting chemicals.Objectives: We discuss the need for an endocrine component to health assessments for drilling-dense regions in the context of hormonal and anti-hormonal activities for chemicals used.Methods: We discuss the literature on 1) surface and ground water contamination by oil and gas extraction operations, and 2) potential human exposure, particularly in context of the total hormonal and anti-hormonal activities present in surface and ground water from natural and anthropogenic sources, with initial analytical results and critical knowledge gaps discussed.Discussion: In light of the potential for environmental release of oil and gas chemicals that can disrupt hormone receptor systems, we recommend methods for assessing complex hormonally active environmental mixtures.Conclusions: We describe a need for an endocrine-centric component for overall health assessments and provide supporting information that using this may help explain reported adverse health trends as well as help develop recommendations for environmental impact assessments and monitoring programs.

  16. Dynamics of interaction between complement-fixing antibody/dsDNA immune complexes and erythrocytes. In vitro studies and potential general applications to clinical immune complex testing

    International Nuclear Information System (INIS)

    Taylor, R.P.; Horgan, C.; Hooper, M.; Burge, J.

    1985-01-01

    Soluble antibody/ 3 H-double-stranded PM2 DNA (dsDNA) immune complexes were briefly opsonized with complement and then allowed to bind to human erythrocytes (via complement receptors). The cells were washed and subsequently a volume of autologous blood in a variety of media was added, and the release of the bound immune complexes from the erythrocytes was studied as a function of temperature and time. After 1-2 h, the majority of the bound immune complexes were not released into the serum during blood clotting at either 37 degrees C or room temperature, but there was a considerably greater release of the immune complexes into the plasma of blood that was anticoagulated with EDTA. Similar results were obtained using various conditions of opsonization and also using complexes that contained lower molecular weight dsDNA. Thus, the kinetics of release of these antibody/dsDNA immune complexes differed substantially from the kinetics of release of antibody/bovine serum albumin complexes that was reported by others. Studies using the solution phase C1q immune complex binding assay confirmed that in approximately half of the SLE samples that were positive for immune complexes, there was a significantly higher level of detectable immune complexes in plasma vs. serum. Freshly drawn erythrocytes from some SLE patients exhibiting this plasma/serum discrepancy had IgG antigen on their surface that was released by incubation in EDTA plasma. Thus, the higher levels of immune complexes observed in EDTA plasma vs. serum using the C1q assay may often reflect the existence of immune complexes circulating in vivo bound to erythrocytes

  17. Identification of Potential Plants Producing Tannin-protein Complex for a-amylase as Botanical Pesticide

    Directory of Open Access Journals (Sweden)

    Asriyah Firdausi

    2013-05-01

    Full Text Available Research  on  the  development  of  botanical  pesticides  should  be developed  through  new  methods,  such  as  by  inhibiting the  activity  of  digestive enzymes  by  secondary  metabolites.  The  aim  of  this  study  was  to  identify some  of  potential  plants  as  a  source  of  tannin-protein  complexes  to  inhibitthe  activity  of  - amylase.  The  study  of  identification  of  potential  plants producing  the  active  ingredient  tannin-protein  complex  was  divided  into  three stages,  1  identification  of  potential  plants  producing  tannin,  2  isolation  of tannin-protein  complexes,  and  3  in  vitro  test  of  tannin-protein  complexes effect  of  the  -amylase activity.  Some  of  the observed  plants  were  sidaguri  leaf (Sida rhombifolia, melinjo leaf (Gnetum gnemon, gamal leaf (Gliricidia sepium,lamtoro  leaf  (Leucaena  leucocephala ,  betel  nut  (Areca  catechu ,  and  crude gambier  (Uncaria  gambir a s  a  source of  tannins  and  melinjo  seed was  used  asprotein  source.  Betel  nut  and  melinjo  seed  were  the  best  source  of  tannin-protein  complex,  tannin  content  1.77  mg  TAE/mL  with  antioxidant  activity  of  90%,the  ability  to  inhibit  the  activity  of  -amylase by  95%  with  IC 50  values  of 10 mg/mL.Key words: Tannin, protein, -amylase, botanical pesticides,Areca catechu, Gnetum gnemon.

  18. Regional molecular and cellular differences in the female rabbit Achilles tendon complex: potential implications for understanding responses to loading.

    Science.gov (United States)

    Huisman, Elise S; Andersson, Gustav; Scott, Alexander; Reno, Carol R; Hart, David A; Thornton, Gail M

    2014-05-01

    The aim of this study was: (i) to analyze the morphology and expression of extracellular matrix genes in six different regions of the Achilles tendon complex of intact normal rabbits; and (ii) to assess the effect of ovariohysterectomy (OVH) on the regional expression of these genes. Female New Zealand White rabbits were separated into two groups: (i) intact normal rabbits (n = 4); and (ii) OVH rabbits (n = 8). For each rabbit, the Achilles tendon complex was dissected into six regions: distal gastrocnemius (DG); distal flexor digitorum superficialis; proximal lateral gastrocnemius (PLG); proximal medial gastrocnemius; proximal flexor digitorum superficialis; and paratenon. For each of the regions, hematoxylin and eosin staining was performed for histological evaluation of intact normal rabbit tissues and mRNA levels for proteoglycans, collagens and genes associated with collagen regulation were assessed by real-time reverse transcription-quantitative polymerase chain reaction for both the intact normal and OVH rabbit tissues. The distal regions displayed a more fibrocartilaginous phenotype. For intact normal rabbits, aggrecan mRNA expression was higher in the distal regions of the Achilles tendon complex compared with the proximal regions. Collagen Type I and matrix metalloproteinase-2 expression levels were increased in the PLG compared to the DG in the intact normal rabbit tissues. The tendons from OVH rabbits had lower gene expressions for the proteoglycans aggrecan, biglycan, decorin and versican compared with the intact normal rabbits, although the regional differences of increased aggrecan expression in distal regions compared with proximal regions persisted. The tensile and compressive forces experienced in the examined regions may be related to the regional differences found in gene expression. The lower mRNA expression of the genes examined in the OVH group confirms a potential effect of systemic estrogen on tendon. © 2014 Anatomical Society.

  19. Metal complexes of alkyl-aryl dithiocarbamates: Structural studies, anticancer potentials and applications as precursors for semiconductor nanocrystals

    Science.gov (United States)

    Andrew, Fartisincha P.; Ajibade, Peter A.

    2018-03-01

    Dithiocarbamates are versatile ligands able to stabilize wide range of metal ions in their various oxidation states with the partial double bond character of Csbnd N and Csbnd S of thioureide moiety. Variation of the substituents attached to the nitrogen atom of dithiocarbamate moiety generates various intermolecular interactions, which lead to different structural arrangement in the solid state. The presence of bulky substituents on the N atom obviates the supramolecular aggregation via secondary Msbnd S interactions whereas smaller substituents encourage such aggregation that results in their wide properties and applications. Over the past decades, the synthesis and structural studies of metal complexes of dithiocarbamates have received considerable attention as potential anticancer agents with various degree of DNA binding affinity and cytotoxicity and as single molecule precursors for the preparation of semiconductor nanocrystals. In this paper, we review the synthesis, structural studies, anticancer potency and the use of alkyl-phenyl dithiocarbamate complexes as precursors for the preparation of semiconductor nanocrystals. The properties of these compounds and activities are ascribed to be due to either the dithiocarbamate moieties, the nature or type of the substituents around the dithiocarbamate backbone and the central metal ions or combination of these factors.

  20. Potential energy surface of the CO{sub 2}–N{sub 2} van der Waals complex

    Energy Technology Data Exchange (ETDEWEB)

    Nasri, Sameh; Ajili, Yosra [Laboratoire de Spectroscopie Atomique, Moléculaire et Applications-LSAMA, Université de Tunis El Manar, Tunis (Tunisia); Université Paris-Est, Laboratoire Modélisation et Simulation Multi Echelle, MSME UMR 8208 CNRS, 5 bd Descartes, 77454 Marne-la-Vallée (France); Jaidane, Nejm-Eddine [Laboratoire de Spectroscopie Atomique, Moléculaire et Applications-LSAMA, Université de Tunis El Manar, Tunis (Tunisia); Kalugina, Yulia N. [Department of Optics and Spectroscopy, Tomsk State University, 36 Lenin Ave., Tomsk 634050 (Russian Federation); Halvick, Philippe; Stoecklin, Thierry [Institut des Sciences Moléculaires, Université de Bordeaux, CNRS UMR 5255, 33405 Talence Cedex (France); Hochlaf, Majdi, E-mail: hochlaf@univ-mlv.fr [Université Paris-Est, Laboratoire Modélisation et Simulation Multi Echelle, MSME UMR 8208 CNRS, 5 bd Descartes, 77454 Marne-la-Vallée (France)

    2015-05-07

    Four-dimensional potential energy surface (4D-PES) of the atmospherically relevant CO{sub 2}–N{sub 2} van der Waals complex is generated using the explicitly correlated coupled cluster with single, double, and perturbative triple excitation (CCSD(T)-F12) method in conjunction with the augmented correlation consistent triple zeta (aug-cc-pVTZ) basis set. This 4D-PES is mapped along the intermonomer coordinates. An analytic fit of this 4D-PES is performed. Our extensive computations confirm that the most stable form corresponds to a T-shape structure where the nitrogen molecule points towards the carbon atom of CO{sub 2}. In addition, we located a second isomer and two transition states in the ground state PES of CO{sub 2}–N{sub 2}. All of them lay below the CO{sub 2} + N{sub 2} dissociation limit. This 4D-PES is flat and strongly anisotropic along the intermonomer coordinates. This results in the possibility of the occurrence of large amplitude motions within the complex, such as the inversion of N{sub 2}, as suggested in the recent spectroscopic experiments. Finally, we show that the experimentally established deviations from the C{sub 2v} structure at equilibrium for the most stable isomer are due to the zero-point out-of-plane vibration correction.

  1. Social Cognition Dysfunctions in Neurodegenerative Diseases: Neuroanatomical Correlates and Clinical Implications

    Science.gov (United States)

    Santamaría-García, Hernando; Santangelo, Gabriella

    2018-01-01

    Social cognitive function, involved in the perception, processing, and interpretation of social information, has been shown to be crucial for successful communication and interpersonal relationships, thereby significantly impacting mental health, well-being, and quality of life. In this regard, assessment of social cognition, mainly focusing on four key domains, such as theory of mind (ToM), emotional empathy, and social perception and behavior, has been increasingly evaluated in clinical settings, given the potential implications of impairments of these skills for therapeutic decision-making. With regard to neurodegenerative diseases (NDs), most disorders, characterized by variable disease phenotypes and progression, although similar for the unfavorable prognosis, are associated to impairments of social cognitive function, with consequent negative effects on patients' management. Specifically, in some NDs these deficits may represent core diagnostic criteria, such as for behavioral variant frontotemporal dementia (bvFTD), or may emerge during the disease course as critical aspects, such as for Parkinson's and Alzheimer's diseases. On this background, we aimed to revise the most updated evidence on the neurobiological hypotheses derived from network-based approaches, clinical manifestations, and assessment tools of social cognitive dysfunctions in NDs, also prospecting potential benefits on patients' well-being, quality of life, and outcome derived from potential therapeutic perspectives of these deficits. PMID:29854017

  2. Social Cognition Dysfunctions in Neurodegenerative Diseases: Neuroanatomical Correlates and Clinical Implications

    Directory of Open Access Journals (Sweden)

    Foteini Christidi

    2018-01-01

    Full Text Available Social cognitive function, involved in the perception, processing, and interpretation of social information, has been shown to be crucial for successful communication and interpersonal relationships, thereby significantly impacting mental health, well-being, and quality of life. In this regard, assessment of social cognition, mainly focusing on four key domains, such as theory of mind (ToM, emotional empathy, and social perception and behavior, has been increasingly evaluated in clinical settings, given the potential implications of impairments of these skills for therapeutic decision-making. With regard to neurodegenerative diseases (NDs, most disorders, characterized by variable disease phenotypes and progression, although similar for the unfavorable prognosis, are associated to impairments of social cognitive function, with consequent negative effects on patients’ management. Specifically, in some NDs these deficits may represent core diagnostic criteria, such as for behavioral variant frontotemporal dementia (bvFTD, or may emerge during the disease course as critical aspects, such as for Parkinson’s and Alzheimer’s diseases. On this background, we aimed to revise the most updated evidence on the neurobiological hypotheses derived from network-based approaches, clinical manifestations, and assessment tools of social cognitive dysfunctions in NDs, also prospecting potential benefits on patients’ well-being, quality of life, and outcome derived from potential therapeutic perspectives of these deficits.

  3. Estimation of redox potentials of Fe(III)- gallic acid complexes at different pH by spectrophotometric titration with ascorbate

    International Nuclear Information System (INIS)

    Iqbal, M.; Tasneem, Z.; Kazmi, S.A.

    1993-01-01

    Fe(III) is strongly chelated by Gallic acid. This equilibrium as well as the kinetics of reduction of the complex is strongly pH dependent. The complex was prepared in acetate buffers of pH 4.6, 5.0 and 5.6 and in Tris buffer of pH 7.0.The complex was reduced by ascorbate. The reduced absorbance was taken to be a measure of reaction. Nernst equation was then applied to determine the standard redox potentials of the complex taking the literature values of the redox potentials of ascorbate at different pH. The values of redox potentials of complex were found to be 0.197 V at pH 4.6. 0.181 V at pH 5.0 1.132 V at pH 5.6 and 0.092 V at pH 7.0. (author)

  4. Potential responses to climate change in organisms with complex life histories: evolution and plasticity in Pacific salmon.

    Science.gov (United States)

    Crozier, L G; Hendry, A P; Lawson, P W; Quinn, T P; Mantua, N J; Battin, J; Shaw, R G; Huey, R B

    2008-05-01

    Salmon life histories are finely tuned to local environmental conditions, which are intimately linked to climate. We summarize the likely impacts of climate change on the physical environment of salmon in the Pacific Northwest and discuss the potential evolutionary consequences of these changes, with particular reference to Columbia River Basin spring/summer Chinook (Oncorhynchus tshawytscha) and sockeye (Oncorhynchus nerka) salmon. We discuss the possible evolutionary responses in migration and spawning date egg and juvenile growth and development rates, thermal tolerance, and disease resistance. We know little about ocean migration pathways, so cannot confidently suggest the potential changes in this life stage. Climate change might produce conflicting selection pressures in different life stages, which will interact with plastic (i.e. nongenetic) changes in various ways. To clarify these interactions, we present a conceptual model of how changing environmental conditions shift phenotypic optima and, through plastic responses, phenotype distributions, affecting the force of selection. Our predictions are tentative because we lack data on the strength of selection, heritability, and ecological and genetic linkages among many of the traits discussed here. Despite the challenges involved in experimental manipulation of species with complex life histories, such research is essential for full appreciation of the biological effects of climate change.

  5. The energy levels and oscillator strength of a complex atom--Au50+ in a self-consistent potential

    International Nuclear Information System (INIS)

    Feng Rong; Zou Yu; Fang Quanyu

    1998-01-01

    The effects of free electrons in a plasma on a complex atom are discussed, here the authors are interested in the target ion--Au 50+ in inertia confined fusion (ICF). The results are compared with those in the case of hydrogenic ions. Accurate numerical solutions have been obtained for Schroedinger's equation through Debye screened Hartree-Fock-Slater self-consistent potential. Solutions have been computed for 28 eigenstates, 1s through n =3D 7, l =3D 6, yielding the energy eigenvalues for a wide range of Debye screening length Λ. As in the case of hydrogenic ions, under screening, all energy levels are shifted away from their unscreened values toward the continuum, that is, the ionization limits are shifted downward. Conclusions have been made that when Λ>5a 0 , that is, in the weak screening cases, Debye screening has little effect on oscillator strength, average orbital radius, transition matrix elements, etc., of Au 50+ . For each (n,l) eigenstate, there is a finite value of screening length Λ 0 (n,l), for which the energy becomes zero. When Λ is sufficiently small, level crossing appears at high n states. Optical oscillator strength for Au 50+ has also been calculated, the results are compared with those under unscreened potential

  6. Complex Kohn variational principle for two-nucleon bound-state and scattering with the tensor potential

    International Nuclear Information System (INIS)

    Araujo Junior, C.F. de; Adhikari, S.K.; Tomio, L.

    1993-10-01

    Complex Kohn variational principle is applied to the numerical solution of the fully off-shell Lippmann-Schwinger equation for nucleon-nucleon scattering for various partial waves including the coupled 3 S 1 - 3 D 1 channel. Analytic expressions are obtained for all the integrals in the method for a suitable choice of expansion functions. Calculations with the partial waves 1 S 0 , 1 P 1 , 1 D 2 , and 3 S 1 - 3 D 1 of the Reid soft core potential show that the method converges faster than other solution schemes not only for the phase shift but also for the off-shell t matrix elements. It is also shown that its is trivial to modify this variational principle in order to make it suitable for bound-stage calculations. The bound-state approach is illustrated for the 3 S 1 - 3 D 1 channel of the Reid soft-core potential for calculating the deuteron binding, wave function and the D state asymptotic parameters. (author)

  7. Cost-Effective Method for Free-Energy Minimization in Complex Systems with Elaborated Ab Initio Potentials.

    Science.gov (United States)

    Bistafa, Carlos; Kitamura, Yukichi; Martins-Costa, Marilia T C; Nagaoka, Masataka; Ruiz-López, Manuel F

    2018-05-22

    We describe a method to locate stationary points in the free-energy hypersurface of complex molecular systems using high-level correlated ab initio potentials. In this work, we assume a combined QM/MM description of the system although generalization to full ab initio potentials or other theoretical schemes is straightforward. The free-energy gradient (FEG) is obtained as the mean force acting on relevant nuclei using a dual level strategy. First, a statistical simulation is carried out using an appropriate, low-level quantum mechanical force-field. Free-energy perturbation (FEP) theory is then used to obtain the free-energy derivatives for the target, high-level quantum mechanical force-field. We show that this composite FEG-FEP approach is able to reproduce the results of a standard free-energy minimization procedure with high accuracy, while simultaneously allowing for a drastic reduction of both computational and wall-clock time. The method has been applied to study the structure of the water molecule in liquid water at the QCISD/aug-cc-pVTZ level of theory, using the sampling from QM/MM molecular dynamics simulations at the B3LYP/6-311+G(d,p) level. The obtained values for the geometrical parameters and for the dipole moment of the water molecule are within the experimental error, and they also display an excellent agreement when compared to other theoretical estimations. The developed methodology represents therefore an important step toward the accurate determination of the mechanism, kinetics, and thermodynamic properties of processes in solution, in enzymes, and in other disordered chemical systems using state-of-the-art ab initio potentials.

  8. An overview of the molecular mechanisms and novel roles of Nrf2 in neurodegenerative disorders.

    Science.gov (United States)

    Yang, Yang; Jiang, Shuai; Yan, Juanjuan; Li, Yue; Xin, Zhenlong; Lin, Yan; Qu, Yan

    2015-02-01

    Recently, growing evidence has demonstrated that nuclear factor erythroid 2-related factor 2 (Nrf2) is a pivotal regulator of endogenous defense systems that function via the activation of a set of protective genes, and this is particularly clear in the central nervous system (CNS). Therefore, it is highly useful to summarize the current literature on the molecular mechanisms and role of Nrf2 in the CNS. In this review, we first briefly introduce the molecular features of Nrf2. We then discuss the regulation, cerebral actions, upstream modulators and downstream targets of Nrf2 pathway. Following this background, we expand our discussion to the role of Nrf2 in several major neurodegenerative disorders (NDDs) such as Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis and amyotrophic lateral sclerosis. Lastly, we discuss some potential future directions. The information reviewed here may be significant in the design of further experimental research and increase the potential of Nrf2 as a therapeutic target in the future. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. SVM Based Descriptor Selection and Classification of Neurodegenerative Disease Drugs for Pharmacological Modeling.

    Science.gov (United States)

    Shahid, Mohammad; Shahzad Cheema, Muhammad; Klenner, Alexander; Younesi, Erfan; Hofmann-Apitius, Martin

    2013-03-01

    Systems pharmacological modeling of drug mode of action for the next generation of multitarget drugs may open new routes for drug design and discovery. Computational methods are widely used in this context amongst which support vector machines (SVM) have proven successful in addressing the challenge of classifying drugs with similar features. We have applied a variety of such SVM-based approaches, namely SVM-based recursive feature elimination (SVM-RFE). We use the approach to predict the pharmacological properties of drugs widely used against complex neurodegenerative disorders (NDD) and to build an in-silico computational model for the binary classification of NDD drugs from other drugs. Application of an SVM-RFE model to a set of drugs successfully classified NDD drugs from non-NDD drugs and resulted in overall accuracy of ∼80 % with 10 fold cross validation using 40 top ranked molecular descriptors selected out of total 314 descriptors. Moreover, SVM-RFE method outperformed linear discriminant analysis (LDA) based feature selection and classification. The model reduced the multidimensional descriptors space of drugs dramatically and predicted NDD drugs with high accuracy, while avoiding over fitting. Based on these results, NDD-specific focused libraries of drug-like compounds can be designed and existing NDD-specific drugs can be characterized by a well-characterized set of molecular descriptors. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Regulation of motor proteins, axonal transport deficits and adult-onset neurodegenerative diseases.

    Science.gov (United States)

    Brady, Scott T; Morfini, Gerardo A

    2017-09-01

    Neurons affected in a wide variety of unrelated adult-onset neurodegenerative diseases (AONDs) typically exhibit a "dying back" pattern of degeneration, which is characterized by early deficits in synaptic function and neuritic pathology long before neuronal cell death. Consistent with this observation, multiple unrelated AONDs including Alzheimer's disease, Parkinson's disease, Huntington's disease, and several motor neuron diseases feature early alterations in kinase-based signaling pathways associated with deficits in axonal transport (AT), a complex cellular process involving multiple intracellular trafficking events powered by microtubule-based motor proteins. These pathogenic events have important therapeutic implications, suggesting that a focus on preservation of neuronal connections may be more effective to treat AONDs than addressing neuronal cell death. While the molecular mechanisms underlying AT abnormalities in AONDs are still being analyzed, evidence has accumulated linking those to a well-established pathological hallmark of multiple AONDs: altered patterns of neuronal protein phosphorylation. Here, we present a short overview on the biochemical heterogeneity of major motor proteins for AT, their regulation by protein kinases, and evidence revealing cell type-specific AT specializations. When considered together, these findings may help explain how independent pathogenic pathways can affect AT differentially in the context of each AOND. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Gaussian processes with optimal kernel construction for neuro-degenerative clinical onset prediction

    Science.gov (United States)

    Canas, Liane S.; Yvernault, Benjamin; Cash, David M.; Molteni, Erika; Veale, Tom; Benzinger, Tammie; Ourselin, Sébastien; Mead, Simon; Modat, Marc

    2018-02-01

    Gaussian Processes (GP) are a powerful tool to capture the complex time-variations of a dataset. In the context of medical imaging analysis, they allow a robust modelling even in case of highly uncertain or incomplete datasets. Predictions from GP are dependent of the covariance kernel function selected to explain the data variance. To overcome this limitation, we propose a framework to identify the optimal covariance kernel function to model the data.The optimal kernel is defined as a composition of base kernel functions used to identify correlation patterns between data points. Our approach includes a modified version of the Compositional Kernel Learning (CKL) algorithm, in which we score the kernel families using a new energy function that depends both the Bayesian Information Criterion (BIC) and the explained variance score. We applied the proposed framework to model the progression of neurodegenerative diseases over time, in particular the progression of autosomal dominantly-inherited Alzheimer's disease, and use it to predict the time to clinical onset of subjects carrying genetic mutation.

  12. The Role of Co-chaperones in Synaptic Proteostasis and Neurodegenerative Disease

    Directory of Open Access Journals (Sweden)

    Erica L. Gorenberg

    2017-05-01

    Full Text Available Synapses must be preserved throughout an organism's lifespan to allow for normal brain function and behavior. Synapse maintenance is challenging given the long distances between the termini and the cell body, reliance on axonal transport for delivery of newly synthesized presynaptic proteins, and high rates of synaptic vesicle exo- and endocytosis. Hence, synapses rely on efficient proteostasis mechanisms to preserve their structure and function. To this end, the synaptic compartment has specific chaperones to support its functions. Without proper synaptic chaperone activity, local proteostasis imbalances lead to neurotransmission deficits, dismantling of synapses, and neurodegeneration. In this review, we address the roles of four synaptic chaperones in the maintenance of the nerve terminal, as well as their genetic links to neurodegenerative disease. Three of these are Hsp40 co-chaperones (DNAJs: Cysteine String Protein alpha (CSPα; DNAJC5, auxilin (DNAJC6, and Receptor-Mediated Endocytosis 8 (RME-8; DNAJC13. These co-chaperones contain a conserved J domain through which they form a complex with heat shock cognate 70 (Hsc70, enhancing the chaperone's ATPase activity. CSPα is a synaptic vesicle protein known to chaperone the t-SNARE SNAP-25 and the endocytic GTPase dynamin-1, thereby regulating synaptic vesicle exocytosis and endocytosis. Auxilin binds assembled clathrin cages, and through its interactions with Hsc70 leads to the uncoating of clathrin-coated vesicles, a process necessary for the regeneration of synaptic vesicles. RME-8 is a co-chaperone on endosomes and may have a role in clathrin-coated vesicle endocytosis on this organelle. These three co-chaperones maintain client function by preserving folding and assembly to prevent client aggregation, but they do not break down aggregates that have already formed. The fourth synaptic chaperone we will discuss is Heat shock protein 110 (Hsp110, which interacts with Hsc70, DNAJAs, and

  13. Differential diagnosis of neurodegenerative dementias with nuclear medicine methods

    International Nuclear Information System (INIS)

    Kluge, R.

    2015-01-01

    Full text: Neurodegenerative dementias (NDD) are characterized by insidious onset and gradual progression of cognitive dysfunction, initially relatively focal with respect to cognitive domains and brain regions involved. Nuclear medicine techniques help to clarify differential diagnoses of syndromes such as Alzheimer’s disease (AD), dementia with Lewy bodies (DlB), posterior cortical atrophy (PCA), logopenic primary progressive aphasia (PPA), agrammatic PPA, semantic dementia (SD), behavioral variant frontotemporal dementia (bvFTD) and progressive supranuclear palsy syndrome (PSPS). The process of pathologic changes in the brain may start decades before first clinical symptoms become evident. An early diagnosis already in the pre-clinical phase of the diseases will be of immense importance when expected effective therapeutic options have been introduced. NDDs are histopathologically characterized by accumulation of pathological proteins in the brain like beta amyloid or protein tau. While radiotracers for labeling of protein tau are in preclinical evaluation, different radiotracers labeling amyloid plaques ([11C]PIB, [18F]Florbetapir (Amyvid, Fa. EliLilly), [18F]Florbetaben (Neuraceq, Fa. Piramal), [18F]Flutemetamol (vVzamyl, Fa. Ge) have already been established in clinical use during the last years. In AD these tracers are intensively accumulated in the whole cortical brain. Even an early disease can be excluded in case of a negative amyloid PET. The method is, however, not highly specific since amyloid plaques may also be present in DlB (70 – 80%), FTD (30%) orlogopenicPPA (100%). Neuronal dysfunction goes along with decreased glucose consumption. Different diseases are characterized by different topographical zones of reduced [18F]FDG uptake. In AD the posterior cingular, temporopariatal and (later) frontal cortex are affected, in DlB the pattern is similar, including the occipital cortex, in FTD the frontal cortex is affected, in nonfluent PPA the

  14. Association between environmental exposure to pesticides and neurodegenerative diseases

    Energy Technology Data Exchange (ETDEWEB)

    Parron, Tesifon [University of Almeria, Department of Neurosciences and Health Sciences, Almeria (Spain); Andalusian Council of Health at Almeria province, Almeria (Spain); Requena, Mar [Andalusian Council of Health at Almeria province, Almeria (Spain); Hernandez, Antonio F., E-mail: ajerez@ugr.es [University of Granada School of Medicine, Granada (Spain); Alarcon, Raquel [Andalusian Council of Health at Almeria province, Almeria (Spain)

    2011-11-15

    Preliminary studies have shown associations between chronic pesticide exposure in occupational settings and neurological disorders. However, data on the effects of long-term non-occupational exposures are too sparse to allow any conclusions. This study examines the influence of environmental pesticide exposure on a number of neuropsychiatric conditions and discusses their underlying pathologic mechanisms. An ecological study was conducted using averaged prevalence rates of Alzheimer's disease, Parkinson's disease, multiple sclerosis, cerebral degeneration, polyneuropathies, affective psychosis and suicide attempts in selected Andalusian health districts categorized into areas of high and low environmental pesticide exposure based on the number of hectares devoted to intensive agriculture and pesticide sales per capita. A total of 17,429 cases were collected from computerized hospital records (minimum dataset) between 1998 and 2005. Prevalence rates and the risk of having Alzheimer's disease, Parkinson's disease, multiple sclerosis and suicide were significantly higher in districts with greater pesticide use as compared to those with lower pesticide use. The multivariate analyses showed that the population living in areas with high pesticide use had an increased risk for Alzheimer's disease and suicide attempts and that males living in these areas had increased risks for polyneuropathies, affective disorders and suicide attempts. In conclusion, this study supports and extends previous findings and provides an indication that environmental exposure to pesticides may affect the human health by increasing the incidence of certain neurological disorders at the level of the general population. -- Highlights: Black-Right-Pointing-Pointer Environmental exposure to pesticides and neurodegenerative-psychiatric disorders. Black-Right-Pointing-Pointer Increased risk for Alzheimer's disease and suicide attempts in high exposure areas. Black

  15. The potential global market size and public health value of an HIV-1 vaccine in a complex global market.

    Science.gov (United States)

    Marzetta, Carol A; Lee, Stephen S; Wrobel, Sandra J; Singh, Kanwarjit J; Russell, Nina; Esparza, José

    2010-07-05

    An effective HIV vaccine will be essential for the control of the HIV pandemic. This study evaluated the potential global market size and value of a hypothetical HIV vaccine and considered clade diversity, disease burden, partial prevention of acquisition, impact of a reduction in viral load resulting in a decrease in transmission and delay to treatment, health care system differences regarding access, and HIV screening and vaccination, across all public and private markets. Vaccine product profiles varied from a vaccine that would have no effect on preventing infection to a vaccine that would effectively prevent infection and reduce viral load. High disease burden countries (HDBC; HIV prevalence > or = 1%) were assumed to routinely vaccinate pre-sexually active adolescents (10 years old), whereas low disease burden countries (LDBC; HIV prevalence rate market value of $210 million to $2.7 billion, depending on the vaccine product profile. If one-time catch-up campaigns were included (11-14 years old for HDBC and higher risk groups for LDBC), the additional cumulative approximately 70-237 million doses were needed over a 10-year period with a potential market value of approximately $695 million to $13.4 billion, depending on the vaccine product profile. Market size and value varied across market segments with the majority of the value in high income countries and the majority of the demand in low income countries. However, the value of the potential market in low income countries is still significant with up to $550 million annually for routine vaccination only and up to $1.7 billion for a one-time only catch-up campaign in 11-14 years old. In the most detail to date, this study evaluated market size and value of a potential multi-clade HIV vaccine, accounting for differences in disease burden, product profile and health care complexities. These findings provide donors and suppliers highly credible new data to consider in their continued efforts to develop an HIV-1

  16. Autoimmune Aspects of Neurodegenerative and Psychiatric Diseases : A Template for Innovative Therapy

    NARCIS (Netherlands)

    de Haan, Peter; Klein, Hans C; 't Hart, Bert A

    2017-01-01

    Neurodegenerative and psychiatric diseases (NPDs) are today's most important group of diseases, surpassing both atherosclerotic cardiovascular disease and cancer in morbidity incidence. Although NPDs have a dramatic impact on our society because of their high incidence, mortality, and severe

  17. The role of DNA methylation and histone modifications in neurodegenerative diseases: A systematic review

    NARCIS (Netherlands)

    K.-X. Wen (Ke-Xin); J. Milic (Jelena); El-Khodor, B. (Bassem); K. Dhana (Klodian); J. Nano (Jana); Pulido, T. (Tammy); B. Kraja (Bledar); A. Zaciragic (Asija); W.M. Bramer (Wichor); J. Troup; R. Chowdhury (Rajiv); Arfam Ikram, M.; A. Dehghan (Abbas); T. Muka (Taulant); O.H. Franco (Oscar)

    2016-01-01

    textabstractImportance Epigenetic modifications of the genome, such as DNA methylation and histone modifications, have been reported to play a role in neurodegenerative diseases (ND) such as Alzheimer's disease (AD) and Parkinson's disease (PD). Objective To systematically review studies

  18. Cannabinoids and value-based decision making: Implications for neurodegenerative disorders

    NARCIS (Netherlands)

    Lee, AM; Oleson, E.B.; Diergaarde, L.; Cheer, J.F.; Pattij, T.

    2012-01-01

    In recent years, disturbances in cognitive function have been increasingly recognized as important symptomatic phenomena in neurodegenerative diseases, including Parkinson's disease (PD). Value-based decision making in particular is an important executive cognitive function that is not only impaired

  19. The ubiquitin proteasome system in glia and its role in neurodegenerative diseases

    NARCIS (Netherlands)

    Jansen, Anne H. P.; Reits, Eric A. J.; Hol, Elly M.

    2014-01-01

    The ubiquitin proteasome system (UPS) is crucial for intracellular protein homeostasis and for degradation of aberrant and damaged proteins. The accumulation of ubiquitinated proteins is a hallmark of many neurodegenerative diseases, including amyotrophic lateral sclerosis, Alzheimer's, Parkinson's,

  20. Combination Comprising Parthenolide For Use In The Treatment Of Alzheimer's Disease And Other Neurodegenerative Disorders

    KAUST Repository

    Bajic, Vladimir B.; Essack, Magbubah

    2015-01-01

    The present invention generally concerns particular methods and compositions for treatment of a neurodegenerative disease, such as Alzheimer's Disease. In particular embodiments, there is a composition comprising Parthenolide and a second agent

  1. 4 Tesla Whole Body MRI MRSI System for Investigation of Neurodegenerative Diseases

    National Research Council Canada - National Science Library

    Weiner, Michael W

    2004-01-01

    The overall long-term goal of imaging research to be performed with this 4 Tesla Siemens/Bruker MRI system is the development of improved diagnostic methods for accurate detection of neurodegenerative...

  2. Modeling Human Neurological and Neurodegenerative Diseases: From Induced Pluripotent Stem Cells to Neuronal Differentiation and Its Applications in Neurotrauma.

    Science.gov (United States)

    Bahmad, Hisham; Hadadeh, Ola; Chamaa, Farah; Cheaito, Katia; Darwish, Batoul; Makkawi, Ahmad-Kareem; Abou-Kheir, Wassim

    2017-01-01

    With the help of several inducing factors, somatic cells can be reprogrammed to become induced pluripotent stem cell (iPSCs) lines. The success is in obtaining iPSCs almost identical to embryonic stem cells (ESCs), therefore various approaches have been tested and ultimately several ones have succeeded. The importance of these cells is in how they serve as models to unveil the molecular pathways and mechanisms underlying several human diseases, and also in its potential roles in the development of regenerative medicine. They further aid in the development of regenerative medicine, autologous cell therapy and drug or toxicity screening. Here, we provide a comprehensive overview of the recent development in the field of iPSCs research, specifically for modeling human neurological and neurodegenerative diseases, and its applications in neurotrauma. These are mainly characterized by progressive functional or structural neuronal loss rendering them extremely challenging to manage. Many of these diseases, including Parkinson's disease (PD), Huntington's disease (HD), Amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD) have been explored in vitro . The main purpose is to generate patient-specific iPS cell lines from the somatic cells that carry mutations or genetic instabilities for the aim of studying their differentiation potential and behavior. This new technology will pave the way for future development in the field of stem cell research anticipating its use in clinical settings and in regenerative medicine in order to treat various human diseases, including neurological and neurodegenerative diseases.

  3. Memory-rescuing effects of cannabidiol in an animal model of cognitive impairment relevant to neurodegenerative disorders.

    Science.gov (United States)

    Fagherazzi, Elen V; Garcia, Vanessa A; Maurmann, Natasha; Bervanger, Thielly; Halmenschlager, Luis H; Busato, Stefano B; Hallak, Jaime E; Zuardi, Antônio W; Crippa, José A; Schröder, Nadja

    2012-02-01

    Cannabidiol, the main nonpsychotropic constituent of Cannabis sativa, possesses a large number of pharmacological effects including anticonvulsive, sedative, hypnotic, anxiolytic, antipsychotic, anti-inflammatory, and neuroprotective, as demonstrated in clinical and preclinical studies. Many neurodegenerative disorders involve cognitive deficits, and this has led to interest in whether cannabidiol could be useful in the treatment of memory impairment associated to these diseases. We used an animal model of cognitive impairment induced by iron overload in order to test the effects of cannabidiol in memory-impaired rats. Rats received vehicle or iron at postnatal days 12-14. At the age of 2 months, they received an acute intraperitoneal injection of vehicle or cannabidiol (5.0 or 10.0 mg/kg) immediately after the training session of the novel object recognition task. In order to investigate the effects of chronic cannabidiol, iron-treated rats received daily intraperitoneal injections of cannabidiol for 14 days. Twenty-four hours after the last injection, they were submitted to object recognition training. Retention tests were performed 24 h after training. A single acute injection of cannabidiol at the highest dose was able to recover memory in iron-treated rats. Chronic cannabidiol improved recognition memory in iron-treated rats. Acute or chronic cannabidiol does not affect memory in control rats. The present findings provide evidence suggesting the potential use of cannabidiol for the treatment of cognitive decline associated with neurodegenerative disorders. Further studies, including clinical trials, are warranted to determine the usefulness of cannabidiol in humans suffering from neurodegenerative disorders.

  4. Role of Different Alpha-Synuclein Strains in Synucleinopathies, Similarities with other Neurodegenerative Diseases

    OpenAIRE

    Melki, Ronald

    2015-01-01

    Abstract Misfolded protein aggregates are the hallmark of several neurodegenerative diseases in humans. The main protein constituent of these aggregates and the regions within the brain that are affected differ from one neurodegenerative disorder to another. A plethora of reports suggest that distinct diseases have in common the ability of protein aggregates to spread and amplify within the central nervous system. This review summarizes briefly what is known about the nature of the protein ag...

  5. Decision-making under Ambiguity in Neurodegenerative Disease

    OpenAIRE

    Rogers, Denise

    2011-01-01

    Decision-making is a complex skill that is essential for daily life. Yet the complexities of this process are often overlooked in favour of more obvious cognitive deficits during neuropsychological assessment, such as memory or attention impairments. Decision-making involves affective and motivational aspects of executive functions (Happaney, Zelazo & Stuss, 2004). Executive functions include a range of abilities that can be divided into three categories: 1) goal setting and planning, 2) acti...

  6. Complex sparse spatial filter for decoding mixed frequency and phase coded steady-state visually evoked potentials.

    Science.gov (United States)

    Morikawa, Naoki; Tanaka, Toshihisa; Islam, Md Rabiul

    2018-07-01

    Mixed frequency and phase coding (FPC) can achieve the significant increase of the number of commands in steady-state visual evoked potential-based brain-computer interface (SSVEP-BCI). However, the inconsistent phases of the SSVEP over channels in a trial and the existence of non-contributing channels due to noise effects can decrease accurate detection of stimulus frequency. We propose a novel command detection method based on a complex sparse spatial filter (CSSF) by solving ℓ 1 - and ℓ 2,1 -regularization problems for a mixed-coded SSVEP-BCI. In particular, ℓ 2,1 -regularization (aka group sparsification) can lead to the rejection of electrodes that are not contributing to the SSVEP detection. A calibration data based canonical correlation analysis (CCA) and CSSF with ℓ 1 - and ℓ 2,1 -regularization cases were demonstrated for a 16-target stimuli with eleven subjects. The results of statistical test suggest that the proposed method with ℓ 1 - and ℓ 2,1 -regularization significantly achieved the highest ITR. The proposed approaches do not need any reference signals, automatically select prominent channels, and reduce the computational cost compared to the other mixed frequency-phase coding (FPC)-based BCIs. The experimental results suggested that the proposed method can be usable implementing BCI effectively with reduce visual fatigue. Copyright © 2018 Elsevier B.V. All rights reserved.

  7. Comparative “Omics” of the Fusarium fujikuroi Species Complex Highlights Differences in Genetic Potential and Metabolite Synthesis

    Science.gov (United States)

    Niehaus, Eva-Maria; Münsterkötter, Martin; Proctor, Robert H.; Brown, Daren W.; Sharon, Amir; Idan, Yifat; Oren-Young, Liat; Sieber, Christian M.; Novák, Ondřej; Pěnčík, Aleš; Tarkowská, Danuše; Hromadová, Kristýna; Freeman, Stanley; Maymon, Marcel; Elazar, Meirav; Youssef, Sahar A.; El-Shabrawy, El Said M.; Shalaby, Abdel Baset A.; Houterman, Petra; Brock, Nelson L.; Burkhardt, Immo; Tsavkelova, Elena A.; Dickschat, Jeroen S.; Galuszka, Petr; Güldener, Ulrich; Tudzynski, Bettina

    2016-01-01

    Species of the Fusarium fujikuroi species complex (FFC) cause a wide spectrum of often devastating diseases on diverse agricultural crops, including coffee, fig, mango, maize, rice, and sugarcane. Although species within the FFC are difficult to distinguish by morphology, and their genes often share 90% sequence similarity, they can differ in host plant specificity and life style. FFC species can also produce structurally diverse secondary metabolites (SMs), including the mycotoxins fumonisins, fusarins, fusaric acid, and beauvericin, and the phytohormones gibberellins, auxins, and cytokinins. The spectrum of SMs produced can differ among closely related species, suggesting that SMs might be determinants of host specificity. To date, genomes of only a limited number of FFC species have been sequenced. Here, we provide draft genome sequences of three more members of the FFC: a single isolate of F. mangiferae, the cause of mango malformation, and two isolates of F. proliferatum, one a pathogen of maize and the other an orchid endophyte. We compared these genomes to publicly available genome sequences of three other FFC species. The comparisons revealed species-specific and isolate-specific differences in the composition and expression (in vitro and in planta) of genes involved in SM production including those for phytohormome biosynthesis. Such differences have the potential to impact host specificity and, as in the case of F. proliferatum, the pathogenic versus endophytic life style. PMID:28040774

  8. Biodistribution of radioactive organocations and cationic technetium complexes - implications to the uptake mechanism of potential heart-affine radiopharmaceuticals

    International Nuclear Information System (INIS)

    Muenze, R.; Shyre, R.; Seifert, S.; Guethert, I.; Kretschmar, M.; Kampf, G.; Knop, G.; Mohnike, W.; Schmidt, J.

    1986-01-01

    The biodistribution of various 14 C labeled organocations (ammonium, phosphonium) and cationic technetium complexes (TcCl 2 DMPE 2 ,TcDMPE 3 + ) was studied in rats to find potential relations between the chemical composition, structure, molecular size, lipophilicity and heart uptake. All of the radioactive cations were distributed in a similar manner, but with different biokinetics. Molecules containing several electronegative atoms in their ligand structure, e.g. nitrogen or oxygen which enhance polarity, were rapidly accumulated, but washed out again with resultant transient and diminished heart uptake. More highly lipophilic materials, by contrast, showed more extensive accumulation and persistent retention in the heart. The effect of human serum albumin on heart uptake was studied in a perfused heart model. Strong albumin binding prevented extensive heart uptake. This undesirable effect was neutralized by adding detergents to the perfusion bath. Evidence from these animal experiments was considered in the development of a new heart-seeking technetium compound (Tc-DPO), which is characterized by rapid accumulation in the human heart and substantially delayed washout. Heart images with minimal overlap of the inferoposterior wall and the right liver lobe were available in no more than 10 minutes p.i. in both planar and SPECT modes. A deficit in the inferior region was much more clearly defined than on the corresponding Thallium image. (Author)

  9. New understanding of the complex structure of knee menisci: implications for injury risk and repair potential for athletes.

    Science.gov (United States)

    Rattner, J B; Matyas, J R; Barclay, L; Holowaychuk, S; Sciore, P; Lo, I K Y; Shrive, N G; Frank, C B; Achari, Y; Hart, D A

    2011-08-01

    Menisci help maintain the structural integrity of the knee. However, the poor healing potential of the meniscus following a knee injury can not only end a career in sports but lead to osteoarthritis later in life. Complete understanding of meniscal structure is essential for evaluating its risk for injury and subsequent successful repair. This study used novel approaches to elucidate meniscal architecture. The radial and circumferential collagen fibrils in the meniscus were investigated using novel tissue-preparative techniques for light and electron microscopic studies. The results demonstrate a unique architecture based on differences in the packaging of the fundamental collagen fibrils. For radial arrays, the collagen fibrils are arranged in parallel into ∼10 μm bundles, which associate laterally to form flat sheets of varying dimensions that bifurcate and come together to form a honeycomb network within the body of the meniscus. In contrast, the circumferential arrays display a complex network of collagen fibrils arranged into ∼5 μm bundles. Interestingly, both types of architectural organization of collagen fibrils in meniscus are conserved across mammalian species and are age and sex independent. These findings imply that disruptions in meniscal architecture following an injury contribute to poor prognosis for functional repair. © 2010 John Wiley & Sons A/S.

  10. Through-Space Paramagnetic NMR Effects in Host-Guest Complexes: Potential Ruthenium(III) Metallodrugs with Macrocyclic Carriers.

    Science.gov (United States)

    Chyba, Jan; Novák, Martin; Munzarová, Petra; Novotný, Jan; Marek, Radek

    2018-04-05

    The potential of paramagnetic ruthenium(III) compounds for use as anticancer metallodrugs has been investigated extensively during the past several decades. However, the means by which these ruthenium compounds are transported and distributed in living bodies remain relatively unexplored. In this work, we prepared several novel ruthenium(III) compounds with the general structure Na + [ trans-Ru III Cl 4 (DMSO)(L)] - (DMSO = dimethyl sulfoxide), where L stands for pyridine or imidazole linked with adamantane, a hydrophobic chemophore. The supramolecular interactions of these compounds with macrocyclic carriers of the cyclodextrin (CD) and cucurbit[ n]uril (CB) families were investigated by NMR spectroscopy, X-ray diffraction analysis, isothermal titration calorimetry, and relativistic DFT methods. The long-range hyperfine NMR effects of the paramagnetic guest on the host macrocycle are related to the distance between them and their relative orientation in the host-guest complex. The CD and CB macrocyclic carriers being studied in this account can be attached to a vector that attracts the drug-carrier system to a specific biological target and our investigation thus introduces a new possibility in the field of targeted delivery of anticancer metallodrugs based on ruthenium(III) compounds.

  11. Flavonoid-Based Therapies in the Early Management of Neurodegenerative Diseases12

    Science.gov (United States)

    Solanki, Isha; Parihar, Priyanka; Mansuri, Mohammad Lukman; Parihar, Mordhwaj S

    2015-01-01

    During the past several years, there has been enormous progress in the understanding of the causative factors that initiate neuronal damage in various neurodegenerative diseases, including Alzheimer disease, Parkinson disease, multiple sclerosis, amyotrophic lateral sclerosis, and Huntington disease. Preventing neuronal damage and neuronal death will have a huge clinical benefit. However, despite major advances in causative factors that trigger these neurodegenerative diseases, to date there have been no therapies available that benefit patients who suffer from these diseases. Because most neurodegenerative diseases are late-onset and remain asymptomatic for most of the phases, the therapies initiated in advanced stages of the disease have limited value to patients. It may be possible to prevent or halt the disease progression to a great extent if therapies start at the initial stage of the disease. Such therapies may restore neuronal function by reducing or even eliminating the primary stressor. Flavonoids are key compounds for the development of a new generation of therapeutic agents that are clinically effective in treating neurodegenerative diseases. Regular consumption of flavonoids has been associated with a reduced risk of neurodegenerative diseases. In addition to their antioxidant properties, these polyphenolic compounds exhibit neuroprotective properties by their interaction with cellular signaling pathways followed by transcription and translation that mediate cell function under both normal and pathologic conditions. This review focuses on human intervention studies as well as animal studies on the role of various flavonoids in the prevention of neurodegenerative diseases. PMID:25593144

  12. On the Role of Store-Operated Calcium Entry in Acute and Chronic Neurodegenerative Diseases

    Directory of Open Access Journals (Sweden)

    Agnese Secondo

    2018-03-01

    Full Text Available In both excitable and non-excitable cells, calcium (Ca2+ signals are maintained by a highly integrated process involving store-operated Ca2+ entry (SOCE, namely the opening of plasma membrane (PM Ca2+ channels following the release of Ca2+ from intracellular stores. Upon depletion of Ca2+ store, the stromal interaction molecule (STIM senses Ca2+ level reduction and migrates from endoplasmic reticulum (ER-like sites to the PM where it activates the channel proteins Orai and/or the transient receptor potential channels (TRPC prompting Ca2+ refilling. Accumulating evidence suggests that SOCE dysregulation may trigger perturbation of intracellular Ca2+ signaling in neurons, glia or hematopoietic cells, thus participating to the pathogenesis of diverse neurodegenerative diseases. Under acute conditions, such as ischemic stroke, neuronal SOCE can either re-establish Ca2+ homeostasis or mediate Ca2+ overload, thus providing a non-excitotoxic mechanism of ischemic neuronal death. The dualistic role of SOCE in brain ischemia is further underscored by the evidence that it also participates to endothelial restoration and to the stabilization of intravascular thrombi. In Parkinson’s disease (PD models, loss of SOCE triggers ER stress and dysfunction/degeneration of dopaminergic neurons. Disruption of neuronal SOCE also underlies Alzheimer’s disease (AD pathogenesis, since both in genetic mouse models and in human sporadic AD brain samples, reduced SOCE contributes to synaptic loss and cognitive decline. Unlike the AD setting, in the striatum from Huntington’s disease (HD transgenic mice, an increased STIM2 expression causes elevated synaptic SOCE that was suggested to underlie synaptic loss in medium spiny neurons. Thus, pharmacological inhibition of SOCE is beneficial to synapse maintenance in HD models, whereas the same approach may be anticipated to be detrimental to cortical and hippocampal pyramidal neurons. On the other hand, up-regulation of

  13. Heteroleptic Copper(I) Complexes of "Scorpionate" Bis-pyrazolyl Carboxylate Ligand with Auxiliary Phosphine as Potential Anticancer Agents: An Insight into Cytotoxic Mode.

    Science.gov (United States)

    Khan, Rais Ahmad; Usman, Mohammad; Dhivya, Rajakumar; Balaji, Perumalsamy; Alsalme, Ali; AlLohedan, Hamad; Arjmand, Farukh; AlFarhan, Khalid; Akbarsha, Mohammad Abdulkader; Marchetti, Fabio; Pettinari, Claudio; Tabassum, Sartaj

    2017-03-24

    New copper(I) complexes [CuCl(PPh 3 )(L)] (1: L = L A  = 4-carboxyphenyl)bis(3,5-dimethylpyrazolyl)methane; (2: L = L B  = 3-carboxyphenyl)bis(3,5-dimethylpyrazolyl)methane) were prepared and characterised by elemental analysis and various spectroscopic techniques such as FT-IR, NMR, UV-Vis, and ESI-MS. The molecular structures of complexes 1 and 2 were analyzed by theoretical B3LYP/DFT method. Furthermore, in vitro DNA binding studies were carried out to check the ability of complexes 1 and 2 to interact with native calf thymus DNA (CT-DNA) using absorption titration, fluorescence quenching and circular dichroism, which is indicative of more avid binding of the complex 1. Moreover, DNA mobility assay was also conducted to study the concentration-dependent cleavage pattern of pBR322 DNA by complex 1, and the role of ROS species to have a mechanistic insight on the cleavage pattern, which ascertained substantial roles by both hydrolytic and oxidative pathways. Additionally, we analyzed the potential of the interaction of complex 1 with DNA and enzyme (Topo I and II) with the aid of molecular modeling. Furthermore, cytotoxic activity of complex 1 was tested against HepG2 cancer cell lines. Thus, the potential of the complex 1 is promising though further in vivo investigations may be required before subjecting it to clinical trials.

  14. Beneficial Role of Coffee and Caffeine in Neurodegenerative Diseases: A Minireview

    Directory of Open Access Journals (Sweden)

    Yenisetti SC

    2016-06-01

    Full Text Available Coffee is among the most widespread and healthiest beverages in the world. Coffee typically contains more caffeine than most other beverages, and is widely and frequently consumed. Thus, it contributes significantly to the overall caffeine consumption within the general population, particularly in adults. Controversies regarding its benefits and risks still exist as reliable evidence is becoming available supporting its health-promoting potential. Several lines of evidence have highlighted the beneficial effects towards several disease conditions including Type II diabetes, hepatitis C virus, hepatocellular carcinoma, nonalcoholic fatty liver disease and neurodegenerative disorders such as Alzheimer's disease (AD, Parkinson's disease (PD and Amyotrophic Lateral Sclerosis (ALS. The health-promoting properties of coffee are largely attributed to its rich phytochemistry, including caffeine, chlorogenic acid, caffeic acid, and hydroxy hydroquinone. In this minireview, an attempt has been made to discuss the various evidences which are mainly derived from animal and cell models. Various mechanisms chiefly responsible for the beneficial effects of caffeine have also been briefly outlined. A short note on the undesirable effects of excessive coffee intakes is also presented.

  15. A Single Neonatal Exposure to BMAA in a Rat Model Produces Neuropathology Consistent with Neurodegenerative Diseases

    Directory of Open Access Journals (Sweden)

    Laura Louise Scott

    2017-12-01

    Full Text Available Although cyanobacterial β-N-methylamino-l-alanine (BMAA has been implicated in the development of Alzheimer’s Disease (AD, Parkinson’s Disease (PD and Amyotrophic Lateral Sclerosis (ALS, no BMAA animal model has reproduced all the neuropathology typically associated with these neurodegenerative diseases. We present here a neonatal BMAA model that causes β-amyloid deposition, neurofibrillary tangles of hyper-phosphorylated tau, TDP-43 inclusions, Lewy bodies, microbleeds and microgliosis as well as severe neuronal loss in the hippocampus, striatum, substantia nigra pars compacta, and ventral horn of the spinal cord in rats following a single BMAA exposure. We also report here that BMAA exposure on particularly PND3, but also PND4 and 5, the critical period of neurogenesis in the rodent brain, is substantially more toxic than exposure to BMAA on G14, PND6, 7 and 10 which suggests that BMAA could potentially interfere with neonatal neurogenesis in rats. The observed selective toxicity of BMAA during neurogenesis and, in particular, the observed pattern of neuronal loss observed in BMAA-exposed rats suggest that BMAA elicits its effect by altering dopamine and/or serotonin signaling in rats.

  16. Progranulin: a new avenue towards the understanding and treatment of neurodegenerative disease.

    Science.gov (United States)

    Chitramuthu, Babykumari P; Bennett, Hugh P J; Bateman, Andrew

    2017-12-01

    Progranulin, a secreted glycoprotein, is encoded in humans by the single GRN gene. Progranulin consists of seven and a half, tandemly repeated, non-identical copies of the 12 cysteine granulin motif. Many cellular processes and diseases are associated with this unique pleiotropic factor that include, but are not limited to, embryogenesis, tumorigenesis, inflammation, wound repair, neurodegeneration and lysosome function. Haploinsufficiency caused by autosomal dominant mutations within the GRN gene leads to frontotemporal lobar degeneration, a progressive neuronal atrophy that presents in patients as frontotemporal dementia. Frontotemporal dementia is an early onset form of dementia, distinct from Alzheimer's disease. The GRN-related form of frontotemporal lobar dementia is a proteinopathy characterized by the appearance of neuronal inclusions containing ubiquitinated and fragmented TDP-43 (encoded by TARDBP). The neurotrophic and neuro-immunomodulatory properties of progranulin have recently been reported but are still not well understood. Gene delivery of GRN in experimental models of Alzheimer's- and Parkinson's-like diseases inhibits phenotype progression. Here we review what is currently known concerning the molecular function and mechanism of action of progranulin in normal physiological and pathophysiological conditions in both in vitro and in vivo models. The potential therapeutic applications of progranulin in treating neurodegenerative diseases are highlighted. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  17. Non-Clinical Models for Neurodegenerative Diseases: Therapeutic Approach and Drug Validation in Animal Models

    Directory of Open Access Journals (Sweden)

    Caridad Ivette Fernandez

    2017-12-01

    Full Text Available In 2016, 19.8% of the Cuban population was aged 60 or over. As a result, age-associated degenerative diseases and other diseases have become priority targets from a prophylactic, diagnostic and therapeutic perspective. As a result, the Cuban biomedical scientific community has addressed its basic, preclinical and epidemiological research in order to rise up to the challenge. A firm step in this direction has been the international congress “State of the art in non-clinical models for neurodegenerative diseases” which has brought together preclinical and clinical researchers, technicians and regulatory staff members from different countries to review the state of the art in neurodegenerations, find unifying ideas, objectives and collaborations or partnership. The objective is to expose the perspectives of new biotechnological products from Cuba and other countries from the diagnostic, therapeutic and neuroprotective point of view. It is crucial, therefore, that the irreplaceable role of laboratory animals in achieving these objectives is understood but they must be used in rational, adequate and ethical manner. We expose the current development trends in this field, being of common interest to the work directed to the search for potential drugs, diagnostic tools and the promotion of changes in lifestyle as a preventive projection.

  18. Study of complex resistivity measurement using current and potential waveform data; Denryu to den`i hakei data wo riyoshita fukusohi teiko sokutei no kento

    Energy Technology Data Exchange (ETDEWEB)

    Shima, H; Sakurai, K; Yamashita, Y [OYO Corp., Tokyo (Japan)

    1997-10-22

    This paper proposes a measurement method for complex resistivity using both current and potential waveforms. This method was applied to actual data. Especially, chargeability was discussed among complex resistivities. A method was proposed for determining the complex resistivity. At first, digital measurements of both current and potential waveforms were conducted. For the potential waveform, zero-order self-potential was canceled. Then, the FFT technique was applied to both current and potential waveforms, to determine both current and potential in the frequency domain. Hereafter, complex resistivity was determined through simple division. Since the inductive coupling was observed at higher frequencies, it was difficult to apply Cole-Cole model, simply. However, the inductive coupling could be removed using proper sampling frequency. Thus, a proper Cole-Cole dispersion curve could be obtained. Using this Cole-Cole dispersion curve, new chargeability could be defined. A linear relation between this chargeability and the ordinary time domain chargeability was made clear. 4 refs., 10 figs.

  19. Cellobiose dehydrogenase entrapped within specifically designed Os-complex modified electrodeposition polymers as potential anodes for biofuel cells

    International Nuclear Information System (INIS)

    Shao, Minling; Guschin, Dmitrii A.; Kawah, Zahma; Beyl, Yvonne; Stoica, Leonard; Ludwig, Roland; Schuhmann, Wolfgang; Chen, Xingxing

    2014-01-01

    Electron-transfer pathways between cellobiose dehydrogenase from Myriococcum thermophilum (MtCDH) and the related flavodehydrogenase domain (FAD-MtCDH) and electrodes were evaluated using specifically designed Os-complex modified electrodeposition paints (EDPs). The properties of the Os-complex modified EDPs were varied by variation of the monomer composition, the coordination sphere of the polymer-bound Os-complexes, and the length and flexibility of the spacer chain between Os complex and polymer backbone. The MtCDH-to-EDP weight ratio, the pH value, as well as the operational temperature have been optimized

  20. The Neuroprotective Effects of Brazilian Green Propolis on Neurodegenerative Damage in Human Neuronal SH-SY5Y Cells

    Directory of Open Access Journals (Sweden)

    Junjun Ni

    2017-01-01

    Full Text Available Oxidative stress and synapse dysfunction are the major neurodegenerative damage correlated to cognitive impairment in Alzheimer’s disease (AD. We have found that Brazilian green propolis (propolis improves the cognitive functions of mild cognitive impairment patients living at high altitude; however, mechanism underlying the effects of propolis is unknown. In the present study, we investigated the effects of propolis on oxidative stress, expression of brain-derived neurotrophic factor (BDNF, and activity-regulated cytoskeleton-associated protein (Arc, the critical factors of synapse efficacy, using human neuroblastoma SH-SY5Y cells. Pretreatment with propolis significantly ameliorated the hydrogen peroxide- (H2O2- induced cytotoxicity in SH-SY5Y cells. Furthermore, propolis significantly reduced the H2O2-generated reactive oxygen species (ROS derived from mitochondria and 8-oxo-2′-deoxyguanosine (8-oxo-dG, the DNA oxidative damage marker but significantly reversed the fibrillar β-amyloid and IL-1β-impaired BDNF-induced Arc expression in SH-SY5Y cells. Furthermore, propolis significantly upregulated BDNF mRNA expression in time- and dose-dependent manners. In addition, propolis induced Arc mRNA and protein expression via phosphoinositide-3 kinase (PI3K. These observations strongly suggest that propolis protects from the neurodegenerative damage in neurons through the properties of various antioxidants. The present study provides a potential molecular mechanism of Brazilian green propolis in prevention of cognitive impairment in AD as well as aging.

  1. New light on an old friend: targeting PUMA in radioprotection and therapy of cardiovascular and neurodegenerative diseases.

    Science.gov (United States)

    Tichy, Ales; Marek, Jan; Havelek, Radim; Pejchal, Jaroslav; Seifrtova, Martina; Zarybnicka, Lenka; Filipova, Alzbeta; Rezacova, Martina; Sinkorova, Zuzana

    2018-04-05

    This review summarizes recent progress in understanding the role of p53-upregulated mediator of apoptosis (PUMA) in molecular pathways with respect to its potential therapeutic applications. Particular emphasis is given to the PUMA´s role in ionizing radiation-induced signalling as radiotoxicity of normal tissue is mediated mostly via apoptosis. PUMA and its p53-dependent and p53-independent induction is described and potential use as a new target for the development of radioprotective agents is suggested. Further implications, including targeting PUMA to prevent and treat cardiovascular and neurodegenerative diseases, are also discussed together with overview of other therapeutic applications. Finally, basic chemical structures for development of novel PUMA modulators such as pifithrine derivativeses, kinase inhibitors or modulators of Bcl-2 protein family are described. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  2. Integration of technology-based outcome measures in clinical trials of Parkinson and other neurodegenerative diseases.

    Science.gov (United States)

    Artusi, Carlo Alberto; Mishra, Murli; Latimer, Patricia; Vizcarra, Joaquin A; Lopiano, Leonardo; Maetzler, Walter; Merola, Aristide; Espay, Alberto J

    2018-01-01

    We sought to review the landscape of past, present, and future use of technology-based outcome measures (TOMs) in clinical trials of neurodegenerative disorders. We systematically reviewed PubMed and ClinicalTrials.gov for published and ongoing clinical trials in neurodegenerative disorders employing TOMs. In addition, medical directors of selected pharmaceutical companies were surveyed on their companies' ongoing efforts and future plans to integrate TOMs in clinical trials as primary, secondary, or exploratory endpoints. We identified 164 published clinical trials indexed in PubMed that used TOMs as outcome measures in Parkinson disease (n = 132) or other neurodegenerative disorders (n = 32). The ClinicalTrials.gov search yielded 42 clinical trials using TOMs, representing 2.7% of ongoing trials. Sensor-based technology accounted for over 75% of TOMs applied. Gait and physical activity were the most common targeted domains. Within the next 5 years, 83% of surveyed pharmaceutical companies engaged in neurodegenerative disorders plan to deploy TOMs in clinical trials. Although promising, TOMs are underutilized in clinical trials of neurodegenerative disorders. Validating relevant endpoints, standardizing measures and procedures, establishing a single platform for integration of data and algorithms from different devices, and facilitating regulatory approvals should advance TOMs integration into clinical trials. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Refined ab initio intermolecular ground-state potential energy surface for the He-C2H2 van der Waals complex

    DEFF Research Database (Denmark)

    Fernández, Berta; Henriksen, Christian; Farrelly, David

    2013-01-01

    A refined CCSD(T) intermolecular potential energy surface is developed for the He-C2H2 van der Waals complex. For this, 206 points on the intermolecular potential energy surface, evaluated using the CCSD(T) method and the aug-cc-pVQZ basis set extended with a set of 3s3p2d1f1g midbond functions...

  4. Preparation and in-vitro characterization of Risperidone-cyclodextrin inclusion complexes as a potential injectable product

    Directory of Open Access Journals (Sweden)

    D Shukla

    2009-12-01

    Full Text Available "n  "n Background and the purpose of the study: This investigation deals with risperidone cyclodextrin (CD complexation for parenteral administration to improve its aqueous solubility which would be beneficial over immediate and sustained release formulations available in market especially for agitated and non-cooperative psychotic patients. "nMethods: The phase solubility study of the drug with β-CD, hydroxypropyl (HP-β-CD and γ-CD was conducted and CDs with higher stability constants were selected for complexation. The complexes of Risperidone with β-CD and HP-β-CD were prepared by precipitation and vacuum drying methods, respectively. Fourier transform-infrared, X-ray diffraction and differential scanning calorimetry techniques were used for characterization of complexes. Drug precipitation study of complex's solution in water for injection and 100 ml of 0.1 M pH 7.4 phosphate buffer saline and stability study in accelerated condition were also carried out. "nResults: The stability constants of the CD were in the following order: β-CD (341.953±11.87 M-1 > HP-β-CD (170.817± 5.93 M-1 > γ-CD (93.716 ± 3.25 M-1. CDs with high stability constants were selected to prepare the drug CD complex. The complexation efficiencies of β-CD and HP-β-CD were 95.23 ± 2.27% and 97.59 ±1.97%, respectively. Both types of CDs exhibited complexation at 1:2 molar stoichiometric ratio. The drug precipitation study indicated complete solubility (100% drug dissolution without a trace of precipitate within 5 mins. The complexes were found to be stable for a period of 3 months under accelerated stability conditions. Major conclusion:Stable complexes of risperidone were successfully formulated using both β-CD and HP-β-CD by simple and highly efficient methods of complexation for parenteral administration.

  5. Lipophilic hexadentate Gallium, indium and iron complexes of new phenolate derivatized cyclohexanetriamine ligands as potential in vivo metal transfer reagents

    International Nuclear Information System (INIS)

    Bollinger, J.E.; Roundhill, D.M.

    1995-01-01

    The compounds (RsalH 2 ) 3 tachH 3 (R=H, NO 2 , OMe) have been synthesized by Schiff base condensation between cis-1,3,5-triaminocyclohexane and a substituted salicylaldehyde, followed by reduction with KBH 4 . Reaction of these compounds with gallium(III), indium(III) and iron(III) salts neutral hexacoordinate N 3 O 3 complexes of type M(RsalH 2 )3tach (M = Ga, In, Fe). The complexes have been characterized by a combination of infrared, 1 H and 13 C [ 1H] NMR and mass spectroscopy. The distribution coefficient between 1-octanol and water indicate that complexes are lipophilic. The electronic absorption spectra of the high spin Fe(III) complexes show LMCT bands in the 450-500 nm range. The structures of (RsalH 2 ) 3 tachH 3 (R=H, NO 2 , OMe), and In(SalH 2 ) 3 tach have been confirmed by single-crystal X-ray crystallography. Solutions of the three ligands ((salH 2 ) 3 tach, (NO 2 salH 2 ) 3 tach) and (MeOsalH 2 ) 3 tach) complexed to radioactive 59 were prepared in a fashion similar to solutions of ligands complexed with non-radioactive iron, except on a much smaller scale. Biodistribution data for 5 9Fe(RsalH 2 ) 3 tach (R=H, NO 2 , and OMe) complexes over a 24 hour period ere obtained. These 24 hour data show that the complexes are more effectively cleared from the body than is the control solution of 59 Fe. These data will be discussed and possible medical applications for these compounds will be offered. (authors), 2 tabs., 1 figs., 7 refs

  6. Kaempferol-Phospholipid Complex: Formulation, and Evaluation of Improved Solubility, In Vivo Bioavailability, and Antioxidant Potential of Kaempferol

    OpenAIRE

    Darshan R. Telange; Arun T. Patil; Anil M. Pethe; Amol A. Tatode; Sridhar Anand; Vivek S. Dave

    2016-01-01

    The current work describes the formulation and evaluation of a phospholipid complex of kaempferol to enhance the latter’s aqueous solubility, in vitro dissolution rate, in vivo antioxidant and hepatoprotective activities, and oral bioavailability. The kaempferol-phospholipid complex was synthesized using a freeze-drying method with the formulation being optimized using a full factorial design (32) approach. Our results include the validation of the mathematical model in order to ascertain the...

  7. Exploring the complexities of leprosy-related stigma and the potential of a socio-economic intervention in a public health context in Indonesia

    NARCIS (Netherlands)

    Dadun,; Peters, Ruth; Lusli, Mimi; Miranda-Galarza, Beatriz; Van Brakel, Wim; Zweekhorst, Marjolein; Damayanti, Rita; Irwanto, A.; Bunders-Aelen, J.G.F.

    2016-01-01

    Purpose: This article explores the complexities of leprosy-related stigma and the potential effectiveness of a socio-economic intervention in Cirebon District, Indonesia. Methods: A qualitative approach was adopted. 53 people affected by leprosy were interviewed, and 17 focus group discussions were

  8. Development of a symptoms questionnaire for complex regional pain syndrome and potentially related illnesses: the Trauma Related Neuronal Dysfunction Symptoms Inventory

    NARCIS (Netherlands)

    Collins, S.; van Hilten, J.J.; Marinus, J.J.; Zuurmond, W.W.A.; de Lange, J.J.; Perez, R.S.G.M.

    2008-01-01

    Collins S, van Hilten JJ, Marinus J, Zuurmond WW, de Lange JJ, Perez RS. Development of a symptoms questionnaire for complex regional pain syndrome and potentially related illnesses: the Trauma Related Neuronal Dysfunction Symptoms Inventory. Objective: To develop a questionnaire to evaluate

  9. Recent trends in the transdermal delivery of therapeutic agents used for the management of neurodegenerative diseases.

    Science.gov (United States)

    Ita, Kevin

    2017-06-01

    With the increasing proportion of the global geriatric population, it becomes obvious that neurodegenerative diseases will become more widespread. From an epidemiological standpoint, it is necessary to develop new therapeutic agents for the management of Alzheimer's disease, Parkinson's disease, multiple sclerosis and other neurodegenerative disorders. An important approach in this regard involves the use of the transdermal route. With transdermal drug delivery systems (TDDS), it is possible to modulate the pharmacokinetic profiles of these medications and improve patient compliance. Transdermal drug delivery has also been shown to be useful for drugs with short half-life and low or unpredictable bioavailability. In this review, several transdermal drug delivery enhancement technologies are being discussed in relation to the delivery of medications used for the management of neurodegenerative disorders.

  10. Possible Role of the Transglutaminases in the Pathogenesis of Alzheimer's Disease and Other Neurodegenerative Diseases

    Directory of Open Access Journals (Sweden)

    Antonio Martin

    2011-01-01

    Full Text Available Transglutaminases are ubiquitous enzymes which catalyze posttranslational modifications of proteins. Recently, transglutaminase-catalyzed post-translational modification of proteins has been shown to be involved in the molecular mechanisms responsible for human diseases. Transglutaminase activity has been hypothesized to be involved also in the pathogenetic mechanisms responsible for several human neurodegenerative diseases. Alzheimer's disease and other neurodegenerative diseases, such as Parkinson's disease, supranuclear palsy, Huntington's disease, and other polyglutamine diseases, are characterized in part by aberrant cerebral transglutaminase activity and by increased cross-linked proteins in affected brains. This paper focuses on the possible molecular mechanisms by which transglutaminase activity could be involved in the pathogenesis of Alzheimer's disease and other neurodegenerative diseases, and on the possible therapeutic effects of selective transglutaminase inhibitors for the cure of patients with diseases characterized by aberrant transglutaminase activity.

  11. Progress of the relationship between serum uric acid and neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Yang FU

    2018-04-01

    Full Text Available Serum uric acid (sUA, a natural antioxidant in human body, has been found to be related to the occurrence and development of various neurodegenerative diseases in recent years, including Parkinson's disease (PD, multiple system atrophy (MSA, Alzheimer's disease (AD and amyotrophic lateral sclerosis (ALS. Increasing of sUA level has been found to reduce the incidence of PD and ALS, but the relationship between sUA and AD, MSA remains largely unknown. The in vitro studies and animal experiments revealed that sUA can enhance the antioxidant capacity of neurons and delay neurodegeneration and apoptosis. This paper mainly reviews the progress in epidemiological and basic studies of the relationship between sUA and neurodegenerative diseases in recent years, and aims to provide a reference for future novel prevention and treatment strategies for neurodegenerative diseases. DOI: 10.3969/j.issn.1672-6731.2018.03.010

  12. Intervention modalities for targeting cognitive-motor interference in individuals with neurodegenerative disease: a systematic review.

    Science.gov (United States)

    Wajda, Douglas A; Mirelman, Anat; Hausdorff, Jeffrey M; Sosnoff, Jacob J

    2017-03-01

    Individuals with neurodegenerative disease (NDD) commonly have elevated cognitive-motor interference, change in either cognitive or motor performance (or both) when tasks are performed simultaneously, compared to healthy controls. Given that cognitive-motor interference is related to reduced community ambulation and elevated fall risk, it is a target of rehabilitation interventions. Areas covered: This review details the collective findings of previous dual task interventions in individuals with NDD. A total of 21 investigations focusing on 4 different neurodegenerative diseases and one NDD precursor (Parkinson's disease, multiple sclerosis, Alzheimer's disease (AD), dementia other than AD, and mild cognitive impairment) consisting of 721 participants were reviewed. Expert commentary: Preliminary evidence from interventions targeting cognitive-motor interference, both directly and indirectly, show promising results for improving CMI in individuals with neurodegenerative diseases. Methodological limitations, common to pilot investigations preclude firm conclusions. Well-designed randomized control trials targeting cognitive motor interference are warranted.

  13. Research progress on the pathogenesis of rapid eye movement sleep behavior disorder and neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Hai-yang JIANG

    2017-10-01

    Full Text Available Rapid eye movement sleep behavior disorder (RBD is a sleep disorder characterized by the disappearance of muscle relaxation and enacting one's dreams during rapid eye movement (REM, with most of the dreams being violent or aggressive. Prevalence of RBD, based on population, is 0.38%-2.01%, but it becomes much higher in patients with neurodegenerative diseases, especially α - synucleinopathies. RBD may herald the emergence of α-synucleinopathies by decades, thus it may be used as an effective early marker of neurodegenerative diseases. In this review, we summarized the progress on the pathogenesis of RBD and its relationship with neurodegenerative diseases. DOI: 10.3969/j.issn.1672-6731.2017.10.003

  14. The Role of Musk in Relieving the Neurodegenerative Changes Induced After Exposure to Chronic Stress.

    Science.gov (United States)

    Abd El Wahab, Manal Galal; Ali, Soad Shaker; Ayuob, Nasra Naeim

    2018-06-01

    This study aimed to evaluate the effect induced by musk on Alzheimer's disease-such as neurodegenerative changes in mice exposed to chronic unpredictable mild stress (CUMS). Forty male Swiss albino mice were divided into 4 groups (n = 10); control, CUMS, CUMS + fluoxetine, CUMS + musk. At the end of the experiment, behavior of the mice was assessed. Serum corticosterone level, hippocampal protein level of the glucocorticoid receptors, and brain-derived neurotropic factor were also assessed. Hippocampus was histopathologically examined. Musk improved depressive status induced after exposure to CUMS as evidenced by the forced swimming and open field tests and improved the short-term memory as evidenced by the elevated plus maze test. Musk reduced both corticosterone levels and the hippocampal neurodegenerative changes observed after exposure to CUMS. These improvements were comparable to those induced by fluoxetine. Musk alleviated the memory impairment and neurodegenerative changes induced after exposure to the chronic stress.

  15. Synthesis and Biological Evaluation of Ru(II) and Pt(II) Complexes Bearing Carboxyl Groups as Potential Anticancer Targeted Drugs.

    Science.gov (United States)

    Martínez, Ma Ángeles; Carranza, M Pilar; Massaguer, Anna; Santos, Lucia; Organero, Juan A; Aliende, Cristina; de Llorens, Rafael; Ng-Choi, Iteng; Feliu, Lidia; Planas, Marta; Rodríguez, Ana M; Manzano, Blanca R; Espino, Gustavo; Jalón, Félix A

    2017-11-20

    The synthesis and characterization of Pt(II) (1 and 2) and Ru(II) arene (3 and 4) or polypyridine (5 and 6) complexes is described. With the aim of having a functional group to form bioconjugates, one uncoordinated carboxyl group has been introduced in all complexes. Some of the complexes were selected for their potential in photodynamic therapy (PDT). The molecular structures of complexes 2 and 5, as well as that of the sodium salt of the 4'-(4-carboxyphenyl)-2,2':6',2″-terpyridine ligand (cptpy), were determined by X-ray diffraction. Different techniques were used to evaluate the binding capacity to model DNA molecules, and MTT cytotoxicity assays were performed against four cell lines. Compounds 3, 4, and 5 showed little tendency to bind to DNA and exhibited poor biological activity. Compound 2 behaves as bonded to DNA probably through a covalent interaction, although its cytotoxicity was very low. Compound 1 and possibly 6, both of which contain a cptpy ligand, were able to intercalate with DNA, but toxicity was not observed for 6. However, compound 1 was active in all cell lines tested. Clonogenic assays and apoptosis induction studies were also performed on the PC-3 line for 1. The photodynamic behavior for complexes 1, 5, and 6 indicated that their nuclease activity was enhanced after irradiation at λ = 447 nm. The cell viability was significantly reduced only in the case of 5. The different behavior in the absence or presence of light makes complex 5 a potential prodrug of interest in PDT. Molecular docking studies followed by molecular dynamics simulations for 1 and the counterpart without the carboxyl group confirmed the experimental data that pointed to an intercalation mechanism. The cytotoxicity of 1 and the potential of 5 in PDT make them good candidates for subsequent conjugation, through the carboxyl group, to "selected peptides" which could facilitate the selective vectorization of the complex toward receptors that are overexpressed in

  16. High-school football and late-life risk of neurodegenerative syndromes, 1956–1970

    Science.gov (United States)

    Janssen, Pieter HH; Mandrekar, Jay; Mielke, Michelle M; Ahlskog, J. Eric; Boeve, Bradley F; Josephs, Keith; Savica, Rodolfo

    2017-01-01

    BACKGROUND Repeated head trauma has been associated with risk of neurodegenerative diseases. Few studies have evaluated the long-term risk of neurodegenerative diseases in collision sports like football. OBJECTIVE To assess whether athletes who played American varsity high-school football between 1956 and 1970 have an increased risk of neurodegenerative diseases later in life. PATIENTS AND METHODS We identified all male varsity football players between 1956 and 1970 in the public high schools of Rochester, Minnesota, compared to non-football-playing male varsity swimmers, wrestlers or basketball players. Using the records-linkage system of the Rochester Epidemiology Project, we ascertained the incidence of late-life neurodegenerative diseases: dementia, parkinsonism, or amyotrophic lateral sclerosis. We also recorded medical record-documented head trauma during high school years. RESULTS We identified 296 varsity football players and 190 athletes engaging in other sports. Football players had an increased risk of medically documented head trauma, especially if they played football for more than one year. Compared to non-football athletes, football players did not have an increased risk of neurodegenerative disease overall, nor the individual conditions of dementia, parkinsonism, or amyotrophic lateral sclerosis. CONCLUSION In this community based study, varsity high school football players from 1956 to 1970 did not have an increased risk of developing neurodegenerative diseases compared with athletes engaged in other varsity sports. This was from an era where there was a generally nihilistic view of concussion dangers, less protective equipment and without prohibition of spearing (head-first tackling). However, size and strength of players from prior eras may not be comparable to current high-school athletes. PMID:27979411

  17. Synthesis, Spectral, Thermogravimetric, XRD, Molecular Modelling and Potential Antibacterial Studies of Dimeric Complexes with Bis Bidentate ON–NO Donor Azo Dye Ligands

    Directory of Open Access Journals (Sweden)

    Bipin Bihari Mahapatra

    2013-01-01

    Full Text Available The dimeric complexes of Co(II, Ni(II, Cu(II, Zn(II, Cd(II, and Hg(II with two new symmetrical ON–NO donor bis bidentate (tetradentate azo dye ligands, LH2 = 4,4′-bis(4′-hydroxyquinolinolinylazodiphenylsulphone, and L′H2 = 4,4′-bis(acetoacetanilideazodiphenylsulphone have been synthesized. The metal complexes have been characterised by elemental analytical, conductance, magnetic susceptibility, IR, electronic spectra, ESR, NMR, thermogravimetry, X-ray diffraction (powder pattern spectra, and molecular modelling studies. The Co(II and Ni(II complexes are found to be octahedral, Cu(II complexes are distorted octahedral, and a tetrahedral stereochemistry has been assigned to Zn(II, Cd(II, and Hg(II complexes. The thermogravimetric study indicates that compounds are quite stable. The energy optimized structures are proposed using the semiempirical ZINDO/1 quantum mechanical calculations. The potential antibacterial study of the ligands and some metal complexes has been made with one gram positive bacteria Staphylococcus aureus and one gram negative bacteria E. coli which gives encouraging results. Both the Co(II complexes are found to possess monoclinic crystal system.

  18. Synthesis of new oxovanadium (IV) complexes of potential insulinmimetic activity with coumarin-3-carboxylic acid ligands and substituted derivatives

    International Nuclear Information System (INIS)

    Salas Fernandez, Paloma; Alvino de la Sota, Nora; Galli Rigo-Righi, Carla

    2013-01-01

    This work comprises the design and synthesis of four new oxovanadium (IV) complexes, a metal which possesses insulin-mimetic action. Coumarin-3-carboxylic acid and three of its 6 -and 6,8- derivatives were used as ligands. Coumarins are of interest due to their well-known biological properties and pharmacological applications; these include the insulino-sensibilizing effect of certain alcoxy-hydroxy-derivatives which might lead to the eventual existence of a synergetic effect with the active metal center. The synthesis of the vanadyl complexes was preceded by the synthesis of the coumarin-3-carboxylic acid and its 6-bromo- derivative, as well as the syntheses of three derivatives not previously reported: 6-bromo-8-metoxi-, 6-bromo-8-nitro-, and 6-bromo-8-hydroxy-, which were prepared by a Knoevenagel condensation reaction. The complexes, on their part, were prepared by a metathesis reaction between VOSO 4 and the corresponding ligands, on the basis of methods reported for other vanadyl complexes and under strict pH control. The coumarin-3-carboxylic ligands and the derivatives were characterized by 1 H-NMR-, FTIR- and UV-Vis-spectroscopy. In the case of the complexes, their paramagnetic character did not allow for NMR characterization, being thus identified by FT-IR-spectroscopy and by the quantitative determination of their vanadium contents. (author)

  19. Serum Levels of Progranulin Do Not Reflect Cerebrospinal Fluid Levels in Neurodegenerative Disease.

    Science.gov (United States)

    Wilke, Carlo; Gillardon, Frank; Deuschle, Christian; Dubois, Evelyn; Hobert, Markus A; Müller vom Hagen, Jennifer; Krüger, Stefanie; Biskup, Saskia; Blauwendraat, Cornelis; Hruscha, Michael; Kaeser, Stephan A; Heutink, Peter; Maetzler, Walter; Synofzik, Matthis

    2016-01-01

    Altered progranulin levels play a major role in neurodegenerative diseases, like Alzheimer's dementia (AD), frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), even in the absence of GRN mutations. Increasing progranulin levels could hereby provide a novel treatment strategy. However, knowledge on progranulin regulation in neurodegenerative diseases remains limited. We here demonstrate that cerebrospinal fluid progranulin levels do not correlate with its serum levels in AD, FTD and ALS, indicating a differential regulation of its central and peripheral levels in neurodegeneration. Blood progranulin levels thus do not reliably predict central nervous progranulin levels and their response to future progranulin-increasing therapeutics.

  20. Aging leads to altered microglial function that reduces brain resiliency increasing vulnerability to neurodegenerative diseases.

    Science.gov (United States)

    Bickford, Paula C; Flowers, Antwoine; Grimmig, Bethany

    2017-08-01

    Aging is the primary risk factor for many neurodegenerative diseases. Thus, understanding the basic biological changes that take place with aging that lead to the brain being less resilient to disease progression of neurodegenerative diseases such as Parkinson's disease or Alzheimer's disease or insults to the brain such as stroke or traumatic brain injuries. Clearly this will not cure the disease per se, yet increasing the ability of the brain to respond to injury could improve long term outcomes. The focus of this review is examining changes in microglia with age and possible therapeutic interventions involving the use of polyphenol rich dietary supplements. Published by Elsevier Inc.

  1. Energy saving analysis and management modeling based on index decomposition analysis integrated energy saving potential method: Application to complex chemical processes

    International Nuclear Information System (INIS)

    Geng, Zhiqiang; Gao, Huachao; Wang, Yanqing; Han, Yongming; Zhu, Qunxiong

    2017-01-01

    Highlights: • The integrated framework that combines IDA with energy-saving potential method is proposed. • Energy saving analysis and management framework of complex chemical processes is obtained. • This proposed method is efficient in energy optimization and carbon emissions of complex chemical processes. - Abstract: Energy saving and management of complex chemical processes play a crucial role in the sustainable development procedure. In order to analyze the effect of the technology, management level, and production structure having on energy efficiency and energy saving potential, this paper proposed a novel integrated framework that combines index decomposition analysis (IDA) with energy saving potential method. The IDA method can obtain the level of energy activity, energy hierarchy and energy intensity effectively based on data-drive to reflect the impact of energy usage. The energy saving potential method can verify the correctness of the improvement direction proposed by the IDA method. Meanwhile, energy efficiency improvement, energy consumption reduction and energy savings can be visually discovered by the proposed framework. The demonstration analysis of ethylene production has verified the practicality of the proposed method. Moreover, we can obtain the corresponding improvement for the ethylene production based on the demonstration analysis. The energy efficiency index and the energy saving potential of these worst months can be increased by 6.7% and 7.4%, respectively. And the carbon emissions can be reduced by 7.4–8.2%.

  2. Integration of potential and quasipotential geophysical fields and GPR data for delineation of buried karst terranes in complex environments

    Science.gov (United States)

    Eppelbaum, L. V.; Alperovich, L. S.; Zheludev, V.; Ezersky, M.; Al-Zoubi, A.; Levi, E.

    2012-04-01

    Karst is found on particularly soluble rocks, especially limestone, marble, and dolomite (carbonate rocks), but is also developed on gypsum and rock salt. Subsurface carbonate rocks involved in karst groundwater circulation considerably extend the active karst realm, to perhaps 14% of the world's land area (Price, 2009). The phenomenon of the solution weathering of limestone is the most widely known in the world. Active sinkholes growth appears under different industrial constructions, roads, railways, bridges, airports, buildings, etc. Regions with arid and semi-arid climate occupy about 30% of the Earth's land. Subsurface in arid regions is characterized by high variability of physical properties both on lateral and vertical that complicates geophysical survey analysis. Therefore for localization and monitoring of karst terranes effective and reliable geophysical methodologies should be applied. Such advanced methods were developed in microgravity (Eppelbaum et al., 2008; Eppelbaum, 2011b), magnetic (Khesin et al., 1996; Eppelbaum et al., 2000, 2004; Eppelbaum, 2011a), induced polarization (Khesin et al., 1997; Eppelbaum and Khesin, 2002), VLF (Eppelbaum and Khesin, 1992; Eppelbaum and Mishne, 2012), near-surface temperature (Eppelbaum, 2009), self-potential (Khesin et al., 1996; Eppelbaum and Khesin, 2002), and resistivity (Eppelbaum, 1999, 2007a) surveys. Application of some of these methodologies in the western and eastern shores of the Dead Sea area (e.g., Eppelbaum et al., 2008; Ezersky et al., 2010; Al-Zoubi et al., 2011) and in other regions of the world (Eppelbaum, 2007a) has shown their effectiveness. The common procedures for ring structure identification against the noise background and probabilistic-deterministic methods for recognizing the desired targets in complex media are presented in Khesin and Eppelbaum (1997), Eppelbaum et al. (2003), and Eppelbaum (2007b). For integrated analysis of different geophysical fields (including GPR images) intended

  3. Effect of Neuroinflammation on Synaptic Organization and Function in the Developing Brain: Implications for Neurodevelopmental and Neurodegenerative Disorders

    Directory of Open Access Journals (Sweden)

    Amin Mottahedin

    2017-07-01

    Full Text Available The brain is a plastic organ where both the intrinsic CNS milieu and extrinsic cues play important roles in shaping and wiring neural connections. The perinatal period constitutes a critical time in central nervous system development with extensive refinement of neural connections, which are highly sensitive to fetal and neonatal compromise, such as inflammatory challenges. Emerging evidence suggests that inflammatory cells in the brain such as microglia and astrocytes are pivotal in regulating synaptic structure and function. In this article, we will review the role of glia cells in synaptic physiology and pathophysiology, including microglia-mediated elimination of synapses. We propose that activation of the immune system dynamically affects synaptic organization and function in the developing brain. We will discuss the role of neuroinflammation in altered synaptic plasticity following perinatal inflammatory challenges and potential implications for neurodevelopmental and neurodegenerative disorders.

  4. Current status of treating neurodegenerative disease with induced pluripotent stem cells.

    Science.gov (United States)

    Pen, A E; Jensen, U B

    2017-01-01

    Degenerative diseases of the brain have proven challenging to treat, let alone cure. One of the treatment options is the use of stem cell therapy, which has been under investigation for several years. However, treatment with stem cells comes with a number of drawbacks, for instance the source of these cells. Currently, a number of options are tested to produce stem cells, although the main issues of quantity and ethics remain for most of them. Over recent years, the potential of induced pluripotent stem cells (iPSCs) has been widely investigated and these cells seem promising for production of numerous different tissues both in vitro and in vivo. One of the major advantages of iPSCs is that they can be made autologous and can provide a sufficient quantity of cells by culturing, making the use of other stem cell sources unnecessary. As the first descriptions of iPSC production with the transcription factors Sox2, Klf4, Oct4 and C-Myc, called the Yamanaka factors, a variety of methods has been developed to convert somatic cells from all germ layers to pluripotent stem cells. Improvement of these methods is necessary to increase the efficiency of reprogramming, the quality of pluripotency and the safety of these cells before use in human trials. This review focusses on the current accomplishments and remaining challenges in the production and use of iPSCs for treatment of neurodegenerative diseases of the brain such as Alzheimer's disease and Parkinson's disease. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Neuro degenerative diseases: clinical concerns; Les maladies neuro-degeneratives: problemes cliniques

    Energy Technology Data Exchange (ETDEWEB)

    Ibanez, V. [Hopitaux Universitaires de Geneve (HUG), Unite de Neuroimagerie, Dept. de Psychiatrie (Switzerland)

    2005-04-15

    Idiopathic Parkinson's disease (PD) and Alzheimer's disease (AD) are the main neuro-degenerative diseases (NDDs) seen clinically. They share some common clinical symptoms and neuro-pathological findings. The increase of life expectancy in the developed countries will inevitably contribute to enhance the prevalence of these diseases. Behavioral disorders, common in NDDs, will produce major care management challenges. Idiopathic Parkinson's disease corresponds to a histopathological diagnosis, based on the observation of a de-pigmentation and a neuronal loss in the substantia nigra, as well as on the presence of intra-neuronal inclusion bodies. AD is insidious with slowly progressive dementia in which the decline in memory constitutes the main complaint. The diagnosis of definite AD requires the presence of clinical criteria as well as the histopathological confirmation of brain lesions. The two main lesions are the presence of senile plaques and neuro-fibrillary tangles. Positron emission tomography (PET) explores cerebral metabolism and neurotransmitter kinetics in NDDs using principally [{sup 18}F]-deoxyglucose and [{sup 18}F]-dopa. Nigrostriatal dopaminergic function is altered in PD, as evidenced by the low uptake of [{sup 18}F]-dopa in the posterior putamen as compared to anterior putamen and caudate nucleus. In contrast, [{sup 18}F]-dopa uptake is equally depressed in all striatal structures in progressive supra-nuclear palsy. Regional glucose metabolism at rest is preserved in elderly once cerebral atrophy is taken into account. On the contrary, glucose metabolism is globally reduced in AD, with marked decrease in the parietal and temporal regions. PET has proved to be useful to study in vivo neurochemical processes in patients suffering from NDDs. The potential of this approach is still largely unexploited, and depends on new ligand production to establish early diagnosis and treatment follow-up. (author)

  6. Confocal Synaptology: Synaptic Rearrangements in Neurodegenerative Disorders and upon Nervous System Injury

    Directory of Open Access Journals (Sweden)

    Maja Vulovic

    2018-02-01

    Full Text Available The nervous system is a notable exception to the rule that the cell is the structural and functional unit of tissue systems and organs. The functional unit of the nervous system is the synapse, the contact between two nerve cells. As such, synapses are the foci of investigations of nervous system organization and function, as well as a potential readout for the progression of various disorders of the nervous system. In the past decade the development of antibodies specific to presynaptic terminals has enabled us to assess, at the optical, laser scanning microscopy level, these subcellular structures, and has provided a simple method for the quantification of various synapses. Indeed, excitatory (glutamatergic and inhibitory synapses can be visualized using antibodies against the respective vesicular transporters, and choline-acetyl transferase (ChAT immunoreactivity identifies cholinergic synapses throughout the central nervous system. Here we review the results of several studies in which these methods were used to estimate synaptic numbers as the structural equivalent of functional outcome measures in spinal cord and femoral nerve injuries, as well as in genetic mouse models of neurodegeneration, including Alzheimer’s disease (AD. The results implicate disease- and brain region-specific changes in specific types of synapses, which correlate well with the degree of functional deficit caused by the disease process. Additionally, results are reproducible between various studies and experimental paradigms, supporting the reliability of the method. To conclude, this quantitative approach enables fast and reliable estimation of the degree of the progression of neurodegenerative changes and can be used as a parameter of recovery in experimental models.

  7. Stab injury and device implantation within the brain results in inversely multiphasic neuroinflammatory and neurodegenerative responses

    Science.gov (United States)

    Potter, Kelsey A.; Buck, Amy C.; Self, Wade K.; Capadona, Jeffrey R.

    2012-08-01

    An estimated 25 million people in the US alone rely on implanted medical devices, ˜2.5 million implanted within the nervous system. Even though many devices perform adequately for years, the host response to medical devices often severely limits tissue integration and long-term performance. This host response is believed to be particularly limiting in the case of intracortical microelectrodes, where it has been shown that glial cell encapsulation and localized neuronal cell loss accompany intracortical microelectrode implantation. Since neuronal ensembles must be within ˜50 µm of the electrode to obtain neuronal spikes and local field potentials, developing a better understanding of the molecular and cellular environment at the device-tissue interface has been the subject of significant research. Unfortunately, immunohistochemical studies of scar maturation in correlation to device function have been inconclusive. Therefore, here we present a detailed quantitative study of the cellular events and the stability of the blood-brain barrier (BBB) following intracortical microelectrode implantation and cortical stab injury in a chronic survival model. We found two distinctly inverse multiphasic profiles for neuronal survival in device-implanted tissue compared to stab-injured animals. For chronically implanted animals, we observed a biphasic paradigm between blood-derived/trauma-induced and CNS-derived inflammatory markers driving neurodegeneration at the interface. In contrast, stab injured animals demonstrated a CNS-mediated neurodegenerative environment. Collectively these data provide valuable insight to the possibility of multiple roles of chronic neuroinflammatory events on BBB disruption and localized neurodegeneration, while also suggesting the importance to consider multiphasic neuroinflammatory kinetics in the design of therapeutic strategies for stabilizing neural interfaces.

  8. Neuroimaging Studies of Essential Tremor: How Well Do These Studies Support/Refute the Neurodegenerative Hypothesis?

    Directory of Open Access Journals (Sweden)

    Elan D. Louis

    2014-05-01

    Full Text Available Background: Tissue‐based research has recently led to a new patho‐mechanistic model of essential tremor (ET—the cerebellar degenerative model. We are not aware of a study that has reviewed the current neuroimaging evidence, focusing on whether the studies support or refute the neurodegenerative hypothesis of ET. This was our aim.Methods: References for this review were identified by searches of PubMed (1966 to February 2014.Results: Several neuroimaging methods have been used to study ET, most of them based on magnetic resonance imaging (MRI. The methods most specific to address the question of neurodegeneration are MRI‐based volumetry, magnetic resonance spectroscopy, and diffusion‐weighted imaging. Studies using each of these methods provide support for the presence of cerebellar degeneration in ET, finding reduced cerebellar brain volumes, consistent decreases in cerebellar N‐acetylaspartate, and increased mean diffusivity. Other neuroimaging techniques, such as functional MRI and positron emission tomography (PET are less specific, but still sensitive to potential neurodegeneration. These techniques are used for measuring a variety of brain functions and their impairment. Studies using these modalities also largely support cerebellar neuronal impairment. In particular, changes in 11C‐flumazenil binding in PET studies and changes in iron deposition in an MRI study provide evidence along these lines. The composite data point to neuronal impairment and likely neuronal degeneration in ET.Discussion: Recent years have seen a marked increase in the number of imaging studies of ET. As a whole, the combined data provide support for the presence of cerebellar neuronal degeneration in this disease.

  9. Synthesis, physicochemical characterization, DFT calculation and biological activities of Fe(III) and Co(II)-omeprazole complexes. Potential application in the Helicobacter pylori eradication

    Science.gov (United States)

    Russo, Marcos G.; Vega Hissi, Esteban G.; Rizzi, Alberto C.; Brondino, Carlos D.; Salinas Ibañez, Ángel G.; Vega, Alba E.; Silva, Humberto J.; Mercader, Roberto; Narda, Griselda E.

    2014-03-01

    The reaction between the antiulcer agent omeprazole (OMZ) with Fe(III) and Co(II) ions was studied, observing a high ability to form metal complexes. The isolated microcrystalline solid complexes were characterized by elemental analysis, X-ray powder diffraction (XRPD), Scanning Electron Microscopy (SEM), magnetic measurements, thermal study, FTIR, UV-Visible, Mössbauer, electronic paramagnetic resonance (EPR), and DFT calculations. The metal-ligand ratio for both complexes was 1:2 determined by elemental and thermal analysis. FTIR spectroscopy showed that OMZ acts as a neutral bidentate ligand through the pyridinic nitrogen of the benzimidazole ring and the oxygen atom of the sulfoxide group, forming a five-membered ring chelate. Electronic, Mössbauer, and EPR spectra together with magnetic measurements indicate a distorted octahedral geometry around the metal ions, where the coordination sphere is completed by two water molecules. SEM and XRPD were used to characterize the morphology and the crystal nature of the complexes. The most favorable conformation for the Fe(III)-OMZ and Co(II)-OMZ complexes was obtained by DFT calculations by using B3LYP/6-31G(d)&LanL2DZ//B3LYP/3-21G(d)&LanL2DZ basis set. Studies of solubility along with the antibacterial activity against Helicobacter pylori for OMZ and its Co(II) and Fe(III) complexes are also reported. Free OMZ and both metal complexes showed antibacterial activity against H. pylori. Co(II)-OMZ presented a minimal inhibitory concentration ˜32 times lower than that of OMZ and ˜65 lower than Fe(III)-OMZ, revealing its promising potential use for the treatment of gastric pathologies associated with the Gram negative bacteria. The morphological changes observed in the cell membrane of the bacteria after the incubation with the metal-complexes were also analyzed by SEM microscopy. The antimicrobial activity of the complexes was proved by the viability test.

  10. Examining the Potential of Web-Based Multimedia to Support Complex Fine Motor Skill Learning: An Empirical Study

    Science.gov (United States)

    Papastergiou, Marina; Pollatou, Elisana; Theofylaktou, Ioannis; Karadimou, Konstantina

    2014-01-01

    Research on the utilization of the Web for complex fine motor skill learning that involves whole body movements is still scarce. The aim of this study was to evaluate the impact of the introduction of a multimedia web-based learning environment, which was targeted at a rhythmic gymnastics routine consisting of eight fine motor skills, into an…

  11. Physiological Levels of Nitric Oxide Diminish Mitochondrial Superoxide. Potential Role of Mitochondrial Dinitrosyl Iron Complexes and Nitrosothiols

    Directory of Open Access Journals (Sweden)

    Sergey I. Dikalov

    2017-11-01

    Full Text Available Mitochondria are the major source of superoxide radicals and superoxide overproduction contributes to cardiovascular diseases and metabolic disorders. Endothelial dysfunction and diminished nitric oxide levels are early steps in the development of these pathological conditions. It is known that physiological production of nitric oxide reduces oxidative stress and inflammation, however, the precise mechanism of “antioxidant” effect of nitric oxide is not clear. In this work we tested the hypothesis that physiological levels of nitric oxide diminish mitochondrial superoxide production without inhibition of mitochondrial respiration. In order to test this hypothesis we analyzed effect of low physiological fluxes of nitric oxide (20 nM/min on superoxide and hydrogen peroxide production by ESR spin probes and Amplex Red in isolated rat brain mitochondria. Indeed, low levels of nitric oxide substantially attenuated both basal and antimycin A-stimulated production of reactive oxygen species in the presence of succinate or glutamate/malate as mitochondrial substrates. Furthermore, slow releasing NO donor DPTA-NONOate (100 μM did not change oxygen consumption in State 4 and State 3. However, the NO-donor strongly inhibited oxygen consumption in the presence of uncoupling agent CCCP, which is likely associated with inhibition of the over-reduced complex IV in uncoupled mitochondria. We have examined accumulation of dinitrosyl iron complexes and nitrosothiols in mitochondria treated with fast-releasing NO donor MAHMA NONOate (10 μM for 30 min until complete release of NO. Following treatment with NO donor, mitochondria were frozen for direct detection of dinitrosyl iron complexes using Electron Spin Resonance (ESR while accumulation of nitrosothiols was measured by ferrous-N-Methyl-D-glucamine dithiocarbamate complex, Fe(MGD2, in lysed mitochondria. Treatment of mitochondria with NO-donor gave rise to ESR signal of dinitrosyl iron complexes while ESR

  12. Analysis of neurodegenerative Mendelian genes in clinically diagnosed Alzheimer Disease.

    Directory of Open Access Journals (Sweden)

    Maria Victoria Fernández

    2017-11-01

    Full Text Available Alzheimer disease (AD, Frontotemporal lobar degeneration (FTD, Amyotrophic lateral sclerosis (ALS and Parkinson disease (PD have a certain degree of clinical, pathological and molecular overlap. Previous studies indicate that causative mutations in AD and FTD/ALS genes can be found in clinical familial AD. We examined the presence of causative and low frequency coding variants in the AD, FTD, ALS and PD Mendelian genes, in over 450 families with clinical history of AD and over 11,710 sporadic cases and cognitive normal participants from North America. Known pathogenic mutations were found in 1.05% of the sporadic cases, in 0.69% of the cognitively normal participants and in 4.22% of the families. A trend towards enrichment, albeit non-significant, was observed for most AD, FTD and PD genes. Only PSEN1 and PINK1 showed consistent association with AD cases when we used ExAC as the control population. These results suggest that current study designs may contain heterogeneity and contamination of the control population, and that current statistical methods for the discovery of novel genes with real pathogenic variants in complex late onset diseases may be inadequate or underpowered to identify genes carrying pathogenic mutations.

  13. Radiosynthesis and biodistribution of 99mTc-tricarbonyl complex of temafloxacin dithiocarbamate. A potential Streptococci pneumoniae infection radiotracer

    International Nuclear Information System (INIS)

    Syed Qaiser Shah; Muhammad Rafiullah Khan

    2011-01-01

    In the current investigation the complexation of derivatized temafloxacin with 99m Tc using [ 99m Tc(CO) 3 (H 2 O) 3 ] + precursor was assessed. The tricarbonyl complex of the temafloxacin dithiocarbamate ( 99m Tc(CO) 3 -TAND) was characterized in terms of radiochemical purity (RCP) yield in saline, in vitro radiochemical stability in serum, in vitro binding with Streptococci pneumoniae and biodistribution in male Wister rats (MWR) artificially infected with living and heat killed Streptococci pneumoniae. The 99m Tc(CO) 3 -TAND complex showed 98.10 ± 15% RCP value at 30 min of the reconstitution and remained more than 90% stable up to 120 min in normal saline at room temperature. In serum a stable behavior with the appearance of 15.30% unwanted side product up to 16 h of incubation was observed. A saturated in vitro binding with Streptococci pneumoniae was observed. The complex showed almost six times higher uptake in the infected muscle as compared to the inflamed and normal muscles of the MWR infected with living Streptococci pneumoniae. Insignificant difference in the uptake of the tracer in the infected, inflamed and normal muscles of the MWR infected with heat killed Streptococci pneumoniae was noted. Based on the elevated RCP in saline, in vitro stability in serum at 37 deg C, saturated in vitro binding with pathogens and better biodistribution behavior with higher accumulation of the tracer in target organs confirmed the suitability of the 99m Tc(CO) 3 -TAND complex as promising infection radiotracer. (author)

  14. The Diagnosis and Understanding of Apraxia of Speech: Why Including Neurodegenerative Etiologies May Be Important

    Science.gov (United States)

    Duffy, Joseph R.; Josephs, Keith A.

    2012-01-01

    Purpose: To discuss apraxia of speech (AOS) as it occurs in neurodegenerative disease (progressive AOS [PAOS]) and how its careful study may contribute to general concepts of AOS and help refine its diagnostic criteria. Method: The article summarizes our current understanding of the clinical features and neuroanatomical and pathologic correlates…

  15. High School Football and Late-Life Risk of Neurodegenerative Syndromes, 1956-1970.

    Science.gov (United States)

    Janssen, Pieter H H; Mandrekar, Jay; Mielke, Michelle M; Ahlskog, J Eric; Boeve, Bradley F; Josephs, Keith; Savica, Rodolfo

    2017-01-01

    To assess whether athletes who played American varsity high school football between 1956 and 1970 have an increased risk of neurodegenerative diseases later in life. We identified all male varsity football players between 1956 and 1970 in the public high schools of Rochester, Minnesota, and non-football-playing male varsity swimmers, wrestlers, and basketball players. Using the medical records linkage system of the Rochester Epidemiology Project, we ascertained the incidence of late-life neurodegenerative diseases: dementia, parkinsonism, and amyotrophic lateral sclerosis. We also recorded medical record-documented head trauma during high school years. We identified 296 varsity football players and 190 athletes engaging in other sports. Football players had an increased risk of medically documented head trauma, especially if they played football for more than 1 year. Compared with nonfootball athletes, football players did not have an increased risk of neurodegenerative disease overall or of the individual conditions of dementia, parkinsonism, and amyotrophic lateral sclerosis. In this community-based study, varsity high school football players from 1956 to 1970 did not have an increased risk of neurodegenerative diseases compared with athletes engaged in other varsity sports. This was from an era when there was a generally nihilistic view of concussion dangers, less protective equipment, and no prohibition of spearing (head-first tackling). However, the size and strength of players from previous eras may not be comparable with that of current high school athletes. Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  16. The Central Biobank and Virtual Biobank of BIOMARKAPD: A Resource for Studies on Neurodegenerative Diseases

    NARCIS (Netherlands)

    Reijs, B.L.; Teunissen, C.E.; Goncharenko, N.; Betsou, F.; Blennow, K.; Baldeiras, I.; Brosseron, F.; Cavedo, E.; Fladby, T.; Froelich, L.; Gabryelewicz, T.; Gurvit, H.; Kapaki, E.; Koson, P.; Kulic, L.; Lehmann, S.; Lewczuk, P.; Lleo, A.; Maetzler, W.; Mendonca, A. de; Miller, A.M.; Molinuevo, J.L.; Mollenhauer, B.; Parnetti, L.; Rot, U.; Schneider, A.; Simonsen, A.H.; Tagliavini, F.; Tsolaki, M.; Verbeek, M.M.; Verhey, F.R.J.; Zboch, M.; Winblad, B.; Scheltens, P.; Zetterberg, H.; Visser, P.J.

    2015-01-01

    Biobanks are important resources for biomarker discovery and assay development. Biomarkers for Alzheimer's and Parkinson's disease (BIOMARKAPD) is a European multicenter study, funded by the EU Joint Programme-Neurodegenerative Disease Research, which aims to improve the clinical use of body fluid

  17. Isoprostanes and Neuroprostanes as Biomarkers of Oxidative Stress in Neurodegenerative Diseases

    Directory of Open Access Journals (Sweden)

    Elżbieta Miller

    2014-01-01

    Full Text Available Accumulating data shows that oxidative stress plays a crucial role in neurodegenerative disorders. The literature data indicate that in vivo or postmortem cerebrospinal fluid and brain tissue levels of F2-isoprostanes (F2-IsoPs especially F4-neuroprotanes (F4-NPs are significantly increased in some neurodegenerative diseases: multiple sclerosis, Alzheimer's disease, Huntington's disease, and Creutzfeldt-Jakob disease. Central nervous system is the most metabolically active organ of the body characterized by high requirement for oxygen and relatively low antioxidative activity, what makes neurons and glia highly susceptible to destruction by reactive oxygen/nitrogen species and neurodegeneration. The discovery of F2-IsoPs and F4-NPs as markers of lipid peroxidation caused by the free radicals has opened up new areas of investigation regarding the role of oxidative stress in the pathogenesis of human neurodegenerative diseases. This review focuses on the relationship between F2-IsoPs and F4-NPs as biomarkers of oxidative stress and neurodegenerative diseases. We summarize the knowledge of these novel biomarkers of oxidative stress and the advantages of monitoring their formation to better define the involvement of oxidative stress in neurological diseases.

  18. Neurodegenerative diseases : Lessons from genome-wide screens in small model organisms

    NARCIS (Netherlands)

    van Ham, Tjakko J.; Breitling, Rainer; Swertz, Morris A.; Nollen, Ellen A. A.

    2009-01-01

    Various age-related neurodegenerative diseases, including Parkinson's disease, polyglutamine expansion diseases and Alzheimer's disease, are associated with the accumulation of misfolded proteins in aggregates in the brain. How and why these proteins form aggregates and cause disease is still poorly

  19. Percutaneous Endoscopic Gastrostomy Tube Insertion in Neurodegenerative Disease: A Retrospective Study and Literature Review

    Directory of Open Access Journals (Sweden)

    Pamela Sarkar

    2017-05-01

    Full Text Available Background/Aims With the notable exceptions of dementia, stroke, and motor neuron disease, relatively little is known about the safety and utility of percutaneous endoscopic gastrostomy (PEG tube insertion in patients with neurodegenerative disease. We aimed to determine the safety and utility of PEG feeding in the context of neurodegenerative disease and to complete a literature review in order to identify whether particular factors need to be considered to improve safety and outcome. Methods A retrospective case note review of patients referred for PEG insertion by neurologists in a single neuroscience center was conducted according to a pre-determined set of standards. For the literature review, we identified references from searches of PubMed, mainly with the search items “percutaneous endoscopic gastrostomy” and “neurology” or “neurodegenerative disease.” Results Short-term mortality and morbidity associated with PEG in patients with neurological disease were significant. Age greater than 75 years was associated with poor outcome, and a trend toward adverse outcome was observed in patients with low serum albumin. Conclusions This study highlights the relatively high risk of PEG in patients with neurodegenerative disease. We present points for consideration to improve outcome in this particularly vulnerable group of patients.

  20. Relationships between Rapid Eye Movement Sleep Behavior Disorder and Neurodegenerative Diseases: Clinical Assessments, Biomarkers, and Treatment

    Directory of Open Access Journals (Sweden)

    Min Li

    2018-01-01

    Conclusions: More longitudinal studies should be conducted to evaluate the predictive value of biomarkers of RBD. Moreover, because the glucose and dopamine metabolisms are not specific for assessing cognitive cognition, the molecular metabolism directly related to cognition should be investigated. There is a need for more treatment trials to determine the effectiveness of interventions of RBD on preventing the conversion to neurodegenerative diseases.

  1. Ocimum basilicum improve chronic stress-induced neurodegenerative changes in mice hippocampus.

    Science.gov (United States)

    Ayuob, Nasra Naeim; El Wahab, Manal Galal Abd; Ali, Soad Shaker; Abdel-Tawab, Hanem Saad

    2018-01-22

    Alzheimer's disease (AD), one of the progressive neurodegenerative diseases might be associated with exposure to stress and altered living conditions. This study aimed to evaluate the effectiveness of Ocimum basilicum (OB) essential oils in improving the neurodegenerative-like changes induced in mice after exposed to chronic unpredictable mild stress (CUMS). Forty male Swiss albino mice divided into four groups (n = 10); the control, CUMS, CUMS + Fluoxetine, CUMS + OB were used. Behavioral tests, serum corticosterone level, hippocampus protein level of the glucocorticoid receptors (GRs) and brain-dreived neurotropic factor (BDNF) were determined after exposure to CUMS. Hippocampus was histopathologically examined. Data were analyzed using statistical package for the social sciences (SPSS) and P value of less than 0.05 was considered significant. OB diminished the depression manifestation as well as impaired short term memory observed in the mice after exposure to the CUMS as evidenced by the forced swimming and elevated plus maze test. OB also up-regulated the serum corticosterone level, hippocampal protein level of the glucocorticoid receptor and the brain-derived neurotropic factor and reduced the neurodegenerative and atrophic changes induced in the hippocampus after exposure to CUMS. Essential oils of OB alleviated the memory impairment and hippocampal neurodegenerative changes induced by exposure to the chronic unpredictable stress indicating that it is the time to test its effectiveness on patients suffering from Alzheimer disease.

  2. Pig Models of Neurodegenerative Disorders: Utilization in Cell Replacement-Based Preclinical Safety and Efficacy Studies

    Czech Academy of Sciences Publication Activity Database

    Doležalová, D.; Hruška-Plocháň, M.; Bjarkam, C. R.; Sorensen, J. C. H.; Cunningham, M.; Weingarten, D.; Ciacci, J. D.; Juhás, Štefan; Juhásová, Jana; Motlík, Jan; Hefferan, M. P.; Hazel, T.; Johe, K.; Carromeu, C.; Muotri, A.; Bui, J. D.; Strnádel, J.; Marsala, M.

    2014-01-01

    Roč. 522, č. 12 (2014), s. 2784-2801 ISSN 0021-9967 R&D Projects: GA TA ČR(CZ) TA01011466; GA MŠk ED2.1.00/03.0124 Institutional support: RVO:67985904 Keywords : pig * neurodegenerative models * stem cells Subject RIV: FH - Neurology Impact factor: 3.225, year: 2014

  3. Astrocytes and endoplasmic reticulum stress: A bridge between obesity and neurodegenerative diseases.

    Science.gov (United States)

    Martin-Jiménez, Cynthia A; García-Vega, Ángela; Cabezas, Ricardo; Aliev, Gjumrakch; Echeverria, Valentina; González, Janneth; Barreto, George E

    2017-11-01

    Endoplasmic reticulum (ER) is a subcellular organelle involved in protein folding and processing. ER stress constitutes a cellular process characterized by accumulation of misfolded proteins, impaired lipid metabolism and induction of inflammatory responses. ER stress has been suggested to be involved in several human pathologies, including neurodegenerative diseases and obesity. Different studies have shown that both neurodegenerative diseases and obesity trigger similar cellular responses to ER stress. Moreover, both diseases are assessed in astrocytes as evidences suggest these cells as key regulators of brain homeostasis. However, the exact contributions to the effects of ER stress in astrocytes in the various neurodegenerative diseases and its relation with obesity are not well known. Here, we discuss recent advances in the understanding of molecular mechanisms that regulate ER stress-related disorders in astrocytes such as obesity and neurodegeneration. Moreover, we outline the correlation between the activated proteins of the unfolded protein response (UPR) in these pathological conditions in order to identify possible therapeutic targets for ER stress in astrocytes. We show that ER stress in astrocytes shares UPR activation pathways during both obesity and neurodegenerative diseases, demonstrating that UPR related proteins like ER chaperone GRP 78/Bip, PERK pathway and other exogenous molecules ameliorate UPR response and promote neuroprotection. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Home video monitoring system for neurodegenerative diseases based on commercial HD cameras

    NARCIS (Netherlands)

    Abramiuc, B.; Zinger, S.; De With, P.H.N.; De Vries-Farrouh, N.; Van Gilst, M.M.; Bloem, B.; Overeem, S.

    2016-01-01

    Neurodegenerative disease (ND) is an umbrella term for chronic disorders that are characterized by severe joint cognitive-motor impairments, which are difficult to evaluate on a frequent basis. HD cameras in the home environment could extend and enhance the diagnosis process and could lead to better

  5. NeuroX, a fast and efficient genotyping platform for investigation of neurodegenerative diseases

    NARCIS (Netherlands)

    Nalls, M.A.; Bras, J.; Hernandez, D.G.; Keller, M.F.; Majounie, E.; Renton, A.E.; Saad, M.; Jansen, I.E.; Guerreiro, R.; Lubbe, S.; Plagnol, V.; Gibbs, J.R.; Schulte, C.; Pankratz, N.; Sutherland, M.; Bertram, L.; Lill, C.M.; DeStefano, A.L.; Faroud, T.; Eriksson, N.; Tung, J.Y.; Edsall, C.; Nichols, N.; Brooks, J.; Arepalli, S.; Pliner, H.; Letson, C.; Heutink, P.; Martinez, M.; Gasser, T.; Traynor, B.J.; Wood, N.; Hardy, J.; Singleton, A.B.

    2015-01-01

    Our objective was to design a genotyping platform that would allow rapid genetic characterization of samples in the context of genetic mutations and risk factors associated with common neurodegenerative diseases. The platform needed to be relatively affordable, rapid to deploy, and use a common and

  6. Combination Comprising Parthenolide For Use In The Treatment Of Alzheimer's Disease And Other Neurodegenerative Disorders

    KAUST Repository

    Bajic, Vladimir B.

    2015-06-18

    The present invention generally concerns particular methods and compositions for treatment of a neurodegenerative disease, such as Alzheimer\\'s Disease. In particular embodiments, there is a composition comprising Parthenolide and a second agent, including an inhibitor of TLR4/MD-2/CD14, nAChR agonist, Resatorvid, Curcumin, Tilorone or a Tilorone analog, or a combination thereof.

  7. Badass gullies: Fluvio-mass-movement gully complexes in New Zealand's East Coast region, and potential for remediation

    Science.gov (United States)

    Marden, Michael; Fuller, Ian C.; Herzig, Alexander; Betts, Harley D.

    2018-04-01

    This paper reviews gully erosion in the East Coast region of New Zealand's North Island and conceptualises fluvio-mass-movement gully complexes as badass gully systems. Tectonic setting and lithological control, with steep slopes and a climate influenced by tropical cyclones, predispose hill country in the East Coast region to gully erosion. The clearance of indigenous forest since the late 1800s has dramatically increased catchment erosion and paved the way for development of large-scale fluvio-mass-movement gully complexes. These features are a composite of fluvial and mass movement processes. They are conceptualised as 'badass' by not conforming to any existing gully model and by generating disproportionate results in East Coast catchment sediment cascades. Their remediation is discussed, but their nature means that prevention is better than a cure.

  8. Effect of task complexity on intelligence and neural efficiency in children: an event-related potential study.

    Science.gov (United States)

    Zhang, Qiong; Shi, Jiannong; Luo, Yuejia; Liu, Sainan; Yang, Jie; Shen, Mowei

    2007-10-08

    The present study investigates the effects of task complexity, intelligence and neural efficiency on children's performance on an Elementary Cognitive Task. Twenty-three children were divided into two groups on the basis of their Raven Progressive Matrix scores and were then asked to complete a choice reaction task with two test conditions. We recorded the electroencephalogram and calculated the peak latencies and amplitudes for anteriorly distributed P225, N380 and late positive component. Our results suggested shorter late positive component latencies in brighter children, possibly reflecting a higher processing speed in these individuals. Increased P225 amplitude and increased N380 amplitudes for brighter children may indicate a more efficient allocation of attention for brighter children. No moderating effect of task complexity on brain-intelligence relationship was found.

  9. Reduced GABAA receptor density contralateral to a potentially epileptogenic MRI abnormality in a patient with complex partial seizures

    International Nuclear Information System (INIS)

    Kuwert, T.; Stodieck, S.R.G.; Puskas, C.; Diehl, B.; Puskas, Z.; Schuierer, G.; Vollet, B.; Schober, O.

    1996-01-01

    Imaging cerebral GABA A receptor density (GRD) with single-photon emission tomography (SPET) and iodine-123 iomazenil is highly accurate in lateralizing epileptogenic foci in patients with complex partial seizures of temporal origin. Limited knowledge exists on how iomazenil SPET compares with magnetic resonance imaging (MRI) in this regard. We present a patient with complex partial seizures in whom MRI had identified an arachnoid cyst anterior to the tip of the left temporal lobe. Contralaterally to this structural abnormality, interictal electroencephalography (EEG) performed after sleep deprivation disclosed an intermittent frontotemporal dysrhythmic focus with slow and sharp waves. On iomazenil SPET images GRD was significantly reduced in the right temporal lobe and thus contralaterally to the MRI abnormality, but ipsilaterally to the pathological EEG findings. These data suggest that iomazenil SPET may significantly contribute to the presurgical evaluation of epileptic patients even when MRI identifies potentialy epileptogenic structural lesions. (orig.)

  10. Activity, polypeptide and gene identification of thylakoid Ndh complex in trees: potential physiological relevance of fluorescence assays.

    Science.gov (United States)

    Serrot, Patricia H; Sabater, Bartolomé; Martín, Mercedes

    2012-09-01

    Three evergreen (Laurus nobilis, Viburnum tinus and Thuja plicata) and two autumnal abscission deciduous trees (Cydonia oblonga and Prunus domestica) have been investigated for the presence (zymogram and immunodetection) and functionality (post-illumination chlorophyll fluorescence) of the thylakoid Ndh complex. The presence of encoding ndh genes has also been investigated in T. plicata. Western assays allowed tentative identification of zymogram NADH dehydrogenase bands corresponding to the Ndh complex after native electrophoresis of solubilized fractions from L. nobilis, V. tinus, C. oblonga and P. domestica leaves, but not in those of T. plicata. However, Ndh subunits were detected after SDS-PAGE of thylakoid solubilized proteins of T. plicata. The leaves of the five plants showed the post-illumination chlorophyll fluorescence increase dependent on the presence of active Ndh complex. The fluorescence increase was higher in autumn in deciduous, but not in evergreen trees, which suggests that the thylakoid Ndh complex could be involved in autumnal leaf senescence. Two ndhB genes were sequenced from T. plicata that differ at the 350 bp 3' end sequence. Comparison with the mRNA revealed that ndhB genes have a 707-bp type II intron between exons 1 (723 bp) and 2 (729 bp) and that the UCA 259th codon is edited to UUA in mRNA. Phylogenetically, the ndhB